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1

Multifunctional Magnetic

Nanoparticles Bio-application

2

Multifunctional magnetic nanoparticles

components

Magnetic Nanoparticles (MNP)

Gold NPs (GNP)

Nanosilicas (solgels)

Modified Biomolecules- Antibody

- Aptamer

- Single strand DNA

- SiRNA

- hellip

3

4

La Mer theory

and

5

MNP synthetic methods

Coprecipitation

Sol-gel synthesis

Microemulsion synthesis

Sonochemical reaction

Hydrothermal reaction

Thermal decomposition

Electrospray synthesis

Laser pyrolysis

6

7

1- Coprecipitation methods

Morphology Size and Quantity of MNP have been

control by a series of experimental parameters such as

- pH

- Reaction temperature

- Precursor

Disadvantage Expanded size distribution

8

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Multifunctional Magnetic

Nanoparticles Bio-application

2

Multifunctional magnetic nanoparticles

components

Magnetic Nanoparticles (MNP)

Gold NPs (GNP)

Nanosilicas (solgels)

Modified Biomolecules- Antibody

- Aptamer

- Single strand DNA

- SiRNA

- hellip

3

4

La Mer theory

and

5

MNP synthetic methods

Coprecipitation

Sol-gel synthesis

Microemulsion synthesis

Sonochemical reaction

Hydrothermal reaction

Thermal decomposition

Electrospray synthesis

Laser pyrolysis

6

7

1- Coprecipitation methods

Morphology Size and Quantity of MNP have been

control by a series of experimental parameters such as

- pH

- Reaction temperature

- Precursor

Disadvantage Expanded size distribution

8

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Multifunctional magnetic nanoparticles

components

Magnetic Nanoparticles (MNP)

Gold NPs (GNP)

Nanosilicas (solgels)

