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Dr. Arthur ChiouInstitute of Biophotonics
School of Biomedical Science & EngineeringBiophotonics Interdisciplinary Research Center
National Yang-Ming UniversityTaipei, Taiwan
A Brief Introduction to Biophotonicswith Selected Illustrative Examples
A Brief Introduction to A Brief Introduction to BiophotonicsBiophotonicswith Selected Illustrative Exampleswith Selected Illustrative Examples
geology.com
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.
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
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
Faculty (2007): 297
NYMUNYMU-- Faculty Faculty BodyBody
Lecturer
Professor
Associate ProfessorAssistant
Professor
102 (34%)
114 (39%)39 (13%)42 (14%)
Students (2007): 3,815
Undergraduate~850 med students
GraduatePhD
Master
NYMUNYMU-- Student CompositionStudent Composition
632 (17%)
1,210 (32%) 1,973 (52%)
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
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)
NYMU-VGH-TCHAS-NHRI-NDL-NSRL
Biophotonics & NanobiophotonicsTeam
Biophotonics Inter-disciplinaryResearch Center (BIRC)
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
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
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
BioPhotonics
Biosensing
Biomanipulation
Microscopy/spectroscopy
Raman/SERSNanowire
SPRSMD
Optical capturing and stretchingTissue engineering
Nanofabrication
MoleculeCellTissueAnimal
FLIM/FRETPhotoactivation
PhotonicsLife ScienceMedical Science
Biophotonics
Photonics Science & Technology for Biomedical ApplicationsBiological Materials for Photonics Applications
The Interaction of Photons with Biological Materials
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
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
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
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
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
• 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
• 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
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
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)
Implantable Co-Axial Microlight Guide
* *
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)
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.
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
-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
732
700440
700
4400
a
b
d
c
732732700
440
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
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
Nano-Medicine
Dr. Chung Shi Yang, Dr. Lue-Wei LoCenter for Nano Medicine Research
NHRI, Taiwan
Liposome
Biocompatible
Biodegradable
Targeted DeliveryControlled Release
Nano-Medicine: Drug Delivery
Free Tc-99-m
Liposomal Tc-99-m
PEG Liposomal Tc-99-m
Div Nuclear Med, TCVGH
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
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
Green Fluorescence Protein (GFP)
Fluorescence Proteins (FPs)
Fluorescence Proteins:Donor-Acceptor Pairs for FRET
Structural & FunctionalDynamics of Ion ChannelsIn Cellular Membranes
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.
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
Quantum Dots as Quantum Dots as fluorescence markersfluorescence markers
Nature Biotechnology, Han et al 2001Nature Biotechnology, Han et al 2001
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
Nano-scaled ECM patterned growth substrates affect cell morphogenesis,
motility and proliferation
QuickTime?and aYUV420 codec decompressor
are needed to see this picture.
QuickTime?and aYUV420 codec decompressor
are needed to see this picture.
Neurite outgrowth on a homogeneous substrate
Neurite outgrowth on a patterned substrate
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.
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
Holographic Optical Tweezers:Experimental Demonstration
Miles Padgett, University of Glasgowhttp://www.physics.gla.ac.uk/Optics/
Fiber-Optical Dual-Beam Trap
Experimental Demonstration:Trapping of a String of Particles
Experimental Demonstration:Trapping of a String of Particles
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)
Photonics Force Microscopy Photonics Force Microscopy (PFM)(PFM)
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
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
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))
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
Dynamics of Molecular Interactions
Antigen-AntibodyActin-MyosinLectin-GlycoproteinCell-CellRibosome-RNA
at single molecule resolutionat single molecule resolution
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
Cell-Cell Interaction:Experimental Demo
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
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
PhagocytosisPhagocytosis of E. Coli by Macrophageof E. Coli by Macrophage
Control Pre-treated with EORP
200X
LPS Particle and MacrophageLPS Particle and MacrophageLPS Conjugated Particle +
MacrophageLPS Conjugated Particle +
Reishi Induced Macrophage
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
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)
RBC StretchingUsing a Parallel Dual-Tweezers
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
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
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)
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
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
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
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
Optical Forced Oscillation byOscillatory Optical Tweezers
AOMAOM--BasedBasedOscillatoryOscillatoryTweezers Tweezers
Liposome
AO square waveDC5.5V±2.5v 1kHz
Diameter=3μm
2beam distance=2.88μm
1064nm laserOptical tweezers
Oscillation of two 1.5Oscillation of two 1.5μμm Silica m Silica Beads via Oscillatory TweezersBeads via Oscillatory Tweezers
Mice RBC: Mice RBC: Original vs. StretchedOriginal vs. Stretched
1μm1μm
Liposome Deformation inOscillatory Optical Stretcher
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
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
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
-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
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
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
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
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))
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
Thank You
http://photoms.ym.edu.tw
The Laboratory of Photonics Manipulation and Sensing for Biomedical Applications