Ilko K. Ilev, Ph.D. - Washington Academy of Sciences

Ilko K. Ilev, Ph.D.
Optical Therapeutics and Medical Nanophotonics Lab (OTMN Lab)
Division of Physics, Office of Science and Engineering Laboratories
Center for Devices and Radiological Health (CDRH)
U.S. Food and Drug Administration (FDA)
New CDRH Labs
March 27, 2010
Capital Science 2010 Conference: 50th Anniversary of the Discovery of the Laser

PHOTONICS – to – BIOPHOTONICS – to – NANOBIOPHOTONICS
PHOTONICS
PHOTONICS
►laser physics
►electro-optics
►fiber optics
►sensors
►imaging
OPTICAL
THERAPEUTICS
BIOPHOTONICS
BIOPHOTONICS
►optical diagnostics/therapeutics
►biosensing/bioimaging
►tissue engineering
►cell manipulation
MEDICAL
NANOPHOTONICS
(NANOBIOPHOTONICS)
►sizes/distances

Interest in Bioimaging/Microscopy: History of Microscopy
Ernst Ruska
Invented the first Electron
Microscope
It is a Transmission Electron
Microscope (TEM)
Imaging of objects as small as
the diameter of an atom
1668 1932 1981
1931 1957
Antony van Leeuwenhoek
(1632-1723)
The first man who make
and use a real one lens
light microscope
Marvin Minsky
Invented the Confocal
Microscope
Based on the rejection of
out-of-focus information
Three-dimensional and sharp
imaging of thick specimens
Frits Zernike
Invented the Phase-Contrast
Microscope (PCM)
PCM allows the study of
colorless and transparent
biological materials
He won the Nobel Prize in
Physics in 1953
Gerd Binning &
Heinrich Rohrer
Invented the Scanning
Tunneling Microscope (STM)
Three-dimensional imaging
of objects down to the atomic
level

MOTIVATION: Why the Interest in Optical Bioimaging/Microscopy?
PUBLIC HEALTH AND REGULATORY IMPACT
optical bioimaging and microscopy remain the most widespread
imaging techniques with important public health impact
optical diagnostics/therapeutic techniques are potential alternatives
to conventional medical methods for diagnosis and therapy
ADVANTAGES OF OPTICAL IMAGING/MICROSCOPY
non-ionizing radiation
non-invasive or minimally invasive imaging, microscopy and
biosensing
high resolution in micron, submicron and nanometric range
MRI - sub-mm; Ultrasound - 150 µm; X-ray - 0.1-1 mm
Electron, Atomic Force and Tunneling Microscopy - nm/sub-nm
limited to specimen surface
not compatible with live cells
require a detrimental sample preparation and vacuum
bulk and expensive equipment
the only imaging method for probing live tissue with subcellular
resolution; potential for imaging and spectroscopic diagnostics

CUTTING EDGE OPTICAL IMAGING DEVICES
Based primarily on confocal microscopy and optical
coherence tomography (OCT)
Cutting edge applications include:
scanning confocal microscope for skin monitoring and diagnostics*
confocal microscope for tissue monitoring and diagnostics*
scanning confocal microscope for corneal diagnostics*
OCT ophthalmology monitoring device*
endoscopic confocal microscope for in vivo imaging *
early cancer detection
intravascular monitoring
human brain function imaging
cellular/intracellular monitoring gene mapping
*FDA Approved

TYPICAL CONFOCAL AND OCT IMAGES
Confocal image of neuron growth in mouse brain
[Science, 300 (2003) 76]
Laser scanning confocal image of optic disk
OCT image of intravascular plaques in human
coronary artery
OCT cellular image in a living African frog
[Science, 298 (2002) 1360]

From Biophotonics to Nanobiophotonics:
From Microscopy To Nanoscopy and Nanobiosensing
in the Subwavelength Nanoscale Spatial Range
MOTIVATION: Why the Interest in Nanobiophotonics?
noninvasive imaging/sensing in subwavelenght (

Diffraction Rayleigh Barrier:
A Fundamental Resolution Limit in Nanobiophotonics
LASER BEAM
LENS
Ultrahigh-Resolution (10000x)
Digital Microscope
Rayleigh Diffraction Resolution Limit
theoretically about one-half
of the laser wavelength
d lateral
× λ
=
NA
61 . 0
the highest achievable resolution with objective:
about 180 nm lateral (x-y) resolution
about 500 nm axial (z) resolution
Airy Patterns and the Resolution
Limit

