Biophotonics201203 DL

www.Photonics.
com OPTICS, LASERS, IMAGING, MICROSCOPY, SPECTROSCOPY

March 2012
Laser Turn Signals
Guide Nerve Fiber Growth
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4
8 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:
Particle manipulation using light made accessible
Optochemical genetics to turn pain off, sight on
Single step creates quantum dots in bulk
for biomedical imaging
17 BUSINESSSCAN
SPIE honors Robert Alfano with Britton Chance Award
NEWS
20
BioPhotonics March 2012
20 COLLABORATION SPARKS NERVE-FIBER TURN SIGNAL DISCOVERY
by Laura S. Marshall, Managing Editor
A recent multidisciplinary, multi-institution, multinational project has found
a way to direct nerve-fiber growth using laser-driven spinning microparticles.
24 PDT FOR CANCER DEPENDS ON IMPROVED PHOTOSENSITIZERS
by Lynn Savage, Features Editor
Compared with chemotherapy and radiation, photodynamic therapy may target
tumors more precisely, but the technique demands better photosensitizers
than are currently available.
28 MOVING NONINVASIVE CANCER IMAGING INTO THE CLINIC
by Gary Boas, News Editor
The challenges of applying coherence imaging technologies to cancer treatment
include developing turnkey systems, overcoming business hurdles and
building clinical partners.
31 TRANSORAL LASER MICROSURGERY FIGHTS LARYNGEAL CANCER
by Lynn Savage, Features Editor
The benefits of light-based microsurgery include speed,
precision and the various options for follow-up care.
FEATURES
NEWS
www.photonics.com
Volume 19 Issue 3
6 EDITORIAL
35 BREAKTHROUGHPRODUCTS
40 APPOINTMENTS
Upcoming Courses and Shows
41 ADVERTISER INDEX
42 POST SCRIPTS
by Laura S. Marshall, Managing Editor
The art of science
DEPARTMENTS
PHOTONICS
The technology of generating and harnessing light and other forms of radiant energy whose
quantum unit is the photon. The range of applications of photonics extends from energy generation
to detection to communications and information processing.
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.
THE COVER
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www.iridian.ca
istsales@iridian.ca
613-741-4513
IRIDIAN
Group Publisher Karen A. Newman
Editorial Staff
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Light Is Cancers Latest Foe
T
he race to cure a killer disease first got federal support back
in 1937, when US President Franklin D. Roosevelt signed
the National Cancer Institute (NCI) Act. On Jan. 3, 1938, the
National Advisory Cancer Council recommended approval of the
first cancer research fellowships.
Decades of research, both privately and federally funded, have
certainly broadened our understanding of this disease about the
causes, risk factors, treatments and more yet so much about
cancer is still unknown or not well understood. Meanwhile, can-
cer deaths are projected to continue rising, with an estimated 13.1
million deaths expected in 2030, according to the World Health
Organization.
In its 2012 annual plan and budget report, Cancer: Changing
the Conversation, the NCI discussed our new understanding of
the disease and its complexity as well as the range of opportuni-
ties to confront its many incarnations.
The report also described a vital opportunity to speed up
cancer study and treatment. The emerging scientific landscape
offers the promise of significant advances for current and future
cancer patients, just as it offers scientists at the National Cancer
Institute and in the thousands of laboratories across the United
States that receive NCI support the opportunity to dramatically
increase the pace of lifesaving discoveries where progress has
long been steady but mostly incremental.
Biophotonics is part of that emerging scientific landscape. A
great deal of effort is going into applying light to cancer research,
diagnosis and treatment throughout the photonics community,
with coherence imaging for cancer diagnosis among the topics
getting a lot of attention lately. There also is a growing under-
standing among researchers about just what it will take to
increase the pace of lifesaving discoveries.
In Moving Noninvasive Cancer Imaging into the Clinic
(page 28), BioPhotonics news editor Gary Boas reveals the
challenges researchers face in getting their light-based technolo-
gies into clinical trial and use, and talks with two researchers
working to move new imaging options into clinical use. In the
article, Jon Holmes, CEO of Kent, UK-based Michelson Diag-
nostics Ltd., advises physics and engineering groups should
closely partner with clinical teams and work with them on a
specific clinical need over a long period of time (decades) in a
focused manner with a clear long-term goal of developing an
exploitable device evaluated with clinical trials. Funders should
also actively support this type of collaborative work.
BioPhotonics features editor Lynn Savage contributes two
reports on the topic of cancer. PDT for Cancer Depends on
Improved Photosensitizers (page 24) explains how photody-
namic therapy could be the future of cancer treatment.
Photodynamic therapy (PDT) is proving to be a more than
viable option for cancer treatment. Compared with other treat-
ments, such as chemotherapy and radiation therapy, PDT is more
selective, causing far less damage to healthy cells near cancer-
ous targets due to the precise way in which photosensitizers
can locate and infiltrate tumor cells.
In his second article, Transoral Laser Microsurgery Fights
Laryngeal Cancer (page 31), Lynn says that, thanks to laser
surgery refinements, your life or your voice is a choice fewer
people in the world have to face. In the US alone, 10,000 people
are diagnosed each year with laryngeal carcinoma, according
to the American Cancer Society. This cancer affects the vocal
cords and the connective tissues surrounding them, and laser
microsurgery could help save both lives and voices.
Despite the very long strides taken over the past few decades,
there is much more work to be done to further our understanding
of this disease of many parts. Asking new questions based on
the growing body of knowledge, finely focusing and directing
research, and adequately funding those efforts will go a long
way toward achieving the ultimate goal of many fewer deaths
from cancer. Light and the dedicated people in this industry who
harness it to understand this killer are bringing new direction to
the fight.
6 BioPhotonics March 2012
EDITORIAL
Karen A. Newman
karen.newman@photonics.com
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Photonics Medias industry-leading site features the latest industry news and events
from around the world.
Welcome to
Biophotonics News:
A round-up of the industrys top
bio-related research headlines.
Visit: Photonics.com/Biophotonics
Editors from photonics.com,
Photonics Spectra and Bio-
Photonics magazines bring
you the top photonic research
and business news of the week.
For the photonics industrys
only weekly newscast,
visit: Photonics.com/LightMatters.
Photonics.com Forum
Join the Discussion!
Our photonics community
provides a place where all
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Visit: Photonics.com/Forum
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BIOSCAN
URBANA, Ill. Dexterous optical tweez-
ing and size-sorting of particles can now
be done by tuning the properties of laser
light illuminating arrays of metal nano-
antennas.
In work conducted at the University of
Illinois at Urbana-Champaign, assistant
professor of mechanical science Kimani
Toussaint Jr. and his research team have
demonstrated for the first time the use of
gold bowtie nanoantenna arrays for multi-
purpose optical trapping and manipulation
of submicrometer- to micrometer-size
objects. The findings could prove useful
for the growing interest in lab-on-a-chip
devices.
The field enhancement and confinement
properties of bowtie nanoantenna arrays
also make them accessible for formation
of optical matter, manipulation of biologi-
cal matter with reduced specimen photo-
damage and for basic physics studies of
colloidal dynamics.
We believe that our work shows that
optical nanoantennas could serve as inte-
gral components in potential lab-on-chip
devices, Toussaint said. The basic idea
is to use nanoantennas to augment the
optical forces on objects (e.g., cells) in
aqueous environments. This will consider-
ably relax the requirements on the optics
used for such experiments.
Using empirically obtained optical
trapping phase diagrams to achieve the
desired trapping response, the researchers
demonstrated several types of particle ma-
nipulation, including single-beam optical
tweezing of single particles over the entire
nanoantenna area, single-beam optical
tweezing of two-dimensional hexagonal-
packed particles over the entire nano-
antenna area, and optical sorting of parti-
cles by size. They also showed stacking
of submicron- to micron-size particles in
three dimensions.
For a given particle size, wavelength
and desired type of manipulation, the trap-
ping phase diagrams provide information
on the input power and nanoantenna array
spacing required to achieve the desired
task. They are empirically derived and
become an easy way to harness the forces
in the nanoantenna platform that are
otherwise complex to fully model,
Toussaint said.
This is the first demonstration of a
range of particle manipulation behavior
for a given nanoantenna array, according
to Toussaint.
Perhaps the most immediate impact is
that we have helped to make general parti-
cle manipulation (using light) accessible,
he said. Single- and multiple-particle
trapping, as well as sorting, is now very
doable using a fixed nanoantenna platform
and without the use of high-power lasers,
extremely tight focusing or multiple laser
beams.
In fact, his team conducted most of its
experiments using an average power at
least 1000 times less than that of a stan-
dard laser pointer. A laser pointer was
used for some proof-of-concept experi-
ments to show that ubiquitous off-the-
shelf technology could be used easily with
the nanoantenna system because of the
structures ability to enhance optical
fields, he said.
The beam quality of a laser pointer is
often not ideal for conventional optical
trapping experiments without a fair
amount of spatial filtering, but for our
system it does not matter, he said. We
could get away with using relatively
cheap and dirty optics.
The research appeared online Dec. 30
in Nano Letters (doi: 10.1021/nl203811q).
Particle manipulation using light made accessible
A closer look at the most significant biophotonics research and technology headlines of the month
Concept art depicting the various potential bowtie nanoantenna array trapping states. Courtesy of
Kimani C. Toussaint Jr., University of Illinois.
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BERKELEY, Calif., and MUNICH
Optogenetic tools that use light to control
neurons could lead to highly targeted pain
relief and might even restore sight to the
blind, say biologists at the University of
California, Berkeley (UCB) and Ludwig
Maximilian University (LMU) of Munich.
UCBs Richard H. Kramer and Dirk
Trauner of LMU sought to develop a mol-
ecule that can block the activity of pain-
sensing neurons in a controlled and re-
versible way. Local anesthetics suppress
pain by blocking the activity of pain-
sensing neurons, but most act nonselec-
tively on all nervous system cells.
The researchers synthesized the mole-
cule quaternary ammonium-azobenzene-
quaternary ammonium, or QAQ, which is
structurally similar to a lidocaine derivate
they had used in the past. While the two
molecules use the same mechanism to
selectively enter pain-sensing neurons,
QAQ features an important difference: Its
activity can be controlled by light. Specifi-
cally, ultraviolet light turns it on, and
green light turns it off.
They demonstrated the capacity of QAQ
as a light-sensitive analgesic in the retina
of living rats in a paper published online
Feb. 19 in Nature Methods (doi: 10.1038/
NMETH.1897).
Unblinded by the light
Another collaborative venture between
chemists at the two universities success-
fully converted an intrinsically blind re-
ceptor molecule into a photoreceptor, a
feat that one day might allow use of such
synthetic photoreceptors to restore sight to
those with certain types of blindness, said
Trauner, a professor of chemical biology
and genetics at LMU and one of the pro-
jects leaders.
Communication between nerve cells
relies on specialized receptor molecules
on the surfaces of the neurons to relay sig-
nals back and forth. But the investigators
found that they could use molecular ge-
netic techniques to attach what amounts
to a light-controlled chemical switch to
a receptor that normally is activated by
the endogenous neurotransmitter acetyl-
choline.
