Biophotonics201404 DL

April 2014
Photonics Continues to Improve Eyesight
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Volume 21 Issue 4
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NEWS
7 BIOSCAN
BioPhotonics editors curate the most significant headlines

of the month for photonics in the life sciences and take you
deeper inside the news. Featured stories include:
Noninvasive optical system reveals oral cancer signs
3-D AFM could advance understanding of proteins
Silk-diamond hybrid shows promise for cell imaging
14 RAPIDSCAN

3 Questions with Dr. Robert Hart, Optofluidics Inc.

Endoscopy equipment market set to expand
19 SEEING THE LIGHT: HOW PHOTONICS

CONTINUES TO IMPROVE EYESIGHT
FEATURES
by Valerie Coffey, Science Writer

The latest laser technologies are advancing the treatment
of cataracts, macular disease and other eye conditions.
23 FRET PURSUES AFFORDABLE, ROBUST,

USER-FRIENDLY INSTRUMENTS

by Marie Freebody, Contributing Editor

Upgrades to this versatile spectroscopy technique would
make it easier to use and more widely applicable.
27 SOFTWARE ENHANCES LIFE SCIENCES

APPLICATIONS, BIOMEDICAL SIMULATIONS
23
by Dr. Edward Freniere and Michael Gauvin, Lambda Research Corp.

Optomechanical design software can minimize a products
development time while optimizing its technical agility.
by Gary Boas, News Editor

Adding 3-D capabilities to techniques such as PALM and STED
should further lengthen the reach of bioimaging.
30 SUPERRESOLUTION IMAGING

ADDS ANOTHER DIMENSION
5 EDITORIAL
DEPARTMENTS
THE COVER
A surgical laser can score
a cataract in a cross, pie,
bulls-eye or grid formation.
Image courtesy of Lensar.
Design by Art Director
Suzanne L. Schmidt.
32 BREAKTHROUGHPRODUCTS
35 APPOINTMENTS

37 ADVERTISER INDEX
38 POST SCRIPTS

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PHOTONICS
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BIOPHOTONICS
The application of photonic products and techniques to solve problems for researchers,
product developers, clinical users, physicians and others in the fields of medicine,
biology and biotechnology.
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EDITORIAL
Seeing the Future:

Visionaries and
Vision Correction
his month, we congratulate the winners of the 2014 SPIE Awards. Among them are
the following three, who have had an impact on the world of biophotonics. (For a list
of all the winners, visit www.photonics.com/a55977.)
The SPIE Britton Chance Biomedical Award was awarded to Dr. Brian Wilson, head
of the Division of Biophysics and Bioimaging at the Ontario Cancer Institute, in honor
of Wilsons many contributions to biomedical optics over the past 30 years, including
his pioneering work in photodynamic therapy (PDT). His work included the concepts of
PDT beacons, metronomic PDT and nanotechnology-enabled PDT, as well as technology
development and clinical trials in the brain, the prostate and metastatic bone lesions.
The recipient of the SPIE Biophotonics Technology Innovator Award is Dr. Naomi
Halas, director of the Laboratory for Nanophotonics and the Stanley C. Moore Professor
in Electrical and Computer Engineering at Rice University in Houston. Halas is recognized for her invention of biocompatible nanoparticles and their innovative applications in imaging, diagnostics and photothermal cancer therapy. She invented a class of
nanoparticles with optical resonances that can be designed in to a nanostructure. Her
use of gold nanoshells in living systems is in clinical trials.
Also on the list is Dr. Jeff Squier, a professor in the department of physics at the Colorado School of Mines in Golden, recipient of the Harold E. Edgerton Award. His achievements include the demonstration of the first Ti:sapphire-based regenerative amplifier for
high-energy ultrashort pulse generation as part of a group at the University of Rochester
in New York. Most recently, he introduced a method to simultaneously capture nonlinear
optical images from multiple depths. He is recognized for his seminal contributions to,
among others, femtosecond lasers and amplifiers, laser filamentation, ultrafast spectroscopy and ophthalmic procedures with ultrafast lasers.
BioPhotonics Editorial Advisory Board
Mark A. Anastasio, Ph.D.

Professor of Biomedical Engineering
Washington University in St. Louis
Stephen A. Boppart, M.D., Ph.D.

Bliss Professor of Engineering
Electrical and Computer
Engineering, Bioengineering and Medicine
Beckman Institute for Advanced
Science and Technology
University of Illinois at Urbana-Champaign
David Benaron, M.D.

Professor, Medicine (consulting)
Founder, Stanford Biomedical Optics program
Stanford University School of Medicine
CEO, Spectros Corp.
Aydogan Ozcan, Ph.D.

Associate Professor
Electrical Engineering, Bioengineering
University of California, Los Angeles
Adam Wax, Ph.D.

Theodore Kennedy Associate Professor
Director of Masters Studies at the Department
of Biomedical Engineering, Duke University
Chairman and Founder, Oncoscope Inc.
Speaking of ophthalmic lasers, in our cover story, science writer Valerie Coffey takes
an unblinking look at cutting-edge laser technologies advancing ophthalmological
treatments. Refractive laser surgery is used to treat eye conditions including near- and
farsightedness, astigmatism and one day soon the scourge of middle age: presbyopia.
Look into the latest on lasers in eye treatment in Seeing the Light: How Photonics Continues to Improve Eyesight, beginning on page 19.
Also in this issue, contributing editor Marie Freebody examines the versatile FRET
spectroscopy technique in FRET Pursues Affordable, Robust, User-Friendly Instruments, starting on page 23; Dr. Edward Freniere and Michael Gauvin of Lambda Research Corp. explain the role of optomechanical design software in developing efficient
and effective biomedical optical products in Software Enhances Life Sciences Applications, Biomedical Simulations, beginning on page 27; and, in Superresolution Imaging
Adds Another Dimension, news editor Gary Boas outlines the potential impact of 3-D
capabilities added to the technique, beginning on page 30.
Enjoy the issue. Send comments to me at karen.newman@photonics.com.
Karen A. Newman
karen.newman@photonics.com
CONTRIBUTORS
News editor Gary Boas has
extensive experience as
a writer and editor in the
research community; he is
also a contributing editor to
Photonics Spectra. Page 30.
Valerie C. Coffey is a freelance

science and technology writer
in Massachusetts with a masters degree in astronomy. Her
articles on optics, photonics,
astronomy and physics have
appeared in various industry
publications. Page 19.
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Michael Gauvin is vice president of sales and marketing

at Lambda Research Corp.;
he has more than 25 years
of experience in the optical
engineering eld. Page 27.
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BIOSCAN
A closer look at the most significant biophotonics research and technology headlines of the month
Noninvasive optical system reveals oral cancer signs
The diffuse reflectance imaging system (DRIS) captures monochrome images to

generate a pseudocolor map. Blue denotes healthy tissue, red shows premalignant tissue, and yellow designates malignant tissue. Courtesy of the Centre for
Earth Science Studies.
KERALA, India A new spectral imaging system holds promise

for rapid, noninvasive screenings for oral cancers. The death rate
associated with this type of cancer has historically been high because it is routinely discovered late in its development, according to the Oral Cancer Foundation in Newport Beach, Calif.
The diffuse reflectance imaging system (DRIS), developed by
a team from the Centre for Earth Science Studies, identifies the
margins of a lesion that cannot be easily visualized by the naked
eye during invasive surgical interventions, said team leader Dr.
Narayanan Subhash.
The rapid, easy-to-use system exhibits accuracy comparable
to the gold standard histopathology of a biopsy sample. DRIS
works with a Luca-R electron multiplying CCD (EMCCD)
camera to capture monochrome images of a patients mouth at
545 and 575 nm.
Software then uses the images to generate a pseudocolor
map to identify premalignant and malignant tissue and lesions,
enabling early detection and treatment.
[DRIS] also delineates the boundaries of neoplastic changes
and locates sites with the most malignant potential for biopsy,
thereby avoiding unnecessary repeated biopsies and delay in
diagnosis, Subhash said.
The system has the potential to be a valuable tool as an adjunct
to colposcopy in the screening of cervical precancers and in
the identification of the most malignant site for biopsy, the
researchers believe.
3-D AFM could advance understanding of proteins

COLUMBIA, Mo. An advanced 3-D
atomic force microscope will allow the
study of membrane proteins in conditions
similar to those found in the body, an
improvement that could lead to increased
understanding of proteins on the microscopic level and to faster drug therapies.
The study of complex proteins that
allow information and molecules to
pass into and out of a cell has long been
restricted by the limitations of 1-D force
microscopes. Preparation requirements
dont allow specimens to be studied as
they would behave in their normal environments.
Researchers at the University of Missouri, using a traditional 1-D force microscope as a guide, added another laser to
measure the second and third dimensions
of tip movement. This provided real-time
access to the measurement of peaks and
valleys in the membrane protein and
dynamic changes in those structures.
The 3-D atomic force microscope developed by researchers at the University of Missouri could help
researchers understand proteins better. Images courtesy of the University of Missouris Department
of Physics and Astronomy and Department of Biochemistry.
BIOSCAN
Using this new laser, we collect the

backscattered light from not only the
cantilever holding the needle, but also
the tip of the needle that gives additional measurements, said Dr. Gavin M.
King, assistant professor of physics and
astronomy in the College of Arts & Science at the university, and joint assistant
professor of biochemistry. This added
flexibility allows us to collect information faster and allows our microscope to
work in near-native conditions in fluid
like those found in the cell, yielding more
realistic results.
By studying how proteins shapes
change, researchers can determine how
drugs bind and interact with cells, King
said. The membrane protein information
can assist pharmaceutical companies in
determining which molecules to pursue.
The work was published in Nano
Letters (doi: 10.1021/nl403423p).
Researchers scattered a focused laser directly off an atomic force microscope tip apex to rapidly and precisely measure the tapping tip trajectory in a 3-D space. F = Force; pN = pico Newton; = angstrom.
Silk-diamond hybrid shows promise for cell imaging

SYDNEY and MELBOURNE, Australia,
and BOSTON A new hybrid nanodiamond-silk material could enhance
biological imaging and refine medication
delivery.
The new particles developed by a
team from the University of Melbourne,
the University of Sydney and the Silk Lab
at Tufts University in Medford, Mass.,
and just tens of nanometers across are
made of nanodiamonds and covered in
silk. They can be injected into living
cells, and they glow when illuminated
with certain kinds of light. Biologists can
use them to peer inside cells and untangle
the molecular circuitry that governs cellular behavior, and to study how cells react
to a new medication.
The team did discover one challenge:
The edges around the hybrid particles
tend to be rough, which could cause the

nanodiamonds to become trapped inside
cell membranes. Previous studies have addressed this issue by coating the particles
with lipids, but this new study found that
using silk to coat the nanodiamonds not
only preserves the nanoparticles optical
properties, but also enhances their brightness by two to four times.
The new material appears to be safe
for use in the body, the researchers say,
because it left no damaging effects, even
after spending two weeks implanted inside
living tissue. The hybrid particles also
could potentially be used in clinics, allowing doctors to send infection-fighting antibiotics to a targeted area of the body, they
say. Silk also can be designed to degrade at
a certain rate, which would allow clinicians to control the release of medications.
Nanodiamonds similar to those used

in this study have been explored in the
past to determine potential medical uses,
but this is the first time silk has been
incorporated. During testing of the new
hybrid material, the silk remained transparent and did not block the glow of the
nanodiamonds.
In the future, the team anticipates
developing a range of nanodiamond-silk
structures that could help researchers
improve techniques for fighting infections in targeted areas of the body. A
thin film of the new substance, carrying
medication, could be implanted directly
into an infected area, minimizing patient
exposure to the drug.
The work was published in Biomedical Optics Express (doi: 10.1364/
boe.5.000596).
Lighting up brain stops liquored-up rats

BUFFALO, N.Y. Stimulating brain cells with light stops binge
drinking in rodents, a new study has found. The results suggest
the possibility of using optogenetics to treat substance abuse,
neurological diseases and mental illnesses.
A team at the University at Buffalo, in collaboration with
Wake Forest University and the University of North Carolina
Neuroscience Center, used light to stimulate neurons in rodents
that had been trained to drink alcohol in a way that mimics human binge drinking. The work is the first to demonstrate a causal
relationship between the release of dopamine in the brain and
the drinking behaviors of animals, and helps explain the underlying neurochemical basis of drug addiction.
By stimulating certain dopamine neurons in a precise pattern, resulting in low but prolonged levels of dopamine release,
we could prevent the rats from bingeing. The rats just flat-out
stopped drinking, said Dr. Caroline E. Bass, assistant professor
of pharmacology and toxicology in the UB School of Medicine
and Biomedical Sciences.
The rodents continued to avoid alcohol even after the stimulation of neurons ended.
BIOSCAN
Dr. Caroline E. Bass holds two fiber optic implants used in the experiments to
deliver light to the brain. The light induces dopamine release, which changes
the behavior of the animals. Courtesy of Douglas Levere, University of Buffalo.
For decades, we have observed that particular brain regions

light up or become more active in an alcoholic when he or she
drinks or looks at pictures of people drinking, for example, but
we didnt know if those changes in brain activity actually governed the alcoholics behavior, Bass said.
Electrical stimulation doesnt discriminate, she added. It
hits all the neurons, but the brain has many different kinds of
neurons, with different neurotransmitters and different functions. Optogenetics allows you to stimulate only one type of
neuron at a time.
Bass specializes in using viral vectors to study the brain in
substance abuse. In this study, she used a virus to introduce
a gene encoding a light-responsive protein into the animals
brains. That protein then activated a specific subpopulation
of dopamine neurons in the brains reward system.
I created a virus that will make this protein only in dopaminergic neurons, Bass said.
The neuronal pathways affected in this research are involved
in many neurological disorders, she said. For that reason, the
results have application not only in understanding and treating
drinking behaviors in humans, but also in many devastating
mental illnesses and neurological diseases that have a dopamine
component. This ability to target genes to dopamine neurons
could potentially lead to the use of gene therapy in the brain to
mitigate many of these disorders, she said.
We can target dopamine neurons in a part of the brain called
the nigrostriatal pathway, which is what degenerates in Parkinsons disease, she said. If we could infuse a viral vector into
that part of the brain, we could target potentially therapeutic
genes to the dopamine neurons involved in Parkinsons. And
by infusing the virus into other areas of the brain, we could
potentially deliver therapeutic genes to treat other neurological diseases and mental illnesses, including schizophrenia and
depression.
Bass is first author on a paper published in Frontiers in Behavioral Neuroscience (doi: 10.3389/fnbeh.2013.00173).
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BIOSCAN
Light-emission studies may improve bioimaging