How to Break the Theoretical Diffraction
Barrier in Nanobiophotonics?
RECENTLY DEVELOPED ALTERNATIVE NANOSCOPY
APPROACHES
ULTRAHIGH-RESOLUTION CONFOCAL FIBER-OPTIC
NANOSCOPY AND BIOMEDICAL APPLICATIONS
NOVEL COMBINED BIOPHOTONICS AND
NANOBIOPHOTONICS SENSOR AND IMAGING
APPROACHES

How to Break the Theoretical Diffraction
Barrier in Nanobiophotonics?
RECENTLY DEVELOPED ALTERNATIVE NANOSCOPY
APPROACHES:
Fluorescent Nanoscopy Based on Stimulated Emission
Depletion (STED) Microscopy
[Hell S., Nature Methods 4, 915-918 (2007)]
Near-Field Scanning Optical Microscopy
[Lewis A., Nature Biotechnology 21, pp. 1378-1386 (2003)]
[Betzig E., Science 251, pp. 1468-1470 (1991)]
Widefield Topography
[Lichtman J., Nature Methods 2, pp. 920-931 (2005)]
Dynamic Light Scattering
[EYE, Nature Publishing Group, 16, pp. 429-439 (2002)]

FLUORESCENT NANOSCOPY BASED ON STIMULATED
EMISSION DEPLETION (STED) MICROSCOPY
mitochondrial matrix of a live yeast cell
Spatial resolution smaller than 30 nm
Stefan Hell, “Toward Fluorescence Nanoscopy”, Nature Biotechnology 21, 1347 (2003).

How to Break the Theoretical Diffraction
Barrier in Nanobiophotonics?
RECENTLY DEVELOPED ALTERNATIVE NANOSCOPY
APPROACHES
ULTRAHIGH-RESOLUTION CONFOCAL FIBER-OPTIC
NANOSCOPY AND BIOMEDICAL APPLICATIONS
NOVEL COMBINED BIOPHOTONICS AND
NANOBIOPHOTONICS SENSOR AND IMAGING
APPROACHES

ADVANCED BIOPHOTONICS IMAGING TECHNIQUES
CONFOCAL MICROSCOPY
FLUORESENCE REFLECTANCE MULTIPHOTON
PINHOLE-BASED FIBER-OPTIC-BASED
ADVANTAGES:
three-dimensional
sharp
sub-µm resolution
SINGLE-MODE
FIBER
imaging and sensing
of thick specimens
MULTI-MODE
FIBER
FIBER BUNDLE
by rejection of
out-of-focus
information
OCT
OPTICAL COHERENCE
TOMOGRAPHY
NFM
NEAR FIELD
MICROSCOPY
DM
DIFFUSED
MICROSCOPY
ODT
OPTICAL DOPPLER
TOMOGRAPHY
OIM
OPTICAL INTERFERENCE
MICROSCOPY

Single-Mode Optical Fiber
Why the Interest in Fiber-Optic Biomedical Technologies
(2 - 9 µm core-diameter)
Advanced Optical Fiber Features
non-invasive or minimally invasive precise delivery of
non-ionizing laser irradiation
non-invasive or minimally invasive imaging and sensing with
ultrahigh-resolution in micron, sub-micron and nanorange
low attenuation losses at long interaction length (km)
SMF: 3-µm Single hair: 100-µm
small core diameter - micron, sub-micron and nanometer size
flexibility, compactness, scanning potential
Gaussian Laser Beam Intensity Distribution
free of gases, dyes, solvents, immunity to external interference
electro-magnetic passive operation (MRI, X-ray compatible)
near-to-the-theoretical paraxial conditions
optimum collimated/focused laser beam
Fiber Tapered Nanoprobes
(20 nm - 1 µm tip-diameter)
biosensing and nanobiosesing: high sensitivity, large dynamic
range and multiparameter sesnsor measurements
point light source
point light receiver
multimodality endoscopic system: imaging, sensing, diagnostics,
and therapeutics
advantages in imaging/sensing designs

