Department of Biomedical Engineering

Faculty of Fundamental Technical Problems, Wroclaw University of Technology

www.ibp.pwr.edu.pl

VARIOUS FACES OF BIOMEDICAL ENGINEERING

Wrocław University of Technology WrUT is an inheritor of the tangible

property of the German Königliche Technische Hochschule Breslau and

the intellectual and research traditions of the Polish Lvov Polytechnic.

The university has been functioning under the current name since 1945. It

was established and organised after WWII by researchers from Lvov and

Warsaw.

Today, it belongs to the best technical universities in Poland – over 32.000

students study here under the guidance of 2.000 academic teachers, at the

12 faculties and the Department of Fundamental Studies, as well as in the

3 regional branches.

Department of Biomedical Engineering

Faculty of Fundamental Technical Problems, Wroclaw University of Technology

www.ibp.pwr.edu.pl

Department of Biomedical Engineering (former the Institute of

Biomedical Engineering and Instrumentation) belongs to the Faculty

of Fundamental Problems of Technology. Dozens of students study

the Biomedical Engineering at our Faculty (ca. 150 are enrolled

each year).

Seven research groups are actively involved in the research projects:

Bio-Optics Group, Laboratory of Biophysics of Macromolecular

Aggregates, Group of Bioinformatics and Biophysics of Nanopores,

Biomedical Signal Processing Laboratory, Group of

Biospectroscopy, Group of Biomedical Electronics and

Measurements, Group of Computer Simulations of Biomedical

Systems.

Department of Biomedical Engineering

Faculty of Fundamental Technical Problems, Wroclaw University of Technology

www.ibp.pwr.edu.pl

Department of Biomedical Engineering

Faculty of Fundamental Technical Problems, Wroclaw University of Technology

www.ibp.pwr.edu.pl

Our research groups

Bio-Optics GroupGroup leader: Prof. Dr. Halina Podbielska

Optical systems and methods for quick bacteria characterization by optical methods. Antibacterialmaterials. Photosensitive nanomaterials. Nanoscale measurements (AFM). Computer aided analysis ofmedical images. Physcial medicine. Thermal imaging. Pattern recognition.

Laboratory of Biophysics of Macromolecular AggregatesGroup leader: Prof. Dr. Marek Langner

Procedures to evaluate sample stability using calorimetric methods. Procedures to evaluate chemicalcomposition of complex solid materials using LIBS (Laser Induced Breakdown Spectroscopy). Size andzeta-potential determination using DLS (Dynamic Light Scattering) method. Study of supramolecularaggregates formation and stability for targeted drug delivery systems

Group of Bioinformatics and Biophysics of NanoporesGroup leader: Dr. hab. Małgorzata Kotulska, Assoc. Prof.

Biological nanopores, such as electropores and protein ionic channels. Conductivity characteristics,structure-function relations, and medical applications. Experimental study on electro-nanopores inplanar lipid membranes. Electrochemiotherapy of cancer cells in vitro. Computer modeling ofconductivity of various nanopores. Bioinformatical methods for modeling structure of membranechannel proteins.

Biomedical Signal Processing LaboratoryGroup leader: Dr. hab. Robert D. Iskander, Assoc. Prof.

Monitoring, modeling and analysis of intracranial pressure, arterial blood pressure and cerebral bloodflow velocity in patients with hydrocephalus. Modeling and clinical applications of the eye pupilreactivity. Modeling and study of correlation between intraocular pressure (IOP) measurements andgeometry and biomechanical properties of the human eyeball.

Group of BiospectroscopyGroup leader: Prof. Dr. Małgorzata Komorowska

Studies of the influence of near infrared radiation on tissue, proteins, nucleotides, and aminoacids bymeans of different spectroscopic methods. Red blood cells protection by IR irradiation. Spin labels ESRspectroscopy. ATR-FTIR and Raman vibrational spectroscopy, UV-Vis and fluorescence spectroscopy.