These molecular machines transmit
nerve impulses by converting an incoming
chemical signal into an electrical response,
which is then propagated along the length
of the nerve fiber. Binding acetylcholine
to the external surface of the receptor acts
as a switch a research method known
as optochemical genetics.
As with the light-sensitive pain relief
applied to rat eyes, the synthetic photo-
receptors can be switched on using UV
light and switched off using green light.
The project was carried out under the
auspices of the Collaborative Research
Center on Formation and Function of
Neuronal Circuits in Sensory Systems,
which is funded by the German Research
Foundation.
Trauner received a European Research
Council grant in 2010 for a project that is
also based on a photopharmacological
approach. The long-term goal of this
ongoing research is to find ways of com-
pensating for the loss of dedicated photo-
receptors in the eye, the most common
cause of blindness. He is working to
develop hybrid photoreceptors.
The basic idea, which has in principle
been shown to work in animal models,
is to confer light sensitivity on surviving
neurons in the eye that do not normally
respond to light, Trauner said.
The work was published online Jan. 8 in
Nature Chemistry (doi: 10.1038/NCHEM.
1234).
BioPhotonics March 2012 9
Optical control of pain-sensing neurons. QAQ selectively enters pain-sensing neurons and silences
their activity (top, green light). Illumination with violet light (bottom) quickly restores signal conduction.
Courtesy of Alexandre Mourot.
Optochemical genetics to turn pain off, sight on
b
BIOSCAN
HOUSTON A simple one-step chemical
process for turning carbon fiber into semi-
conducting nanocrystals could prove use-
ful in biomedical, optical and electronic
applications.
There have been several attempts to
make graphene-based quantum dots with
specific electronic and luminescent prop-
erties using chemical breakdown or
e-beam lithography of graphene layers,
said Pulickel Ajayan, a Rice University
materials scientist who discovered the
process in collaboration with colleagues
at the Texas Medical Center and in China,
India and Japan. We thought that as these
nanodomains of graphitized carbons
already exist in carbon fibers, which are
cheap and plenty, why not use them as
the precursor?
Quantum dots semiconductors that
contain a size- and shape-dependent
bandgap were discovered in the 1980s
and are seen as promising for applications
ranging from medical imaging devices to
computers, LEDs, solar cells and lasers.
The sub-5-nm carbon-based quantum dot
analogues are produced in bulk through a
wet chemical process discovered at Rice.
The particles are highly soluble, and their
size can be controlled via the temperature
at which theyre created.
The Rice researchers were attempting
another experiment when they came
across the technique.
When attempting to selectively oxidize
carbon fiber, the team ended up with a
solution that, when analyzed under a
transmission electron microscope, was
seen to contain oxidized nanodomains of
graphene extracted via chemical treatment
of carbon fiber.
That was a complete surprise, said
graduate student Wei Gao. We call them
quantum dots, but theyre two-dimen-
sional, so what we really have here are
graphene quantum discs.
Gao said that other techniques are ex-
pensive and require weeks to make small
batches of graphene quantum dots.
Our starting material is cheap, com-
mercially available carbon fiber. In a one-
step treatment, we get a large amount of
quantum dots. I think thats the biggest
advantage of our work, she said.
Their luminescent properties give graph-
ene quantum dots potential for imaging,
Single step creates quantum dots
in bulk for biomedical imaging
This transmission electron microscope image shows
a graphene quantum dot with zigzag edges. The
quantum dots can be created in bulk from carbon
fiber through a chemical process discovered at Rice
University. Images courtesy of Ajayan Lab/Rice
University.
Green-fluorescing graphene quantum dots created
at Rice University surround a blue-stained nucleus
in a human breast cancer cell. Cells were placed in
a solution with the quantum dots for four hours.
The quantum dots, each smaller than 5 nm, easily
passed through the cell membranes, showing their
potential value for bioimaging.
Dark spots on a transmission electron microscope
grid are graphene quantum dots made through a
wet chemical process at Rice University. The inset is
a close-up of one quantum dot. Graphene quantum
dots may find use in electronics, optical and bio-
medical applications.
protein analysis, cell tracking and other
biomedical applications, Gao said. Tests at
Houstons MD Anderson Cancer Center
and Baylor College of Medicine on two
human breast cancer lines showed that the
quantum dots easily found their way into
the cells cytoplasm and did not interfere
with their proliferation.
The green quantum dots yielded a very
b
BIOSCAN
good image, said co-author Rebeca
Romero Aburto, a graduate student in the
Ajayan Lab who also studies at MD An-
derson. The advantage of graphene dots
over fluorophores is that their fluores-
cence is more stable and they dont photo-
bleach. They dont lose their fluorescence
as easily. They have a depth limit, so they
may be good for in vitro and in vivo stud-
ies, but perhaps not optimal for deep tis-
sues in humans.
The quantum dots could help bioimag-
ing, she said. In the future, these graphene
quantum dots could have high impact be-
cause they can be conjugated with other
entities for sensing applications too.
The results were published online Jan. 4
in Nano Letters (doi: 10.1021/nl2038979).
Superlens nears reality in theory
HOUGHTON, Mich. A new theoretical
model shows that a superlens could view
objects as small as 100 nm using visible
light. If this model is realized, ultrahigh-
resolution microscopes could become as
commonplace as cell phone cameras.
Scientists have yet to create a superlens,
or perfect lens, although they have tried.
Optical lenses are shackled by the diffrac-
tion limit, so even the best cannot see ob-
jects smaller than 200 nm across, or about
the size of the smallest bacterium. Scan-
ning electron microscopes can capture ob-
jects that are significantly smaller about
1 nm wide but they are heavy, expensive
and large about the size of a desk.
Metamaterial model
Scientists are beginning to fabricate
metamaterials in their quest to make real
seemingly magical phenomena like invisi-
bility cloaks, quantum levitation and
superlenses. At Michigan Technological
University, Durdu Guney has demon-
strated a theoretical model for stretching
metamaterial to refract light from the
infrared to the visible and ultraviolet
regimes.
An assistant professor of electrical and
computer engineering, Guney demon-
strated through his model that the secret
lies in plasmons charge oscillations near
the surface of thin metal films that com-
bine with special nanostructures. When
excited by an electromagnetic field, the
surface plasmons gather light waves from
an object and refract them in a manner
known as negative refraction. This phe-
nomenon enables the lens to overcome
the diffraction limit, and in the case of
Guneys model, could enable scientists
to see objects smaller than 1/1000th the
width of a human hair. His research
appeared in the journal Physical Review B
(doi: 10.1103/PhysRevB.84.195465).
Producing the superlenses is inexpen-
sive, according to Guney, which is why
they could find their way into cell phones.
Lithography would be another suitable
application, since the size of a feature to
be produced depends on lens size. Even
smaller features could be created, and at
a lower cost, by replacing old lenses with
the theoretical superlenses, Guney said.
With the help of these superlenses, even
a red laser could be used to produce com-
puter chips, he explained.
The publics access to high-powered
microscopes is negligible, Guney said.
With superlenses, everybody could be
a scientist. People could put their cells on
Facebook. It might just inspire societys
scientific soul.
An illustration of Durdu Guneys theoretical negative-index metamaterial, which would be the heart of a perfect
lens. The colors show magnetic fields generated by plasmons. The black arrows show the direction of electrical
current in metallic layers, and the numbers indicate current loops that contribute to negative refraction.
Courtesy of Durdu Guney, Michigan Technological University.
b
BIOSCAN
LONDON The technology used for full-
body security scanners could one day lead
to the development of a handheld scanner
similar to the tricorder made famous by
Star Trek. The device will be suitable for
medical scanning thanks to a new tech-
nique for creating terahertz waves (T-
rays).
Scientists from the Institute of Materials
Research and Engineering (IMRE), a
branch of the Agency for Science, Tech-
nology and Research in Singapore, and
from Imperial College London have made
T-rays into a much stronger directional
beam than previously thought possible and
have done so in room-temperature condi-
tions. This breakthrough should allow
future T-ray systems to be smaller, more
portable, easier to operate and cheaper to
develop than current devices.
The researchers say the stronger, more
efficient continuous-wave T-rays could be
used to make better medical scanning
gadgets.
The scanner and detector could function
much like the tricorder a portable sens-
ing, computing and data communications
device because the waves can detect
biological events such as increased blood
flow around tumorous growths, the re-
searchers say. Future scanners also could
perform fast wireless data communication
to transfer a high volume of information
on the measurements it makes.
T-rays, waves in the far-infrared part of
the electromagnetic spectrum, are already
in use in airport security scanners, proto-
type medical scanning devices and in
spectroscopy systems for materials analy-
sis. They can sense molecules such as
those present in cancerous tumors and liv-
ing DNA because every molecule has its
unique signature in the terahertz range.
They also can be used to detect explosives
or drugs, to monitor gas pollution, or to
nondestructively test semiconductor inte-
grated circuit chips.
Current T-ray imaging devices are very
expensive and operate only at a low output
power because creating the waves con-
T-rays could lead to real-life tricorder
Research author professor Stefan Maier in the
laboratory. Courtesy of Imperial College London.
sumes large amounts of energy and must
take place at very low temperatures.
In the new technique, the researchers
demonstrated that it is possible to produce
a strong beam of T-rays by shining light
of differing wavelengths on a pair of elec-
trodes two pointed strips of metal sepa-
rated by a 100-nm gap on top of a semi-
conductor wafer. The structure of the
tip-to-tip nanosize-gap electrode greatly
enhances the terahertz field and acts as a
nanoantenna to amplify the wave gener-
ated. In this method, terahertz waves are
produced by an interaction between the
electromagnetic waves of the light pulses
and a powerful current passing between
the semiconductor electrodes. The scien-
tists can tune the wavelength of the T-rays
to create a usable beam in the scanning
technology.
The secret behind the innovation lies
in the new nanoantenna that we had devel-
oped and integrated into the semiconduc-
tor chip, said Dr. Jing Hua Ten of IMRE,
who was the lead author of the study. The
work was published in Nature Photonics
(doi: 10.1038/nphoton.2011.322).
Arrays of these nanoantennas create
much stronger terahertz fields that gener-
ate a power output 100 times higher than
that of commonly used terahertz sources
that have conventional interdigitated an-
tenna structures. A stronger T-ray source
gives more power and higher resolution
to the T-ray imaging devices.
T-rays promise to revolutionize med-
b
BIOSCAN
ical scanning to make it faster and more
convenient, potentially relieving patients
from the inconvenience of complicated
diagnostic procedures and the stress of
waiting for accurate results, said Stefan
Maier, a visiting scientist at IMRE and
professor in the department of physics at
Imperial College London.
With the introduction of a gap of only
0.1 micrometers into the electrodes, we
have been able to make amplified waves
at the key wavelength of 1000 microme-
ters that can be used in such real-world
applications.
Photoacoustic device
hunts melanoma
COLUMBIA, Mo. A new photoacoustic
device will aid the fight against metastatic
melanoma by detecting single melanoma
cells in blood samples at a fraction of the
cost of current cancer tests.