Single-Mode Optical Fiber
Why the Interest in Fiber-Optic Biomedical Technologies
(2 - 9 µm core-diameter)
Advanced Optical Fiber Features
non-invasive or minimally invasive precise delivery of
non-ionizing laser irradiation
non-invasive or minimally invasive imaging and sensing with
ultrahigh-resolution in micron, sub-micron and nanorange
low attenuation losses at long interaction length (km)
SMF: 3-µm Single hair: 100-µm
small core diameter - micron, sub-micron and nanometer size
flexibility, compactness, scanning potential
Gaussian Laser Beam Intensity Distribution
free of gases, dyes, solvents, immunity to external interference
near-to-the-theoretical paraxial conditions
Fiber Tapered Nanoprobes
(20 nm - 1 µm tip-diameter)
electro-magnetic passive operation (MRI, X-ray compatible)
optimum collimated/focused laser beam
biosensing and nanobiosesing: high sensitivity, large dynamic
range and multiparameter sesnsor measurements
point light source
point light receiver
multimodality endoscopic system: imaging, sensing, diagnostics,
and therapeutics
advantages in imaging/sensing designs

FIBER-OPTIC-BASED vs CONVENTIONAL PINHOLE-BASED
CONFOCAL MICROSCOPY
CONVENTIONAL PINHOLE-BASED CONFOCAL MICROSCOPE
L
DISADVANTAGES:
HIGH SIGNAL ATTENUATION
DIFFRACTION AND ABERRATION EFFECTS
MISALIGNMENT PROBLEMS
INFLEXIBLE
Ain
BS
D
Aout
O
OBJECT

OUR SUGGESTION
A SIMPLE SUBMICRON CONFOCAL FIBER-OPTIC-BASED
MICROSCOPE
Ilev, EYE, 21, 2007, pp. 818-823, Nature Publishing Group
Kim, Kang, Ilev, Optics Letters, 33, pp. 425-427, 2008
Ilev, Waynant, Gannot, Gandjbakhche, RSI, 78, 2007
Ilev, Pending Patent, March 2006
Ilev, Waynant, Gannot, Gandjbakhche, Pending Patent, Apr 2006
Ilev, Waynant, Byrnes, Anders, Opt. Lett., 27, 1693, 2002
Operating Confocal
Principle
an aperturless reflection
confocal design
no diffraction effects
a regime of high output
power is achieved
high sensitivity to spatial
displacements
submicron/nanometric
spatial resolution

How to get over the theoretical diffraction
limit in the Confocal Microscopy?
Signal Power [ µ W]
90
80
70
60
50
40
30
20
10
0
approach A:
B
conventional confocal approach
around the maximum of the confocal
response curve
diffraction limited confocal imaging
200-500 nm diffraction limited resolution
A
-12 -8 -4 0 4 8 12
Axial Displacement [ µ m]
approach B:
ultrahigh-resolution confocal fiber-optic
nanoimaging
use of the sharp diffraction-free slope of
the confocal response curve
diffraction-free confocal nanoimaging

ULTRAHIGH-RESOLUTION CONFOCAL FIBER-OPTIC IMAGING
BEYOND THE DIFFRACTION LIMIT IN THE NANOMETRIC SCALE
PRINCIPLE EXPERIMENTAL DESIGN
LASER
POWER
METER
ISO
O1
SINGLE-MODE
FIBER COUPLER
D
Single-mode fiber coupler confocal design: high sensitivity, no diffraction/aberration,
flexibility, scanning potential, point light source/receiver, Gaussian distribution
Combining the advantages of the fiber-optic confocal design and the differential
confocal pinhole microscope: working in the subwavelength nanometric range
The use of tools and detecting techniques with high signal-to-noise potential
Ilev, Waynant, Gannot and Gandjbakhche, PCT International Pending Patent, April 14, 2006
Ilev, Waynant, Gannot, Gandjbakhche, Review of Scientific Instruments 78, 2007
Ilev, Waynant, Gannot, Gandjbakhche, Virtual Journal of Nanoscale Science & Technology 16, 2007
Ilev, Waynant, Gannot, Gandjbakhche, Virtual Journal of Biological Physics Research 14, 2007
Small, Ilev, Chernomordik, Gandjbakhche, Optics Express, v. 14, 3195 (2006)
O2
S
PZT

Signal Power [mW]
1000
900
800
700
600
SPATIAL RESOLUTION OF THE CONFOCAL FIBER-OPTIC
NANOIMAGING SYSTEM
Signal Power [mW]
875
850
825
800
775
750
725
700
ultrahigh-resolution
fiber-optic
confocal approach
conventional
diffraction limited
confocal approach
An experimental axial
confocal response curve
showing the diffraction-free
slope on the left side of the
confocal maximum
100 nm 50 nm 10 nm 2 nm
500
675
750
772
1200 1300 1400 1500 1600 1700 1800 1900 1450 1500 1550 1600 1650 1700 1750 1570 1580 1590 1600 1610 1620 1630 1594 1596 1598 1600 1602 1604 1606
Axial Displacement [nm]
Axial Displacement [nm]
Axial Displacement [nm]
Axial Displacement [nm]
Experimental confocal responses obtained using the ultrahigh-resolution fiber-optic confocal microscope for
achieving a subwavelength depth resolution of 100 nm (a), 50 nm (b), 10 nm (c), and 2 nm (d), respectively.
800
790
780
770
760
782
780
778
776
774