Group of Biomedical Electronics and MeasurementsGroup leader: Dr. hab. Zbigniew Moroń, Assoc. Prof.

Bioelectronics. Biomedical measurements and instrumentation. Modeling of biomedical structures andsystems. Medical electronics. Medical navigation.

Group of Computer Simulations of Biomedical SystemsGroup leader: Dr hab. Krystian Kubica, Assoc. Prof.

Membrane properties modeling by computer simulation technique . Study the interaction betweenbiologically active compounds and membranes.

Novel Perspectives on the Characterization of Species-Dependent Optical Signatures of Bacterial

Colonies by Digital Holography

Novel Perspectives on bacterial identification by light diffraction

Bio-optics and Biophotonics for MicrobiologicalApplications

BASIC CONCEPTS OF LABEL-FREE DETECTION OF BACTERIA

BY LIGHT DIFFRACTION

Genotypic features of bacterial

cells affect the phenotypic

properties of bacterial cells

Morphology and metabolic

properties of bacteria cells

Pseudomonas aeruginosa

Pseudomonas vulgaris

Staphylococcus aureus

Species/strains – dependentd

morphological and optical

properties of bacterial colonies

Unique diffraction signatures of

bacterial colonies

„BACTERIA FINGERPRINTS”

DEVELOPMENT OF THE OPTICAL SYSTEM FOR BACTERIA

IDENTIFICATION

(1) Laser diode module, (2) Linear polarizer, (3) Amplitude filter, (4) Beam

expander, (5) Iris diaphragm, (6) Transforming lens, (7) Sample of bacterial

colonies in Petri Dish, (8) Holder, (9) CCD camera, (10) Computer.

I. Buzalewicz, A.Wieliczko, H. Podbielska, Influence of various growthconditions on Fresnel diffraction patterns of bacteria colonies examinedin the optical system with converging spherical wave illumination, OpticsExpress 19(22), 21768-21785, (2011)

2010

2013

2015

Staphylococcus aureus

(ATCC 43300)

Salmonella Typhimurium

(ATCC 13311)

Proteus mirabilis

(ATCC 43071)

Salmonella Enteritidis

(ATCC 13076)

Listeria monocytogenes

(ATCC 19115)

Enterococcus faecalis

(ATCC 51299)

Bacillus subtilis

(ATCC 6633)

Klebsiella pneumoniae

(ATCC 700603)

Citrobacter freundii

(ATCC 43864) Escherichia coli

(ATCC 35401)

Pseudomonas aeruginosa

(ATCC 27853)

Staphylococcus intermedius

(PCM 2405)

A.Suchwałko, I. Buzalewicz, H. Podbielska, Bacteria identification inan optical system with optimized diffraction pattern registrationcondition supported by enhanced statistical analysis, Optics Express22(21), 26312-26327, (2014)

A.Suchwałko, I. Buzalewicz, A. Wieliczko, H. Podbielska, Bacteriaspecies identification by the statistical analysis of bacterial coloniesFresnel patterns, Optics Express 21(9), 11322-11337, (2013)

A. Suchwałko, I. Buzalewicz, H. Podbielska, Statistical identificationof bacteria species, Microbial pathogens and strategies forcombating them: science, technology and education , vol. 1, A.Mendez-Vilas (Eds.), Formatex Research Center (2013), s. 711-721

Fresnel diffraction patterns analysis supported bystatistical methods enable the bacteriaclassification with the accuracy over 98%.

The reference database contains over 10000diffraction patterns of 30 bacterial species and over15 strains.

I. Buzalewicz, K. Liżewski, M. Kujawińska, H. Podbielska, Degeneration of Fraunhoferdiffraction on bacterial colonies due to their light focusing properties examined in digitalholographic microscope system, Optics Express 21(22), 26493-26505, (2013)

Digital holography for bacterial colonies characterization

Characterization of species-dependent bacterial coloniesprofiles by digital

holography.