URBANA-CHAMPAIGN, Ill. New understanding of secondary light emission by plasmonic nanostructures could lead to
improvements in medical imaging.
Work by materials scientists and engineers at the University of
Illinois at Urbana-Champaign presents an alternate description of
secondary light emission from plasmonic nanostructures, which
is typically described as two-photon absorption followed by fluorescence, as a resonant electronic Raman scattering process.
Plasmonic nanostructures are of great current interest as
chemical sensors, in vivo imaging agents and for photothermal therapeutics, said professor David G. Cahill, head of the
Department of Materials Science and Engineering. Applications
in imaging and sensing typically involve the emission of light
at a different wavelength than the excitation, or secondary light
emission. The interpretation of resonant secondary light emission in terms of fundamental processes has been controversial
for 40 years.
In this work, we point out that resonant electronic Raman
scattering and resonant fluorescence may both be useful descriptions of the secondary emission. Better understanding of these
principles and their limitations can result in improved biological
and medical imaging modalities.
Illustration of resonant electronic Raman scattering and resonant
fluorescence. Courtesy of Jingyu Huang, University of Illinois.
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BIOSCAN
Light emission from plasmonic nanostructures at wavelengths shorter than

the wavelength of pulsed laser excitation
is typically described as the simultaneous absorption of two photons followed
by fluorescence, which is used a lot in
biological imaging, said Jingyu Huang,
first author of the paper, which appears in
PNAS (doi: 10.1073/pnas.1311477111).

However, we found that by modeling
the emission as Raman scattering from

electron-hole pairs, we can predict how
the light emission depends on laser power,
pulse duration and wavelength.
Since we understand more of the
mechanism of this kind of light emis-
sion, we can help to design the biological

and medical imaging experiments better,
and at the same time we can also have
more insight into the broad background
of surface-enhanced Raman scattering,
which is also related to this kind of light
emission.
Harnessing randomness to improve lasers

SINGAPORE Randomness could be key
in improving the performance of lasers in
sensing and imaging applications, a new
study shows. Those applications include
biomedical imaging.
Randomly arranged, or irregular,
surfaces typically have poor optical
properties, as the roughness (randomness)
can obscure the view of an object. But
now, a team from the A*STAR Singapore
Institute of Manufacturing Technology
(SIMTech) and Nanyang Technological University has discovered a way to
make efficient use of randomness. In its
research, the team demonstrated the first

electrically pumped mid-IR random laser,
which is as bright as conventional diode
lasers but produces less-speckled images.
Lightwaves from a conventional laser
oscillate in perfect synchronicity across
both time and space. Perfect alignment of
the lightwaves at different times and locations across the beam profile is known as
temporal and spatial coherence, respectively.
When a laser illuminates a surface,
a speckled pattern typically is visible,
which indicates spatial coherence. The
speckles are the result of the laser beams

reflectance from different parts of the
surface. Because the waves are in sync,
they create spatial interference effects in
the eye of an observer.
This distortion is undesirable, particularly in biomedical imaging applications conducted in the IR region of the
spectrum. Random lasers are the solution
to this type of distortion, says Ying Zhang
of SIMTech.
Random lasers show the same high
temporal coherence as that of other lasers
but have a lower spatial coherence, he
BIOSCAN
said. High temporal coherence gives the

desirable brightness, but it is the low spatial coherence that removes the speckles
caused by interferences.
To realize a random laser in the mid-IR
spectrum, researchers used a semiconductor quantum cascade laser into which they
had drilled a random pattern of nanoholes.
At a sufficiently high density, these holes
prevented the formation of a regular laser
pattern within the semiconductor. Instead,
the pattern of a random laser forms, with
low spatial coherence.
More work is needed to bring random
lasers to the current market, however.
In the long term, we plan to extend
random lasers from the infrared to even
longer wavelengths for quality control
of printed electronics, biomedical imaging, among other applications, said Hou
Kun Liang of SIMTech.
The simulated random laser mode in the transverse-magnetic polarization. Designed at A*STAR, the first
electrically pumped mid-IR random laser will enhance sensing and imaging applications. Courtesy of
SIMTech.
UV-activated adhesive treats heart defects

BOSTON A bio-inspired, light-activated adhesive used to treat congenital heart
defects could soon replace more invasive
treatments such as sutures, new research
indicates.
A preclinical study conducted by Boston Childrens Hospital (BCH), Brigham
and Womens Hospital (BWH) and MIT
shows that the adhesive could rapidly
attach biodegradable patches inside a
beating heart, in the exact place where
congenital holes in the heart occur, such
as with ventricular heart defects.
This study demonstrated that the adhesive was strong enough to hold tissue and
patches onto the heart equivalent to suturing, said the studys co-first author Dr.
Nora Lang of the Department of Cardiac
Surgery at BCH. Nothing foreign or toxic
stays in the bodies of these patients.
The adhesive properties are activated
with UV light and provide an on-demand,
anti-bleeding seal within five seconds
when applied to large blood vessels and
cardiac wall defects.
Waterproof and light-activated, the adhesive secures biodegradable patches to
seal holes in a beating heart and close transmural cardiac wall defects. Images
courtesy of Randal McKenzie/McKenzie Illustrations.
12
BIOSCAN
When we attached patches coated with

our adhesive to the walls of a beating
heart, the patches remained despite the
high pressures of blood flowing through
the heart and blood vessels, said co-first
author Dr. Maria N. Pereira of the Division of Biomedical Engineering in BWHs
Department of Medicine.
The adhesive is also waterproof,
biodegradable, elastic and biocompatible.
It will be useful in reducing the invasiveness of surgical procedures as well as
operating times, and it will improve heart
surgery outcomes, the researchers say.
This adhesive platform addresses all
of the drawbacks of previous systems,
said co-senior study author, Dr. Pedro del
Nido, chief of cardiac surgery at BCH. It
should provide the physician with a completely new, much simpler technology and
a new paradigm for tissue reconstruction
to improve the quality of life of patients
following surgical procedures.
The research was published in Science
Translational Medicine (doi: 10.1126/scitranslmed.3006557).
The activation of glue with UV light promotes adhesion and locks the patch in place.
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RapidSCAN Business and Markets

As chief technology officer and president of Optofluidics Inc., Dr. Robert Hart has
helped the Cornell-born startup develop microfluidic and biophotonic nanomanipulation technologies for biological, materials science and pharmaceutical applications.
With CEO Dr. Bernardo Cordovez, Hart and Optofluidics have garnered industrywide
attention culminating in a 2014 Prism Award nomination for the NanoTweezer, a system
that captures, manipulates and analyzes large numbers of individual nanoparticles.
After receiving his doctorate in biomedical engineering from Drexel University, Hart
completed a postdoctoral fellowship at the University of Pennsylvania. He currently
oversees product development, corporate partnerships and internal R&D for Optofluidics, and has played a central role in landing more than $3.3 million in federal and
private funding. In 2012, Optofluidics was chosen as Life Sciences Startup of the Year
by the Greater Philadelphia Alliance for Capital and Technologies.
BioPhotonics recently asked Hart three questions about his work with nanomanipulation, including its relation to behavior analysis and its potential applications in
cancer treatment.
3 Questions
with Dr. Robert Hart, Optofluidics Inc.

Q: What are you working on right
now?
Q: What are the implications of that

work?
Hart: Since the launch of our advanced

nanoparticle analyzer, the NanoTweezer,
this past December, weve been splitting
our time between driving sales and pushing the frontiers of particle-measurement
science. Typically, people are amazed
when they find out were making actual
tractor beams and that we can suck
nanoparticles down onto a waveguide.
But this is only half the story. Were not
just manipulating nanoparticles; were
measuring them, too. Each particle that
lands on our waveguide scatters light
as if it were a defect. Imagine taking a
fiber optic and nicking it in dozens of
places, allowing you to see the light that
was previously coursing through unseen.
In our system, each spot of light we see
represents a tiny nanoparticle thats been
trapped. The best part is that we can do
this all in the native liquid where they
normally live and function.
We still have some serious technical
work ahead, though. Our technical team is
measuring nanoparticle shape and coating
properties something no other system
can do outside of electron microscopes.
Once we establish the technique and nail
down the theory, we intend to apply these
techniques to some big problems in health
care, specifically nanomedicine, nanotoxicology and biotherapeutics.
Hart: As a developer of analytical equipment, our mission is to make products

containing nanoparticles better and safer.
Our world is awash with nanoparticles
tiny objects around one-thousandth the
width of a human hair. They have found
their way into a wide variety of products,
from dishwashing detergent to batteries to medicine. Yet measuring them is
still extremely difficult, mainly because
they are just so small. Weve had nearly a
thousand conversations with researchers
and engineers around the world who work
with nanoparticles, and the consensus
is clear: New methods of measuring
nanoparticles are desperately needed.
With our new measurement system, we
hope to shed light on nanoparticle behavior enabling scientists and engineers to
unlock their true potential.
One great example is in pharmaceutical R&D. For many years, scientists have
been working on targeted drug delivery. The idea is to use specially coated
nanoparticles that latch onto tumors,
allowing them to deliver the chemotherapy directly to the tumors like a laserguided missile, as opposed to traditional
chemotherapy, which is more like carpet
bombing. This method worked in the lab
but usually failed in animals due to a poor
understanding of what happened to the
14
coating once the nanoparticles entered the

biological tissue. It took years to uncover
the truth, which is that the coating was
fouled by a layer of proteins from the
blood, masking the tumor-targeting
coating. There simply were no systems
capable of doing these kinds of measurements, which is why it took so long to
find out. With the launch of our NanoTweezer system, we hope to shore up this
measurement gap and help make better
pharmaceuticals, including tumor-targeted therapies.
Q: Whats the next step?
Hart: Once we establish ourselves in the
market with the early adopters, we will
launch a second version of our instrument
that is more integrated and user-friendly.
The plan is for this system to be dedicated
specifically to one of the big applications.
Right now, our best bets are in nanomedicine, where a large number of drugs are
being developed with huge potential but
limited ways of analysis; in biopharmaceuticals, where patient safety and drug
efficacy are at stake; or in nanoparticle
toxicity, which is already starting to be
regulated in Europe.
Sarina Tracy
sarina.tracy@photonics.com
Endoscopy equipment market set to expand
he global market for endoscopy

equipment is expected to reach $37.9
billion by 2018, according to Endoscopy Equipment Market by Endoscopes
(Rigid, Flexible, Capsule), by Visualization
Systems (HD, 3D Camera, Wireless Display & Monitor), Others (Endoscopic Ultrasound, Carts), by Application (Colonoscopy, GI Endoscopy) Global Forecasts
to 2018, a new market report published by
MarketsandMarkets of Dallas.
The global endoscopy equipment
market was valued at $28.2 billion
in 2013 and is expected to grow at a
compound annual growth rate of 6.1
percent from 2013 to 2018. This growth
is attributed to the growing preference
for minimally invasive surgeries and
the concern for cost-effective pre- and

postoperative care expenses. Advancements in technology, including increased
angles in the endoscopic field of view,
reduced outer scope diameter, and use of
high-resolution 3-D systems and capsule
endoscopes, are driving this market
expansion. A growing aging population
with favorable reimbursement scenarios
and an increased prevalence of disease
compound this increase.
The report analyzed the market of
rigid, flexible, surgical and capsule endoscopes. Endoscopic instruments such as
high-resolution video systems, endoscopy
cameras, video processors, converters and
light sources were also included, along
with other tools such as insufflators, fluid
Hamamatsu factory in Beijing completed

Construction of Building No. 2 at Hamamatsu Photonics KKs Beijing subsidiary
Hamamatsu Photon Techniques Inc. is
now complete. Operations at the facility,
located at the Langfang factory, were
scheduled to begin in February.
The building will be used for glass processing and scintillator manufacturing, and
for the manufacture of nonphotomultiplier
tube products. The facility allows for expansion of manufacturing capacity as well Courtesy of Hamamatsu.
as for research and development activities,
and also will improve the manufacturing capacity of two other existing factories at
Beijing, including the Yongqing facility.
Ireland backs photonics for economic impact

