3d bio-mems device to detect salmonella bacteria bio-me… · 3d bio-mems device to detect...

CAMDCAMD

Flavio AristoneUFMS: Federal University of South Mato Grosso

CAMD: Center of Advanced Microstructures and DevicesLSU: Louisiana State University

3D Bio-MEMS device to 3D Bio-MEMS device to detect Salmonella Bacteriadetect Salmonella Bacteria

CAMDCAMD

2Flavio Aristone / PASI – MEMS 2004Bariloche - Argentina

26 de junio de 2004

Co-workers

Jost Goettert, Yohannes Desta, Lin Wang,

Jin Yoonyoung, Proyag Datta,

Dawit Yemane, Tracy Morris,

Shaloma Malveuax, Changeng Liu,

Kun Lian, Zhong-Gen Lin, Joseph Kouba,

Antoine Dupuy, Niko Baether,

Alexey Espindola, Thomas Mueller,

Jakob Weimnert

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OUTLINE

Detection of Salmonella BacteriaBiological Protocol Devices and TestsConclusions

LiGALithography; X-ray masksExposuresElectroplating; Hot-embossing

General ConceptsExamples of Micro-systemsSummary

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Miniaturization

By miniaturizing applications you can...

• enhance performance and productivity

• reduce sample and reagent consumption

• work more easily with nanoliter sample volumes

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Integration

By integrating multiple steps into a single streamlined process you can...

• increase productivity

• improve reproducibility

• eliminate the need for user intervention

• minimize the risk of losing samples

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Micro Harmonic Drive® Gear

Output bearingOutput flange

HousingMotor

Circular SplinePlanet gear

Flexspline

Dynamic Spline

Flexspline

Circular SplineDynamic Spline

Dynamic Spline

Planet gear

Planet gear

Flexspline

Sun gear

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Advantages• Zero backlash yet miniature dimensions• Excellent repeatability• High torque capacity• High reduction ratios with 6 parts• High efficiency• Extremely flat design• Very low weight

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Applications for Micro-Motors

Medical Equipment

Optical Communication

Laser Equipment

Measuring Machines

Semicon

Aircraft

Spacecraft

Biotechnology

Microscopes

Robotics

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Bio-MEMS

Biotechnology

Medical Equipment

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Microfluidics

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Microstructures molded in plastic using LIGA fabricated GC mold tool. The SEM pictures show various sections. These structures are 50 microns wide and 420 microns high.

Nickel GC mold insert fabricated using LIGA

Gas Chromatograph - Drawing Board to Plastic Microstructures

Drawing of a micro gas chromatograph (GC)

SEM picture of a small section of the nickel micro GC mold insert

High Aspect Ratio µ-GC

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Some examples

thickness = 500 microns; column diameter = 100 microns; turn diameter = 75 microns

thickness = 500 microns; column diameter = 100 microns; turn diameter = 100 microns

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GC

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Microfluidic lab-on-a-chip technology represents a revolution in laboratory experimentation.

It combines manufacturing methods from the microchip industry with expertise in fluid dynamics, biochemistry and software and hardware engineering to develop miniature, integrated biochemical processing platforms, systems, and instrumentation.

The benefits of miniaturization, integration and automation will strengthen research-based industries and may also lead to new point-of-care medical and analytical devices.

Summary

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• Let technology NOT drive you towards complete miniaturization at the start !

• Stay focused to fabricate a product !

• Develop strategic partnerships !

• Establish a multi-disciplinary TEAM effort !

To keep in mind !

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Late 70’s/early 80’sDevelopment of concept to fabricate separation nozzles for uranium enrichment at IKVT/KfK (today IMT/FZK)

U 235/238

U 235

U 238

Many thousandsof nozzles

cascaded in an array

Tip ~ 3µm

Height ~ 300 µm

The beginning …

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• L i :Lithography• G : Electroforming• A : Molding

LiGA Process

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1. Idea / Project2. Drawing3. Optical Masks4. X-Ray Masks5. Substrate preparation6. Exposure7. Development8. Electroplating9. Mold insert final work10.Device replication11.Testing12.Results / Analysis

Microfabrication

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Shadow printing using x-rays

X-ray mask

Resist

Substrate

Development

Lithography

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Electroplatingof metal structuresand mold inserts

Replication by molding(hot embossing,

injection molding)

Electroforming and Molding

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X-ray masks

Frame

Membrane

Absorber (5-30 µm)

Desirable mask membrane characteristics•Good X-ray and optical transmission•Good mechanical stability, low internal stress•Radiation resistant•Compatible with established mask making processes and equipment•Compatible with plating of Au absorber

Thin membranes:

Silicon, Silicon Nitride, Titanium, Diamond

Thick low Z substrates:

Graphite, Beryllium, Silicon, glass

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Mask fabrication

UV lithography

Electroplate 5-50 µm of Au

E-beam lithography

Electroplate 1.5-2.0 µm of Au

Soft X-ray lithography

Electroplate 5-50 µm of Au

Intermediate X-ray mask

‘Working’ X-ray mask

‘Working’ X-ray mask

Photomask

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Hotplate

Condenser

Water circulation

Magnet stir

Silicon etching setup for making 1µm thick Silicon Nitride Membrane

Window size 4×20×33mm

Thin membrane

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•Extreme structure heights

•2500 µm tall templates for micro-gears

• NiFe gear assembly

•Sub-micrometer structural details

Properties of …

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• Vertical and smooth sidewall

• Wide variety Wide variety of materials of materials possiblepossible

• non-vertical sidewalls

• multi-level pattern

… LiGA Microstructures

•Arbitrary cross-sectional shape•Smallest structures of some micrometer

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Deviation from perfect sidewall ~ 0.06µm / 100 µm Ph.D. Thesis Jürgen Mohr, IMT/FZK, 1987

Patterning Accuracy - DXRL

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Mold insert

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Overplating

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Nickel Mold insert

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Hot embossing

• A thermo-plastic replication process suitable for LiGA HARM structures.