How to Break the Theoretical Diffraction
Barrier in Nanobiophotonics?
RECENTLY DEVELOPED ALTERNATIVE NANOSCOPY
APPROACHES
ULTRAHIGH-RESOLUTION CONFOCAL FIBER-OPTIC
NANOSCOPY AND BIOMEDICAL APPLICATIONS
NOVEL COMBINED BIOPHOTONICS AND
NANOBIOPHOTONICS SENSOR AND IMAGING
APPROACHES

HIGH-RESOLUTION CONFOCAL FIBER-OPTIC-BASED
BIOSENSING/IMAGING APPLICATIONS
CONFOCAL FIBER-OPTIC TESTING OF REGULATORY IOL SAMPLES
LASER
ISO O in
PM
Single-Mode Fiber Coupler
(2×1, 50/50)
DUAL-CONFOCAL FIBER-OPTIC BIOSENSOR
LASER
DETECTOR
50/50 FIBER
COUPLER
O c
L test
M total
Ilev, “Confocal Fiber-Optic Laser Method for Measuring The Focal
Length of Focusing Optics”, Pending Patent, March 3, 2006
Ilev, EYE 21, pp. 818-823, 2007, Nature Publishing Group
O1
O2
Ilev, Waynant, Byrnes, Anders, Opt. Lett., 27, 1693, 2002

Development of Independent Test Methods for Preclinical
Evaluation of Fundamental Optical Properties of IOLs
Examples
Motivation
Three-piece Monofocal IOL
6 mm
13 mm
An estimated 20.5 million Americans over age 40 have
cataracts in at least one eye
>3 million surgeries/year in US, >3 billion USD/year cost
Critical importance of precise preclinical IOL optical
testing for evaluating the safety and effectiveness
Conventional test methods have specific limitations:
high accuracy both +/- IOL testing, spatial alignment and
subjective imaging
λ=546 nm IOL
refractive-index
IOL
central
thickness
P 1
IOL Fundamental Optical Properties
dioptric power: D IOL = 1/f fl
refractive-index of the IOL material
IOL central thickness
reflected glare
light scattering characteristics
imaging quality
spectral transmittance
f fl
F 1

CONFOCAL FIBER-OPTIC LASER METHOD (CFOLM) FOR
MEASURING THE FOCAL LENGTH OF FOCUSING OPTICS
LASER
ISO O in
PM
Single-Mode Fiber Coupler
(2×1, 50/50)
O c
IOL test
Input Gaussian
Laser Beam
CONFOCAL MICROSCOPY FIBER-OPTIC SENSORS AUTOCOLLIMATION METHOD
high-magnification imaging
out-of-focus signal rejection
non-contact optical sectioning
sub-µm resolution
high sensing resolution
micrometer size core diameter
compact, flexible
scanning potential
f t
M total
Ilev, “Confocal Fiber-Optic Laser Method for Measuring The Focal
Length of Focusing Optics”, Pending Patent, March 3, 2006
Ilev, EYE 21, 818, 2007, Nature Publishing Group
Hoffer, Calogero, Faaaland, Ilev, J Cataract Refract Surg, 35, Nov 2009
double increased accuracy
simple and compact design

Development of Independent Method for Precise IOL Power Testing
Confocal Laser Method (CLM) for IOL Dioptric Power Testing
E4
E3
E2
E1
hν
hν
hν
(develop testing protocols, guidance, standard)
Basic Advantages of the Laser Confocal Method
Improved positive and negative power range
Previous: typical – from 5 D to 20 D
New Method: from 0 D to > ±30 D
Greater Accuracy
Previous: typical – several tens of microns
New Method:

E4
E3
E2
E1
Development of Independent Method for Testing/Identifying the
Source of Unwanted Glare Resulting from Implanted IOLs
hν
hν
(proof-of-concept and stakeholder contacts)
Glare Simulation Images for Testing/Identifying the Source of
Unwanted Glare
Landry, Ilev, Pfefer, Wolffe, Alpar, EYE, 21, pp.1083-1086, 2007, Nature
Publishing Group