Modified Biomolecules- Antibody

- Aptamer

- Single strand DNA

- SiRNA

- hellip

3

4

La Mer theory

and

5

MNP synthetic methods

Coprecipitation

Sol-gel synthesis

Microemulsion synthesis

Sonochemical reaction

Hydrothermal reaction

Thermal decomposition

Electrospray synthesis

Laser pyrolysis

6

7

1- Coprecipitation methods

Morphology Size and Quantity of MNP have been

control by a series of experimental parameters such as

- pH

- Reaction temperature

- Precursor

Disadvantage Expanded size distribution

8

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

4

La Mer theory

and

5

MNP synthetic methods

Coprecipitation

Sol-gel synthesis

Microemulsion synthesis

Sonochemical reaction

Hydrothermal reaction

Thermal decomposition

Electrospray synthesis

Laser pyrolysis

6

7

1- Coprecipitation methods

Morphology Size and Quantity of MNP have been

control by a series of experimental parameters such as

- pH

- Reaction temperature

- Precursor

Disadvantage Expanded size distribution

8

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

La Mer theory

and

5

MNP synthetic methods

Coprecipitation

Sol-gel synthesis

Microemulsion synthesis

Sonochemical reaction

Hydrothermal reaction

Thermal decomposition

Electrospray synthesis

Laser pyrolysis

6

7

1- Coprecipitation methods

Morphology Size and Quantity of MNP have been

control by a series of experimental parameters such as

- pH

- Reaction temperature

- Precursor

Disadvantage Expanded size distribution

8

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

MNP synthetic methods

Coprecipitation

Sol-gel synthesis

Microemulsion synthesis

Sonochemical reaction

Hydrothermal reaction

Thermal decomposition

Electrospray synthesis

Laser pyrolysis

6

7

1- Coprecipitation methods

Morphology Size and Quantity of MNP have been

control by a series of experimental parameters such as

- pH

- Reaction temperature

- Precursor

Disadvantage Expanded size distribution

8

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

7

1- Coprecipitation methods

Morphology Size and Quantity of MNP have been

control by a series of experimental parameters such as

- pH

- Reaction temperature

- Precursor

Disadvantage Expanded size distribution

8

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

1- Coprecipitation methods

Morphology Size and Quantity of MNP have been

control by a series of experimental parameters such as

- pH

- Reaction temperature

- Precursor

Disadvantage Expanded size distribution

8

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

2- New modified Coprecipitation

Ref2 Milichko et al Nanoscale Research Letters 2013 8317 9

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

3- Modified Hydrothermal reaction

10

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

4- Thermal decomposition

MNP synthesized by the thermal decomposition of Fe(acac)3 in PEG and in MPEG

Tian XH Wei F Wang TX Wang P Int J Nanomedicine 201271031-4111

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

5- Sol-gel synthesis

Porous or hollow iron oxide nanostructures have

been synthesized by sol gel process

12

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Wrapndash BakendashPeel process

Reduction

MagnetiteSilicaMagnetite

Removal of

silica using

NaOH

β-FeOOH β-FeOOHSilicaHematiteSilica

Removal of

silica using

NaOH

Hematite

Silica

coating

Heat

treatment

13

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

6- Kirkendall process(Nano hollow structures)

The rate of oxygen diffusion towards the core is slower than

diffusion of iron outwards from the core leading to the formation

of hollow structures

Fe

Fe3O4 Fe3O4

Fe

Fe3O4

Amorphous Crystalline

1 Oxidation by

(CH3)3NO

2 Heating

gt200oC

14

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

15

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Colloidal stability by citrate

Au Au

- ---- - -

- ---O O

OO O

O

O H

Lowis bond

16

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Color is size dependent

Size(nm) Emission(nm) Suspension in

5 515-520 PBSsurfactant

10 515-520 PBSsurfactant

15 520 PBSsurfactant

20 524 PBSsurfactant

30 526 PBSsurfactant

40 530 PBSsurfactant

50 535 PBSsurfactant

60 540 PBSsurfactant

80 553 PBSsurfactant

100 572 PBSsurfactant

17

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

18

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

GNP Advantage

- Color size dependent

- No toxicity

- DNA strong bonding

- Thiol covalent bond

19

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

The surface Hydrophobicity can be modified by

thiol compound

20

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

The surface self-assembling by thiol compound

21

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

GNP Application

Different bio sensor based self assemble design

22

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

23

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

The Sol-Gel Process is

a method for producing solid materials from small molecules

inn RT The method is used for the fabrication of metal oxides

especially the oxides of silicon and titanium

24

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Alkoxide-sol-gel-method-preparation

25

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

HydrolysisCondensation

26

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

27

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Why silica sol-gel coating

- Biocompatible

- Functionalization

- Physical trapping

- Chemical stability

- Physical stability

28

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

I Byun AW Coleman B Kim Micromech Microeng 23 (2013) 085016 29

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Three Dimensional

Multi Dimensional matrix

One Dimensional

Layer by layer coatingSi

OR

ORRORO

Si

OR

RORO

NH2

Si

OR

RORO

SH

Si

OR

RORO O

O

n

Si

OR

RORO

HN

NH

NH2

Si

R

RRORO

30

Two Dimensional

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Physical trapping in sol gel

31

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

32

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

apto ldquoto fitrdquo

mer ldquosmallest unit of repeating structurerdquo

What is an Aptamer

Oligonucleotide or Peptide

molecules that bind to a specific

target molecule

33

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Types of Aptamer

- ssDNA

- dsDNA

- RNA

- Peptide

34

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

SELEX(Systematic Evolution of Ligands by Exponential Enrichment)

Selection of ligand sequences that bind to a target

partitioning of aptamers from

non-aptamers via affinity methods

amplification of bound aptamers

35

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Targets of Aptamers

- Small Molecules

- Proteins

- Nucleic Acids

- Cells

- Tissues

- Organisms

lysozym Thrombin HIV TAR Hemin Interferon γ Vascular

endotherial growth factor (VEGF) Prostate specific antigen(PSA)

Dopamine hellip 36

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

37

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

MFMNP Design

Core Shell

Dumbbell Structure

Multicomponent Hybrid NP

38

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

39

Polymer Shell

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Core Shell

Metal alloy

(FePt)

Magnetic nanolayer

(Fe3O4)