Melanoma, an aggressive cancer, is char-
acterized by skin growths that in and of
themselves arent seriously dangerous but
that can become a quick killer: After metas-
tasis, patients often live less than a year,
and fewer than 20 percent live five years,
which is why early detection is critical.
But finding metastatic melanoma as it
spreads through the body has proved diffi-
cult. Detection with MRI or CT imaging
equipment requires tumors that are at least
a few millimeters in diameter (similar to
a grain of rice); at that size, they already
consist of millions of cells.
With the new test, scientists can look
in the blood system for single melanoma
cells propagating through the body, said
John Viator of the Bond Life Sciences
Center at the University of Missouri.
This is much more effective, because
youre looking for a cancer sooner than
you could ever detect it with an imaging
test, he said. Thats good for the patient,
and its good for the clinician, because if
you can find cancer when its just at the
cellular level, then youre fighting a small
number of cells versus trying to fight a
tumor the size of a softball thats growing
around your kidney.
The prototype, when refined into a com-
mercial product, should be about the size
of a small copy machine. Clinicians would
put blood samples into the device, which
would then provide a readout of the sam-
ples results in about 10 minutes. Com-
pared to current techniques for testing, this
new machine has the advantages of being
inexpensive, fast, compact and easy to use,
along with offering earlier detection.
At its center is a photoacoustic technol-
ogy called laser-induced ultrasound. Viator
uses this tool in conjunction with the prop-
erties of density, light, heat and color to
cause cancer cells to react in a manner that
makes them detectable and distinguishable
from surrounding cells.
A first step in the testing process is
using a centrifuge to separate a patients
blood into white and red blood cells. Mela-
noma cells are about the same density as
white blood cells but less dense than red
ones, so melanoma cells are naturally
thrown in with white blood cells as the
b
BIOSCAN
No more finger-sticks: Chip measures glucose in saliva
PROVIDENCE, R.I. A new sensor mea-
sures blood sugar levels by determining
glucose concentrations in saliva, which
could mean that diabetics no longer have
to draw their own blood.
Drawing blood through finger-sticks or
other means is invasive and at least mini-
mally painful but for the 26 million
Americans with diabetes, it is the most
prevalent and effective method of check-
ing glucose levels on a daily basis.
Each plasmonic interferometer thousands of them
per square millimeter consists of a slit flanked by
two grooves etched in a silver metal film. The
schematic shows glucose molecules dancing on
the sensor surface, illuminated by light with different
colors. Changes in light intensity transmitted through
the slit of each plasmonic interferometer yield infor-
mation about the concentration of glucose molecules
in solution. Courtesy of Domenico Pacifici.
blood separates. The resulting batch of
white blood cells (plus any cancer cells
present) is then pumped through narrow
tubing that contains a tiny glass box where
the cells are hit with a short pulse of high-
intensity laser light as they pass by. Be-
cause white objects reflect light, the white
blood cells are not affected, but any cell
with pigment will absorb the light. The
intense laser beam heats such a cell rap-
idly, causing thermoelastic expansion,
which in turn causes the expanding cell
to emit a measurable pressure wave.
Detection equipment senses this photo-
acoustic wave and thus locates the can-
cer cell.
Using this method, pigmented mela-
noma cells stand out and can be separated
from the healthy white blood cells, which
then are individually tested using biomole-
cular assays or imaging.
Not all melanoma cells are the same,
Viator said. You can do some molecular
tests and find out [details such as] do they
have this genetic type? Or do they have
these cell surface markers? We know that
such-and-such a cell responds really well
to this type of drug, so you could person-
alize your cancer therapy, potentially, by
capturing the cells youve detected
in the blood sample and understanding
the disease better.
Current treatment tools for melanoma
include surgery and a drug, interferon,
which is only about 20 percent effective,
Viator said. But two new melanoma drugs
have been approved this year, and a dozen
more are in Phase III trials.
The availability of melanoma therapies
is going to explode, Viator said. The
more therapies there are, the more valuable
this [photoacoustic technology] will be,
because it can track response to disease.
Initially, the tool will detect and monitor
only metastatic melanoma. But Viators
lab is continuing research, with the goal
of using photoacoustic methods to detect
other cancers such as breast and prostate.
Viator recently signed royalty and
licensing agreements with the university
to clear the way for his new company,
Viator Technologies Inc., to develop a
commercial prototype.
Due to the machines comparatively
low cost, he is confident that early cancer
diagnosis will become more accessible
because it could be available in places
where medical facilities cant justify
purchasing a much higher-priced MRI
machine.
Unfortunately for cancer patients, the
new device may not be available for a
few more years, as it has not passed FDA
tests for safety and effectiveness. Viator
is confident, however, that these required
tests will demonstrate that it is highly
reliable. The machine can grab and save
any suspect cell; therefore, the cells can
be examined microscopically or geneti-
cally to confirm their identity.
The machine does not need FDA clear-
ance before it is used for research. Scien-
tists in academia or industry could use the
device for cancer studies as soon as it is
produced. Thus, companies testing new
cancer drugs could use it to assess their
drugs effectiveness.
The desktop device should be available
to researchers by the end of next year;
after two or three more years, it may be
commercially available for clinical use,
Viator said.
John Viator, associate professor of biomedical
engineering and dermatology, demonstrates a new
photoacoustic method with a tabletop device that
scans a lymph node biopsy with laser pulses. This
method could help doctors identify the stage of
melanoma with more accuracy. Courtesy of
University of Missouri.
b
BIOSCAN
The new technique, developed at Brown University, combines
nanotechnology and surface plasmonics. The Brown engineers
etched thousands of plasmonic interferometers onto a fingernail-
size biochip and measured the concentration of glucose molecules
in water on the chip. Their results showed that the specially de-
signed biochip can detect glucose levels similar to those found in
human saliva, where it typically is about 100 times less concen-
trated than in blood.
The technique also could be used to detect chemicals and sub-
stances such as anthrax in biological compounds.
The researchers created the sensor by carving a 100-nm-wide
slit and etching two 200-nm-wide grooves on either side. The
slit captures incoming photons and confines them, while the
grooves scatter the incoming photons, which interact with the
free electrons bounding around on the sensors metal surface.
The free electron-photon interactions create a surface plasmon
polariton. These surface plasmon waves move along the sen-
sors surface until they encounter the photons in the slit.
The interference between the two waves determines maxima
and minima in the light intensity transmitted through the slit.
The presence of an analyte on the sensor surface generates a
change in the relative phase difference between the two surface
plasmon waves, which in turn causes a change in light intensity,
which the researchers measure in real time.
The slit is acting as a mixer for the three beams the incident
light and the surface plasmon waves, said Domenico Pacifici,
assistant professor of engineering.
The scientists discovered that they could vary the phase shift
for an interferometer by changing the distance between the
grooves and the slit, meaning that they can tune the wave-
generated interference. They tuned thousands of interferome-
ters to establish baselines, which then could be used to accur-
ately measure concentrations of glucose in water as low as
0.36 mg/dl.
It could be possible to use these bio-chips to carry out the
screening of multiple biomarkers for individual patients, all at
once and in parallel, with unprecedented sensitivity, Pacifici
said.
The research was published in Nano Letters (doi: 10.1021/
nl203325s) and was funded by the National Science Foundation
and Brown (through a Richard B. Salomon Faculty Research
Award).
Microscopy reveals
skin-allergen connection
GOTHENBURG, Sweden Two-photon microscopy has shown
that skin absorbs various substances differently, depending upon
what is mixed with them. These differences may determine
whether a material causes contact allergy.
We have also been able to identify specific cells and proteins
in the skin with which a contact allergen interacts, said Carl
Simonsson of the University of Gothenburg. The results increase
our understanding of the mechanisms behind contact allergy.
The skin is the largest organ in the human body and plays
many vital roles, one of which is to prevent harmful microorgan-
isms from invading the body. The principal barrier is the stratum
corneum a layer of skin cells about a few microns thick. De-
b
BIOSCAN
Ashley N. Paddock
ashley.paddock@photonics.com
Melinda A. Rose
melinda.rose@photonics.com
spite being so thin, this layer effectively
protects us from bacteria and viruses.
The skin, however, has not adapted to
deal with and prevent absorption of many
of the chemicals to which we are exposed
today. This may lead to various types of
diseases, such as contact allergy, which
affects approximately 20 percent of people
in Sweden.
With two-photon microscopy, sub-
stances can be followed as they are ab-
sorbed into the skin. The method is unique
in that it allows researchers not only to see
how well a substance is absorbed, but also
what happens to it, and to find the location
in the skin where the substance eventually
arrives.
In addition, the skin barrier and the way
in which various substances are absorbed
are highly significant for the development
of new drugs. Creams and ointments are
for many reasons an interesting alternative
to tablets, which must be taken orally. The
barrier properties of the skin may present,
in this case, an obstacle to drug absorp-
tion, making it difficult for sufficient
amounts of the drug to penetrate the skin
to produce a clinical effect.
We have used two-photon microscopy
to study a new type of ointment that it
may be possible to use to improve the
absorption, and thus the clinical effect,
of certain drugs that are used on the skin,
Simonsson said.
Skin photographed in a two-photon microscope, showing epidermal cells and the collagen present
in the dermis. Courtesy of Carl Simonsson.
Carl Simonsson, whose thesis showed the utility of two-photon microscopy in the exploration of contact
allergens in the skin. Courtesy of University of Gothenburg.
BUSINESSSCAN
SAN FRANCISCO To recognize his
pioneering work in biomedical optics and
ultrafast laser spectroscopy, SPIE pre-
sented Robert Alfano, distinguished pro-
fessor of physics at City College of New
York, with the first Britton Chance Bio-
medical Optics Award during the BiOS
conference at Photonics West.
Some of Alfanos work has focused on
using light to perform noninvasive optical
biopsies that reveal molecular information
on the spot. The techniques can eliminate
the wait for test results and reduce the
physical trauma of surgery, since there
is no need to remove tissue unless cancer
is found.
This field was nonexistent before
1984. Thats when we discovered you
could use the colors of light to detect can-
cer, Alfano said. When you shine a little
light on the tissue, it glows.
He found that different combinations of
molecules on healthy and cancerous sam-
ples produced specific spectral emissions
when excited by a laser. The colors of the
emissions are different. If the molecules
are good, you get one glow; if theyre bad,
you get another.
Its like a fingerprint, he added. In
that glow is all the information you need
about the molecules that are there.
In 1991 Alfano and his colleagues ex-
tended their early work using Raman scat-
tering, which doesnt rely on fluorescence
and has higher resolution and sharper spec-
tral lines to detect differences between
cancerous, precancerous and normal tis-
sue. More recently, his lab has been refin-
ing cancer detection using Stokes shift
spectroscopy, which combines absorption
and fluorescence for a higher degree of
accuracy.
Alfano also co-discovered the supercon-
tinuum ultrafast white light source, among
other achievements recognized by the
award, which spans from the visible to the
near-infrared part of the light spectrum.