The newly opened Irish Photonic Integration Centre, focused on information and communications technology, and on the medical device sector, is expected to create 200
new jobs over the next six years and to bring global scientific recognition to Ireland.
Development efforts will focus on improving data transfer speeds, creating new
energy-efficient devices, and delivering medical components for disease diagnostics
and treatments.
One of seven centers in the country, the center will bring together researchers from
Tyndall National Institute, University College Cork, Cork Institute of Technology and
Dublin City University. The Irish government has invested 20 million (about $27.46
million) in the center, adding to the 10 million (about $13.73 million) investment
made by commercial partners.
The researchers will work with industry partners ranging from multinationals such
as Intel, BT and Verizon to photonics specialists such as Finisar, and with smaller
Irish companies and high-tech startups. Among newly added industry partners are
Cork-based X-Celeprint a company looking to commercialize a microtransfer printing process that could enable mounting of optoelectronic materials and devices such
as LEDs and lasers on flexible substrates and Stryker Corp. of Kalamazoo, Mich.
management and ultrasound systems,

biopsy forceps and valves.
North America holds the largest share
of the global endoscopy market, followed
by Europe and Asia. Increased health care
spending, the establishment of endoscopic
training centers and increased patient
awareness of minimally invasive surgeries have poised countries such as India,
China and Japan for market expansion.
Middle Eastern, North African, South
American and Pacific countries are likely
to witness steady growth through training
and investment, while several government
initiatives in New Zealand are working to
develop an efficient workforce for endoscopy services.
Nipro to make TVC

imagers for Infraredx
Nipro Corp. has established a
manufacturing subsidiary in Yamanashi, Japan, that will produce
biomedical devices. Nipro is the
exclusive distributor of Infraredx
Inc.s TVC Imaging System in Japan;
the companies signed a five-year
distribution agreement in 2012.
Production is scheduled to begin
in 2015, following regulatory approval from Japans Pharmaceuticals
and Medical Devices Agency.
The TVC Imaging System uses
intravascular ultrasound and NIR
spectroscopy to monitor coronary
artery disease by evaluating vessel
structure and composition, and by
monitoring for plaque and stenosis.
Japan makes up 50 percent of
the worldwide intravascular imaging
market representing a significant global growth opportunity,
said Don Southard, president and
CEO of Infraredx. The expansion
of manufacturing to Nipros new
facility boosts our capacity to meet
the anticipated demand for the TVC
Imaging System in Japan and supports our commercialization efforts
in China, Korea and other emerging
Asia-Pacific markets.
The TVC Imaging system is the
first of nine products slated for commercial manufacture at the Nipro
facility.
15
Compact &
Versatile
RAPIDSCAN
Courtesy of Bruker Corp.
The Fiber-Coupled
Laser Scanner
Bruker opens Preclinical Imaging Center

of Excellence for the Americas
Bruker has opened the Preclinical Imaging Center of Excellence for the Americas in
Billerica, Mass., with advanced development, demonstration and support facilities for
preclinical imaging instrumentation and multimodal platforms.
I am really excited to see the establishment of a full-featured, preclinical imaging
laboratory in the Boston area, said Frederic Fahey, director of Nuclear Medicine Physics
at Boston Childrens Hospital. We look forward to the development of many new collaborations and innovations.
The center aims to play a key role in promoting the successful application of complementary imaging information in preclinical research in oncology, cardiology, inflammation,
musculoskeletal imaging and the neurosciences. Multiple modalities such as optical imaging, x-ray, PET and MRI enable researchers to acquire complementary image information
such as morphology and function for use in translational research and medical science.
Light Sheet Microscopy

Optogenetics
Local Uncaging
FRAP
For More Information
Visit: www.asiimaging.com
Email: info@asiimaging.com
Call: (800) 706-2284
or (541) 461-8181
PEOPLE IN THE NEWS

Sean Bagshaw has
stepped into the role of
chief operating officer for
The Optical Society (OSA).
He also will continue as
chief information officer,
a post he has held for
five years. Since 2009,
Bagshaw has managed
software and Web development, business systems
analysis, and technological infrastructure and support as CIO. In his additional role as COO, he will
run the finance, legal and facilities operations for
OSA. Bagshaw has more than 25 years of experience in the nonprofit, health care and technology
services industries. Before joining OSA, he was
vice president and chief technology officer for
the Mortgage Bankers Association. Before that,
he served as vice president of engineering and
operations at Oleran Net Solutions. He holds a
bachelors degree in computer science from Siena
College in Loudonville, N.Y.
Samuel Sadoulet has been named the new
president of Edmund Optics. He has served as
the companys chief operating officer for more
than a year, a role he will maintain along with that
of president. Sadoulet has a wide range of experience across many divisions within the company,
including front-line sales, technology development
and manufacturing, according to Robert Edmund,
chairman and CEO of Edmund Optics. Sadoulet is
a member of The Optical Society, SPIE and the Automated Imaging Association. He holds a masters
16
from the University of Arizona and a bachelors in

physics from the University of Rochester. He also
recently received his Executive Master of Business
Administration from INSEAD business school in
France.
Optical scientist Dr. Michael
D. Duncan has joined The
Optical Society (OSA) staff
as a senior science adviser.
He will provide strategic direction on the scientific and
technical aspects of OSAs
programs and services for
optics and photonics professionals. Mike is an involved
and effective leader, said
OSA CEO Elizabeth Rogan. His contributions in
scientific publishing and long-range planning have
provided considerable value to OSA. Duncan
worked as an optical scientist for the US Navy for
more than 30 years. At the Naval Research Laboratory, his research focused on lasers, nonlinear
optics and optical reconnaissance systems. He
also worked at the Office of Naval Research, helping direct a portfolio of basic and applied research
for the Navy in the area of IR and electro-optic
sensors. The author of more than 65 technical
papers and holder of four patents, he also has
served on a number of advisory committees for
the US government and presented more than 100
seminars and technical papers, both invited and
contributed, at laboratories, universities and technical conferences worldwide. He is an OSA Fellow
and served as editor of OSAs open-access journal
Courtesy of OSA.
The Fiber-Coupled Laser Scanner

is a compact and versatile 2D
galvo unit originally designed
for generating SPIM light
sheets. The unit can be C-mount
coupled to most microscopes
and can be used for several
applications, including:
Courtesy of The Optical Society.
Fiber-Coupled
Laser Scanner
RAPIDSCAN
Femtosecond laser processing enhances medical device applications

LSA Laser now offers femtosecond laser
processing capabilities for medical
device manufacturing, a method that
avoids thermal damage while drilling
and cutting high-precision shapes for
micromachining applications.
This capability creates new opportunities for advanced micro designs, particularly for difficult-to-process metals
that are not feasible with conventional
lasers and for composite materials,
said Tom Noll, president of LSA.
The new laser processing has the potential to cut multiple materials at once
or to drill and cut microshapes, reducing operations in the manufacturing of
medical assemblies such as catheters.
The ultrafast laser allows a wide range
of materials and composite processing,

including polymers, platinum, stainless
steel and nitinol.
The shortened pulse from a femtosecond laser decreases the heat-affected zone around the material being cut,
resulting in an overall cleaner cut and
less damage to the surrounding areas.
Parts processed with this system require

little to no postprocessing.
The system was designed to be
flexible and suitable for on- or off-axis
cutting, as well as for R&D or volume
applications. It can handle both flat
stock and tube cutting on the same
system with minimal setup.
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Optics Express from 2002 to 2006. He is currently

serving as an OSA representative on the board of
the American Institute of Physics. He received his
bachelors degree in physics from Rice University,
and his masters and doctorate from the Applied
Physics Department at Stanford University.
FLUORESCENCE
FILTERS
Courtesy of ASLMS.
Dr. George J. Hruza has

been named the new
public policy director for
the American Society for
Laser Medicine & Surgery
(ASLMS) Inc. His duties
include identifying and
prioritizing relevant state
and federal legislative and
regulatory proposals for the
organization and its members. The new position
will enhance the ASLMS function as a resource for
the US Food & Drug Administration in discussing
ways to improve the ability of getting safe and
effective devices available for the treatment of
our patients, Hruza said. I will work with other organizations with an interest in energy-based medical technologies to help educate regulators and
legislators and to comment on relevant proposed
regulations or legislation about the safe, effective
and ethical use of energy-based devices. A clinical professor of dermatology and otolaryngology
at St. Louis University School of Medicine, Hruza is
also director of the Laser & Dermatologic Surgery
Center in St. Louis, where he directs a dermatologic surgery fellowship training program.
Pre-mounted cubes or
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RAPIDSCAN
Agilent joins Picometrics

in biopharma deal
Agilent Technologies Inc. and Picometrics
Technologies have signed a marketing
agreement to improve efficiency in the research and development of complex largemolecule biopharmaceutical compounds.
Analysis technologies such as capillary
electrophoresis (CE), laser-induced fluorescence detection and mass spectrometry
are particularly useful for the research
and development of new biological entities, said Michael Frank, marketing director of liquid phase separations at Agilent.
As conventional drug research becomes outmoded in meeting the increasing demands of complex, large-molecule
drug development, scientists need highly
sophisticated tools like these to advance
therapeutic discovery, Frank said.
Several Agilent products can be used
with Picometrics Zetalif LED and Zetalif
Laser instruments, including CE and CE/
mass spectrometry technologies, and
high-performance liquid chromatography/
ultrahigh-pressure liquid chromatography
solutions.
Fifteen years ago, the cover story in our April issue

explored the use of confocal laser scanners in gene
analysis. At the time, the Human Genome Project,
an international collaboration with the goal of mapping the genes of human beings, was expected to be
completed by 2002. A rough draft was finished in
2001, with the final project completed in 2003. With
this feat came the logistics of its study. Microarrays
and confocal laser scanning helped revolutionize
the field of genomics and gene expression through
scanning and analyzing fluorescently labeled gene
targets at the microscopic level.
1999
The human genome, consisting of 3 billion base pairs of DNA,

is expected to be sequenced within the next two to five years.
At the same time, the sequence of hundreds of other non-human
genomes, including mammalian, plant, bacterial and viral
species, will be determined. We will know the entire genetic
makeup of a myriad of organisms, and this will present us
with a daunting task of analyzing the biology of millions
of genes. How can we accomplish this?
Ernest Kawasaki, Mack Schermer and Rolland Zeleny

of General Scanning Inc., writing in the feature article.
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18
Seeing the Light: How Photonics

Continues to Improve Eyesight
Cutting-edge laser technology and new techniques are enabling
amazing diagnostic and treatment advances in ophthalmology.
BY VALERIE COFFEY, SCIENCE WRITER
n 1981, Rangaswamy Sri Srinivasan, a researcher at IBMs Thomas J.

Watson Research Center, experimented
with a pulsed argon fluoride (ArF)
excimer laser on turkey leftovers, and
lasers have had an ever-growing role in
ophthalmology ever since. That landmark resulted in the first laser-based
vision-correction techniques, including laser-assisted in situ keratomileusis
(lasik) and photorefractive keratectomy
(PRK) techniques.
Ophthalmology uses numerous photonic technologies Nd:YAG and femtosecond excimer lasers, 3-D imaging
techniques and OCT (optical coherence

tomography) to diagnose and treat eye
diseases and vision problems. Today,
these techniques are being combined into
systems that are revolutionizing the eye
surgeons job. Even moderately powered
lasers can be dangerous to the eyes when
mishandled (see sidebar), but (perhaps
ironically) because of this ability to
burn tissue, surgical laser systems have
become indispensable in the operating
theater for treatment of numerous eye
conditions. They deliver less painful,
faster, more reliable and precise results
than traditional incision techniques.1
Surgical laser systems such as the Lensar Laser System break up the cloudy cataract via laser-scored
patterns (a-d: cross, pie, bulls-eye and grid). The use of a laser reduces the amount of ultrasound
required, which reduces postoperative inflammation. Courtesy of Lensar.
Cataracts
Cataracts, a cloudiness of the eyes
clear crystalline lens, are the leading
cause of vision loss in the world, affecting
half of all individuals over the age of 60.
Nearly 22 million cataract surgeries were
performed globally in 2013, according to
estimates from MarketScope. The global
market for femtosecond lasers for cataract
surgery is growing exponentially and will
reach $2.4 billion by 2019, according to a
market report from RnR Market Research
of Dallas.
Cataract surgery involves fragmentation of the cloudy cornea, and its emulsification and removal (aspiration of the fragments), followed by the transplantation of
an artificial intraocular lens (IOL) made
of silicone or acrylic. Since the use of
femtosecond excimer lasers became common in 2009, the surgery has evolved into
an outpatient technique that takes only
a few minutes. Use of lasers reduces or
eliminates the use of ultrasound, typically
administered manually to break up and
emulsify the cataract. This helps reduce
damage to epithelial cells in the eye. The
results are more consistent, accurate and
predictable.
Recent advances in cataract treatment
include the development of better IOLs
that can compensate for the natural ability
of the cornea. One type of IOL, the multifocal IOL, mimics accommodation the
ability to focus from near to far distances
by providing multiple focal points at
near, intermediate and far distances.
Pseudoaccommodative IOLs flex to help
restore near vision by using the muscles
and natural physiological mechanisms of
the eye to bring a focus from far to near.2
What is remarkable about the latest versions of IOLs is that they can be used not
only to reclaim vision lost to cataracts,
but also to address myopia (nearsightedness), astigmatism (blurred vision),
hyperopia (farsightedness) or presbyopia
(the need for reading glasses) at the same
19
Photonics for Ophthalmology
Human donor lenses from the Bristol Eye Bank reveal spectral responses similar to those obtained
with pigs lenses in an experiment to explore early cataract diagnosis via tryptophan fluorescence:
80-year-old female (27552A); 79-year-old male (27553B); 60-year-old female (27554A);
and 66-year-old male (27557B). Courtesy of B. Dhillon/Edinburgh Instruments.
The Lensar Laser System prepares the patient for a surgical procedure using a liquid interface of a
balanced salt solution to irrigate the eye and reduce laser incision pressure. Courtesy of Lensar.
20
time. By some accounts, todays cataract