Demonstration thatbacterial colonies

exhibit analogical light-focusing properties as

classical lenses.

I. Buzalewicz, M. Kujawińska, W. Krauze, H. Podbielska, Novel Perspectives on the Characterization of Species-Dependent Optical Signatures of Bacterial Colonies by Digital Holography, PLoS One 11(3): e0150449.(2016) doi:10.1371/journal.pone.0150449

Novel Perspectives on the Characterization of Species-Dependent Optical Signatures of Bacterial Colonies by Digital Holography

In comparison with previous forward scattering/diffraction sensors it ispossible by digital holography to extract more species-dependent opticalsignatures: digital holograms of bacterial colonies, amplitude and phase patterns ofbacterial colonies, amplitude and phase patterns of diffracted field on bacterial colonies inall observation space.

Staphylococcusintermedius

Escherichia coli

Biomedical Engineering in nanoscale

11

Biofunctionalization of stent surface

2013-2016 Grant FP7-PEOPLE-2012-IAPP”Antibody-functionalised cardiovascular

stents for improved biocompatibility and reduced restenosis”

Grant FP7 nr CP-FP 212533-2, “Electrically modified biomaterials’ surfaces: From Atom

to Application”, grant acronym: “BioElectricSurface”

Problems after coronary angioplasty

restenosis

http://vueklar.com/MyImages/MRI%20of%20VueKlar%20stent%20with%20thrombosis.gif

SMC

restenosis

thrombosis

Modification of stent surface

Collaboration with Balton and the Medical University of Wroclaw

Photoactive coating for implantable medical devices for interventional cardiology. Design

of photosensitive coating to prevent restenosis and thrombosis.

Stainless steel surface functionalization for immobilization of antibody fragments for cardiovascular applications.

Foerster A, Hołowacz I, Sunil Kumar GB, Anandakumar S, Wall JG, Wawrzyńska M, Paprocka M, Kantor A,

Kraskiewicz H, Olsztyńska-Janus S, Hinder SJ, Bialy D, Podbielska H, Kopaczyńska M.

J Biomed Mater Res A. 2016 Apr;104(4):821-32

Immunofluorescence images of endothelial cells after 4h

adhesion and 5 days of proliferation on bar stainless

steel and titania coatings

Biocompatibile coating has potential activity against restenosis.

The photoactive stent was produced in prototype series by Balton, tested in vitro and in

vivo and is currently preparing to undertake clinical trials.

Patent P. 395888.

The implantation of photoactive stent

Angiografia Histopatologia OCT

Stent in the vessel

Explanted stent

In vivo study

Patent Application P.412016

17

The photoactive formulation of

nanoliposomes as a new strategy in the

photodynamic therapy of unstable

atherosclerotic plaque

2014– 2017 Grant NCN, „The photoactive formulation of nanoliposomes as a new

strategy in the photodynamic therapy of unstable atherosclerotic plaque”.

18

Application of photosensitizing drug in a liposomal nanoformulation

TEM image of liposomal

nanoformulation with encapsulated

photoactive drug

100 nm

Colocalization of liposomal

nanoformulation with encapsulated

photoactive drug in the cells

19

The prototype system for intravascular PDT

20

Nanostructural changes in the cellular

structures induced by drugs used in

chemotherapy of malignant tumors

2012-2015 Grant NCBiR, “Optical tweezers in biomedical engineering”

groove binding

DNA-drug complexes

intercalationelectrostatic

interaction

Nanostructural changes of DNA caused by doxorubicin

AFM images

DNA DNA + DOX

Anthracycline antibiotic :

doksorubicin,

daunorubicin,

epirubicin;

Nanostructural changes of DNA caused by

aminoglycosides

AFM images: A) free DNA on mica surface, B) toroidal structures

caused by tobramycin, C) DNA strands degradation caused by

kanamycin

New strategies of targeted molecular therapy

Molecular model of the toroidal structures

Selective condensation of DNA by aminoglycoside antibiotics.

