Transcript
Page 1: A Brief Introduction to A Brief Introduction to Biophotonics A Brief … · 2011-12-30 · Diagnostics Therapeutics Imaging Sensing Photodynamic Therapy (PDT) Light-Guided Gene Therapy

Dr. Arthur ChiouInstitute of Biophotonics

School of Biomedical Science & EngineeringBiophotonics Interdisciplinary Research Center

National Yang-Ming UniversityTaipei, Taiwan

[email protected]

A Brief Introduction to Biophotonicswith Selected Illustrative Examples

A Brief Introduction to A Brief Introduction to BiophotonicsBiophotonicswith Selected Illustrative Exampleswith Selected Illustrative Examples

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geology.com

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1994~PresentNational Yang-Ming University

1975~19941975~1994

National YangNational Yang--Ming Medical CollegeMing Medical College

NYMUNYMU-- HistoryHistory

A research university that focuses on life science and medicine.

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NYMUNYMUNYMU

Taipei City Hospital SystemVeterans General Hospital-TaipeiVeterans General Hospital-TaichungVeterans General Hospital-Kaohsiung

Leading medical centers in TaiwanMore than 10,000 beds

NYMU Teaching Hospital SystemNYMU Teaching Hospital System

4 teaching hospitals

39 affiliated hospitals

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National YangNational Yang--Ming UniversityMing UniversityTaipei, TaiwanTaipei, Taiwan

1975 National Yang-Ming Medical College1994 National Yang-Ming University

School ofMedicine

School ofBio-Medical Science

& Engineering

School ofLife Science

School ofNursing

School ofDentistry

General EducationCenter

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Faculty (2007): 297

NYMUNYMU-- Faculty Faculty BodyBody

Lecturer

Professor

Associate ProfessorAssistant

Professor

102 (34%)

114 (39%)39 (13%)42 (14%)

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Students (2007): 3,815

Undergraduate~850 med students

GraduatePhD

Master

NYMUNYMU-- Student CompositionStudent Composition

632 (17%)

1,210 (32%) 1,973 (52%)

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School of BioSchool of Bio--Medical ScienceMedical Science& Engineering& Engineering

Baccalaureate Programs• Faculty of Medical Technology • Faculty of Physical Therapy• Faculty of Radiological Technology

Master & PhD Degree Programs• Institute of Biomedical Engineering• Institute of Biotechnology in Medicine• Institute of Radiological Science• Institute of Biophotonics• Institute of Physical Therapy & Rehabilitation Science

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Institute of Institute of BiophotonicsBiophotonicsSchool of Biomedical Science & EngineeringSchool of Biomedical Science & Engineering

7 Full-time Faculty Members16 Adjunct Faculty Members

2 (to 3) Year Master Degree Program (since 2001)40 MS Students (currently)

25 with Phys. and Eng. Background15 with Bio. Background

30 New MS Students (08/2008)

3 (to 5) Year PhD Program (since 2006)11 PhD Students (currently)

7 with Phys. and Eng. Background4 with Bio. Background

10 New PhD Students (08/2008)

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NYMU-VGH-TCHAS-NHRI-NDL-NSRL

Biophotonics & NanobiophotonicsTeam

Biophotonics Inter-disciplinaryResearch Center (BIRC)

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NYMUNYMU-- National Core FacilityNational Core Facility

• National Genomic Medicine Projects

• National Nano Science Technology Program

• National Genome Sequencing Center• National Microarray and Gene

Expression Center• National Micro-Pet and Gene Probe

Center• National NanoBio Technology Core

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Complex SciencesNew Paradigms

New Technologies

TopicsTopics--orientated Researchorientated Research

Genome Research

Brain Research

Immunology Research

BiophotonicsResearch

Received an awarded from Ministry of Education of Taiwan-“Aim for Excellence, 5 years 50 billion NT$”Program, 2006-2010

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Enable platform

technology

Microscopy

&

Spectroscopy

In vivo imaging

Magnetic resonanceImaging (MRI)