The discovery enabled research resulting
in two Nobel Prizes. The winner of the
chemistry Nobel in 1999 used the super-
continuum to monitor chemical reactions.
Winners of the 2005 Nobel Prize in phys-
ics tapped it to create the most accurate
clock in existence. Others, Japanese re-
searchers in particular, are using it in com-
munications to boost available channels
and bandwidth into the terabits-per-second
range.
He was instrumental in the founding of
the BiOS symposium and has published
more than 700 papers; he also holds 108
patents and has been cited more than
11,000 times. He has served as a member
of the editorial board of the Journal of
Biomedical Optics since the journals
founding in 1996, and he long contributed
to Photonics Medias publications as an
editorial advisory board member.
His most recent achievement was the
approval of a patent for a pill-size cancer
detection device. But theres more to come.
Someday, he said, I want to have a cell
phone to diagnose cancer.
In his acceptance speech at the Photon-
ics West event, Alfano credited Britton
Chance and others for their inspiration and
contributions to the field. Britton Chance
was the real giant, he said. Everything is
built on giants its not done alone. But
Britton was one of those guys that did it
alone.
Chance pioneered the field of biomed-
ical optics and contributed to a wide range
of fields, including the identification and
functioning of enzyme-substrate com-
pounds, and made advancements in breast
cancer diagnostics, radio-frequency elec-
tronics, spectroscopy for noninvasive clin-
ical diagnosis, and other areas.
Brit Chances research, training and
leadership have helped fuel the growth
of biomedical optics and biophotonics
throughout the world, said Bruce Trom-
berg, director of the Beckman Laser Insti-
tute at the University of California, Irvine,
and a longtime colleague of Chance. His
lifelong passion for measuring and under-
standing physiology and metabolism using
light has inspired our community for
decades.
More than any other individual, Brit
brought together people and ideas that
spanned across disciplines, creating a spe-
cial spirit of creativity, innovation and en-
thusiasm that has characterized the field of
biomedical optics.
SPIE honors Alfano with Britton Chance Award
Dr. Katarina Svanberg of Lund University in Sweden, a past president of SPIE, presents Dr. Robert Alfano with
the Britton Chance Award for Biomedical Optics during the BiOS portion of Photonics West. Courtesy of SPIE.
Laura S. Marshall
laura.marshall@photonics.com
In that glow
is all the
information you
need about the
molecules that
are there.
Robert Alfano
312BusinessScan_Layout 1 3/6/12 12:40 PM Page 17
The first handheld device intended to aid in the
detection of life-threatening bleeding in the
skull has been approved for marketing by the
FDA. The device, called the Infrascanner Model
1000, can help health care providers identify
patients with critical head injuries who need
an immediate brain imaging study. Made by
InfraScan Inc. of Philadelphia, the device uses
a near-IR scanner, which can nondestructively
penetrate the skull through tissue and bone.
Blood from the intracranial hematomas absorbs
the light differently than that from other areas
of the brain. The scanner detects differences in
light absorption and transmits the information
wirelessly to a display on a handheld computer.
Boston Micromachines Corp. (BMC) of Cam-
bridge, Mass., has been awarded a Phase I
Small Business Innovation Research contract
for $125,000 by NASA to advance exoplanet
imaging research involving deformable mirrors.
BMC will develop and demonstrate an innova-
tive microfabrication process to substantially
improve the surface quality achievable in high-
resolution continuous-membrane microelectro-
mechanical systems deformable mirrors. The
goals include at least a twofold improvement
in small-scale surface flatness in comparison
with the state of the art, and corresponding
reductions in diffraction. The research also
could have an impact on commercial applica-
tions such as optical communications, surveil-
lance, pulse shaping and biological imaging.
Based in Santa Clara, Calif., OptiMedica
Corp., a global ophthalmic device company,
has received FDA 510(k) market clearance for
its Catalys laser, a next-generation cataract
surgery system. Catalys combines a femtosec-
ond laser, integrated OCT imaging and propri-
etary pattern scanning technology in an ergo -
nomic system that allows surgeons to perform
image-guided preoperative laser lens condition-
ing. The FDA cleared the system for capsulo-
tomy (a circular incision in the lens capsule)
and lens fragmentation (segmenting and soften-
ing of the lens to prepare for removal). Catalys
was CE mark-approved in August 2011 and
has since been shipped to ophthalmic centers
outside the US.
In California, Optovue Inc. of Fremont and
Carl Zeiss Meditec Inc. of Dublin have signed
a settlement agreement resolving two pending
US District Court patent infringement cases.
Terms of the settlement were not disclosed.
The companies dismissed all pending litigation
and entered into a cross-license agreement of
certain issued and soon-to-be-issued patents
owned or controlled by each party. Optovue is
a privately held ophthalmic device company,
and Carl Zeiss Meditec is a medical technology
supplier.
Specialty photonics packaging company PD-LD
Inc. of Pennington, N.J., has been granted US
Patent No. 7,982,869, which protects the use
of dual laser sources for analysis of a single
substance. The technique, based on proprietary
VBG (volume Bragg grating) laser wavelength
stabilization, provides the underlying mecha-
nism for shifted excitation Raman differential
spectroscopy. CEO Vladimir Ban said that the
patent will allow PD-LD to offer Raman excita-
tion sources that extend portable and lab-based
instruments, and that the patent is particularly
relevant to the life sciences and security indus-
tries, where fluorescence is widespread.
A prototype of a high-power 532-nm compact
green laser module developed by QD Laser
Inc. of Kanagawa, Japan, was displayed at
SPIE Photonics West in San Francisco in January.
The device, developed with the Institute for
Nano Quantum Information Electronics,
the University of Tokyo and Fujitsu Labora-
tories Ltd., has confirmed green light output
greater than 100 mW under continuous-wave
conditions and high-speed modulation of more
than 100 MHz. They also obtained a linewidth
of <0.01 nm with a high side-mode suppres-
sion ratio. The green laser is suitable for appli-
cations including fluorescence microscopy and
spectral analysis in the life sciences.
Materion Microelectronics & Services, a unit
of Materion Corp., has completed a 50 per-
cent capacity expansion of its Wheatfield, N.Y.,
facility. The site provides precision parts clean-
ing and surface treatment of physical vapor
deposition shield kits for manufacturers of
photovoltaics, medical consumables, LEDs and
wireless products. The expansion includes a
fully automated robotic twin wire arc spray, new
cleaning processes, increased precious metals
refining capacity and a Class 10,000 certified
cleanroom. Based in Mayfield Heights, Ohio,
Materion Corp., through its wholly owned
subsidiaries, supplies enabling materials such
as specialty metals, coatings and engineered
beryllium alloys.
AMS Technologies AG will acquire Sdertlje,
Sweden-based Azpect Photonics AB, creating
an extended pan-European provider of products
for optical, power and thermal management
technologies. Terms were not disclosed. Azpect
Photonics supplies photonic equipment such as
lasers, optics, spectroscopy products and OEM
components to the Nordic market. Based out-
side Munich, AMS Technologies provides opti-
cal, power and thermal management products
to the renewable energy, medical, defense and
aerospace, telecom and datacom, and research
and scientific markets.
Zecotek Photonics Inc., based in Richmond,
British Columbia, Canada, has achieved com-
mercial production status with its advanced
solid-state micropixel avalanche photodiode
(MAPD) photodetectors, the MAPD-3N. Manu-
factured under a contract with the Malaysian
Institute of Microelectronic Systems and
Omega Semiconductor Sdn Bhd, they offer
good photon detection efficiency and working
gain and reduced dark count rates, making
them suitable for PET medical scanners and
gamma camera applications, particularly
when combined with Zecoteks LFS scintilla-
tion materials.
Daylight Solutions of San Diego has entered
into a strategic business relationship with in-
frared fiber company IRphotonics of Hamden,
Conn., to advance indium fluoride (InF) fiber
technology. Daylight Solutions has begun to
incorporate fiber optic delivery into its product
capabilities, enabling new applications in the
mid-infrared. In addition to advancing InF fiber
technology, Daylight will distribute IRphotonics
infrared product line. IRphotonics InF fiber tech-
nology now offers low loss, high mechanical
quality and broad coverage throughout the
mid-IR spectrum. Daylight manufactures molec-
ular detection and imaging systems for scientific
research, medical diagnostics, environmental
monitoring, industrial process controls and
defense applications.
Seeking to capitalize on its longevity in the
industry, Photonic Products Group has
changed its name to Inrad Optics Inc.,
restoring its original name. The company
was founded as Inrad Inc. in 1973; it operated
under the name Photonics Products Group Inc.
until the name change, which was approved
at a meeting of the shareholders held Jan. 18.
A vertically integrated photonics manufacturer,
Inrad Optics of Northvale, N.J., offers crystal-
based optical components and devices, custom
optical components for glass and metal, and
precision optical and optomechanical assem-
blies for laser, medical, metrology, aerospace
and process control applications.
Optical components supplier Edmund Optics
Inc. of Barrington, N.J., is accepting applica-
tions for its 2012 Edmund Optics Higher Educa-
tion Grant Program. The company will be
awarding grants worldwide totaling $80,000
in products to support outstanding undergradu-
ate and graduate optics programs in science,
technology, engineering and mathematics. Any-
one involved in a project using optics, opto-me-
chanics or imaging components at a nonprofit
college or university is encouraged to apply.
Grant applications can be found at www.ed-
mundoptics.com/grant and must be submitted
by June 30. Winners will be selected based on
technical merit and innovative use of optics in a
research setting or laboratory.
An Internet-based distributor of electronic com-
ponents for design engineers, Digi-Key Corp.
of Thief River Falls, Minn., and Marktech Op-
toelectronics, based in Latham, N.Y., have
signed a global distribution agreement. A spe-
cialist in LED technology and products, Marktech
serves several markets, including the medical
technology sector. Marktechs LED and photo-
sensing products are available for purchase on
Digi-Keys global websites.
In Newton, N.J., Thorlabs has completed its
three-story, 120,000-sq-ft facility, which will
act as the central hub for the companys sales,
service, R&D and manufacturing operations.
Subsequent construction phases are planned for
the next seven to 10 years and will ultimately
expand the companys space to approximately
300,000 sq ft. The privately held company has
experienced double-digit growth since its found-
ing in 1989. It manufactures equipment for
the photonics industry, including optics, laser
diodes, tunable lasers, fiber optics, optical de-
tectors, motion control equipment, optomechan-
ics and vibration isolation systems. It provides
b
BUSINESSSCAN
BUSINESSBRIEFS
system-level solutions such as complete OCT,
confocal and multiphoton imaging systems.
Cutera Inc. of Brisbane, Calif., a provider of
laser and other light-based aesthetic systems
for physicians, announced that it has closed
the previously announced asset purchase
of Iridexs global aesthetic business for
$5.1 million in cash. The acquisition positions
Cutera as a leader in the vascular aesthetic
market, said Kevin Connors, president and chief
executive officer. Its newest product is the
portable VariLite dual-wavelength (532 and
940 nm) system, a solid-state laser for treat-
ment of pigmentation and vascular and cuta-
neous lesions.