E4
E3
E2
E1
Development of Independent Test Method for Precise IOL
Refractive-Index and Thickness Measurement
Non-Contact Dual-Confocal Laser Caliper (proof-of-concept)
hν
Signal Power [arb. un.]
260
250
240
230
220
210
200
190
180
F1
LASER
DETECTOR
d
F2
170
0 200 400 600 800 1000 1200 1400 1600
t s
Axial Displacement [µm]
Operating Principle
S1 S2
d = 0.780 mm
t s = 1.219 mm
n s = 1.416
50/50 FIBER
COUPLER
O1
O2
Direct measurement of the IOL thickness
in absolute units as well as the thickness of
nontransparent or highly scattered
biological and human tissue
Determination of the IOL refractive-index
Direct measurement of local changes in
the refractive index of cancer and noncancer
tissue

Fiber-Optic Laser Delivery and Tissue Ablation
Mid-IR On-The-Spot Goldfish Brain Ablation for Parkinson Disease Simulation
α t
MID-IR Er:YAG
LASER
/λ=2.94 μm/
Hollow Taper
hollow taper/smart fiber principle
θ 1
θi
n 0=1
n s>1
θ 2
smart
tissue-activated
fiber tip
Mid-IR Delivery
Hollow Fiber
Smart
Fiber Tip
grazing-incidence
uncoated hollow
optical funnel
laser taper/fiber parameters
Pulse Er:YAG, λ=2.94 μm
150 μm pulse duration, 20 mJ energy
Pyrex-glass uncoated taper
2 mm/600 µm input/output diameter
Mid-IR Hollow fiber
600 µm diameter, 600 mm length

All-Hollow-Fiber Laser Delivery
A Novel Approach for High-Peak Power Homogenous Laser
Delivery in Digital Particle Image Velocimetry (DPIV)
PRINCIPAL OPTICAL ARRANGEMENT
Nd:YAG
LASER
/2ω, λ=532 nm/
Hollow Tapered
Funnel
Delivery Hollow
Waveguide
Powell Lens
Ilev, Robinson, Waynant, U.S. Pending Patent, October 30, 2006
O
Laser Sheet
IR IR

(a)
NANOBIOSENSOR FIBER-OPTIC PROBES
Fiber tapered nanobiosensor probes with subwavelength scale
tips (< 100 nm), metal coated and uncoated tips
Design and drawing techniques: precise pulling and chemical
etching
Goals: high reproducibility, maximum light transmission, and
minimum leakage of light
(c)
(d)

NANO-PROBES FOR LASER-STIMULATED NEURON GROUTH
illuminating nano-probe Illumination of axon (λ=810 nm)
Illumination of nucleus (λ=810 nm) Illumination of nucleus (λ=632.8 nm)

GRIN
lens
Input fiber
Output fiber
Single Cell/Intracellular Nanoprobing
Input-output fiber
Nano-tip
• Fiber tapered nanoprobes with
subwavelength nanoscale tips (< 100 nm)
• Near-field microscopy combining with
confocal microscopy
• Direct chemical analysis and spectroscopy
of single cell components using absorption,
fluorescence and Raman spectroscopy
•Optical stimulation of single neurons
• Fiber-optic advantages
– Nano-probe attached/fabricated on a single optical fiber
– Confocal/multi-photon microscope using optical fiber(s)
• Endoscopic advantages
– Easier access to single cells
– One device can be used for imaging, sensing and light delivery

NEAR-FIELD SCANNING OPTICAL MICROSCOPY (NSOM)
NSOM Principle
A light source or detector (or
aperture) with dimensions
much smaller than the
wavelength (λ) of light is
placed in close proximity (<
λ/50) to a sample, and then
scanning the aperture or the
sample relative to each other
at a distance much smaller
than a wavelength an image
with spatial resolution better
than the diffraction limit is
generated (