surgery may enable older patients to see
as well as they did in their youth.
A new cataract diagnosis and treatment technique piloted in Edinburgh,
Scotland, may offer improved evaluation
and management of the condition. When
Dr. S. Desmond Smith, professor emeritus
of physics at Heriot-Watt University
and founder of Edinburgh Instruments,
required cataract surgery in his 80s, he
and his surgeon Dr. Baljean Dhillon,
professor of clinical ophthalmology at the
University of Edinburgh decided to find
a better way to diagnose cataracts. The
inadequate current method requires an
ophthalmologist to observe the scattering of visible wavelengths through a slit
lamp microscope, which is subjective and
unquantifiable, Smith said. One cannot
put a detector into a living eye to measure
transmission.
But something else can. After several
years of collaborating with a long line of
scientists at Edinburgh Instruments (and
spinoff Edinburgh Biosciences), the team
came across a technique that quantifies
the amount of cataract damage via the
autofluorescence of tryptophan in the eye
lens.3 Whereas the tryptophan spectral
emission in healthy eyes peaks at 330 nm,
it begins to emit more at 430 nm instead
as the eye becomes cloudier. This quantifiable technique can enable a more reliable diagnosis and a more accurate yes/no
answer as to whether surgery is required.
The team hopes that such an advance may
reduce the amount of premature, invasive
and expensive cataract surgeries.
As a further benefit of the research, a
group at Glostrup Hospital and the University of Copenhagen, led by professor
Michael Larsen and Dr. Line Kessel, simultaneously found that when lenses with
cataracts are exposed to the two-photon
absorption effect at 400 nm of an 800-nm
femtosecond laser, the IR radiation causes
a photobleaching effect that slightly improves the transmission of donor lenses.4
After treating only a small portion of the
lens volume in donor lenses, the researchers measured an 8 percent transmission
improvement. The Edinburgh work may
enable in vivo monitoring of this treatment.
In January, the project received several
international development grants totaling 2.6 million (about $3.6 million) to
continue the work.5 The researchers hope
that the development could save millions
Vision correction
Refractive laser surgery is the treatment of the cornea to correct myopia,
hyperopia, astigmatism and presbyopia.
One recent development in surgical vision
correction is the use of wavefront aberrometry to measure the eye front to back.
The technique maps in 3-D the subtle
optical aberrations that affect vision.
Called adaptive optics by astronomers
who use it to measure and correct aberration introduced by the atmosphere in real
time wavefront mapping enables custom
lasik treatment. The map is transferred to
the laser system and matched to the eyes
position. Surgeons then use the systems
cool blue excimer laser to resurface the
cornea and correct for aberrations.
In all-laser refractive surgery, advanced
femtosecond lasers replace the mechanical instruments called microkeratomes,
which use a steel blade to create the thin
circular flap on the outermost layer of the
cornea. Also called IntraLasik, the technique has been in commercial practice for
several years to treat myopia, hyperopia
and presbyopia.
Late last year, laser system developer
Lensar Inc. of Orlando, Fla., announced
a clinical trial to study the use of a technique called lenticular softening to restore
accommodation of the crystalline lens in
presbyopic patients. Presbyopia is caused
by a loss of elasticity in the lens, hardening it so that it has less accommodating
(zoom) power to focus on nearby objects.
The condition typically occurs in middle
and old age and affects a billion people
worldwide, according to the Archives of
Ophthalmology.
Presbyopia is the holy grail in ophthalmology, said Lensar CEO Nick Curtis.
We look forward to studying and expanding the body of data on the use of a
femtosecond laser for lenticular softening
with the eventual goal of accommodation
restoration.
An initial advanced feasibility study
of 80 subjects demonstrated the Lensar
laser systems ability to soften the lens
The Dangers
of Blue Lasers
Courtesy of Shinp.
of pounds in unnecessary operations and

enable nonsurgical treatment of certain
cases of cataract impairment.
A wide variety of commercially available

high-power blue laser devices can cause
serious eye damage, according to a
study published by the American Academy of Ophthalmology (AAO) in February.7 The study reports various types of
maculopathy in 14 young patients who
lost vision after brief exposure from a
handheld blue laser device (wavelength
450 nm; measured output power 750
mW). It also found that only four of the
injured eyes of the patients (29 percent)
improved spontaneously, while 10 of the
injuries required medical intervention,
including vitrectomy (removal of blood
and scar tissue).
The FDA, the Laser Institute of America
and the American National Standards
Institute have released warnings to the
public that laser devices with an output
power of more than 5 mW can severely
damage the retina, even after momentary exposure.
However, handheld lasers of 1200
mW often are advertised online as
childrens entertainment. Laser stage
show lighting, common in the nightclub/
entertainment industry for lighting up the
smoky air with colorful animation, is also
commercially available at output powers
exceeding those considered eye-safe.
All too often, the actual wattage of
the laser devices sold is actually higher
than the manufacturers claims. The time
it takes to cause injury is shorter than the
eyes blink reflex. The researchers who
conducted the AAO-published study
emphasized that governments should
take action, such as banning the importation of these high-power laser devices;
consumers should be wary of looking
directly at questionable laser sources.
The fundus of the eye shows a pattern of grids placed by the PASCAL laser. The Endpoint Management
software enables physicians to choose whether the burns are invisible or barely visible to provide a visual
reference. Courtesy of Topcon Medical Laser Systems.
21
and restore accommodation, with notable

improvement in BDCNVA (best distancecorrected near visual acuity).
Other conditions
For treatment of diabetes-related
macular disease, a new treatment is
available using a pattern scanning laser
system (PASCAL). Developed by Stanford University spinout Optimedica of
Sunnyvale, Calif., and acquired in 2010

by Topcon Medical Laser Systems of
Santa Clara, Calif., the technology combines a PASCAL laser and proprietary
software called Endpoint Management,
which uses advanced titration algorithms
that precisely control laser power and exposure times to optimize the therapeutic
effect of the laser at less damaging levels.
The laser therapy creates a user-defined
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22
References
Excitation/Emission spectra
Fluorescence decays
Anisotropy and kinetics
Time-resolved emission spectra
Photochemistry
Materials research
Singlet oxygen
phosphorescence detection
out
Its ab
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info@picoquant-usa.com
www.picoquant.com/_mic-course.htm
www.picoquant-usa.com
pattern to treat the diseased area of the

eye. The system produces subvisible
photothermal stimulation, along with an
option to enable visible reference dots so
the physician can outline the treated area.
The burns also can be left invisible.6
The technique significantly speeds up
laser therapy for physicians by eliminating manual placement of spots one by one.
The laser places patterns that automatically advance from point to point.
In February, Dr. Daniel Palanker associate professor of ophthalmology in the
Experimental Physics Lab at Stanford and
a key contributor to the development of the
PASCAL technology received the SPIE
Translational Research Award for his
studies on nondamaging laser therapy.
His clinical partner in the research was
Dr. Daniel Lavinsky, professor of ophthalmology at Federal University of Rio
Grande do Sul in Porto Alegre, Brazil.
The most exciting aspect of this
advance is that it enables subvisible
therapy, Palanker said. Physicians dont
have to see visible burns unless they need
to. The shorter pulses also generate less
pain, so patients love it.
The technique leaves less scarring of
the fragile surfaces of the eye. In current
clinical trials of nondamaging therapy,
this is especially important in the central
area of the eye called the macula, where
90 percent of central vision is, Palanker
said.
stellaredit@gmail.com
time
1. M.H. Niemz (2007). Laser-Tissue Interactions: Fundamentals and Applications. 3rd

ed. Springer Berlin Heidelberg New York,
p. 154. ISBN: 978-3-540-72191-8.
2. Dr. Sandra Belmont, Belmont Eye Center,
New York, www.belmonteyecenter.com.
3. D. Gakamsky et al (April 2011). Exploring
the possibility of early cataract diagnostics
based on tryptophan fluorescence. J R Soc
Interface, Vol. 8, p. 1616 (doi: 10.1098/
rsif.2010.0608).
4. L. Kessel et al (March 2010). Non-invasive
bleaching of the human lens by femtosecond
laser photolysis. PLOS One, Vol. 5, No. 3,
p. 1 (doi: 10.1371/journal.pone.0009711).
5. www.catacure.eu.
6. D. Lavinksy et al (2013). Subvisible retinal
laser therapy: titration algorithm and tissue
response. Retina, Vol. 0, p. 1-11.
7. S. Alsulaiman et al (February 2014). Highpower handheld blue laser-induced maculopathy. J Oph, Vol. 121, pp. 566-572 (doi:
10.1016.j.ophtha.2013.09./006).
The excitation path of a home-built microscope capable of three-color single-molecule FRET and alternating-laser excitation (ALEX) microscopy. The microscope
uses several visible lasers (405, 473, 532, 561 and 640 nm); the modulation and intensity of the lasers are controlled using an acousto-optical tunable filter.
The same microscope can be used for localization-based superresolution imaging techniques. Courtesy of Justin Pinkney.
FRET Pursues Affordable, Robust,

User-Friendly Instruments
From single-molecule studies
to in vivo imaging, FRET
spectroscopy is a versatile
and far-reaching tool. But
further work needs to be done
before the technique becomes
more universally applicable.
BY MARIE FREEBODY
CONTRIBUTING EDITOR
lthough FRET (Frster resonance energy transfer) is now a mature and established
technique, it can always be faster, brighter, more sensitive, more multiplexed
and more selective. So research never ceases to extend FRETs capability and to
expand the range of applications for which it can be used.
Improvements to the technique would not only make it easier to use in existing applications, but also open it up to novel applications such as single-molecule analysis inside
living cells. Visualizing interactions, conformations and dynamics in their natural
biological contexts is still in its infancy, but new developments in internalization proce-
23
FRET Spectroscopy
dures, in vivo labeling and fluorescent

probes will make this a reality.
Another game changer will be to combine FRET with other single-molecule
techniques such as magnetic tweezers,
optical tweezers and atomic force microscopy. Such combinations will allow
combined global (through a force-based
method) and local (through FRET) views
of a system, as well as provide the ability for nanomanipulation of a molecule
while monitoring changes in its structure
and conformation, said Dr. Achillefs
Kapanidis, professor of biological physics
and head of the Gene Machines Group at
Oxford University in England.
Combining FRET with tethered fluorophore motion offers insight into chromosome segregation. (a)
Schematic of the recombination reaction with a DNA substrate for recombination. The DNA substrate
has the fluorophores attached to DNA adjacent to each recombination site (dif site); the positions of the
acceptor and the donor fluorophores are indicated with red and green circles, respectively. Progression
through the recombination was monitored using two observables: Image width (referred to as PSF width)
of the acceptor and FRET. Recombination between two dif sites leads to a formation of product DNA
molecules; one of them remains attached to the slide and has fluorophores flanking dif on both sides.
(b) Nonproductive synaptic complexes (top). Representative time trace of the intensities of donor (green)
and acceptor (red) under donor excitation; and acceptor-under-acceptor excitation (black). FRET
efficiency (middle) and PSF width (bottom) are shown. The nonproductive events are defined by the
ultimate broadening of the PSF coincident with the disappearance of the FRET signal. All data were
acquired at a frame rate of 10 Hz, unless otherwise stated. Histogram of FRET efficiency (right) and
dwell time (inset) of XerCD-dif synaptic complexes (n = 380). Dwell times were fit to single exponentials.
Courtesy of Pawel Zawadzki and Peter May.
Highly sensitive photon-counting detectors are the centerpiece of most multiparameter FRET spectroscopy
techniques. They permit detecting the arrival of single photons with picosecond time resolution. Shown is a
custom-built setup featuring eight photon-counting detectors that permit simultaneous detection of various
colors and polarization directions. Courtesy of the Lemke Group.
24
FRET probes
The design of FRET probes is still
considered an art rather than a science.
Crucial to the efficacy of FRET is the
selection of the right probes and developing new ones tailored to the biological
system under scrutiny.
Already using all the FRET tools that
exist offers incredible possibilities, said
professor Dr. Niko Hildebrandt of the
Nano BioPhotonics Group at the Institute of Fundamental Electronics at the
University of Paris-Sud in Orsay, France.
The challenge is always to find the good
FRET pair (or pairs) for the desired application and to make it work (or to find that
it does not). So the main challenge is to
use existing FRET pairs and to integrate
them into applications which can benefit
from the versatility of FRET.
When it comes to fluorescent proteins,
we are approaching an optimum in terms
of spectroscopic properties, according
to Raik Grnberg of the Institute for Research in Immunology and Cancer at the
University of Montreal. Several recent
variants (such as mTurquoise2) have more
than 90 percent quantum efficiency [and]
mono-exponential decay behavior, and
are fairly photostable, he said.
In recent years due to the work of
groups led by, for example, Markus Sauer
and Thorsten Seidel of Bielefeld University in North Rhine-Westphalia, Germany; Philip Tinnefeld of the University
of Brunswick Institute of Technology in
Lower Saxony, Germany; and Xiaowei
Zhuang of Harvard University in Cambridge, Mass. we have gained a better
understanding of how popular additives
modulate the bleaching and blinking
behavior of organic fluorophores. Along
FRET Spectroscopy
those lines, there has also been some