In vivo optical imaging(GFP/RFP,bioluminscence)

micro-SPECT/CT

micro-PET

Animal sonogram

Fiber-optical dual-beam trap

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BioPhotonics

Biosensing

Biomanipulation

Microscopy/spectroscopy

Raman/SERSNanowire

SPRSMD

Optical capturing and stretchingTissue engineering

Nanofabrication

MoleculeCellTissueAnimal

FLIM/FRETPhotoactivation

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PhotonicsLife ScienceMedical Science

Biophotonics

Photonics Science & Technology for Biomedical ApplicationsBiological Materials for Photonics Applications

The Interaction of Photons with Biological Materials

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Biophotonics

Medical Applications Fundamental Physics & Chemistry of Life at the Molecular Level

Diagnostics Therapeutics

ImagingSensing

Photodynamic Therapy (PDT)Light-Guided Gene TherapyLight-Activated TherapyLaser Tissue WeldingLaser SurgeryNano-medicine

Imaging & Sensingat the Molecular & Cellular Levels

DNA MechanicsCellular MechanicsPlasma MembraneDynamics

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Magnetic resonanceImaging (MRI)

In vivo optical imaging(GFP/RFP,bioluminscence)

nano-SPECT/CT

micro-PET

Animal sonogram

Genes Dev 17: 545-580, 2003

Multimodality In Vivo Imaging

黃正仲黃正仲、、王信二王信二 、、劉仁賢劉仁賢 、、

陳志成陳志成、、李俊信李俊信 、、林慶波林慶波 、、

陳潤秋陳潤秋

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COMPARING DIFFERENT SMALL ANIMAL COMPARING DIFFERENT SMALL ANIMAL MOLECULAR IMAGING TECHNIQUESMOLECULAR IMAGING TECHNIQUES

YesYesYesYesYesYesYesYesYesYesTranslationalTranslational

ExcellentExcellentGoodGoodNoNoPoorPoorNoNoMolecular Molecular targeting targeting

sensitivitysensitivity

ExcellentExcellentExcellentExcellentNoNoGoodGoodNoNoMolecular Molecular TargetTarget

~1 mm~1 mm~1 mm~1 mmSubSub--millimetermillimeter

SubSub--millimetermillimeter

SubSub--millimetermillimeterResolutionResolution

YesYesYesYesNoNoYesYesYesYesFunctionalFunctional

NoNoNoNoYesYesYesYesYesYesAnatomicalAnatomical

PETPETSPECTSPECTXX--ray CTray CTMRIMRIUSUS

YesYes

PoorPoor

ExcellentExcellent

SubSub--micronmicron

YesYes

NoNo

OPTICALOPTICAL

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Monitoring the Monitoring the Tumor Tumor Growth/ProgressionGrowth/Progression with BLIwith BLI

Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Week 9 Week 10

Week 11 Week 12 Week 13

Mean tumor volume (mm3)

0 250 500 750 1000 1250 1500 1750 2000 2250

Mea

n bi

olum

ines

cenc

e (p

h/s)

1e+7

1e+8

1e+9

A

B

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Week 4 week 6 week 8 week 9 week 10 week 11 week 12 week 13

Week 14 week 15 week 16 week 17

weeks after tumor inoculation2 4 6 8 10 12 14 16 18

Phot

on fl

ux (p

h/s)

1e+4

1e+5

1e+6

1e+7

1e+8

1e+9

thorax

BLI for tumor progression and BLI for tumor progression and metastasismetastasis

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• Interference fringes are observed only when optical path lengths are matched within coherence length of the source

• Axial resolution: coherence length of the source: 1-15 µm

Three reflecting surfaces

SLD

Reference mirror

Photodetector

Beam splitter

Optical Coherence TomographyOptical Coherence Tomography

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• Cancer diagnosis (skin, GI, respiratory, and urogenital tracts, etc.)• Burn depth determination and tissue viability monitoring• Vasoactive drug screen• Surgical guidance (brain, etc.)• Developmental biology• Ocular diseases

GI tract

Brain

Oral cancers

Eye

larynx

Cochlear

Tracheal

skin

Applications

Drug screen

Burn depth

Drug screen

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Biophotonics

Medical Applications Fundamental Physics & Chemistry of Life at the Molecular Level