Thermal decomposition

of Fe(acac)3 on FePt

Magnetic NP

(Fe3O4)

Metal alloy

(Au Ag)

(Fe3O4) in Au3+ solution

at reduction condition

40

1 Core Shell structure

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

41

- Mix of NP during the growth of nanocrystals

- Sol-gel process

Core Shell synthesis

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

2 Dumbbell structures

42

- Mix of NP during the growth of nanocrystals

- Thermal rearrangement

- self-assemble at a liquid-liquid interface

- Functional sol-gel matrix

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

3 Multicomponent Hybrid NPs

Self-assembly processes provide an approach to

fabricating multicomponent hybrid NPs with

integrated multifunctionality

43

- Surfactant polymers

- Sol-gel process

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

44

Poly(lactico-co-glycolicacid)

(PLGA)

Poly(L-lysine)-PEG-folate

(PLL-PEG-FOL)

By mechanical

stirring at RT

in CH3Cl

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

45

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

46

W Lu SR Arumugam D Senapati ACSNANO 2010 4(3) 1739ndash1749

GNP GNP

GNP

RNA Aptamer

Anti-HER2C-reb-2 antibody

GNPCTAB

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

47

Magnetic nanoparticle surface modification Glucose oxidasse

(GOx)

PEGGPS

APSMNP

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

48Z Lin et al Analytica Chimica Acta 818 (2014) 54ndash60

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

49

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

P Sun H Zhang C Liu Langmuir 2010 26(2) 1278ndash1284 50

Immuno-labeling using Fe3O4CdTe nanocomposites which are formed by

linking multiple TGA-stabilized CdTe QDs with the thiol-functionalized silica

coated iron oxide nanoparticles

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

23-dimercaptosuccinic

acids (DMSA)Dopamine

Mercaptoundecanoic acid

(MUA)

HS COOH

4 Small multifunctional molecules

Glutaraldehyde 51

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

C J Xu K M Xu H W Gu R K Zheng H Liu X X Zhang Z H Guo B Xu J Am Chem Soc 2004 126 9938

Dopamine

Conditions (a) NaOH tert-butyl dicarbonate dioxane H2O 24 hrs (b) BnBr K2CO3 DMF

RT 24 h (c) 10 CF3COOH CH2Cl2 rt 5 h (d) succinic anhydride pyridine RTt 3 h (e)

NHS DCC DMAP CHCl3 RTt 3 h

NTA

52

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

3-mercapto trimethoxysilane

(MPS)

3-amino trimethoxysilane

(APS)

5 Silane multifunctional monomers

Glycidoxypropyltrimethoxy-silane

(GPS)

53

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

54

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Multifunctional magnetic nanoparticles

application

Bioseparation

Biodetection(Real time monitoring)

Targeted drug delivery

Magnetic fluid Hyperthermia therapy

55

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

1 Specific Bio-Separation

bull Magnetic properties

bull Targeting agent

Cell organism molecule

56

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

His-tagged protein purification as

the first step towards recombinant

protein purification

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

58

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Lysing Binding

Nickel

affinity

nanoparicle

His tag

fusion protein

Washing Elusion

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Digestion

Binding

Nickel

affinity

nanoparticle

Washing Target

Recombinant

Protein

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

1- Preparation of Fe3O4SiO2Layered Double Hydroxide CoreminusShell

Microspheres for Magnetic Separation of Proteins J Am ChemSoc (2012)

18 134(2) 1071-7

Ni2+

2- Magnetic Nanocomposite Spheres Decorated with NiO Nanoparticles for a

Magnetically Recyclable Protein Separation System J Kim Y Piao N Lee Y

Park I-H Lee J-H Lee Adv Mater (2010) 22 57ndash60

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

His-tagged protein purification

Purification of His6-lipase using Fe3O4AundashLAndashIDAndashCu2+ NPs with various

amounts of NPs (lane 1 01 mg lane 2 02 mg lane 3

63

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Synthetic procedure for the coreshell structure spheres

64

glutaraldehyde

(GLH)

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

[14] S Santra H S Yang P H Holloway J T Stanley R A Mericle J Am Chem Soc 2005 127