speculation about self-healing dyes,
where an additive is covalently coupled
to the dye, as recently introduced by the
lab of Scott Blanchard at Weill Medical
College of Cornell University in Ithaca,
N.Y. Further understanding the blinking and bleaching mechanisms and how
to control them will advance the field,
especially when these processes can be
realized inside a living cell or organism.
Another option that is gathering
interest is the use of gold, which doesnt
bleach or blink. The combination of
DNA nanostructures with the use of gold
nanoparticles for fluorescence enhancement of organic dyes [from Tinnefelds
laboratory] is really exciting, especially when practical and facile ways
for coupling labeled biomolecules to the
DNA-gold nanostructures are available,
Kapanidis said.
Although fluorescent proteins continue
to be the workhorse for FRET measurements in cells, it seems we should see an
increase in the use of organic-dye FRET
constructs (proteins or nucleic acids)
delivered in either bacteria or eukaryotic
cells with various means of internalization. These constructs will go beyond
stating whether two proteins interact as
in the case of fluorescent-protein-based
FRET and will allow monitoring of
structure, interactions and dynamics of
molecules that exhibit different diffusion
properties in living cells.
One of the main challenges is site-specific protein labeling, a complicated process, especially for large proteins. Before
FRET can even be applied, much work
needs to be done to the sample to prepare
it, which can be both time-consuming
and labor-intensive, but the result is very
specific, as only the protein of interest is
labeled.
When it comes to labels, size matters
to Dr. Edward Lemke, who heads the
European Molecular Biology Laboratory
in Heidelberg, Germany. And the smaller
the better, as far as Lemke is concerned.
Currently, FRET probes distances of 3 to
10 nm, and to use FRET as a molecular
tool, the labels have to shrink in size.
Strategies that reliably allow the sitespecific introduction of small synthetic
fluorophores into proteins in live cells
would mark a major advance, and systems
for the genetic incorporation of unnatural
amino acids may hold big promise.
This illustration shows a SWIFT device to which, for example, nucleosomes (also shown) can be
loaded via the sample inlet. Courtesy of the Lemke Group.
By streamlining unnatural amino acid

mutagenesis (for example, in combination
with click chemistry, in which substances
are generated quickly and reliably by
joining small units together), labeling will
become more predictable and efficient.
Such advances will allow generation of sets of labeled proteins that will
permit generation of several distance
restraints for getting FRET-based solution
structures for large and flexible proteins
and their complexes, something that is
quite challenging to do using standard
structural biology techniques such as
x-ray crystallography and NMR [nuclear
magnetic resonance], Kapanidis said.
Also on the horizon for its potential to

take FRET to the next level is multiplexing this refers to simultaneous FRET
with different FRET pairs. Hildebrandt
and colleagues Igor Medintz at the US
Naval Research Laboratory in Washington and Russ Algar at the University of
British Columbia in Vancouver, Canada,
are exploring the detection of different biomarkers and the simultaneous
measurement of different interactions
(e.g., protein-protein interaction in and on
cells), which are most often functions of
diseases.
Such multiplexing can be made spectrally (distinction of different colors), but
25
FRET Spectroscopy
also temporally (looking at the photoluminescence lifetimes), Hildebrandt said.

Measuring two FRET pairs (or more)
simultaneously is useful for looking
at signaling cascades, but to be able to
measure FRET dynamically i.e., to
make FRET movies would also take
FRET to the next level, according to Dr.
Klaus Suhling in the physics department
at Kings College London.
FRET movies, not only of one donoracceptor FRET pair, but of two, so you
could tell whether one protein interaction event comes before or after another
one so to see whether one interaction
triggers another, he said. The imaging
technology to make FRET movies has to
be perfected. FLIM [uorescence-lifetime
imaging microscopy] movies of FRET
are, at present, tricky to obtain with good
sensitivity.
For work where the size of the probe is
less important, such as tracking studies on cellular membranes and in vitro
motility assays, large uorescent donors
such as quantum dots and upconversion
nanoparticles will be an attractive option
for biosensing.
The largest distance over which FRET
can be measured is with quantum dots
and lanthanides, with a Frster radius of
over 10 nm, Suhling said. The brighter
the donor, the better but as the quantum
yield of many donors is high already, improvements in brightness will be limited,
as the quantum yield can only ever be a
maximum of 100 percent. More photostable uorophores will, however, be very
useful for prolonged studying of protein
interactions or conformational changes.
FRET challenges
One of the biggest headaches for FRET
users is the sample preparation, which
requires routine molecular biology/biochemistry and cell biological work that is
both slow and labor-intensive. But lab-ona-chip technologies could alleviate some
of the drudgery.
Lemke and colleagues recently published a possible way to overcome this
in their latest paper, which appeared in
Nature Methods (doi:10.1038/nmeth.2809)
in January. Their automated microuidic
platform performs multisecond observation of single molecules with millisecond

time resolution while bypassing the need
for immobilization procedures. The biomolecules are conned to a thin excitation
eld by reversibly collapsing microchannels to nanochannels.
Currently, many single-molecule
FRET measurements still rely on homebuilt instruments that are complex and
expensive, and require in-house written
software, which has limited the wide
availability of single-molecule FRET.
The interest in single-molecule
uorescence in general driven by the
immense interest of biologists in localization-based superresolution imaging will
provide the large market needed to push
innovation to the level needed to provide
the required instruments that will further
increase the popularity of single-molecule
FRET, and FRET in general, Kapanidis
said.
marie.freebody@photonics.com
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Software Enhances Life Sciences

Applications, Biomedical Simulations
Optomechanical design software helps develop efficient and effective biomedical product designs.
BY DR. EDWARD FRENIERE AND MICHAEL GAUVIN
LAMBDA RESEARCH CORPORATION
he interdisciplinary nature of optical modeling for life

sciences applications implies a high degree of collaboration among medical doctors, life scientists and biomedical
design engineers with collective specialties in medicine, optics,
mechanics, materials, chemistry and biology. The collaborative
efforts of scientists and engineers across these areas require efficient, accurate applications to reduce costs and improve efficacy.
Additionally, medical device manufacturers are facing pressure
to accelerate time to market while dealing with increasingly
tighter R&D budgets and significantly higher cost barriers for
certification.
To advance fundamental research and realize product innovation in biomedical optics, software tools can not only facilitate
biomedical optical design, but also instill an iterative process
allowing engineers to optimize products for the best applicationspecific results such as tissue characterization for noninvasive
procedures. Optomechanical design software provides a high-
productivity environment for developing effective biomedical

optical products.
This kind of software tool will lead the designer through a
process to maximize the technical merits of the device or system
in the shortest amount of time. It minimizes the learning curve,
decreases development costs for new products and saves valuable time while offering visual and quantitative feedback.
Modeling light propagation
One such tool, TracePro, is used for modeling the propagation
of light in imaging and nonimaging optomechanical systems.
Models are produced by creating solid geometry directly within
the program or by importing geometry from a lens design or
CAD program. Sources can be defined as grids of rays, surface
sources or ray files. Rays can propagate through the model
nonsequentially with portions of the flux for each ray allocated
according to the absorption, specular reflection and transmis-
LED emission into the brain to determine oxygenation in tissue. Images courtesy of Lambda Research Corp.
27
Software for Life Sciences
Optical simulation software

such as TracePro has enabled
innovation and research
discoveries in:
Medical imaging and
endoscopy
Flow cytometry and cell
imaging
Medical imaging
Pulse oximetry
In vitro diagnostics
Biosensors
Molecular spectroscopy
Microscopy
In vivo diagnostics
Laser and LED surgical devices
sion, and scattering characteristics of the
surface property as defined by the user.
The designer using this tool is not required to be an optical expert to precisely
simulate optical systems and produce
expedient and accurate models; it includes
biomedical properties for tissue and
fluorescence applications, enabling both
engineers and scientists to work together
to produce sophisticated optical models
for life sciences applications.
Using such software, a designer
can analyze:
2-D and 3-D light distributions in
illumination and imaging systems
Stray light, scattered light,
and aperture diffraction
Throughput, loss, or system
transmittance
Flux absorbed by surfaces
and bulk media
Light scattered in biological tissue
Crosstalk problems in multiple-path
systems
Polarization effects
Fluorescence effects
Birefringence effects
Model representation, design
work flow
Users can define and manage spectral
and angular data for each unique source
and combine different sources into a
single simulation. To enhance ray-tracing
performance, multithreaded algorithms
process ray traces in parallel. After ray
tracing is complete, a plethora of visualization and analysis capabilities are
available to analyze light distribution
and fluorescence effects at any point in
the optomechanical system. The built-
28
b
LED emission into human tissue with bulk scatter shown: (a) is the same as (b), except that the
setup in (b) has a paddle to hold the LED and detector.
in interactive optimizer is specifically

devised for nonsequential design of LEDbased biomedical systems and has been
proved to reduce design time dramatically
compared to traditional trial-and-error
prototyping methods. The 2-D and 3-D
optimizers feature a sketch utility for
quick design entry, interactive ray tracing
for design verification, and a downhill
simplex optimizer with interactive entry
of target specifications.
In addition, a user-configurable system
tree creates assemblies, and standard
drag-and-drop operations arrange parts
and assemblies. Two new irradiance
options to enhance imaging are rainbow
palette and normalization for identification of stray-light problems in medical
devices.
2-D and 3-D optimization

The tools 2-D symmetric and 3-D
nonsymmetric optimizers are set up with
productivity and utility in mind. It allows
interactive sketching to quickly enter
2-D and 3-D geometry profiles to create
surfaces and then extrude, revolve and
combine these surfaces to create sophisticated geometry such as light pipes,
biconic reflectors and free-form optics.
Three-dimensional visualization plots
allow users to visually track the propagation of light through any ray-traced
system with complete pan, zoom and
rotational capability using the mouse. The
detailed graphics offer new insight and
understanding as to how energy and color
propagate through an optical system,
providing in-depth views to identify
Software for Life Sciences
Medical product design, evaluation and analytic

applications of optical simulation software include:
Laser- and LED-based surgical devices

Laser beam delivery systems for surgical instrumentation
Light distribution devices for both in vivo and in vitro illumination systems
Reducing stray light and scattered light in biomedical devices
Studying throughput loss or system transmittance
Analytical applications specific to the life sciences include:
Tissue propagation
Glucose monitoring
Heart rate monitoring
Fluorescence, Raman, UV, VIS, NIR and IR spectroscopy
Flow cytometry
Microarrays and plate readers
Nucleic acid amplification
Assay, cell and tissue-based imaging
Confocal laser scanning and fluorescence microscopy
Medical imaging and endoscopy
In vitro and in vivo diagnostics
Biosensors
Molecular detection: quantum dots, nanocrystals and luminescent reporters
Laser-induced fluorescence (LIF) detection
Frster resonance energy transfer (FRET)
Flux absorbed by surfaces and bulk media
Light scattering in biological tissue
unwanted light, stray light and uniformity

issues.
Collaborative development
Optical and mechanical assemblies
may be designed, analyzed and toleranced
using a combination of commercially
available lens design software and SolidWorks 3-D mechanical design software.
Once imported into the software, lens
designs (including parameterized geometry), tolerances, optical materials and
CAD geometry are captured in a single
model-definition file that can be used and
modified. Physical and optical properties
are thus encapsulated in one place.
Biological samples, fluorophores, light
sources, detectors, coatings and filter
data can be specified. The software then
performs system-level modeling, analysis
and optimization of light distributions,
stray light, throughput, flux absorbed
by surfaces and bulk media, polarization
effects and fluorescence effects.
Libraries of commercially available optical components, light sources, detectors,
fluorophores and phosphors, biological
tissue and mechanical surface properties
are also available or can be customized
and added by the user.
TracePro can also be used in complement with another simulation and design
program by Lambda Research called
OSLO; the two work in tandem for the
development of advanced medical systems. OSLO enables a user to design and
analyze simple to complex optical models,
especially for lenses, mirrors, diffraction
gratings, Fresnel lenses and holographic
optical elements. The two programs have
been successfully used for multiple biomedical applications, including:
Developing pulsed light systems
like the StarLux and Medilux systems
by Palomar Medical Technologies Inc.
to reduce varicose veins, to treat acne,
wrinkles and vascular lesions, and to
remove scars and tattoos.
Locating and eliminating early cancer
in the lungs, colon, cervix and other tissues using fluorescence, laser ablation,
photodynamic therapy and other techniques.
Measuring glucose through optical
measurements of skin and blood samples
using LED and photodiode sensing
systems.
Developing oximeters to assess blood
oxygenation in the brain and other tissue.
Detecting an object within a tissue
(e.g., a tumor) or mapping of functional

status within a tissue (e.g., blood perfusion).
Fluorescence
A designer can model fluorescence
by importing absorption and emission
curves, extinction coefficients and quantum efficiency values from stock fluorophore catalogs or input from proprietary
data. Additionally, the designer can enter
concentration and wave band of interest. The software calculates excitation
efficiency, path length and absorption,
and propagates fluorescence-emission
rays through the model. It also analyzes
light distribution, scatter and fluorescence
effects at any point in the optomechanical
system.
Material properties can be created from
actual measured excitation and emission
spectra, extinction coefficients and quantum efficiencies, or by applying material
properties from the programs libraries of
Invitrogen and Clontech fluorophores.
Light interaction with biological tissue
can be simulated using a choice of bulk
scatter phase functions; energy propagation can be viewed through tissue with the
volume flux viewer. Slice a volume along
any axis and analyze it for absorbed,
incident, originated or exiting radiation.
Designers can use a human tissue catalog
or enter unique tissue characteristics,
including fluorescence properties.
Design simulation at work
A team of faculty and students at the
University of South Florida Colleges of
Engineering and Medicine, working with
Tampa General Hospital, used TracePro
simulations to design state-of-the art
laparoscopic endoscopic single-site
(LESS) procedures for minimally invasive abdominal surgery. Their innovative
research is the first step in developing
semiautonomous, wirelessly controlled
and networked laparoscopic devices.
Their design and implementation of a
MARVEL (miniature anchored robotic
videoscope for expedited laparoscopy)
and camera module will optimize LESS
surgery through the self-contained, cablefree MARVEL platform, streamlining the
surgical process.
Meet the authors
Dr. Edward Freniere is president and Michael