Diagnostics Therapeutics

ImagingSensing

Photodynamic Therapy (PDT)Light-Guided Gene TherapyLight-Activated TherapyLaser Tissue WeldingLaser SurgeryNano-medicine

Imaging & Sensingat the Molecular & Cellular Levels

DNA MechanicsCellular MechanicsPlasma MembraneDynamics

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Ti:Sapphire Oscillator

PMT

Pinhole

FiberCoupler

FilterDichroicMirror

Fiber

λ= 830 nm80 fsPulse Duration

Spec

trom

eterPhoton Counter

Pulse Stretcher

TwoTwo--photon optical fiber fluorescence probe photon optical fiber fluorescence probe for for in vivoin vivo biosensingbiosensing

M.T. Myaing, J.Y. Ye, T.B. Norris, T. Thomas, J. Baker, Jr., W.J. Wadsworth, G. Bouwmans, J.C. Knight, and P.St.J. Russell, Enhanced Two-photon Biosensing With Double-clad Photonic Crystal Fibers," Optics Letters (in press)

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Implantable Co-Axial Microlight Guide

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* *

On-going and potential projects:

1. Monitor chemo/radiation therapy response of colorectal cancer

2. Monitor low dose PDT response in early lung cancer

3. Measure oxygenation, fat and water contents in various tissues (brain, muscle, etc.)

4. Diffuse optical tomography

Diffuse Reflectance Spectroscopy (DRS)

Wang, H. W., et. al., “Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome,” Cancer Res., 64(20): 7553-7561, 2004.

Wang, H. W., et. al., “In-vivo measurements of optical and physiological properties in human intraperitonealtissues before and after photodynamic therapy,” J Biomedical Optics 10(1), 014004, 2005

Wang, H. W., et. al., “Quantitative comparison of tissue oxygen and motexafin lutetium uptake by ex-vivo and noninvasive in-vivo techniques in patients with intraperitoneal carcinomatosis,”J Biomedical Optics, 12(3), 034023, 2007.

Wang, H. W., et. al., “Effect of photosensitizer dose on fluence rate responses to photodynamic therapy,”Photochem. Photobiol., 83, 1-9, 2007

Portable DRS system

Hsing-Wen Wang, PhD. (Inst Biophotonics)Fu-Jen Kao, PhD. (Inst Biophotonics)姜正愷醫師, MD. PhD. (台北榮總直腸)Vladimir Gukassyan, PhD. (Inst Biophotonics外科) 謝義山醫師, MD. PhD. (新光胸腔外科)Chi-Hung Lin , MD. PhD. (Inst Microbiol Immunol)Yau-Huei Wei, PhD. (Inst Biochem Mol Biol)

Diffuse Reflectance Spectroscopy:(Oxygenation, Hemoglobin Concentration, Water, Lipid)

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Study of drug resistance and kinetics of Study of drug resistance and kinetics of bacteriumbacterium--host cell interaction based on host cell interaction based on

Surface Plasmon ResonanceSurface Plasmon Resonance(Chi(Chi--Hung Lin, HowHung Lin, How--FooFoo Chen) Chen)

Specific aim:1. Study of drug resistance using surface plasmon

resonance.2. Real-time observation of surface activities of cells and

bacteria based on surface plasmon resonance with spatial resolution.

3. Integration of SPR system and surface enhanced Raman spectroscopy for chemically selective observation of bacteria invasion process on cell surface.

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Cell Immobilization

Antibiotic effect detection

Ampicillin

Laser CCD

Laser CCD

Laser CCD

DI water

Study of drug resistance of bacteria Study of drug resistance of bacteria using surface plasmon resonanceusing surface plasmon resonance

Generation of surface plasmon

Testing result

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-0.02128-0.06876

E-Coli subject to ampicillin:

S. epidermis subject to tetracycline:

Ampicillin resistance Ampicillin susceptible

tetracycline resistance tetracycline susceptible

Add antibiotics

Add antibiotics

Add antibiotics Add antibiotics

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732

700440

700

4400

a

b

d

c

732732700

440

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Biophotonics

Medical Applications Fundamental Physics & Chemistry of Life at the Molecular Level