Cynosure Inc. of Westford, Mass., has an-
nounced that the FDA has cleared its Cellulaze
cellulite laser workstation for commercial distri-
bution. The workstation provides a minimally
invasive solution for reducing cellulite in just
one treatment by restoring the normal structure
of the skin and underlying connective tissue.
Clinical data has demonstrated that the treat-
ment can increase the thickness of the skin
by 25 percent and elasticity by 29 percent at
one year.
Hamilton Thorne Ltd. of Beverly, Mass., a
provider of laser devices and imaging systems
for the fertility, stem cell and developmental
biology research markets, has expanded its
distribution partnership with Leica Microsys-
tems of Wetzlar, Germany, a microscope and
scientific instrumentation supplier. The collabo-
ration will give the German company access to
Hamiltons portfolio of laser and select pipeline
products, including the IMSI STRICT software
for the fertility market. The multiyear agreement
provides Leica with nonexclusive rights to mar-
ket and distribute Hamilton products in Spain,
Portugal, Italy and North America.
John Millerick was elected to the board of direc-
tors during Dynasil Corp. of Americas annual
stockholder meeting. Millerick, a senior global
financial executive, has more than 25 years
of experience in the technology industry. From
2000 to 2009, he served as senior vice presi-
dent, chief financial officer and treasurer of
Analogic Corp. Before that, he worked at
CalComp Technology. Millerick and Dynasil
Chairman Peter Sulick were among eight direc-
tors elected at the meeting. Dynasil of Water-
town, Mass., develops and manufactures detec-
tion, sensing and analysis technology, precision
instruments and optical components for the
homeland security, medical and industrial
markets.
Fiber laser maker IPG Photonics Corp. of
Oxford, Mass., has announced that it will sell
up to 2.8 million shares and that its chairman
and CEO, Dr. Valentin P. Gapontsev, will sell
another 200,000 shares in a public offering.
Proceeds of the sale will be used to fund capital
expenditures and provide working capital and
could be used to fund acquisitions, although
none are currently pending. Underwriters also
will be granted a 30-day option to purchase up
to an additional 450,000 shares. IPGs products
have applications in a variety of areas, includ-
ing the medical sector.
A pocket-size accessory that turns an ordinary
camera phone into a high-resolution micro-
scope can accurately obtain images with a
resolution of 0.01 mm. Scientists at VTT Tech-
nical Research Centre of Finland in Espoo
have developed an optical accessory that can
examine various surfaces and structures in
microscopic detail and that can take high-
resolution images that can be forwarded as
Multimedia Messaging Service. The accessory
has applications in health care and other indus-
tries. VTT and KeepLoop Oy of Tampere, Fin-
land, are exploring the commercial potential of
the device. The first industrial applications and
consumer models were expected to be released
in early 2012.
For breaking news at the boundary
of light and tissue, visit
www. photonics.com/biophotonics.
BUSINESSSCAN
b
The latest in photonics for researchers, engineers,
product developers, clinicians and others in medicine,
biotechnology and other life sciences.
Subscribe at www.Photonics.com/Subscribe
From the publisher of
Photonics Spectra magazine.
MICROSCOPY
SPECTROSCOPY
IMAGING
OPTICS
LASERS
BRI NGI NG LI GHT TO LI FE SCI ENCE
BY LAURA S. MARSHALL, MANAGING EDITOR
T
he human brains billions of neurons
make countless connections every
day, collaborating to help us eat,
dress, read, exercise, avoid danger and
more. Its a big job, but by working to-
gether, they get it done.
The human research teams who study
them have a daunting job and, like the
neurons themselves, they have to work
together to do it.
One multidisciplinary, multi-institution,
multinational project recently found a way
to direct nerve-fiber growth by using
laser-driven spinning microparticles. The
breakthrough could someday lead to chip-
grown neuronal networks and even ad-
vanced treatments for injuries to the brain
or spinal cord.
It started with an idea that neurons
could show responses to physical cues
such as fluid flow, not just chemical cues.
As neurons grow and develop in a fetus
a process called neurogenesis the flow
of spinal fluid can guide neurons to their
destinations, said Samarendra Mohanty,
now an assistant professor of physics at
the University of Texas at Arlington.
As a postdoctoral fellow working in
Michael Berns lab at the Beckman Laser
Institute at the University of California,
Irvine, Mohanty observed that a spinning
calcite microparticle could direct neuron
growth; the particles rotation creates a mi-
crofluidic flow, causing a shearing effect,
and guiding the neuron to turn left or right.
This is the first report to demonstrate
that neurons can be turned in a controlled
manner by microfluidic flow, Mohanty
said. With this method, we can direct
them to turn right or turn left, and we can
quickly insert or remove the rotating beads
as needed.
The UC Irvine researchers, in collabora-
tion with professor Halina Rubinsztein-
Dunlop of the University of Queensland
in Brisbane, Australia, switched from the
calcite to more controllable and more uni-
form 8-m-diameter vaterite particles,
Collaboration Sparks Nerve-Fiber
Turn Signal Discovery
Global, multidisciplinary cooperation has led to a significant advance
in neuroscience a way to guide growth in neurons that ultimately
could have big implications for nerve disorders.
312_Feat Nerve_Layout 1 3/6/12 12:41 PM Page 20
which were placed near axonal growth
cones the tips of neurons where connec-
tions are made with other neurons or cells.
Because of the circular polarization of the
laser beam, the birefringent particle rotates
and creates the flow.
In the lab experiments, the new method
turned the growing axon in a new direc-
tion up to 42 percent of the time. The
method also could funnel growth between
two rotating particles, the researchers re-
ported, adding that the effects also may be
reproducible on a larger scale.
One can envision large arrays of these
devices that can direct large numbers of
axons to different locations, they wrote.
This may have the potential for use in
vivo to direct regenerating axons to medi-
ate brain and spinal cord repair.
The paper also noted that the effect of
shear on neuron growth may even apply to
other forms of cell growth. The authors of
the Nature Photonics paper included lead
author Tao Wu, a current postdoc in
Berns lab, who did the cell experiments
described in the paper; Mohanty, who did
the first experiments using the calcite par-
ticles demonstrating the effect; neurosci-
entists Ronald Meyer and Jill Miotke from
UC Irvine; and collaborators Rubinsztein-
Dunlop and Timo Nieminen at the Univer-
sity of Queenslands Quantum Science
Nerve-Fiber Growth
Two spinning beads with a nerve fibers growth
cone growing between them. The beads generate a
weak microfluidic shear in the direction that the cell
is migrating. The shear is somehow causing the
growth cone to grow in between both of the spin-
ning beads, like a funnel, according to Michael
Berns of the University of California, Irvine. Courtesy
of Tao Wu and Berns, Beckman Laser Institute.
Laboratory, who developed the physical
model described in the paper and who
were the group that produced and rotated
vaterite particles in optical tweezers by
transfer of spin angular momentum of
light. The study was supported by the US
Air Force Office of Scientific Research,
the Beckman Laser Institute Foundation
and the Australian Research Council.
I am very grateful that we could work
together on this problem, Rubinsztein-
Dunlop said. In fact, I am looking for-
ward to further collaboration and further
experiments that can explain more fully all
the questions that we were asking.
As Berns pointed out, These days, one
person cannot claim ownership on such
a complex study as this.
Nerve-Fiber Growth
T
he Beckman Laser Institute in
Irvine, Calif. like all re-
search institutions strives to
bring ideas to life. Its leaders
encourage collaboration as an
essential part of advancing sci-
entific and human interests.
One of their main goals is to
translate technology from bench
to bedside, according to Dr.
Bruce Tromberg, BLIs director.
Were really focused on put-
ting insights we can get from
measurements and computa-
tional models of light-tissue in-
teractions to work in the clinic,
Tromberg said. It takes a long
time, a lot of investment and a
certain culture.
And a lot of people with very
different backgrounds. We
have 20 faculty-level scientists about 100 to 120 people
here, he said. Its an interdisciplinary group: chemistry,
biology, veterinary science, medicine, math ... We have tech
labs, bio labs, cell culture, histopathology, biochemistry, mo-
lecular pathology.
These diverse teams pursue fundamental research and
technology development in a wide range of fields, especially
biology and medicine, from cancer to brain injury to wound
healing.
Any good research institution has people who are visionar-
ies, said George Peavy, BLIs veterinary director. Hes a big
proponent of multidisciplinary collaboration, within a lab and
around the world. Everybody here works really well together.
They know what they know and what they dont know, too.
Were not just focusing on photonics. Collaboration allows
us to do what we do.
In the BLI clinic, there is an advanced technology suite where
researchers conduct Institutional Review Board-approved stan-
dardization on patients using new techniques and instruments,
from a laser breast scanner based on diffuse optical spectros-
copy to multiphoton tomography, optical coherence tomogra-
phy, photodynamic therapy, and laser therapies, dynamic
cooling, spatial frequency domain imaging, speckle tomogra-
phy and more. Its not just abstract diagnosis, Tromberg
said, but also about providing clinicians with feedback for
real decision making.
The Military Photomedicine Program is one such effort. As
part of that project, researchers including teams from BLI,
Stanford University and Harvard University are working to
develop new technologies for battlefield medicine. One device
at UCI is a laser scanner to detect hemorrhagic shock before
its too late, Peavy said. He added that the same scanner
ultimately could be used for breast imaging, brain perfusion
assessment (especially in anesthetized patients) and hydration
monitoring, among other applications.
Many concepts are also undergoing commercialization,
Tromberg pointed out. Companies working with BLI currently
have about $5 million in Small Business Innovation Research
grants, with prototypes in studies around the world. One
project under way in Japan combines optics, positron emission
tomography and MRI to measure oxygenation in tumors;
multimodality clinical studies such as this are too expensive
to do here.
Developing prototypes and improving instrumentation in
advance of commercialization are big opportunities for small
companies, Tromberg said. This is risk abatement. Big com-
panies want to acquire low-risk smaller companies, but they
dont like to develop the technology themselves.
On the academic side, we innovate we dont just iterate
and improve. But with commercialization, we have to be able
to duplicate and standardize the technology.
Some of these ventures will succeed; others will fail. But,
ultimately, its worth the risk. Its like Vegas, Peavy said. You
hear stories about big wins, but theres a lot of money left on
the table.
Collaboration in Action: Beckman Laser Institute
Collaboration allows us to do
what we do, says George Peavy,
the Beckman Laser Institutes
veterinary director. Photos by
Laura S. Marshall.
One of the clinic rooms at the Beckman Laser Institute and
Medical Clinic at the University of California, Irvine.
The institute exemplifies the spirit of collaboration.
The implications of the research for
treatment of brain and spinal cord injuries
may be stimulating. It will definitely be
useful for fabrication of in vitro neuronal
circuits and [interfacing with a] silicon-
based stimulation and detection device,
Mohanty said. Such a chip might be im-
planted to connect injured nerves, possibly
regenerating or restoring certain functions.
But we arent there yet. It will take
years for the nerve-growth discovery to af-
fect human lives directly, Berns cautioned.