• Key process steps include heating, evacuating, stamping, and demolding.

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Replication process

Insert plastic, close press,evacuate, and heat up.

Apply high pressureto transfer structures.

Cool down, vent, and demold structured

plastic parts.

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LiGA Process

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Definition

To make things clear….

XRL or soft XRL: X-ray lithography in thin resists

DXRL: Deep X-ray lithography (up to 1mm)

UDXRL: Ultra-deep x-ray lithography (above 1mm)

LiGA is not to make the next generation micro-chips.

It is a ultra-precision micromachining process using lithographic tools !

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CAMD – LSUa Synchrotron Radiation Facility Dedicated to Microfabrication

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CAMD

SSRL

ALSAPS

CHESS NSLS

SRC

SURF

Synchrotrons in the U.S.

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Synchrotron radiation is electromagnetic radiation (light) emitted from electrons (positrons) moving with relativistic velocities on macroscopic circular orbits.

Shield Wall

Storage Ring

Synchrotron Radiation

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I PI P

B E A M

B S S

( 4 8 . 0 0 0 )

~ 7 5 “ t o S . P .

D I P O L E V A C T A N K

P S

G V 1

F S

G V 2P u m pP o r t

P u m pP o r t

G V 3S c a n n e rB e W i n d o w

F i l t e r C h a m b e r

S h i e l d W a l l

5. 0000

D i a g n o s t i c F l a g

IP

~ 3 3 2 “ t o M a s k P l a n e

Vacuum safety

Radiation safetyHeat protection

4 Synchrotron lines operating at 1.3 - 1.5 GeV for µfab1 for SOFT X-rays from Cr double mirror system1 for HARD X-rays from 7 T Wiggler

CAMDCAMD

Lightening the sample

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Inside the clean room

Plating Station

Temescal e-beam evaporator

Oxford ion milling

Quintel UV aligner

Some Infrastructure at CAMD

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and more …

CAMD Infrastructure• Metrology• Material characterization• Chemistry lab• Surface finishing• Molding

SPM

Micro hardness testing

Resist Press

Lapper

SEM/EDAX

Veeco RST NT3300DSC, DMA, TGA, TMAMaterial testing

HEX 02 Hot Embossing Machine

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Concept of 3D µ−Fluidic-S

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Modular Test Structure• Molded Modular Micro-fluidic Structure

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Multilevel Microfluidic Device

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Result

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SpindleRotates 360o

in horizontal planeRotates 180o

in vertical plane

G-vector

Centrifugal Bio-Chips For the Analysis of Biologically Fluid SamplesCentrifugal Bio-Chips For the Analysis of Biologically Fluid Samples

Collaboration: Mark F. Clarke, University of Texas at Houston

Lab-on-a-CD – Centrifugal Bio-Chips For the Analysis of Biologically Fluid Samples

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Quasi 3D-CentrifugeMicro-Mechanics Parts

4” or 100mm

Molded CD

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Simulation

(AGAIN)Last time !!

Last time !!!

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First test

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Solutions

• 1) Protein G = IgG immunoglobulins

• 2) Sample containing (or not) Salmonella

• 3) Washing (detergent) solution: rinse

Minimum requirement

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Solution 1 & 2

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Solution 3

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Sealing troubles

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Ideas for Sealing

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DAVD-DOF designdirectional acceleration vector driven – displacement of fluids

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Macro-results

15000 16000 17000 18000

15000 16000 17000 18000

QC A (1:1000)

QC B (1:1000)

QC E2 (1:1000)

0

10

20

30

15000 16000 17000 18000

15279.0+H

17111.4+H

0

10

20

30

15000 16000 17000 18000

15268.8+H

16172.9+H 16473.3+H

0

10

20

30

15000 16000 17000 18000

15267.2+H

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Meaning …

TOFMS Spectrums Obtained Using the “Direct Capture-In Situ Solubilization” Technique For Purified Sub Strains of Salmonella (QC A, QC B and QC E2). All Sub-strains tested have a peak at a MW of ∼15, 270 including sub-strain E2.

Only sub-strain A has an additional peak at ∼17, 110,

whereas only sub-strain B has peaks at ∼16, 170 and ∼16, 470. Signal associated with each sample of Salmonella sub-strain detected using this approach is associated with a maximum theoretical number of 1600 captured bacteria.

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Actual situation: waiting for the feedback from the measurements to be done at Houston to compare results and see whether or not the µ−device works.

Thank you !

The end

3d bio-mems device to detect salmonella bacteria bio-me… · 3d bio-mems device to detect...

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