Kopaczynska M, Schulz A, Fraczkowska K, Kraszewski S, Podbielska H, Fuhrhop JH.

Eur Biophys J. 2015 Dec 8.

25

The studies of the mechanical properties of the

cell structures induced by drugs used in

chemotherapy of malignant tumors

2012-2015 Grant NCBiR, “Optical tweezers in biomedical engineering”

Optical tweezers in mechanical studies of nanomaterials

27

Optical tweezers in oncology

Collaboration with Medical University of Wroclaw. Studies on biomechanical

properties of the blastic cell membranes of acute myeloid leukemia, comparison

between healthy blood cells and aggressive cancer cells.

Blood smear patient with

acute myeloid leukemia

Mechanical properties study of blastic stem

cells of acute myelogenous leukemia in

optical trap

Nanomanipulation of the cells by using optical

tweezers

28

Stem cells of acute myelogenous

leukemia blastsErythrocyte in the trap

Novel Perspectives of IR imaging for early detection and therapy monitoring of lipodystrophy

Novel Perspectives of IR imaging’ applications for personalized physiotherapeutic approach

Bio-optics and Biophotonics for Predictive, Preventive and Personalized Medicine

INFRARED IMAGING IN

MEDICINE AND

PHYSIOTHERAPY

THERMOVISION (THERMOGRAPHY) measurement technique which enables

registration and visualization of Infra

Red radiation emitted by each body

which temperature is above absolute

zero.

Image of the body’s surface

temperature distribution, obtained

as a result of IR radiation

recording, is called thermogram.

Patient with spine disease

The following stages of coronary circulation after

LIMA-LAD anastomosis

Healthy patient on the right and patient with

thromboembolism and inflammatory process on the

left

Patient with Reynaud disease

DETECTING OF EARLY STAGES OF

LIPODYSTROPHY

AND ASSESSMENT OF TREATMENT

PROGRESS

Patient with

Stage 1

Patient with

Stage 3

Healthy tissue

Stage 0

Patient with

Stage 2

Nürnberger-Müller scale (1978)

Stages of cellulite

Cellulite

diagnostics

Nürnberger -Müller scale

CT

NMRDermatoscopy

Thermography

USG

THERMAANALYZER – NEW SOFTWARE FOR DIAGNOSTIC,

REAL-TIME THERAPY MONITORING AND TREATMENT

PROGRESS’ASSESSMENT BY USE THERMOVISION

ThermaAnalyzer –working with the

program

Calculation the spots

number and size

Open fileSelect ROI /Set parametrs/

AnalyzeView results

in new window

THERMAANALYZER – LIPODYSTROPHY TREATMENT MONITORING

Patient nr 10, initially stage 3 Patient nr 8, initially stage 1

Before treatment After 4 weeks

treatment

Before treatment After 4 weeks

treatment

Persons with higherdegree of cellulitehave more irregularsuperficialtemperaturedistribution seen asthe spots on thethermal image.

Thermal imaging canbe an objectivemethod forlipodystrophydiagnosis and therapymonitoring.

SCIENTIFIC OBJECTIVES OF THE RESEARCH:

1.Establishment of personalized procedures for monotherapies, based on such parameters like: age, gender, BMI, parameters of physical agents

2.Establishment of personalized procedures for polytherapies, including such parameters like: treatment order, optimal break between treatments parameters of physical agents

Person 1 Person 5 Person 13

Person 10 Person 17

RESEARCH:

1. Personalization of physical treatment is not a trivial task, as a proper planning of the procedures, especially in case of joined therapies, requires an extensive and profound knowledge of physiological and pathological conditions of the body's response to stimuli and regular tracking of the organism’s reaction.