This is a tool/method to understand, and
based on future studies, new ways to ap-
proach the treatment of brain and spinal
cord injury may be developed.
It certainly opens up a new way to
study nerve cells and, in particular, how
the growth cones the key element of the
nerve cell responsible for its growth
and migration function. Understanding
the molecular signaling that causes the
growth cone to turn one way or another
is important to understanding how they
form networks and interconnections,
so there is normal nervous system func-
tion.
Until that is accomplished, the work
will spawn further studies as any break-
through research will do. Mohanty is
working on a method that allows long-
range optical guidance of neurons without
any additional external objects.
Flow can be generated by any means,
Mohanty said. He noted that it would be
easier to use a microfluidic tube for work
within the human body. We are trying
microfluidic flow in channels to further
this idea. Laser trapping in vivo and rotat-
ing beads is a little unrealistic, though our
lab has developed a method to trap and ro-
tate beads fiber optically.
Only light can guide neurons without
trapping or rotating bead-generating fluid
flow. So, we can use just optical fiber
(without bead, trapping, rotation, etc.)
to do axonal guidance with almost 100
percent efficiency. It amazes me how
unplanned research can lead to exciting
discoveries.
Collaboration is what science is all
about. We are all very specialized now,
so bringing people together with different
expertise to attack a problem is very pow-
erful and successful if everyone gets
along and puts egos aside, Berns said. He
and his team are working on a number of
projects with fellow researchers around
the globe and he wouldnt have it any
other way. Collaboration both within and
outside an institution is vital. Its what
each person/lab brings to the project that
is important, not necessarily whether it is
inter-institution or intra-institution.
Mohanty agrees; his lab also has several
projects at various stages of development
with several outside researchers. The bio-
medical or biological problems are no
longer confined to specific disciplines, he
said. The advantages are: First, it leads to
cross-fertilization of ideas. Second, com-
plementary expertise and, third, sharing
of resources reduces burden on one lab.
Also, funding agencies seem to like that.
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Laura S. Marshall
Photodynamic therapy could be
the future of cancer treatment
that is, once the photoactive
chemicals behind it start doing
their jobs better.
P
hotodynamic therapy (PDT) is prov-
ing to be a more than viable option
for cancer treatment. Compared with
other treatments, such as chemotherapy
and radiation therapy, PDT is more selec-
tive, causing far less damage to healthy
cells near cancerous targets due to the
precise way in which photosensitizers can
locate and infiltrate tumor cells.
The task remains to find the best combi-
nations of photosensitizers and conjugates
to propel the technique past chemotherapy
and other traditional methods.
Basically, a photoreactive chemical
compound called a photosensitizer is in-
troduced into a patient, where it aggre-
gates near an active tumor site. A clinician
then shines light from a diode laser or
LED source onto the tumor region. The
light, which has a specific wavelength,
activates the photosensitizer without af-
fecting surrounding healthy tissue. Once
activated, the photosensitizer transfers
some of its energy to nearby ground-state
molecular oxygen, producing excited sin-
glet oxygen. The result is oxidation of
tumor cells in the site, destroying the can-
cer while harming as few of the adjacent
healthy cells as possible.
Bringing light to the site is an ongoing
issue. Early studies of PDT focused on
skin cancers, such as various types of
for Cancer Depends
on Improved Photosensitizers
Fluorescence micrographs of HeLa cells show how the photosensitizer chlorin e6 (top row) and a complex of chlorin e6 and
poly-L-lysine (bottom row) accumulate inside HeLa cells after 10 min (left), 1 h (center) and 2 h (right). Note how the photosensitizer
alone remains in the cytoplasm near the cell membrane, while the conjugated pair works its way from the inner wall to the cell
nucleus. Courtesy of Current Topics in Medicinal Chemistry.
BY LYNN SAVAGE, FEATURES EDITOR
PDT
PDT
312_Feat PDT_Layout 1 3/6/12 12:45 PM Page 24
melanoma, because it was easier to shine
near-infrared wavelengths a couple of mil-
limeters through the skins surface to the
tumor site. This drove design of the first
photosensitizers to favor compounds that
would preferentially react to light in that
range. More recently, advances in endo-
scopic light-delivery systems have made
deeper tumors easier to reach and have
broadened the range of potential wave-
lengths and matching photosensitizers.
Different compounds are now used
as photosensitizers, including phthalo-
cyanine, chlorine, bacteriochlorin and
porphyrin. None, however, is a perfect
candidate.
Getting a photosensitizer to find and at-
tach itself to a tumor cell is a major battle.
The bodys immune system, for example,
seeks out and annihilates some forms of
photosensitizers, reducing the effective-
ness of the overall treatment. Adding anti-
bodies to photosensitizers can help their
affinity for cancer cells, but some re-
searchers feel that protecting them with
shells composed of lipoproteins is a better
way to go. Lipoproteins not only help
their cargo locate and infiltrate tumors, but
also help protect them from enzymes and
macrophages that might alter or destroy
them before they even arrive at the treat-
ment site.
Gold nanoparticles and liposomes also
have been considered as adjuncts that
could help photosensitizers directly enter
cancer cells.
Gold rush
Researchers at Rhodes University in
Grahamstown and in the biophotonics
department of the National Laser Center
in Pretoria, both in South Africa, are
among the groups looking at the possible
improvements to photosensitizer action
provided by gold nanoparticles.
Tebello Nyokong of Rhodes University
and her colleagues had gold nanoparticles
in mind during efficiency tests of a partic-
ular photosensitizer, as they reported in
the Feb. 6 issue of the Journal of Photo-
chemistry and Photobiology B: Biology.
Phthalocyanine compounds strongly ab-
sorb in the 600- to 800-nm range, yet tis-
sues are transparent to a useful degree to
these wavelengths. The result is an ability
to reach deeply into tissue and provide
sufficient energy to the photosensitizer to
activate it.
Several attributes must be considered
when designing a photosensitizer, said
Nyokong, director of the Nanotechnology
Innovation Center at Rhodes. One is that it
should have a high specificity for cancer,
which is achieved through inclusion and
coordination of molecules such as folic
acid and vitamin B
12
. Another highly val-
ued attribute is good absorption in the red
wavelengths, which is aided by sulfur link-
ages in the photosensitizer compound. The
final product also should be water-soluble
and initiate large production of singlet oxy-
gen, which drives tumor cell death.
The groups candidate was [2,9,17,23-
tetrakis-(1,6-hexanedithiol)phthalocyani-
nato]zinc(II), a second-generation phthalo-
cyanine-based compound. Its target:
human malignant breast cancer cells
(MCF-7).
The researchers chose zinc over more
typical sulfur in their compound because it
enhances the production of singlet oxygen
while being somewhat easier to assemble.
After forming the phthalocyanine com-
plexes, they introduced some to gold
nanoparticles, which self-assembled with
the compound. Others were bound to lipo-
somes as a delivery vehicle.
Using a Shimadzu spectrophotometer,
a Varian Inc. spectrofluorimeter, and a sin-
gle-photon counter and diode laser made
by PicoQuant GmbH, the investigators
measured the absorption spectra, fluores-
cence excitation and fluorescence lifetimes
of their photosensitizer in action against
MCF-7.
After determining that a light dose of
4.5 J/cm
2
provided adequate intensity
without harming nearby healthy cells, the
researchers compared how well the gold
nanoparticles and the liposomes aided the
overall phototoxic effect.
They found that, after photoactivation
of the two complexes, 60.1 percent of the
tumor cells treated with nanoparticle-
enhanced phthalocyanine remained viable,
whereas the liposome-enhanced com-
Controlled release can eliminate side
effects but the active treatment is
phototoxicity, so you still need an efficient
photosensitizer.
Bruno Therrien, University of Neuchtel
Side and top views show 3-D models of prism-shaped (left) and cubic (right)
metalla-cages designed to transport photosensitizers to tumor cells.
Courtesy of the Journal of the American Chemical Society.
plexes fared much better with 51.9 percent
cell viability.
Nyokongs work with PDT is focused
on synthesizing bifunctional agents com-
pounds that serve two functions, generally
enhancing location and attachment to
tumor cells. In her lab, the desired result
is agents that combine the action of PDT
and other treatments, such as hyperthermia
(destroying tumors with applied heat,
which increases the uptake of oxygen,
thus accelerating cell destruction).
Nyokongs lab also is looking at combi-
nations of chemotherapy and PDT via in-
troduction of platinum to common photo-
sensitizers. Next up for her group is the
ongoing search for water-soluble phthalo-
cyanine compounds that include lipo-
somes. Better water solubility, the re-
searchers say, should improve the ability
of phthalocyanine to generate singlet oxy-
gen inside cells.
Cage death matches
Phthalocyanine- and porphyrin-based
photosensitizers struggle to reach the
tumor site because they are fairly poorly
water soluble. Placing either type of com-
plex inside the hydrophobic cavity of an
otherwise water-soluble vessel designed to
wend its way breezily toward target cancer
cells is thought by several research groups
potentially to improve the situation.
The tricky part is getting the vessel to
unload its cargo upon arrival.
Another way to bring the photosensi-
tizer to the cell is to wrap it inside an
organometallic cage. This helps address
the water-solubility issue while offering
control of photosensitizer release, accord-
ing to Bruno Therrien, an associate pro-
fessor at the University of Neuchtel in
Switzerland.
Therrien and his colleagues at the uni-
versity and at Centre Hospitalier Vaudois
in Lausanne, Switzerland, devised and
tested two types of carrier vessels to ferry
porphyrin to its target. One, in the form of
a prism, locks the porphyrin tightly; the
other, a cubelike structure, is a more flexi-
ble jacket. Both vessels are made with
ruthenium-based compounds.
Within the metalla-prism, its a ship-
in-the-bottle system only breakage of the
cage can release the guest, Therrien said.
However, from the metalla-cube, the
Before and after images show the effect of a porphyrin-based photosensitizer that
was carried into HeLa cells by a ruthenium-based, cube-shaped cage. Courtesy of
the Journal of the American Chemical Society.
porphyrin is free to go through one of the
apertures without [breaking] the cage.
With either vessel, the porphyrin re-
mains unreactive to light and only be-
comes photosensitive once released.
The group studied the uptake of both
vessel types and their cargo into HeLa
cells, and then used a 488-nm laser made
by Spectra-Physics at various doses to re-
lease, then activate, the porphyrin once the
metalla-cages were inside the cell mem-
branes.
Once released, porphyrin discharged
from either cage performed well at gener-
ating singlet oxygen and thus destroying
the HeLa cells. Interestingly, the porphyrin
delivered via the cubelike metalla-cages
packed more punch, requiring one-tenth
the energy (0.2 J/cm
2
) to reach the thresh-
old where half the cells are killed com-
pared with the metalla-prism combo
(2.1 J/cm
2
).
Both controlled release of the photosen-
sitizer and its ultimate phototoxicity are
important, according to Therrien. Con-
trolled release can eliminate side effects,
such as skin photosensitivity after and dur-
ing treatment, but the active treatment is
phototoxicity, so you still need an efficient
photosensitizer.