NOVEL CONFOCAL/COMBINED BIOIMAGING/SENSING APPROACHES
(Dr. Do-Hyun Kim, Prof. Jin Kang, Dr. Amir Gandjbakhche, Prof. Juanita Anders)
LASER
BS
OL1
Optical Fibre
ALL-HOLLOW-WAVEGUIDE
CONFOCAL MICROSCOPY
POWER
METER
OL2 OL3
Object
z
Hollow-core photonic bandgap
fiber
Any operating UV, VIS and IR
wavelength can be achieved
Single-mode operation
Small effective area (core
diameter ~ 5 µm)
Wavelength independent
confocal microscopy
Mid-IR confocal microscopy
COMBINED CONFOCAL/OCT
INTERFERENCE MICROSCOPY
SLED
Detector
Kim, Kang, Ilev, Electronics Letters, 43, pp. 608-609, 2007
50:50 Coupler
y
x
z
Reference Arm
Object
Sample Arm
Fiber Stretchers
L1
Mirror
Rotating
Mirror
Improved axial CM and lateral OCT resolution
Improved SNR, intensity measurement of interference CM
Low coherent light source, reduced unwanted interference
Higher fiber stretcher –frequency (15 kHz), higher NA
Kim, Ilev, Kang, IEEE JSTQE, 14, pp. 82-87, 2008
hν e
hν e
Ion-1
UPCONVERSION FLUORESCENCE
CONFOCAL MICROSCOPY
hν f
One-photon process
Energy
transfer
hν e
hν e
hν e
Ion-2
hν f
Two-photon process
hν f
Multiple photons: Excited-state
absorption
Multiple ions: Upconversion by
energy transfer
Unlike the two-photon
microscope, high-efficiency
upconversion fluorophore
enabled the confocal imaging
without using pulse laser and
photo-multiplier tube
SMART, TISSUE-ACTICVATED AND
NANOBIOSENSOR FIBER PROBES
SMART FIBER PROBES
θi
n 0=1
n s>1
NANOBIOSENSOR
FIBER PROBES
Kim, Kang, Ilev, Opt. Lett, 33, 427, 2008
Backreflectance Power [uW]
100
80
60
40
20
A B
C D
0
0 4 8 12 16 20
Fiber Displacement [um]

Optical Coherence Tomography (OCT): More than Imaging
Optical Simulation of Neurons
Stimulation
Laser
SLED Source
Spectrometer
Computer
( )
Coupler
Mechanical
Module
Offset
SMF
MMF
SMF
dOCT
A
d α
Nerve tissue
(b)
MMF

NANOBIOSENSORS: Rear-Earth Nanoparticle Enhanced Up-
/Down-Conversion Nanobiosensing
rear-earth nanoparticles: can be
tuned to emit at specific optical
wavelengths (VIS, NIR, MIR) via
frequency up-conversion or downconversion
effects
Nanoimaging
Nanobiosensing
Optical Therapeutics (PDT)
Kim, Kang, Ilev, “Upconversion fiber-optic confocal
microscopy under near-infrared pumping”, Optics
Letters, 33, 2008
10 nm 50 nm 100 nm 150 nm
hν e
Ion-1
Energy
transfer
hν e
Ion-2
hν f

NANOBIOSENSORS: Plasmonic Nanobiosensor Probes
LSPR (localized surface plasmon resonance): Light incident on the nanoparticles
induces the conduction electrons in them to oscillate collectively with a resonant
frequency that depends on the nanoparticles' size, shape and composition. As a result of
these LSPR modes, the nanoparticles absorb and scatter light so intensely that single
nanoparticles are easily observed and detected
Noble metal nanoparticles exhibit a strong UV–VIS extinction (absorption and Rayleigh
scattering) band, and that the wavelength of maximum extinction is red-shifted by an
increase in the dielectric constant and thickness of the material surrounding
the nanoparticles.
Biochemical nanosensors
Surface-enhanced spectroscopies
(SERS and SEFS)
Labels of immunoassays
Photonics Institute, Duke University
Prof. T. Vo-Dinh

From Microscopy To Nanoscopy and Nanobiosensing:
The Future
non-invasive 3D nanoimaging in subwavelenght (

ACKNOWLEDGEMENTS:
OTMNLab Members
Dr. Ron Waynant
Dr. Darrell Tata
Dr. Do-Hyun Kim
Dr. Sofia Tan
Robert James
Robert Landry
Outside Collaborators
FDA/CDRH Collaborators
Don Calogero, ODE/CDRH
Richard Weiblinger, ODE/CDRH
Dr. Victor Krauthamer, OSEL/CDRH
Dr. Elizabeth Katz, OSEL/CDRH
Ron Robinson, OSEL/CDRH
Dr. Josh Pfefer, OSEL/CDRH
Dr. Amir H. Gandjbakhche, NIH
Prof. Juanita Anders, USUHS
Prof. Jin Kang, JHU
Prof. Yu Chen, UMD
Prof. Lihong Wang, Washington University, UWStL
Prof. Tuan-Vo Dihn, Duke University
Prof. Esen Ekpek, Wilmer Eye Institute, JHU