Diagnostics Therapeutics

ImagingSensing

Photodynamic Therapy (PDT)Light-Guided Gene TherapyLight-Activated TherapyLaser Tissue WeldingLaser SurgeryNano-medicine

Imaging & Sensingat the Molecular & Cellular Levels

DNA MechanicsCellular MechanicsPlasma MembraneDynamics

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Laser

Injection ofphotosensitizer

Illuminated by light

Photo-activated

drug induced singletoxygen

destroys tumor

Tumor

Abs

orpt

ion

Fluo

resc

ence

S1

S0

Intersystem Crossing

T1

ExcitedTriplet

Type I

Type II

1O2

O2-

Singlet

3O2

Photodynamic Therapy (PDT)Photodynamic Therapy (PDT)

Phos

phor

esce

nce

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Nano-Medicine

Dr. Chung Shi Yang, Dr. Lue-Wei LoCenter for Nano Medicine Research

NHRI, Taiwan

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Liposome

Biocompatible

Biodegradable

Targeted DeliveryControlled Release

Nano-Medicine: Drug Delivery

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Free Tc-99-m

Liposomal Tc-99-m

PEG Liposomal Tc-99-m

Div Nuclear Med, TCVGH

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Biophotonics

Medical Applications Fundamental Physics & Chemistry of Life at the Molecular Level

Diagnostics Therapeutics

ImagingSensing

Photodynamic Therapy (PDT)Light-Guided Gene TherapyLight-Activated TherapyLaser Tissue WeldingLaser SurgeryNano-medicine

Imaging & Sensingat the Molecular & Cellular Levels

DNA MechanicsCellular MechanicsPlasma MembraneDynamics

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Fluorescence Proteins, Live Cell Imaging,and Mechanobiology:

Seeing Is BelievingYingxiao Wang*, John Y-J. Shyy¶, and Shu Chien§

* Department of Bioengineering and Beckman Institute for Advanced Science andTechnology, University of Illinois, Urbana-Champaign, Urbana, IL 61801;

¶ Division of Biomedical Sciences, University of California, Riverside, CA 92521

§ Department of Bioengineering and Whitaker Institute of Biomedical Engineering,University of California, San Diego, La Jolla, CA 92093

To appear in Annual Review of Biomedical Engineering

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Green Fluorescence Protein (GFP)

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Fluorescence Proteins (FPs)

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Fluorescence Proteins:Donor-Acceptor Pairs for FRET

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Structural & FunctionalDynamics of Ion ChannelsIn Cellular Membranes

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Time-resolved fluorescence

FLIM

FLIM-FRET

To reveal molecular dynamics or molecular interactions that occur

• in live cells• in a subcellular area or compartment• at very fast dynamics• not by conventional protein-protein binding (but by lipid raft, carbonhydrates, etc.)

FLIM measurements can also be applied to autofluorescence, molecule’s intrinsic fluorescence (such as NADH), or for differentiating fluorescence having overlapping emission spectrums.

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a1/a2 ratio

2

2.5

3

3.5

4

0 2 4 7 14 21 28days

* *

Differentiated stem cell

200 ps 4000 psSTS treated

0 1000 2000 3000 40000

0.5

1

τ (ps)

Hno

rm

(a) (b)(c)(d)

0 50 100 150 600-6750

2000

4000

time (minutes)τ

(ps)

7

11 9 9 7 6 6 5 5 3

3 Cancer cell

2.Monitor cellular metabolism

NADH Intrinsic Fluorescence Lifetime1.Detect apoptosis

free-to-bound NADH ratio

control

Future Plan:Implement fiber probe for Implement fiber probe for nonnon--invasiveinvasive animal and clinical studiesanimal and clinical studies

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Quantum Dots as Quantum Dots as fluorescence markersfluorescence markers

Nature Biotechnology, Han et al 2001Nature Biotechnology, Han et al 2001

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Biophotonics

Medical Applications Fundamental Physics & Chemistry of Life at the Molecular Level

Diagnostics Therapeutics

ImagingSensing

Photodynamic Therapy (PDT)Light-Guided Gene TherapyLight-Activated TherapyLaser Tissue WeldingLaser SurgeryNano-medicine

Imaging & Sensingat the Molecular & Cellular Levels

DNA MechanicsCellular MechanicsPlasma MembraneDynamics

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Nano-scaled ECM patterned growth substrates affect cell morphogenesis,

motility and proliferation

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QuickTime?and aYUV420 codec decompressor

are needed to see this picture.