The ultimate goal of Therrien and his
colleagues is to be able to irradiate at a
specific wavelength to break up the cage
where and when it is desired and, after re-
lease, apply a second dose of light to acti-
vate the photosensitizer.
Location, location, location
One of the most troubling disadvantages
of first- and second-generation photosen-
sitizers, according to researchers at the
Tokyo Institute of Technology, is that they
do not locate cancer cells as well as they
might. The more specifically diseased
cells are targeted, the more healthier
viable cells can remain.
(A) photosensitizer which shows high
tumor localization shows low phototoxic-
ity for normal tissue, said Shun-Ichiro
Ogura of the institutes department of bio-
molecular engineering. It is quite impor-
tant for tumor therapy.
But as importantly, the short lifetime of
singlet oxygen (measured in no more than
microseconds) means that the closer they
are to the right target, the more damage
they can do. Therefore, improving local-
ization can improve PDT efficacy.
Some photosensitizers, such as por-
phyrin-based constructions, accumulate
in a target cells plasma membrane. How-
ever, the nucleus is the place to be if you
want maximum destructive impact. Ogura
and his colleagues found that one possible
way to get to the cell nucleus effectively is
to combine the popular photosensitizer
chlorin e6 with poly-L-lysine. By itself,
chlorin e6 stays in the cytoplasm of the
cell, but the conjugated pair ultimately
travels to the nucleus. After subsequent
light exposure, the complex offered high
phototoxicity.
The group presents its findings on the
localization capabilities of several photo-
sensitizer types in the February issue of
Current Topics in Medicinal Chemistry.
Photosensitizers
Lynn Savage
lynn.savage@photonics.com
Y
ou have probably heard the facts and
figures: One of the leading causes of
death worldwide, cancer accounted
for 7.6 million roughly 13 percent of all
deaths in 2008, according to the World
Health Organization. And deaths from
cancer are on the rise: By 2030, we will
likely see 13.1 million per year world-
wide.
The need for new ways of diagnosing
cancer has never been greater. Today we
are seeing a variety of new diagnostic
techniques that leverage the benefits of
noninvasive and less-invasive optical tech-
nologies and that are made possible by
the development of novel treatments. Op-
portunities for these techniques have been
advanced by new therapies, said Adam
Wax, professor of biomedical engineering
at Duke University in Durham, N.C.
Weve seen this in a number of cancer
models, with radio-frequency ablation and
cryospray ablation, for example. With
therapies targeting cancers at earlier stages,
we need diagnostics that can detect those
early cancers.
Take coherence imaging, for example.
Wax was one of several researchers who
spoke about coherence imaging and cancer
during the BiOS Hot Topics session at this
years Photonics West meeting in San Fran-
cisco (many of the Hot Topics talks can
be viewed on the SPIE website and on
YouTube). In his talk, Early Cancer De-
tection with Coherence Imaging, he de-
scribed a suite of spectroscopic techniques
Moving Noninvasive
Cancer Imaging into the Clinic
Above: Neil Terry (left), Adam Wax (right) and their colleagues at Duke University have described a technique called angle-resolved low-coherence interferometry that
can detect dysplasia in patients with Barretts esophagus, for example, and have developed it further for clinical application. Courtesy of Adam Wax.
So you came up with this great idea for a medical device for cancer imaging, and
even found a way to make it work. Now what? Several researchers involved with
coherence imaging technologies discuss the challenges of clinical translation.
BY GARY BOAS, NEWS EDITOR
312_Feat Imaging_Layout 1 3/6/12 12:46 PM Page 28
designed to assess cell structure and diag-
nose disease using low-coherence interfer-
ometry (LCI) to detect scattered light.
The techniques combine the advantages
of optical coherence tomography and
light-scattering approaches. Angle-re-
solved LCI, for instance, marries the
ability of LCI to isolate scattering from
subsurface tissue layers to the ability of
light-scattering spectroscopy to obtain
structural information using angular
scattering measurements.
The researchers explored the clinical
potential of angle-resolved LCI for in vivo
depth-resolved nuclear morphology mea-
surements to detect dysplasia in patients
with Barretts esophagus, who are at in-
creased risk of developing esophageal can-
cer. The results, reported in the January
issue of Gastroenterology, showed that the
technology can provide quantitative depth-
resolved measurements of nuclear mor-
phology measurements used by patholo-
gists for cancer diagnosis without having
to rely on image interpretation or use of
exogenous contrast agents.
Also during this years BiOS Hot Top-
ics session, Stephen Boppart, Bliss profes-
sor of engineering at the Beckman Insti-
tute for Advanced Science and Technology
at the University of Illinois at Urbana-
Champaign, spoke about his work with
coherence imaging and cancer. In his talk,
Coherence Imaging of Cancer with Novel
Optical Sources, he described a technique
called nonlinear interferometric vibrational
imaging, or NIVI.
NIVI offers the high spectral resolution
of Raman spectroscopy with the high
acquisition rates of coherent anti-Stokes
Raman scattering microscopy. Boppart
and colleagues have shown that they could
obtain NIVI spectra with the accuracy of
Raman but at speeds 200 to 500 times
faster, and thus demonstrated the potential
of the technique for rapid tissue imaging,
characterization and diagnosis for diag-
nosis of cancer, for example.
At the same time, they have been devel-
oping novel optical sources to use with
the technique. Weve worked out ways of
controlling the phase and generating a
supercontinuum thats completely coher-
ent, Boppart said in a phone interview
just prior to the BiOS portion of Photonics
West. The sources have been described
in a series of papers all involving
Dr. Haohua Tu, also of the University of
Illinois as well as in Bopparts recent
Hot Topics talk.
Getting into the clinic
With technologies intended for clinical
application, identifying and solving the
problem is, of course, only half the battle.
Clinical translation involves a variety of
challenges, many of which are unique to
this stage of technology development.
You labor under the illusion that youre
going to come up with a solution and
companies are just going to run to you
with bags of money, Wax said, but there
exist any number of hurdles that must be
overcome before the technology gets into
the clinic. In parallel with his academic
efforts, Wax has been seeking to commer-
cialize the technology through a company
he started, Oncoscope Inc., and has run up
against several of these.
The whole translational pathway is full
of challenges, he continued. Its not the
most glamorous work. The most glam-
orous work is really that first paper
describing the breakthrough.
Some of the hurdles have little if any-
thing to do with the technology itself. In
the past several years, for example, com-
panies developing new clinical devices
and techniques have had to contend with
the credit crisis. Other times, they are all
about the technology. For example, many
devices which in the early development
stages might occupy an entire corner of a
room, with fibers and assorted incompre-
hensible add-ons protruding from them,
Academic-Clinical
Partnerships
J
on Holmes, CEO of Kent, UK-
based Michelson Diagnostics
Ltd., has a few thoughts about
developing technology for clinical
application. He developed and
offers the VivoSight OCT scanner
for dermatologists. The device uses
multibeam OCT to obtain higher-
resolution, clearer images than can
be achieved with conventional sin-
gle-beam Fourier-domain OCT
systems.
Many academic groups working
on OCT have developed from phys-
ics or engineering departments, and
so they are focused primarily on de-
veloping the underlying technology,
he said. Put simply, their research
will be published if it studies an ad-
vance in technology, whereas pa-
pers on developments in the clinical
applicability (such as the probe er-
gonomic design) are less likely to be
published.
The upshot, he continued, is that
any technology developed by aca-
demic groups for biomedical appli-
cations might not be properly evalu-
ated, and in many cases it may
never reach commercial exploi-
tation.
My advice is that physics and
engineering groups should closely
partner with clinical teams and work
with them on a specific clinical need
over a long period of time (decades)
in a focused manner with a clear
long-term goal of developing an
exploitable device evaluated with
clinical trials. Funders should also
actively support this type of collabo-
rative work.
Researchers at the University of Illinois at Urbana-Champaign have reported a technique called nonlinear
interferometric vibrational imaging, or NIVI, and are now developing it for breast cancer detection in the
clinic. Shown here is a NIVI image of a tumor, compared to histology. Courtesy of Stephen Boppart.
suggesting nothing so much as an evil
scientists creation will have to be re-
designed before they can be introduced
clinically, providing a reliable, compact,
robust, turnkey system.
There have been heroic studies where
mode-locked lasers have been brought into
the clinic, Boppart said. For translation,
though, youve really got to have these
systems better designed and better engi-
neered.
For example, the angle-resolved LCI in-
strument reported by Wax and colleagues
was developed further by Oncoscope to be
sufficiently robust for broader use. The
Duke prototype was typically operated
by PhD scientists and grad students who
could tune up the instrument if needed and
were able to instantly assess if something
was not functioning correctly, Wax said.
In contrast, the Oncoscope device needs
to be stand-alone, so that a physician can
operate it without difficulty. To achieve
this, they re-engineered several of the in-
ternal components to make them less vul-
nerable to outside influences and added
automated routines to ensure calibration.
The University of Illinois researchers
also are working to translate their technol-
ogy for use in the clinic. At the time of
writing, they were waiting to receive final
word about an Academic-Industry Partner-
ship proposal they had submitted to the
NIH National Cancer Institute to develop
NIVI for intraoperative use, detecting mo-
lecular tumor margins during breast cancer
surgery (the proposal had been scored
very highly).
Boppart noted several challenges to be
addressed in developing the technology
for clinical application. These include:
(1) developing compact, portable, turnkey
fiber-based sources for nonlinear optical
imaging to replace the current mode-
locked lasers, multi-laser systems or opti-
cal parametric oscillators that keep these
techniques in the lab; (2) developing the
imaging, processing and analysis algo-
rithms to make NIVI diagnostically useful;
and (3) developing the portable system
cart and handheld probe for use in clinical
settings. These are all the goals for our
Academic-Industry Partnership, but are
also what is needed to move this field
forward, he said.
For this project, the researchers are de-
veloping handheld microelectromechanical
systems-based scanners for use with NIVI
in the operating room. These, by them-
selves, are rather novel, Boppart said,
because few optical probes currently
exist for intraoperative use in the sterile
surgical field. His startup company, Diag-
nostic Photonics Inc., has developed such
a surgical probe for interferometric syn-
thetic aperture microscopy, a computed
imaging approach to OCT, and began
clinical trials in February.
The NCI proposal included both aca-
demic and industry partners, of course, but
also a clinical partner: Carle Foundation
Hospital of Urbana, Ill. Building strong
relations in the clinical arena is especially
important to translation, Boppart said.
When you have a good clinical partner,
you can step into this very different envi-
ronment and culture the clinical setting
and still be accepted.
The technology still must be well de-
signed and as unobtrusive as possible,
though, if it has any chance of finding
support from the medical community.
Youll find that, where a lot of these
technologies succeed, theres minimal
disruption to the standard of care, he
said. As engineers, we tend to want
to have complicated solutions, but if it
causes clinical practice to change too dra-
matically, its just not going to happen.
gary.boas@photonics.com
Clinical Cancer Imaging
UK-based Michelson Diagnostics developed and
offers a clinical OCT scanner for dermatologists.