Gauvin is vice president of sales and marketing
at Lambda Research Corp.; email: sales@
lambdares.com.
29
Superresolution Imaging
Adds Another Dimension
3-D techniques advance a range of biological research studies.
BY GARY BOAS, NEWS EDITOR
onventional light microscopy is

generally constrained by the diffraction limit, the fundamental
maximum resolution of an optical imaging system resulting from the diffraction
of light. In more recent years, however,
researchers have developed a host of
techniques broadly known as superresolution imaging techniques that enable
them to overcome the diffraction limit.
The implications of this for biological
research were considerable so consider-
able that Nature Methods named superresolution imaging the 2008 Method of
the Year. As electron microscopy did
in the past, superresolution microscopy,
or nanoscopy, provides the ability to see
details of cellular and even macromolecular structure that were not possible to see
before, the editors wrote when explaining their selection. Notably, however,
nanoscopy is compatible with live cells
and has the capability for multiplex labeling with high molecular specificity.
Zeiss has introduced a module that enables photoactivated localization microscopy, or PALM, in 3-D and
with a lateral resolution of 20 to 30 nm and an axial resolution of 50 to 80 nm. Shown is a PALM nuclear
pore image of epithelial kidney cells. Courtesy of Anna Lschberger and Markus Sauer, University of
Wrzburg, Germany.
30
Superresolution techniques have

already made important contributions in
biological research. Now, with the introduction of 3-D capabilities, they have the
potential to make an even greater impact.
One example is the technique known
as superresolution photoactivated localization microscopy, or PALM. Here,
photoswitchable fluorescent molecules
are sparsely and stochastically activated
so that only one in a field of many will be
in the on state at a time. This makes it
possible to distinguish the emissions from
those of neighboring molecules, which
overcomes the diffraction limit.
At the 2013 Society for Neuroscience annual meeting in November, Zeiss
introduced a module called ELYRA P.1
that enables PALM in 3-D, with a lateral
resolution of 20 to 30 nm and an axial
resolution of 50 to 80 nm.
The module combines two superresolution techniques PALM and structured
illumination microscopy (SIM) in a
single system, giving the user the option
of choosing the technique most appropriate for his or her sample.
In SIM, we designed the system to
give the maximum resolution for each
color and the optics to give a large field
of view to capture large areas of interest in one go, said Dr. Klaus Weisshart,
product manager in the Biosciences Div.
at Carl Zeiss Microscopy GmbH in Jena,
Germany. In PALM, we designed the
system flexible enough to deal with most
of the switchable fluorescent proteins
and organic dyes on the market, and we
improved algorithms that allowed higher
accuracies even with more problematic
samples.
A combination of the two techniques
also can be beneficial, he added, as it can
provide structural context to localized
molecules.
PALM isnt the only superresolution
imaging technique getting the 3-D treatment. In a recently published Journal of
The Gathering STORM

in Biological Research
Dr. Michael Brsch and colleagues at Jena University Hospital and Friedrich Schiller University in Jena, Germany, have
been studying FoF1-ATP synthase for the past 15 years, using single-molecule Frster resonance energy transfer (FRET)
to study the membrane enzyme in vitro. But when it came
time to measure the static/dynamic distribution of FoF1-ATP
synthase in E. coli cells so they could measure the rotary
motors of the enzyme in vivo, they turned to 3-D superresolution microscopy.
After exploring several possibilities, the researchers went
with a structured illumination microscopy (SIM)/stochastic
optical reconstruction microscopy (STORM) instrument from
Nikon. It was kind of a big scandal here in Jena, where everyone has a Zeiss laser-scanning microscope, Brsch said,
but the Nikon is providing us with important information.
The researchers reported their findings at the BiOS/Photonics West meeting in February. Using 3-D STORM and
PALM as well as SIM, they probed the spatial distribution
and diffusion properties of bacterial FoF1-ATP synthases
in living E. coli cells. This enabled them to determine the
optimal label strategy for their single-molecule FRET studies
of the rotary motors of FoF1-ATP synthase in vivo.
Shown here are images of 3-D localized FoF1-ATP
synthases in a living E. coli cell. The Nikon SIM/STORM microscope used to obtain the images incorporates the Agilent
4-laser-box, Nikons Perfect Focus System (autofocus) and
an Andor EMCCD IXON Ultra camera. Images courtesy of
Anja Renz/Michael Brsch, Jena University Hospital.
Biophotonics paper, for example, a team

of researchers at Imperial College London
describe 3-D stimulated emission depletion (STED) microscopy with programmable aberration correction.
STED microscopy works by suppressing, or depleting, the fluorescence signal
in a region of interest using a second
beam overlapping the fluorescence excitation beam and effectively narrowing
the point-spread function to below the
diffraction limit by having a minimum
intensity at the center of the second beam.
The setup described in the Journal
of Biophotonics paper achieves a 3-D
depletion point-spread function by incorporating a liquid crystal spatial light
modulator (SLM) device to produce the

desired depletion beam profiles. We
believe this presents a very practical and
convenient approach to 3-D-STED, said
Hugo Sinclair, the studys corresponding
author. The use of an SLM also allows
us to correct for optical aberrations in the
instrument and sample.
Sinclair and colleagues initially developed the microscope to enable superresolved imaging of biological samples,
focusing in particular on the immunological synapse between interacting cells
such as between a natural killer cell and
its target cell here, he said, the synapse
is typically aligned perpendicular to the
coverslip, so improved resolution in both
the lateral and axial directions is desirable. But they anticipate that the technique could be applied to a wide range of
additional biological samples, including
interacting cells and 3-D cell cultures.
They continue to refine the technique
with this in mind. For example, they are
further developing the adaptive optics
schemes used to correct for sample aberrations. More advanced methods may be
required in the presence of higher-order
aberrations stemming from complex
refractive index structure in samples,
Sinclair said. They also are working to incorporate fluorescence lifetime imaging to
enable multilabel 3-D STED microscopy.
gary.boas@photonics.com
31
BREAKTHROUGHPRODUCTS
CCD Cameras
CCD cameras from Raptor Photonics Ltd., developed using Sony ExView HAD II sensor technology, offer a choice of 2.8-, 6- or 9-MP resolution and are available in both mono and RGB. Pixel
size is 4.54 m. The deep-cooled vacuum Kingfisher V provides ultralow readout noise (<3 e s)
and almost negligent dark current (1 e every 16 min). It is suitable for longer-exposure staring
applications such as fluorescence, bioluminescence and astronomy. The compact, stabilized
Kingfisher Standard offers readout noise of <7 e s and low dark current. The board-level Kingfisher OEM provides a detachable sensor, enabling replacement with various resolutions. The
camera is available uncooled or with custom cooling options.
sales@raptorphotonics.com
Galvanometer Laser Scanners
A new series of six galvanometer

laser scanners is available from
Lincoln Laser Co. The compact
PHX-30/50/75 models fit into microscopes and other instruments
for biomedical applications. The
PHX-100/150/300 models have largeaperture mirrors that are suitable
for marking, materials processing,
inspection and lidar systems. Mirrors
may be coated with fused silica,
silicon or silicon carbide.
madkins@lincolnlaser.com
Tissue Cytometry Software
TissueGnostics GmbH has

added StrataQuest to its
line of tissue cytometry
solutions. The software
suite offers a wide range of
choices in image analysis
and multiple combinations
of functions for bright-field,
fluorescence and immunohistochemistry (IHC) tasks.
StrataQuest 5 Solutions is
for predefined work flow
(i.e., quantification of a single IHC marker); StrataQuest 5 is for applications in separate or combined bright-field and fluorescence techniques, offering a broad range of predefined multilayer
analysis macros and individual application tools; and StrataQuest 5 Advanced is for the experienced user, allowing full programming capabilities to create custom image analysis solutions in
bright field, fluorescence or in combination.
georg.stiener@tissuegnostics.com
3-D Printer
The Photonic Professional GT 3-D printer

by Nanoscribe GmbH produces complex
structures on the nano- and micron scale for
research and development, and for potential
industrial applications in medicine, fluidics,
optics, electronics and mechanics. Twophoton polymerization in combination with
pivoted galvo mirrors is implemented into a
commercially available lithography system,
which can execute complex structures with
feature sizes down to 160 nm and heights
ranging from a few hundred nanometers up
to the millimeter range on a 100 100-mm
writing area. The patterning process allows
both additive and subtractive manufacturing
of polymers on a broad range of substrates
and materials.
info@nanoscribe.de
LED Light Engine
Model 2400B-510, an addition to Innovations

in Optics Inc.s line of LumiBright FC fibercoupled LED light engines, was designed
for fiber and lightguide input apertures from
1 to 3 mm in diameter. The device features
patented technologies that encompass nonimaging optics with LED chip-on-board (COB)
metallic substrates for luminous efficacy
and thermal management. Suited for OEM
endoscope and microscope illuminator
applications, it provides a nominal correlated
color temperature of 4700 K and can emit
up to 600 lm through its 3-mm-diameter
aperture with no UV or IR emissions.
Custom connectors and lightguide ferrule
holders are available upon request.
kevinc@innovationsinoptics.com
32
Kinetic Spectroscopy Software
TimePro kinetic spectroscopy software

from Craic Technologies Inc. measures
time-dependent changes in full UV-VIS-NIR
reflectance, absorbance and emission spectra of microscopic samples. Designed for the
companys microspectrophotometers and
proprietary controlling Lambdafire software,
it is suitable for applications ranging from
chemistry to biological research.
sales@microspectra.com
Miniature Camera
Available from Marshall Electronics, the

CV-500M miniature camera provides1080p
resolution for industrial, scientific, machine
vision, automation and OEM applications.
The camera incorporates proprietary highresolution lenses and a Sony 2.2-MP CMOS
sensor. The sensor enables the HD-SDI (highdefinition serial digital interface) camera to
operate at a minimum of 0.5 lux (color) or
0.1 lux (black and white), making it suitable
for low-light environments. A 3.7-mm lens
comes standard, but a variety of lenses can
be used. The progressive-scan camera
features day and night function, automatic
white balance, privacy masking, defog,
motion detection and digital zoom.
support@marshall-usa.com
Vibration-Isolation Platforms
Two new vibration-isolation series platforms
by Newport Corp. are suitable for laboratory
applications, including balances, micrscopes,
shakers and other sensitive equipment. The

LIP275 series features a polyvinyl chloride
platform with a nonstick neoprene surface
supported by three or four vibration-isolation
bearings. The passive mechanical bearings
use proprietary technology to protect equipment from ambient vibrations and mechanical shocks. Platform sizes range from 8 10
in. to 12 22 in. with a load capacity up to
52 lb. The LIP175, which is designed for less
demanding applications, features patentpending elastomeric bearings that isolate
vibrations horizontally and vertically.
pete.neely@newport.com
Spectroscopy Platform
The nanoIR2 atomic force microscope (AFM)based spectroscopy platform by Anasys

Instruments is suitable for measurements
on a variety of sample types, including
semiconductor devices, thin films, nano-
composites, data storage samples, minerals,

tissue sections and polymer blends. The
system operates with top-side illumination,
eliminating the need to prepare samples on
a ZnSe prism. It also features a resonanceenhanced mode that increases sensitivity
and enables measurements on samples less
than 20 nm thick. The platform combines the
nanoscale spatial resolution of an AFM with
the chemical characterization and identification capabilities of IR spectroscopy.
info@anasysinstruments.com
Raman Microscope
The DXRxi Raman imaging microscope from
Thermo Fisher Scientific is suited for applications including pharmaceutical formulation,
life sciences, semiconductor manufacturing and geology. The device can reveal
molecular structure, chemical composition
and sample morphology to identify defects
and confirm product quality. Proprietary
OMNICxi image-centric data acquisition
software provides intuitive sample targeting
and parameter optimization. Other features
include automated alignment and calibration,
near-instant visual chemical profiling, and
quick analysis of large samples.
analyze@thermofisher.com
3-D Optical Microscope

Available from Bruker Corp., the ContourSP
is a large-panel 3-D metrology system for
Lambda DG-4/DG-5 PLUS

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gauging individual layers of printed circuit

board (PCB) panels during manufacturing.
Based on white-light interferometry, the 3-D
optical microscope is designed to enable
minimum recipe development time, maximum uptime, and increased measurement
throughput of high-density interconnect
substrates in multichip modules. The system
features the proprietary Vision64 operating
and analysis software.
steve.hopkins@bruker-nano.com
Camera System
global electronic shutter operates from 1 ms