QuickTime?and aYUV420 codec decompressor

are needed to see this picture.

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Neurite outgrowth on a homogeneous substrate

Neurite outgrowth on a patterned substrate

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Vol. 19, No. 16, Aug. 29, 2005

The Scientist celebrates the 7 Key technologies that have, and are, transforming life science research. Each of them is in its own way shaking the foundation of life science research. As a group, they tell the story of the past and future of molecular biology.

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The 7 Key Technologies

• DNA Sequencer• The BLAST Algorithm• The DNA Microarray• The Yeast Two-Hybrid Assay• The MALDI-TOF Mass Spectrometer• The Lab-on-a-chip• The Optical Trap

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Holographic Optical Tweezers:Experimental Demonstration

Miles Padgett, University of Glasgowhttp://www.physics.gla.ac.uk/Optics/

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Fiber-Optical Dual-Beam Trap

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Experimental Demonstration:Trapping of a String of Particles

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Experimental Demonstration:Trapping of a String of Particles

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Observation of a Single-Beam Gradient Force Optical Trap for Dielectric Particles

A. Ashkin, J. M. Dziedzic, J. E. Bjorkholm, & S. ChuOpt. Lett. Vol. 11, 288 (1986)

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Photonics Force Microscopy Photonics Force Microscopy (PFM)(PFM)

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Position distribution of the Brownian motion (along the axial anPosition distribution of the Brownian motion (along the axial and d the transverse directions) of a 5the transverse directions) of a 5--µµm polystyrene bead trapped in a m polystyrene bead trapped in a

fiberfiber--optical dualoptical dual--beam trapbeam trap

Transverse direction Axial direction

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Brownian Motion of Trapped BeadsBrownian Motion of Trapped Beads

( ) ( ) 21ln ln2B B OTE x k T x k T C k xρ= − + =

X : Kx = 13.85 pN/µm + : Ky = 13.46pN/µm

±10nm

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33--d Optical Force Field ind Optical Force Field inParabolic Potential ApproximationParabolic Potential Approximation

E(xE(x, y, z) = (K, y, z) = (Kxxxx22 + K+ Kyyyy22 + K+ Kzzzz22)/2)/2

ρρ (x, y, z) = C exp[ (x, y, z) = C exp[ -- E(xE(x, y, z)/K, y, z)/KBBT]T]

E(xE(x, y, z) = , y, z) = -- KKBBT T lnln[[ρρ (x, y, z)] + K(x, y, z)] + KBBT T lnln(C(C))

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Cross check (ZCross check (Z--axis)axis)33--D potential well (2.58D potential well (2.58µµm silica)m silica)

x......X-axis (first QPD)

o......Y-axis (second QPD)

Z-axis (first QPD)..…ٱ

+…...Z-axis (second QPD)

kx = 1.61×10-1 pNt/μm, ky = 1.49×10-1 pNt/μm, kz = 4.43×10-2 pNt/μm

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Dynamics of Molecular Interactions

Antigen-AntibodyActin-MyosinLectin-GlycoproteinCell-CellRibosome-RNA

at single molecule resolutionat single molecule resolution

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National Dong Hwa UniversityDepartment of Electronic Engneering

Before adhesion After adhesion

Interaction of an Avidin-Coated 5 μm Beadwith a Biotin-Coated 7.75μm Bead

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Cell-Cell Interaction:Experimental Demo

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Interaction of LPS Conjugated Particle and Interaction of LPS Conjugated Particle and Macrophage via Brownian MotionMacrophage via Brownian Motion

QPD

Optical System

Trapping Laser 15mW

50nm per step

B. M. 50nm

100nm back

B. M. 150nm

Trapping Laser 1mW

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The Influence of Extract of ReishiPolysaccharides on the Binding of

Lipopolysacharides and CD14 membrane protein on macrophage measured by optical tweezers

Arthur Chiou, Hsien-Yeh Hsu,

Min-Tzo Wei, and Kuo-Feng Hua

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PhagocytosisPhagocytosis of E. Coli by Macrophageof E. Coli by Macrophage