2. Physical stimuli should cause specific therapeutic reaction

3. There are still no comprehensive studies of the different physical procedures, depending on such parameters as patient’s age, gender, BMI, dose, stimuli duration as well as the application’s order.

MONITORING OF PHYSIOTHERAPEUTIC

POLYTHERAPIES AND MONOTHERAPIES

Patient No 16

(Woman)

Thermogram

before treatment After

cryotherapy

After

ultrasounds

After 15

minutesAfter 30

minutes

Our study demonstrated that older persons do not react on the physical agents in form of cooling or heating in the same way as the young individuals.

A significant differences can be seen just after applying the second treatment in both cases DD-Soll and Soll-DD polytherapies. However, the thermal effect is short and no significant differences were observed after 15 and 30 minutes

A significant difference can be observed in case of US-CRYO versus CRYO-US polytherapies. In case of US-CRYO order the cooling effect lasts longer (up to 30 min) whereas in case of CRYO-US the thermal effect is shorter ( up to 15 minutes)

These findings have practical significance, especially when the treatment procedure is performed in order to facilitate the kinesiotherapy and physical exercises.

Boerner Ewa*, Bauer Joanna, Kuczkowska Magdalena*, Podbielska Halina, Ratajczak B*: Comparison of the skin surface temperature on the front of thighafter application of combined red-IR radiation and diadynamic currents executed in a different sequence Journal of Thermal Analysis and Calorimetry. 2015, vol. 120, nr 1, s. 921-928, http://dx.doi.org/10.1007/s10973-015-4545-9

Boerner Ewa*, Bauer Joanna, Ratajczak B*, Dereń Ewelina*, Podbielska Halina: Application of thermovision for analysis of superficial temperature distributionchanges after physiotherapy Journal of Thermal Analysis and Calorimetry. 2015, vol. 120, nr 1, s. 261-267, http://dx.doi.org/10.1007/s10973-014-4026-6

Laboratory for Biophysics of Macromolecular Aggregates

prof. Marek Langner

Magda Przybyło, PhD

Sebastian Kraszewski PhD

Maciej Łukawski, MSc

Kamila Szostak, MSc

Dominik Drabik, MSc

Pl. Grunwaldzki 13, bud. D1 pok. 8A

phone: +48 71 320 41 55

E-mail: marek.langner@pwr.edu.pl

www.lbam.pwr.edu.pl

LAB FACILITY:

- Steady-state and time resolved

fluorescence,

- Dynamic light scattering,

- HPLC (UV/VIS, FLUO, ELSD),

- Stopped-flow apparatus,

- UV/VIS spectroscopy,

- LIBS,

- Ultrafiltration,

- Differential Scanning Calorimetry,

- Isothermal Titration Calorimetry

Laboratory for Biophysics of

Macromolecular Aggregates

BASIC RESEARCH : BIOPHYSICS OF LIPID MEMBRANE

Studies of lipid membrane mechanics by microscopic imaging

Drabik, D; Przybylo, M; Chodaczek, G; Iglic, A; Langner, M The modified fluorescence

based vesicle fluctuation spectroscopy technique for determination of lipid bilayer bending

properties Biochimica et Biophysica Acta – Biomembranes 2015; 1858 (2), 244-252

Determination of lipid bilayer bending properties by vesicle

fluctuation analysis based on confocal imaging

Drabik D, Przybyło M., Sikorski A., Langner M., The Effect of a Fluorophore Photo-

Physics on the Lipid Vesicle Diffusion Coefficient Studied by Fluorescence Correlation

Spectroscopy, Journal of Fluorescence DOI 10.1007/s10895-015-1752-5.

Determination of lipid diffusion coefficient by Fluorescence

Correlation Spectroscopy

Studies on lipid membrane permeability

Przybylo M, Drabik D, Lukawski M, Langner M. Effect of Monovalent Anions on Water

Transmembrane Transport. Journal of Physical Chemistry B. 2014;118(39):11470-11479. A

Experimental studies of water transport through

the lipid membrane – development of new

method based on stopped – flow technique

Lis M, Wizert A. Przybylo M. Langner M. Swiatek J. Jungwirth P.