(standard) down to 159 ns and can freeze
the fastest motion without blur. The camera
delivers 12-bit pixel depth (analog-to-digital
converters). Its 20-m-square pixel format
enables camera rotation without sacrificing
image resolution. The included PFV (Photron
FastCam Viewer) camera control/replay/editing software can rotate the image back in real
time. Applications include ballistics, materials science, and plasma and arc studies.
image@photron.com
CW Microlasers
OCT Spectrometer
For applications including ophthalmology,
dermatology and materials inspection,
Wasatch Photonics Inc. has released the
Cobra OCT spectrometer. The device features
volume-phase holographic gratings, and custom optics and electronics for OCT imaging,
while a USB 3.0 interface improves accessibility. Featuring pixel heights of 200 and
500 m, with optional 2048- and 4096-pixel
arrays, the device provides acquisition rates
of 40 and 80 KHz.
info@wasatchphotonics.com
Available from Photron Inc., the FastCam

SA-Z ultrahigh-speed imaging system features 21,000 fps at megapixel resolution and
more than 2 million fps at reduced resolution, making it possible to view previously
unseen phenomena, events and high-speed
processes. The CMOS sensors enhanced
plications ranging from biomedical research

to pharmaceutics. The tray design captures
the entire specimen area of the slide, including the edge, in minutes, and specimens
are presented on virtual slides. For fluorescence applications, filter wheels switch
wavelengths in 50 ms. The device features a
Colibri.2 UV-free LED light source and a focus
finder with oblique illumination, called a ring
aperture contrast.
markus.wiederspahn@zeiss.com
Digital Slide Scanner

Carl Zeiss Microscopy offers an automated,
self-calibrating slide scanner for its Axio
Scan.Z1 microscope, which digitizes fixedtissue sections and cytologic specimens in
bright-field and fluorescence modes for ap-
Do
You
From Elliot Scientific Ltd., the Integrated

Optics UABs MatchBox series CW microlasers have applications in chemistry and
biophotonics, particularly Raman spectroscopy and fluorescence imaging. The series
includes diode-pumped solid-state and diode
lasers, with wavelengths ranging from 405 to
1342 nm and with either free-space or fibercoupled outputs. The sealed, ultracompact
all-in-one laser head is powered by a standard low-voltage DC supply and includes the
optical components, drive electronics and
thermal management. The monolithic design
and cleanroom production environment
eliminate the contamination risks associated
with conventional surface-enhanced Raman
spectroscopy (SERS) substrates, and are
compatible with the use of a cover glass over
the active SERS area.
david.ward@elliotscientific.com
Dictionary+
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34
APPOINTMENTS
CALL FOR PAPERS
Neuroscience 2014 November 15-19
Deadline: Abstracts, May 8, 5 p.m. EDT
Washington. The Society for Neuroscience seeks papers for oral
and poster presentation at its 44th annual meeting, Neuroscience
2014. Among the topics to be considered are development, including
human imaging; Alzheimers disease and other dementia, including imaging and biomarkers; and brain blood flow, metabolism and
homeostasis, including functional imaging. Staining, tracing and
imaging techniques also will be discussed within sessions on novel
methods and technology development.
Contact: Society for Neuroscience
+1 (202) 962-4000
program@sfn.org www.sfn.org
SPIE/COS Photonics Asia October 9-11
Deadline: Abstracts, May 12
Beijing. Researchers are invited to submit their work to Photonics
Asia, a conference sponsored by SPIE and COS (Chinese Optical Society). The event will encompass the meeting Optics in Health Care and
Biomedical Optics VI, which will address areas including tissue optics
MAY
ARVO 2014 Annual Meeting (May 4-8) Orlando, Fla. Contact Association for Research in
Vision and Ophthalmology, +1 (240) 221-2900;
arvo@arvo.org; www.arvo.org.
l DSS 2014, SPIE Defense, Security, and

Sensing (May 5-9) Baltimore. Contact SPIE,
+1 (360) 676-3290; customerservice@spie.
org; http://spie.org.
l Mfg4: Manufacturing for the Future
(May 6-8) Hartford, Conn. Contact SME,
+1 (313) 425-3000; service@sme.org;
www.mfg4event.com.
Graphene 2014 (May 6-9) Toulouse, France.
Contact Phantoms Foundation, +34 91 140
2145; info@grapheneconf.com; www.
grapheneconf.com.
Ninth EOS Topical Meeting on Diffractive
Optics (DO 2014) (May 6-9) Gdansk, Poland.
Contact Oili Kohonen, European Optical
Society, +358 40 564 0480; kohonen@myeos.
org; www.myeos.org.
Fourth EOS Topical Meeting on Terahertz
Science & Technology (TST 2014) (May
11-14) Camogli, Italy. Contact Oili Kohonen,
European Optical Society, +358 40 564 0480;
kohonen@myeos.org; www.myeos.org.
CEN2014: Conferencia Espaola de Nanofotonica (May 13-16) Santander, Spain. Contact
Antonio Correia, Phantoms Foundation,
antonio@phantomsnet.net; www.phantoms
net.net/cen2014.
Translational Biophotonics (May 19-20)
Houston. Contact SPIE, +1 (360) 676-3290;
customerservice@spie.org; http://spie.org.
ANGEL2014: EOS Conference on Advanced
Nanoparticle Generation and Excitation by
Lasers in Liquids (May 19-21) Matsuyama,
Japan. An event of the European Optical
Society. Contact angel2014office@LALnano.
jp; http://lalnano.jp/ANGEL2014.
and light-tissue/cell interaction, photon therapeutics, biomedical

spectroscopy, microscopy and imaging, advanced optical techniques
for clinical medicine, multimodal biomedical imaging, and nanobiophotonics, including nanoscale imaging.
Contact: SPIE
+1 (360) 676-3290
customerservice@spie.org http://spie.org
Frontiers in Optics/Laser Science October 19-23
Deadline: Paper submissions, May 19, 12:00 EDT
Tucson, Arizona. Papers are encouraged for Frontiers in Optics (FiO)
2014, the 98th annual meeting of The Optical Society, which is being
held in conjunction with the 30th annual meeting of Laser Sciences
American Physical Society Division of Laser Science. The submission category Optics in Biology and Medicine includes topics such
as fibers for biomedical applications, microscopy and OCT, optical
trapping and manipulation, lab on a chip and optofluidics, and novel
methods for tissue imaging and therapy.
Contact: The Optical Society
+1 (202) 416-1907
custserv@osa.org www.frontiersinoptics.com
12th Optatec International Trade Fair for

Optical Technologies, Components and
Systems (May 20-22) Frankfurt, Germany.
Contact P.E. Schall GmbH & Co. KG, +49 7025
9206 0; www.optatec-messe.de/en.
Fifth Annual Imaging in Preclinical and
First in Human Clinical Studies in Oncology:
Mastering Multimodality Approach
(May 22-23) Boston. A conference at World
Pharma Congress. Contact Marina Filshtinsky, Cambridge Healthtech Institute,
+1 (781) 972-5455; mfilshtinsky@healthtech.
com; www.worldpharmacongress.com/
molecular-imaging.
ICIEV 14, International Conference on
Informatics, Electronics & Vision (May 23-24)
Dhaka, Bangladesh. Contact office@iciev.org;
http://cennser.org/iciev.
II International Conference on Applications
of Optics and Photonics (AOP2014) (May 2630) Aveiro, Portugal. Contact AOP 2014 Secretariat, Campus Universitrio de Santiago,
+351 234 377 900; aop2014@av.it.pt; http://
aop2014.org.
EIPBN: 58th International Conference on
Electron, Ion, and Photon Beam Technology
and Nanofabrication (May 27-30) Washington. Contact Melissa Widerkehr and Associates, +1 (301) 527-0900, Ext. 101; melissaw@
widerkehr.com; http://eipbn.org.
Photonics North 2014 (May 28-30) Montreal.
Contact Conferium, +1 (418) 522-8182; conference@conferium.com; www.conferium.com/
WPclients/photon14.
JUNE
l SID Display Week 2014 (June 1-6) San

Diego. Contact Mark Goldfarb, Society for
Information Display, +1 (212) 460-8090, Ext.
202; mark@sid.org; www.displayweek.org.
CTLS 2014, Core Technologies for Life Science Congress (June 2-5) Paris. Contact Insti-
tut Pasteur, fax: +33 1 40 61 37 21; ctls2014@

pasteur.fr; www.ctls2014.org.
23rd International Conference on Optical
Fiber Sensors (OFS 23) (June 2-6) Santander,
Spain. Contact Photonics Engineering Group,
University of Cantabria, +34 942 200 877;
ofs23@teisa.unican.es; www.teisa.unican.
es/ofs23.
euspens 14th International Conference and
Exhibition (June 2-6) Dubrovnik, Croatia.
Contact Debbie Nyman, euspen, European Society for Precision Engineering and
Nanotechnology, +44 1234 754154; debbienyman@euspen.eu; www.euspen.eu.
Frontiers in Neurophotonics: an International Summer School on Advanced Optical
Imaging and Photoactivation Techniques
(June 2-12) Quebec City. Contact Mario
Mthot, +1 (418) 663-5747; mariomethot@
crulrg.ulaval.ca; http://neurophotonics.ca.
Sensor + Test 2014 (June 3-5) Nuremberg,
Germany. Contact AMA Service GmbH,
+49 5033 9639 0; info@sensor-test.com;
www.sensor-test.com.
Digital Image Processing Workshop (June
6) London. Contact Royal Microscopical
Society, +44 1865 254760; info@rms.org.uk;
www.rms.org.uk.
l CLEO: 2014 (Conference on Lasers and

Electro-Optics) (June 8-13) San Jose, Calif.
Contact The Optical Society, +1 (202) 2238130; info@osa.org; www.osa.org.
Image Science: Accelerating the Pace of
System Design and Task-Based Evaluation
(June 8-13) Easton, Mass. Contact Gordon
Research Conferences, fax: +1 (401) 783-7644;
www.grc.org.
l Indicates shows Photonics Media will be attending.

Complete listings at www.photonics.com/calendar.
35
APPOINTMENTS
PIBM 2014, 12th International Conference

on Photonics and Imaging in Biology and
Medicine (June 14-17) Wuhan, China. Contact
Huazhong University of Science and Technology, pibm@mail.hust.edu.cn; www.pibm.cn.
ASP 37th Meeting (June 14-19) San Diego. An
event of the American Society for Photobiology. Contact Linda Hardwick, ASP business
office, +1 (785) 865-9405; phot@allenpress.
com; www.photobiology.org.
BIGSS 2014, Biophotonics and Imaging
Graduate Summer School (June 15-20) Galway, Ireland. Contact National Biophotonics
& Imaging Platform Ireland, +353 1 402 8651;
nbipadmin@rcsi.ie; www.nbipireland.ie.
Photonex Cambridge: Photonics Technology
Roadshow (June 18) Cambridge, England.
Contact Xmark Media Ltd., Brenda Hargreaves, +44 1372 750555; brenda@xmark
media.com; www.photonex.org/cambridge.
Twelfth European Congress on Digital
Pathology (June 18-21) Paris. Contact Conference Secretariat, The Office s.r.l., +39 040
368343; digitalpathology2014@theoffice.it;
www.digitalpathology2014.org.
2014 Laser Display Conference (June 19-20)
Taichung City, Taiwan. Contact Yi-Qing
Huang, yqhuang@nchu.edu.tw; http://ldc.
nchu.edu.tw.
Classical Optics (June 22-26) Kohala Coast,
Hawaii. Includes Computational Optical
Sensing and Imaging (COSI); International
Optical Design Conference (IODC); and Optical Fabrication and Testing (OF&T). Contact
The Optical Society, +1 (202) 223-8130; info@
osa.org; www.osa.org.
IFLA International Meeting on Fiber Lasers
and Applications (June 23-24) Ramat Gan,
Israel. Contact Itai Voller, +972 3 520 5818;
itai@aeai.org.il; www.fli.org.il.
Sensors Expo and Conference (June 24-26)
Rosemont, Ill. Contact Wendy Loew, Questex
Media Group LLC, +1 (617) 219-8343; wloew@
questex.com; www.sensorsmag.com/
sensors-expo.
LASYS: International Trade Fair for Laser
Material Processing (June 24-26) Stuttgart,
Germany. Contact Landesmesse Stuttgart
GmbH, +49 711 18560 0; info@messe-stutt
gart.de; www.messe-stuttgart.de/en/lasys.
LALS 2014: International Conference
on Laser Applications in Life Sciences
(June 29-July 4) Ulm, Germany. Contact
ILM, University of Ulm, +49 731 14 29 100;
info@ilm-ulm.de; http://lals2014.ilm-ulm.de.
Microscience Microscopy Congress 2014
(June 30-July 3) Manchester, England.
Contact Royal Microscopy Society, +44 1865
254760; info@rms.org.uk; www.rms.org.uk.
JULY
UP 2014, 19th International Conference on
36
Ultrafast Phenomena (July 7-11) Okinawa,

Japan. Contact Conference Team, up2014@
chem.s.u-tokyo.ac.jp; http://up2014.org.
Imaging and Applied Optics: Optics and
Photonics Congress (July 13-17) Seattle.
Includes Applied Industrial Optics: Spectroscopy, Imaging, and Metrology (AIO); Digital
Holography & 3-D Imaging (DH); Imaging
Systems and Applications (IS); Laser Applications to Chemical, Security and Environmental Analysis (LACSEA); Propaganda through
and Characterization of Distributed Volume
Turbulence (pcDVT); Quantitative Medical
Imaging (QMI); and Signal Recovery & Synthesis (SRS). Contact The Optical Society, +1
(202) 223-8130; info@osa.org; www.osa.org.
Light Microscopy Summer School (July
14-16) Heslington, England. Contact Royal
Microscopical Society, +44 1 865 254760;
info@rms.org.uk.
Advanced Photonics (July 27-31) Barcelona,
Spain. Includes Bragg Gratings, Photosensitivity and Poling in Glass Waveguides
(BGPP); Nonlinear Photonics (NP); Optical
Sensors (SENSORS); and Specialty Optical
Fibers & Applications (SOF). Contact The
Optical Society, +1 (202) 223-8130; info@osa.
org; www.osa.org.
AUGUST
l Microscopy & Microanalysis 2014 (Aug.

