Slides from Randy Glickman's presentation at TPR's Think Science event on Friday, November 16.

1. Nanomaterials and Photonics:
A Marriage Made in Heaven
Randolph D. Glickman, Ph.D.
Professor, Dept. of
Ophthalmology
UT Health – San Antonio
EchoLase, Inc.
NPR Think Science, November 16, 2018

2. What is Nanotechnology?
 In the most general terms, it deals with
structures that are less than 1/1,000 of a mm
(~4/1,000,000 inch)
 Also includes the special processes that
occur in the nanoscale
 Involves making particles in this size range,
as well as the chemistry, physics, and biology
required for practical applications

3. Biomedical Applications of
Nanoparticles
From: Cai et al. “Applications of gold nanopartricles in cancer
nanotechnology”, Nanotech Sci Appl 1:17-32, 2008

4. Diverse Types of Nanoparticles
From Cai et al.,
2008

5. Gold Nanoparticles
From Cai et al., 2008
Physical structure determined by mode of synthesis
Each type optimized for different applications

6. Photonic Applications of
Nanoparticles
 Nanoparticles have strong interactions with
light, supporting many optical (photonic)
applications
 Examples of photonic interactions:
 Strong absorption in optical domain (UV, Vis, NIR)
 Direct absorption  thermal expansion/relaxation
 acoustic response for imaging & sensing, also
for thermal therapy
 Specialized interactions (plasmon resonance) 
fluorescence  optical labeling

7. History of Photoacoustics
 19th
Century: Alexander Graham Bell
observed that sunlight modulated on a
microphone produced an audible response
Mid-20th
Century: Allan Rosencwaig at Bell
Labs worked out physical basis
 Current terminology:
 Photoacoustics: modulated conventional light
sources (“classic” mode, low frequency)
 Optoacoustics: short pulse laser (high
efficiency, high frequency)

8. Photo/Optoacoustics
 Based on the property of
molecules that, when they
absorb light, their
temperature increases,
along with their volumes.
sample
Light
Heating of
Molecules
Light (e.g. laser
beam)
Thermal
Expansion
Pressure
Waves

9. Overview of Nanotech Research in
Glickman Lab
 NanoLisa: Nanoparticle Linked Immuno-
Sorbent Assay for rapid identification of
pathogens (for clinical diagnostics)
 Novel Ocular Drug Delivery (nanoparticles as
vehicles for drugs, targeted delivery)
 Detection of reactive oxygen radicals (assess
oxidative stress)
 Imaging Applications involving nanoparticles

10. Gold Nanoparticles
 Particles 1-100 nm in
size that are synthesized
from either metallic or
semiconducting
materials, e.g. gold.
 Have strong optical
absorption in VIS-NIR,
relax via thermoelastic
expansion (generates
acoustic response

11. Nanorod Linked Immuno-Sorbent Assay
(NanoLISA) for protein detection
 Conventional ELISA uses enzyme-linked
reaction to detect immunocomplexes
 Standard technique for detection of antibody
or antigen in a sample.
 Typical applications: detect and quantify
serum levels of antibody (Ab) against viral or
bacterial pathogens.
 “NanoLISA” uses an Ab-linked nanorod to
produce a strong optoacoustic response

12. Theory of Approach
antigen
Substrate
e.g. plastic
microtiter plate detection antibodies
Antibody-conjugated
gold nanorod
Detection of pathogenic antigens by nanorod-conjugated antibodies
Nanorod conjugated to detection antibody produces
strong optoacoustic response when probed by laser

13. Immunoaffinity Reaction
Ab-NRAb-NR
WashAcoustic

14. Sensitivity to HTLV-1 p24

15. Targeted Drug Delivery to Eye
Light activated release of drug from nanoparticle depot in the
eye for delivery on demand (patient-centric, custom dosing)

16. Detection of Oxygen Radicals
From Yasmin et al., NanoBioMaterials, Vol. 1, Chap 5, 2016

17. Photoacoustic Imaging
Imaging of Radiolucent Object (wood) in Tissue by Different Methods
From Page, PhD Dissertation, 2012

18. Advantages of Optoacoustics
 Depends on optical absorption properties of tissue
 Allows for high contrast and potentially better
spatial resolution compared to RF, Ultrasound
(shorter wavelength)
 Inexpensive compared to MR, PET modalities
 Uses non-ionizing radiation
 Short-pulse (ns) lasers have high-peak power and
produce larger pressure transients than modulated
CW sources

19. Glickman Lab & Collaborators
 Saher Maswadi, Ph.D (UT Health, EchoLase, Inc.)
 Nick Akimov, M.S. (UT Health, EchoLase, Inc.
 Leland Page, Ph.D. (fmr. Grad. Student, UT Health)
 Neeru Kumar, M.S. (Res. Ass’t. UT Health)
 Kelly Nash, Ph.D. (UTSA)
 Zannatul Yasmin, Ph.D. (fmr. Grad. Student, UTSA)
 Alexander Oraevsky, Ph.D. (TomoWave, Inc.)

20. Acknowledgements
Research support from:
 The Office of Naval Research
 National Science Foundation
 San Antonio Area Foundation

21. Additional Slides

22. Improve Biomolecule Detection
with Contrast Agents
Light (laser
beam)
((Sound))
Antigen (Ag)
Absorption
Wavelength
Nanorod (NR)
Absorption
Wavelength
Light (laser
beam)
(((((Sound)))))

23. Optical detection for acoustic wave
Probe Beam Deflection Technique (PBDT): detect refractive index
gradient
no
n1
d d
A
B
C
Incident probe beam direction
Non-contact optical , Non-destructive method, works in hostile
environments, simple to align and it is relatively insensitive to
background noise.
n1 n1
n1

24. Experimental Setup
HeNe Laser
Quadrant detector
Digital Scope
Sample
Energy meter
Lens
OPO Laser
Wavelength 530nm

25. Actual Waveform from
NanoLisa Method
Left: Optoacoustic signal from HIV sample probed with HIV Ab
Middle: Blank - no target protein present
Right: Control – HIV sample probed with Hepatitis B Ab
From Glickman et al., NanoBioMaterials, Vol. 6, Chap 7, 2016

26. Drug Detection
 To evaluate drug treatment of eye tissue, we
need to know drug penetration and
concentration in the target tissue.
Low-Power
Laser Beam

27. Probe beam from
HeNe Laser
Quadrant detector
Saline
OPO Laser
Wavelength 525nm
500 pg/ml 10 pg/ml 1 pg/ml
Scanning to Determine Minimum
Detectable Ag Concentration
100 pg/ml
on X-Y
table

28. Method is at least as sensitive as conventional ELISA
Results:
 Serial dilutions of C.
trachomatis antigen were
prepared and subjected to
optoacoustic testing.
 Limit of detection found to be
5 to 10 pg/ml
 Standard ELISA detection
limit is typically ~1 ng/ml
0
5
10
15
20
25
30
35
40
45
50
1mg/ml 1µg/ml 1ng/ml 1pg/ml
(Arbitraryunits)OptoacousticResponse

29. From:
Cai et al., 2008
Summary … biomedical apps of NP