Control Pre-treated with EORP

200X

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LPS Particle and MacrophageLPS Particle and MacrophageLPS Conjugated Particle +

MacrophageLPS Conjugated Particle +

Reishi Induced Macrophage

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Molecular Basis of Red Blood Cell (RBC) Molecular Basis of Red Blood Cell (RBC) Membrane MechanicsMembrane Mechanics

Normal state of a junctional complex

G actin37 nm

E-Tmod

TM5/5b

The hexagonal network in the erythrocyte membrane skeleton

http://www.rkm.com.au/imagelibrary/thumbnails/CELL-Red-Blood-Cell-150.jpg

The simulation of whole cell

Annals of Biomedical Engineering, Vol. 31, pp. 1314–1326, 2003

Biophysical Journal Volume 93 July 2007 386–400;

Trapped cellTrapped cell

Optical fiberOptical fiberOptical fiberOptical fiber

Stretched cellStretched cell

Optical StretcherOptical StretcherRed blood cell

Oscillatory Optical TweezersOscillatory Optical Tweezers

Knockout

Wild Type

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Feeling with Light for CancerM. Martin, K. Mueller, F. Wottawah, S. Schinkinger, B. Lincoln,

M. Romeyke, J. A. Käs*Institute for Soft Matter Physics, Department of Physics and

Geosciences, University of Leipzig

Proc. of SPIE Vol. 6080, 60800P, (2006)

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RBC StretchingUsing a Parallel Dual-Tweezers

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Optical StretcherOptical Stretcher

•J. Guck et al., Biophys J 81, 767 (Aug, 2001). •J. Guck, R. Ananthakrishnan, T. J. Moon, C. C.Cunningham, J. Kas, Phys Rev Lett 84, 5451 (Jun 5, 2000)

5mW

500mW

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J. Guck, R. Ananthakrishnan, H. Mahmood, T. J. Moon, C. C. Cunningham, and J. Kas, The optical stretcher: A novel laser tool to micromanipulate cells, Biophys. J. 81, 2001, 767-784.J. Guck, R. Ananthakrishnan, C.C. Cunningham and J. Käs, Stretching Biological Cells with Light, J. Phys. Cond. Mat., 14, 2002, 4843-4856.

Optical Stretcher

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Flow ChamberFlow Chamber

Single mode fiberSingle mode fiber

Single mode fiberSingle mode fiber

Laser Laser

國立陽明大學‧生醫光電工程研究所

Fiber-Optical Dual -BeamTrap-and-Stretch(Optical Stretcher)

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Experimental SetupExperimental Setup

PCPC

IR FilterIR FilterOptical CouplerOptical Couplersplittersplitter

100X 100X NA=0.55NA=0.55

CCDCCD

IR Fiber Laser

Lamp

λλ= 1064nm= 1064nm

SingleSingle--Mode fiberMode fiber

Flow ChamberFlow Chamber

ObjectiveObjective

Syringe pumpSyringe pump

tubingtubing

Photo DetectorPhoto Detector Optical CouplerOptical Couplersplittersplitter

FC/PC AA

BB

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Experimental Results:Experimental Results:Optical Stretching of Spherical RBCOptical Stretching of Spherical RBC

RBC Diameter RBC Diameter ::6.5 6.5 ±± 0.50.5μμmmFiberFiber--toto--Fiber distance=150Fiber distance=150μμmmFiber NA=0.14Fiber NA=0.14

Eh=2.0 Eh=2.0 ±± 22μμN/mN/m

19mw19mw 66mw66mw 92mw92mw 174mw174mw43mw43mw 146mw146mw118mw118mw

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Optical Stretching of BiOptical Stretching of Bi--concave RBCconcave RBC

43mw 66mw 92mw 118mw

146mw

174mw 203mw 230mw 260mw

19mw

Each point:Averaging over15 samples

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Deformation of Human RBC:Deformation of Human RBC:Samples taken from different personsSamples taken from different persons

Fiber-to-fiber distance = 50µmRBC samples from two different persons

Each point:Averaging over15 samples

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Optical Forced Oscillation byOscillatory Optical Tweezers