3-7) Hartford, Conn. An event of the Microscopy Society of America. Contact Bob
Dziuban, MSA Association Office, +1 (703)
234-4115; rdziuban@drohanmgmt.com;
http://microscopy.org/mandm/2014.
SIAM Conference on the Life Sciences (Aug.
4-7) Charlotte, N.C. Contact Society for
Industrial and Applied Mathematics, +1 (215)
382-9800; service@siam.org; www.siam.org/
meetings/ls14.
XXIV. International Conference on Raman
Spectroscopy (ICORS 2014) (Aug. 10-15)
Jena, Germany. Contact Daniel Siegesmund,
Institute of Photonic Technology, +49 3641
206 024; daniel.siegesmund@ipht-jena.de;
www.icors2014.org.
SIAM Conference on Nonlinear Waves and
Coherent Structures (Aug. 11-14) Cambridge,
England. Contact Society for Industrial and
Applied Mathematics, +1 (215) 382-9800;
service@siam.org; www.siam.org/meetings/
nw14.
l SPIE Optics + Photonics (Aug. 17-21) San

Diego. Includes NanoScience + Engineering;
Solar Energy + Technology; Organic Photonics + Electronics; and Optical Engineering
+ Applications. Contact SPIE, +1 (360) 6763290; customerservice@spie.org; http://
spie.org.
OMN2014, 2014 International Conference
on Optical MEMS and Nanophotonics
(Aug. 17-21) Glasgow, Scotland. Contact
Conference Team, omn-conf2014@strath.
ac.uk; www.omn2014.org.
Sixth EPS-QEOD Europhoton Conference:

Solid State, Fibre, and Waveguide Coherent
Light Sources (Aug. 24-29) Neuchtel, Switzerland. An event of the European Physical
Society Quantum Electronics and Optics
Division. Contact EPS, +33 389 32 9448;
conferences@eps.org; www.europhoton.org.
AOMD-8, Eighth International Conference:
Advanced Optical Materials and Devices
(Aug. 25-27) Riga, Latvia. Contact asi@asi.lv;
www.aomd8.lv.
LIP 2014, 10th International Conference
Series on Laser-Light and Interactions with
Particles (Aug. 25-29) Marseille, France.
Contact Joyce Bartolini, +33 4 91 10 68 82;
contact@lip2014.eu; www.lip2014.eu.
ICO 23, 23rd Congress, International Commission for Optics (Aug. 26-29) Santiago de
Compostela, Spain. Contact Eva Cid, +34 988
387 276; admin@ico23.org; http://ico23.org.
Photonics Prague 2014, Seventh International Conference on Photonics, Devices and
Systems (Aug. 27-29) Prague. Contact Milena
Zeithamlov, milena@action-m.com; http://
prague2014.photon-czsk.org.
SEPTEMBER
Lasers, Optics and Photonics International

Conference 2014 (Sept. 8-10) Philadelphia.
Contact OMICS Group Conferences, +1 (650)
268-9744; optics2014@omicsgroup.us; http://
omicsgroup.com/lasers-optics-photonicsconference-2014.
l IMTS The International Manufacturing

Technology Show (Sept. 8-13) Chicago. Contact IMST, +1 (703) 827-5283; info@imts.com;
http://imts.com.
European Optical Society Annual Meeting
(EOSAM 2014) (Sept. 15-19) Berlin. Contact
Oili Kohonen, Conference Manager, EOS,
+358 40 564 0480; kohonen@myeos.org;
www.myeos.org.
SPIE Scanning Microscopies (Sept. 16-18)
Monterey, Calif. Contact SPIE, +1 (360) 6763290; customerservice@spie.org; http:
//spie.org.
OCTOBER
SPIE/COS Photonics Asia (Oct. 9-11) Beijing.

An event of SPIE and COS Chinese Optical
Society. Contact SPIE, +1 (360) 676-3290;
customerservice@spie.org; http://spie.org.
OSA Vision Meeting (Oct. 10-12) Philadelphia. Contact The Optical Society, +1 (202)
223-8130; info@osa.org; www.osa.org.
2014 IEEE Photonics Conference (Oct. 1216) San Diego. Contact Ingrid L. Donnelly,
senior conference planner, +1 (732) 562-5597;
i.donnelly@ieee.org; www.ipc-ieee.org.
Photonex (Oct. 15-16) Coventry, England.
Contact Laurence Devereux, Xmark Media
Ltd., +44 1372 750555; ld@xmarkmedia.com;
www.photonex.org.
ADVERTISERINDEX
Photonics Media Advertising Contacts
Please visit our website
Photonics.com/mediakit for all
our marketing opportunities.
Ken Tyburski
Director of Sales
Voice: +1 (413) 499-0514, Ext. 101
Fax: +1 (413) 443-0472
ken.tyburski@photonics.com
New England & FL
Rebecca L. Pontier
Associate Director of Sales
Voice: +1 (413) 499-0514, Ext. 112
Fax: +1 (413) 443-0472
becky.pontier@photonics.com
NY, NJ & PA
Timothy A. Dupree
Regional Manager
Voice: +1 (413) 499-0514, Ext. 111
Fax: +1 (413) 443-0472
tim.dupree@photonics.com
Northern CA, Pacific Northwest,
AK, NV, Yukon & British Columbia
Kathi Simonsen
Regional Manager
Voice: +1 (530) 268-4717
Fax: +1 (413) 443-0472
k.simonsen@photonics.com
a
Andor Technology plc .......................................................................................................... 13
www.andor.com
Applied Scientific Instrumentation Inc. .............................................................................. 16
www.asiimaging.com
e
Edmund Optics ...................................................................................................................... 17
www.edmundoptics.com
h
Hamamatsu Corporation ...................................................................................................... 11
www.hamamatsu.com
Central & Southern CA, HI,

AZ, CO, ID, MT, NM, UT, WY
& Western Canada
Kim Abair
Regional Manager
Voice: +1 (951) 926-4161
Fax: +1 (951) 926-4295
kim.abair@photonics.com
Lumencor Inc. .......................................................................................................................... 4
South Central US & Eastern Canada

Advertising Sales Department
Voice: +1 (413) 499-0514
Fax: +1 (413) 443-0472
advertising@photonics.com
Mad City Labs Inc. .................................................................................................................34
Southeastern US, Midwest,

Europe & Israel
Matt Beebe
Regional Manager
Voice: +1 (413) 499-0514, Ext. 103
Fax: +1 (413) 443-0472
matt.beebe@photonics.com
Asia (except Japan)
Hans Zhong
Voice: +86 755 2872 6973
Fax: +86 755 8474 4362
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PCO AG ................................................................................................................................ CV4
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Photonics Media ......................................................................................CV2, 26, 33, 34, CV3
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37
POSTSCRIPTS
In for the (linear) kill
ost people wouldnt consider birds to

be instruments of wartime sabotage,
but one species a top-notch bird of
prey would have to disagree. During World
War II, falcons were often released by British
forces to kill Nazi carrier pigeons and prevent
important messages from being received by
the German front.
Falcons have very good eyesight and
can spot their next meal up to a mile away.
However, until recently, their hunting
strategy a seemingly basic part of the
raptors behavior remained a mystery.
There were computational studies
that simulated this behavior, said
Dr. Suzanne Amador Kane, associate
professor of physics at Haverford College in Pennsylvania. But no one had
published any behavioral studies. As
falcons hurtle through the air and lock
sights onto their victims, this aerial
attack has obvious lethal strategy. It
just wasnt clear what that was.
Then one day, it hit her: Cameras
mounted on birds of prey could give
humans a falcons-eye view of
the birds flying tactics. It could
finally be known how these birds
maneuver in the sky to prevail
over their victims.
Using personal contacts and
social networking, the team
connected with falconers
around the globe, who attached
miniaturized spy cameras to backpacks and tiny
helmets worn by their falcons to film encounters during flights.
When the footage was completed and sent back to Amador Kane,
she and undergraduate student Marjon Zamani located the preys
position on each frame by hand, then reconstructed each pursuit
from the falcons perspective.
What they found contradicted preconceived notions of raptor
pursuits. The falcons rarely ever flew directly after their prey.
Direct flight is inefficient, wasting the predators time and energy. In the footage, the prey was never found in the center of the
frame, showing that the falcons seldom positioned themselves
directly behind their victims.
The team then looked for evidence of falcons viewing their
prey at an angle of 40 degrees, a widely accepted strategy
proposed by biologist Vance Tucker more than a decade ago.
Tuckers thought was that a falcon would keep its prey in the offcenter specialized region of vision and fly in a spiral path toward
it. It did so very rarely.
Falcons have two regions of very acute vision: one directed
almost in the forward direction and the other dramatically off to
the side 30 degrees off, Amador Kane said.
The truth of the matter is that falcons fix prey in their sights
38
Courte
sy of E
ddy De
M ol &
Frano
is
Lorrain
.
and maneuver to keep the image motionless and centered against

its surroundings so as to head it off in the least amount of time.
This allows the predator to view its prey head-on with its visual
field, often flying at speeds in excess of 200 mph during its
attack. The prey does not see the predator move until the final
instant when the falcon intercepts and strikes. This strategy,
although revolutionary to see, is new neither in the skies nor on
the ground. Once upon a time, your mom or dad might even have
used it on you.
Think about chasing a toddler around in the playground,
Amador Kane said. They keep zigging and zagging away from
you you just have to head them off.
The study appears in The Journal of Experimental Biology.
Sarina Tracy
sarina.tracy@photonics.com
Celebrating
of Industry Growth
and a Light-Driven Future
Photonics Buyers Guide

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60 Years
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Life Sciences for
20 Years
Photonics Spectra
BioPhotonics
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Industrial Photonics
Photonics.com
Light Matters
Photonics Buyers Guide
www.photonics.com/subscribe
Photonics.com
our Online Home
since 1996
Light Matters
Weekly Newscast
3 Years
New in 2014
Industrial Photonics
Manufacturing the Future
on the
cutting
edge
pco.edge 4.2 from the pioneers
in sCMOS image sensor technology
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April 2014

Photonics Continues to Improve Eyesight

FREE mobile app!

To download the app,

Photonics Spectra, EuroPhotonics and

BioPhotonics editors curate the most significant headlines

3 Questions with Dr. Robert Hart, Optofluidics Inc.

19 SEEING THE LIGHT: HOW PHOTONICS

by Valerie Coffey, Science Writer

23 FRET PURSUES AFFORDABLE, ROBUST,

by Marie Freebody, Contributing Editor

27 SOFTWARE ENHANCES LIFE SCIENCES

by Dr. Edward Freniere and Michael Gauvin, Lambda Research Corp.

by Gary Boas, News Editor

BioPhotonics April 2014

Upcoming Courses and Shows

In for the (linear) kill

Digital Media & IT Staff

Editorial Main Office

Laurin Publishing, 100 West Street

BioPhotonics April 2014

Seeing the Future:

BioPhotonics Editorial Advisory Board

Mark A. Anastasio, Ph.D.

Stephen A. Boppart, M.D., Ph.D.

David Benaron, M.D.

Aydogan Ozcan, Ph.D.

Adam Wax, Ph.D.

BioPhotonics April 2014

Valerie C. Coffey is a freelance

The online companion to BioPhotonics magazine

Contributing editor Marie

Michael Gauvin is vice president of sales and marketing

Check out a sample of the digital version of

The Past, Present and Future of Freeform Optics

The Development and Application of an Innovative

And many more!

In the May/June issue of

Terahertz for Biological Applications

In the industrys only weekly

Noninvasive optical system reveals oral cancer signs

The diffuse reflectance imaging system (DRIS) captures monochrome images to

KERALA, India A new spectral imaging system holds promise

3-D AFM could advance understanding of proteins

BioPhotonics April 2014

Using this new laser, we collect the

Silk-diamond hybrid shows promise for cell imaging

tend to be rough, which could cause the

Nanodiamonds similar to those used

Lighting up brain stops liquored-up rats

BioPhotonics April 2014

For decades, we have observed that particular brain regions

BioPhotonics April 2014

High-End Galvanometer Technology

Light-emission studies may improve bioimaging

SOLA The Bright Idea

High Intensity, Low Heat

To find out more on this Bright Idea, visit www.newport.com/solaII.

A-031403 SOLA hlf BioPh-2.indd 1

BioPhotonics April 2014

Light emission from plasmonic nanostructures at wavelengths shorter than

PNAS (doi: 10.1073/pnas.1311477111).

the emission as Raman scattering from