1656

[15] D K Yi S T Selvan S S Lee G C Papaefthymiou D Kundaliya J Y Ying J Am Chem

Soc 2005 127 4990 65

[16] J H Gao B Zhang Y Gao Y Pan X X Zhang B Xu J Am Chem Soc 2007 129 11928 [17] J H Gao W Zhang P B Huang B Zhang X X Zhang B Xu J Am Chem Soc 2008 130 3710 [18] J H Gao G L Liang B Zhang Y Kuang X X Zhang B Xu J Am Chem Soc 2007 129 1428 [19] J H Gao G L Liang J S Cheung Y Pan Y Kuang F Zhao B Zhang X X Zhang E X Wu B Xu J Am Chem Soc 2008 130 11828 [20] A R Kortan R Hull R L Opila M G Bawendi M L Steigerwald P J Carroll L E Brus JAm Chem Soc 1990 112 1327 [21] X G Peng M C Schlamp A V Kadavanich A P Alivisatos J Am Chem Soc 1997 119 7019 [22] S Kim B Fisher H J Eisler M Bawendi J Am Chem Soc 2003 125 11466[23] H Zeng J Li Z L Wang J P Liu S Sun Nano Lett 2004 4 187 [24] H Zeng S Sun J Li Z L Wang J P Liu Appl Phys Lett 2004 85 792 [25] Z Xu Y Hou S Sun J Am Chem Soc 2007 129 8698 [26] Y H Lin N Kim J Q Wang C J Zhong J Phys Chem B 2005 109 21593 [27] C Wang H Daimon S Sun Nano Lett 2009 9 1493 [28] K W Kwon M Shim J Am Chem Soc 2005 127 10269 [29] H Yu M Chen P M Rice S X Wang R L White S Sun Nano Lett 2005 5 379 [30] J S Choi Y W Jun S I Yeon H C Kim J S Shin J Cheon J Am Chem Soc 2006 128 15982 [31] S H Choi H B Na Y I Park K An S G Kwon Y Jang M Park J Moon J S Son I CSong W K Moon T Hyeon J Am Chem Soc 2008 130 15573 [32] H W Gu R K Zheng X X Zhang B Xu J Am Chem Soc 2004 126 5664

66

Reference[1] H W Gu Z M Yang J H Gao C K Chang B Xu J Am Chem Soc 2005 127 34

[2] A Hutten D Sudfeld I Ennen G Reiss K Wojczykowski P Jutzi J Magn Magn Mater 2005

293 93

[3] G S Chaubey C Barcena N Poudyal C B Rong J M Gao S Sun J P Liu J Am Chem

Soc 2007 129 7214

[4] C W Kim Y H Kim H G Cha D K Lee Y S Kang J NanosciNanotechnol 2006 6 3417

[5] Y W Jun J S Choi J Cheon Angew Chem Int Ed 2006 45 3414

[6] X Michalet F F Pinaud L A Bentolila J M Tsay S Doose J J Li G Sundaresan A M Wu

S S Gambhir S Weiss Science 2005 307 538

[7] M Hu J Y Chen Z Y Li L Au G V Hartland X D Li M Marquez Y N Xia Chem Soc

Rev 2006 35 1084

[8] M Vallet-Regi F Balas D Arcos Angew Chem Int Ed 2007 46 7548

[9] S T Selvan P K Patra C Y Ang J Y Ying Angew Chem Int Ed 2007 46 2448

[10] I S Lee N Lee J Park B H Kim Y W Yi T Kim T K Kim I H Lee S R Paik T

Hyeon J Am Chem Soc 2006 128 10658

[11] Y S Lin S H Wu Y Hung Y H Chou C Chang M L Lin C P Tsai C Y Mou Chem

Mater 2006 18 5170

[12] B H Wu H Zhang C Chen S C Lin N F Zheng Nano Res 2009 2 975

[13] J Kim J E Lee J Lee J H Yu B C Kim K An Y Hwang C Shin J G Park J Kim T

Hyeon J Am Chem Soc 2006 128 688

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