Cwiklik Ł. The effect of lipid oxidation on the water permeability of

phospholipids bilayers Phys. Chem. Chem. Phys., 2011, 13, 17555–

17563

Supported by Molecular Dynamic Simulations

Brain Research Lab

Joint time-frequency analysisof dynamic cerebral autoregulation

Research supported by National Science Centre, Poland (no. DEC-2013/10/E/ST7/00117)

www.brainlab.pwr.edu.pl

Non-invasive measurements:

Arterial Blood Pressure – Finapres finger plethysmograph (Finometer®

MIDI, FMS Medical Systems)

Cerebral Blood Flow Velocity – Transcranial Doppler ultrasonography (Doppler-Box™ X DWL)

End tidal CO2 – capnograph (RespSense™, NONIN)

ECG – three lead (ECG module, FMS Medical Systems)

Experimental Procedure Hypercapnia is induced by increasing the

respiratory dead space by attaching plastic sack.

Hypercapnia is used as a model of cerebral autoregulation impairment.

Results: Exemplary Subject

Time (minutes)

Fre

quen

cy (

Hz)

0 1 2 3 4 50.02

0.03

0.04

0.05

0.06

0.07

0

0.2

0.4

0.6

0.8

time-frequency coherence = 0.36

time frequency phase shift = 35.5°

Time (minutes)

Freq

uenc

y (H

z)

0 1 2 3 40.02

0.03

0.04

0.05

0.06

0.07

0

0.2

0.4

0.6

0.8

1

normocapnia hypercapnia

time-frequency phase shift = 17.9°

time-frequency coherence= 0.44

Cerebral autoregulation is less effective in hypercapnia (higher T-F coherence, lower T-F phase shift between arterial blood pressure and cerebral blood flowvelocity )

Research

www.brainlab.pwr.edu.pl

Multimodal monitoring of biosignals in brain injury patients

Decomplexification of biosignals in brain pathology

ABPRenyi entropy=51.05

1st day after SAH (before vasospasm) 10th day after SAH (duringvasospasm)

CBFV (side of vasospasm)Renyi entropy=38.62

ABPRenyi entropy=27.58

CBFV (side of vasospasm)Renyi entropy=29.98

Complexity of T-F representations of arterial blood pressue (ABP) and cerebralblood flow velocity (CBFV) is lower during vasospasm than before vasospasm in patients after subarachnoid haemorrhage (SAH)

Ocular dicrotism, a double-peak shaped feature in corneal pulsation, is a newly observed phenomenon (2015). It was found to increase its prevalencewith age and with glaucoma progression.

Ocular dicrotic pulse, characterised by two corneal pulsations with each cardiac cycle, was detected with innovative ultrasonic transducers.

Oculardicrotism

New instrument for measuring corneo-scleral topography

Typical coverage by a standard Placido disk

videokeratoscope

Wide coverage range

Fluroescein needs to be instilled into the eyeFourier Profilometry

topographer

Department of Biomedical Engineering

Faculty of Fundamental Technical Problems, Wroclaw University of Technology

www.ibp.pwr.edu.pl

CURRENT EUROPEAN PROJECTS

Prof. R. IskanderH2020-MSCA-ITN-2014 EDEN – European Dry Eye Network, ID 642760, European Commission, start: 01-10-2014FP7-PEOPLE-2013-ITN AGEYE – Aging Eye, ID MC608049, European Commission, start: 01-10-2013

Prof. H. PodbielskaFP7- PEOPLE-2012-IAPP EU Industry-Academia Partnerships and Pathways (IAPP) EPICSTENT Antibody-functionalised cardiovascular stents for improved biocompatibility and reduced restenosis, start: 01-05-2013

Thank you for watching!