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AOMAOM--BasedBasedOscillatoryOscillatoryTweezers Tweezers

Liposome

AO square waveDC5.5V±2.5v 1kHz

Diameter=3μm

2beam distance=2.88μm

1064nm laserOptical tweezers

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Oscillation of two 1.5Oscillation of two 1.5μμm Silica m Silica Beads via Oscillatory TweezersBeads via Oscillatory Tweezers

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Mice RBC: Mice RBC: Original vs. StretchedOriginal vs. Stretched

1μm1μm

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Liposome Deformation inOscillatory Optical Stretcher

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Measurement of DNA Elasticity Measurement of DNA Elasticity by Optical Tweezersby Optical Tweezers

Objective

Condenser PZT stage

X’

Step 1 Step 2

Step 3 Step 4

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IR Filter

Objective

Lock-inAmplifierX

Y

Condenser

QPD

Time (s)

Amplitude(Voltage)

Analysis of Brownian motion

PZT stage

X’

Vsum=VA+VB+VC+VD

Vx=[(VB+VD)-(VA+VC)]

Vy=[(VA+VB)-(VC+VD)]D

A BC

DNA Elasticity Measured by Brownian MotionDNA Elasticity Measured by Brownian Motion

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X-axis Y-axisX-axis Y-axis

PZT: 0µm PZT: 2.5µm

TKxE BCex /)()( −=ρ

2/)(ln)(ln)( 2kxCTKxTKxE BB =+−= ρ

Analysis of Brownian motionAnalysis of Brownian motion

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-5

0

5

10

15

0 0.5 1 1.5 2 2.5 3 3.5

DNA relative extension (µm)

Optical force (pN)

dsDNA Force-Extension Curve

NakedDNA

After Bindingwith RecA

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30

35

40

45

50

55

60

65

0 100 200 300 400 500 600

Time (s)

Displacement from

the trapping center (nm)

Dynamics of DNA-RecA Interaction

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Biophotonics

Medical Applications Fundamental Physics & Chemistry of Life at the Molecular Level

Diagnostics Therapeutics

ImagingSensing

Photodynamic Therapy (PDT)Light-Guided Gene TherapyLight-Activated TherapyLaser Tissue WeldingLaser SurgeryNano-medicine

Imaging & Sensingat the Molecular & Cellular Levels

DNA MechanicsCellular MechanicsPlasma MembraneDynamics

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Inflammation

PharmacotherapyEnvironment

Cancer

Genetics

Pharmacokinetics Injury

Contrast

InfectionCell

Adaptation

Phase

Spectroscopy

Nonlinea

r

Opt

ical

Det

ectio

nPolarization

Amplitude

Dynam

icStat

ic

Liposomes

NanoparticlesGenetically-Encoded

ProteinsMolecular

DyesProtein

MicrospheresPlasmon-Resonant

Structures

Fluorescence

Birefringence

ScatteringAbsorptio

n

Optical Activity

Bio

lum

ines

cenc

e

Nonlinear Process

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Biophotonics-Related International ConferencesOrganized & Hosted/Co-hosted

by BIRC (2005 to 2008)2005:International Workshop/Symposium of Time-Resolved Spectroscopy: FRET/FLIM/FCS2006:The 9th International Conference on Optics Within Life Sciences (OWLS9)2007:CSIC (Spain) CSIC (Spain) -- NSC (Taiwan) Joint NSC (Taiwan) Joint Workshop on Photonics: Workshop on Photonics: NanophotonicsNanophotonics, , PlasomonicsPlasomonics, & , & BiophotonicsBiophotonics2008:2008:International Conference on Laser International Conference on Laser Applications in Life Sciences (LALS Applications in Life Sciences (LALS 20082008))

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Our Vision & Mission:Harnessing Light for Life

Optics &Photonics

Bio-Photonics

Bio-NanophotonicsNano-biophotonics

Nano- & Femto-Biophotonics

Nano

Opto Bio

Femto

Nano

Opto BioOpto BioOpto

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Thank You

http://photoms.ym.edu.tw

The Laboratory of Photonics Manipulation and Sensing for Biomedical Applications


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