Courtesy of Michelson Diagnostics Ltd.
BY LYNN SAVAGE, FEATURES EDITOR
I
n the US alone, 10,000 people are diag-
nosed each year with laryngeal carci-
noma, according to the American Cancer
Society. This cancer affects the vocal
cords and the connective tissues surround-
ing them. Of these, nearly 4000 will die of
the disease. Smoking tobacco is the major
force behind laryngeal cancer, also known
as glottic cancer, although alcohol con-
sumption seems to magnify the effect
smoking has.
When a patient is first diagnosed with
glottic cancer, the immediate goal is cure
of the disease. Secondarily, the physician
strives to preserve the patients voice and
ability to swallow well, which both can
be dramatically affected after chemical,
radiation or surgical treatment. Laser mi-
crosurgery is becoming an effective tool
to help doctors meet these goals.
Glottic cancer treatment has evolved
from complete removal of the larynx
(laryngectomy) to radiotherapy, chemother-
apy and partial laryngectomy, as well as
combinations of these. Today, total laryn-
gectomies are seldom performed unless
chemotherapy and radiation have failed.
Tumor stage is the primary factor that
determines the treatment chosen, although
available facilities and patients structure
such as their general health or whether
they naturally have a restricted airway
also are considered.
Early-stage tumors generally are treated
with surgical excision of the least amount
of tissue practical. More advanced tumors
receive chemotherapy or radiation over a
span of several weeks. In recent years,
CO
2
laser-based endoscopic surgery has
been investigated as a potential replace-
ment for chemotherapy and radiotherapy
for T3-stage glottic cancer.
The main benefits of laser surgery for
glottic cancer are speed and precision,
said Dr. Mohssen Ansarin of the European
Institute of Oncology in Milan, Italy. The
technique also does not rule out further
treatments, should the physician deem
radiotherapy, open neck surgery or a sec-
ond laser microsurgery necessary as a
follow-up.
Laser surgery also has lower complica-
tion rates, comparable or better treatment
outcomes, and lower hospital costs due to
shorter patient stays. For certain patients,
the technique also has fewer contraindica-
tions to treatment than traditional surgery,
chemotherapy or radiation therapy.
Researchers at Royal Derby Hospital
in Derby, UK, completed a retrospective
study last year of several patients who had
undergone the procedure, which is for-
mally called transoral laser microsurgery.
Twenty-two patients, all with either Tis,
T1 or T2 stage cancer (see sidebar above
for stage definitions), were evaluated for
response to treatment, including success
of tumor resection, restoration of the pa-
tients voice and changes in the patients
ability to swallow.
Five years after surgery, the rate of
successful preservation of the larynx was
89 percent for those patients with T1
Transoral Laser Microsurgery
Fights Laryngeal Cancer
Stages of Glottic Cancer
Tis: Cancer has not spread beyond
the epitheliums basement mem-
brane.
TI: Cancer confined to the true
vocal cords.
T1a: Cancer confined to one vocal
cord.
T1b: Cancer on both vocal cords.
T2: Cancer has spread to the areas
of soft tissue above or below the
vocal cords.
T3: Cancer has fixed the vocal
cords or has invaded the area be-
hind the cricoid cartilage or the soft
tissue in front of the epiglottis.
T4: Cancer has spread beyond the
larynx by moving through the thy-
roid cartilage into either the esoph-
agus or the soft tissues of the neck.
Thanks to laser surgery refinements, your life or your voice
is a choice fewer people in the world have to face.
312_Laser Surgery Feat_Layout 1 3/6/12 12:47 PM Page 31
tumors and 56 percent for those with T2.
Their mortality rate was 4.5 percent, and
overall disease-free survival rate was
77 percent, which is comparable to pa-
tients who had undergone radiotherapy,
according to the researchers. Both swal-
lowing and voice preservation outcomes
were comparable to or better than those
resulting from radiotherapy. The results
appear in the 2011 volume of ISRN
Otolaryngology.
The group noted that, compared with
radiotherapy, laser surgery offers surgeons
the advantage of being able to continu-
ously evaluate glottal tumors during a pro-
cedure. It allows accurate tumor staging
during surgery and enables repeat resec-
tions to maximize clean tumor margins.
However, the group also noted that heat
from the laser caused some thermal dam-
age to healthy tissues, which confounded
histopathological assessment of the tumor
margins.
After Ansarin and colleagues at the
European Institute of Oncology undertook
a similar retrospective review of patients
undergoing laser surgery, they also were
satisfied with the advantages of the tech-
nique. However, the researchers also
determined that stenosis, or abnormal
narrowing, of the larynx was a common
occurrence among the female patients.
The group has adopted multislice com-
puted tomography as a means to better as-
sess patients before laser surgery, and is
exploring the possibility that lower-power
lasers may be more beneficial, especially
to women at risk of stenosis.
Researchers in Japan and South Korea
also are refining laser surgery for their
laryngeal cancer patients and, along with
their European counterparts, are likely to
provide other advances in the years ahead.
Lynn Savage
lynn.savage@photonics.com
Compared to other options, laser surgery offers
comparable or better treatment outcomes for patients,
ease of use for surgeons, lower hospital costs
and fewer contraindications that would preclude
some patients from receiving treatment.
312_Laser Surgery Feat_Layout 1 3/7/12 11:49 AM Page 32
Laser Microsurgery
How is early glottic cancer defined? Has transoral
laser microsurgery (TLM) been studied in more
advanced tumors?
We define early as a glottic suspicious lesion clini-
cally staged as cTis, cT1a, cT1b or cT2. All those lesions
are suitable for TLM, but even cT3 lesions (for involvement
of paraglottic space, but with normal arytenoid mobility)
are curable using transoral laser surgery in the hands of
expert surgeons.
Does TLM have benefits over radiotherapy or
other treatments for glottic cancer?
The main benefits of TLM are: very fast treatment for
early glottic cancer (Tis, T1a, T2). The duration of [a] full
course of radiotherapy is six to seven weeks; [TLM] can be
done in day surgery. It spares radiotherapy and its side ef-
fects on the neck. Finally, in the case of recurrence, TLM
does not preclude further treatment like a second laser sur-
gery, radiotherapy or open neck surgery. The main treat-
ment after radiotherapy failure is total laryngectomy.
The disadvantages of TLM are: 1) In our experience,
about 5 percent of patients are not amenable to laser sur-
gery due to poor exposure of the larynx; 2) in the case of
radical cordectomy (type IV-V cordectomies), in T1b and
with involvement of the anterior commissure, the quality
of voice could be worse than [after] radiotherapy.
Is it difficult to determine successful resection
during the procedure or even immediately
afterward?
As I mentioned in my paper published in Archives Oto-
laryngology Head & Neck Surgery in 2009, the evalua-
tion of the lesion with angled telescopes before starting
the operation allows me to obtain greater distance be-
tween the resection margin and the margin of the macro-
scopically visible lesion. Regardless of tumor location, the
excision includes the arytenoid vocal process, the anterior
commissure on the medial line, and all the mucosa of the
floor of the ventricle and lower face of the vocal fold.
Is TLM better by itself or in conjunction
with radiotherapy?
The early glottic cancer should be treated with a uni-
modal approach. In our protocol, we suggest adjuvant
radiotherapy after TLM in the case of patients with two
or more positive margins that are not amenable to further
endoscopic surgery, or in T3 tumors with massive para-
glottic space involvement.
An interview with Dr. Mohssen Ansarin,
Head and Neck Surgeon, European Institute of Oncology
312_Laser Surgery Feat_Layout 1 3/6/12 12:47 PM Page 33
New High-Performance 4.2-MP Cooled Scientific CMOS Camera
The OSPREY Scientific CMOS camera, model OS4MPc-CL, features a 2k 2k
low-noise scientific CMOS sensor that stands out with its extreme sensitivity,
high resolution, high speed and excellent quantum efficiency. The camera is
Peltier-cooled to 20 C, uses a 12-bit A/D converter and offers a standard
Camera Link output.
Raptor Photonics Limited is a global leader and manufacturer of high-
performance and rugged low-light digital cameras. Raptor specializes in
complete cameras and core engine solutions using EMCCD, scientific CMOS
and SWIR sensors. Raptor Photonics is a registered ISO 9001:2008 company
and is headquartered in Larne, Northern Ireland.
+44 2828 270 141
info@raptorphotonics.com
www.raptorphotonics.com
New iXon Ultra EMCCD Camera
The iXon Ultra platform takes the popular back-illuminated 512 512
frame transfer sensor and overclocks readout to 17 MHz, pushing speed
performance to 56 fps (>60% faster), while maintaining quantitative stability
throughout. This speed boost offered in the iXon Ultra facilitates a new level
of temporal resolution, ideal for speed-challenged low-light applications such
as superresolution microscopy, single-molecule tracking, ion signaling, cell
motility, single-photon counting, lucky imaging and adaptive optics.
+44 28 9023 7126
info@andor.com
www.andor.com
312_Spotlight_Layout 1 3/6/12 3:30 PM Page 34
Ultrahigh-Power Single-Mode Laser Diodes
Intense Inc. has released a 300-mW version of its Series 6030
and 6130 ultrahigh-power, high-brightness single-mode laser
diodes. Designed for medical applications, they are available
at 980, 830, 808, 785 and 780 nm. Proprietary and patented
Quantum Well Intermixing technology increases brightness
and reliability while avoiding the problems associated with
catastrophic optical mirror damage. Uses include illumination,
spectroscopy, life sciences and atomic clock applications.
Operating temperatures range from 25 to 50 C. The lasers are
available in free-space packages, including 9-mm, C-mount and
5.6-mm, with optional pulse duration modulation. A variety of
standard beam divergences are offered to match specific requirements. The company also can
fabricate ultrahigh-power, single-mode, individually addressable multichannel arrays in wave-
lengths ranging from 650 to 980 nm, with 10 to 270 channels per array.
Intense Inc.
sales@intenseco.com
Red Diode Laser
The lux red diode laser launched by Laser Quantum
Ltd. delivers up to 1 W at 660 nm. Features include
a diffraction-limited TEM
00
beam with M
2
<1.2, auto-
matic power control, rms noise levels of 0.6% and
power stability of 1%. The compact laser is based on
diode-pumped optical technology. Applications
include fluorescence imaging, spectroscopy, DNA
sequencing, Raman spectroscopy and stimulated
emission depletion nanoscopy. The hermetically
sealed laser offers >40,000 h mean time to failure,
RS-232 control, and a permanently aligned and zero-stress cavity. Beam diameter is
0.75 0.15 mm, bandwidth is ~30 GHz, beam divergence is <1.5 mrad, pointing stability is 10
rad/C, and polarization ratio is >100:1. Coherence length is <1 cm, beam angle is <2 mrad,
and operating temperature is from 22 to 37 C.
Laser Quantum Ltd.
sales@laserquantum.com
Biosensor System
SAW Instruments GmbHs samX biosensor
for real-time, label-free assays using living
cells is optimized for a mammalian cell-based
binding assay work flow. Two sensor chips
provide eight available channels. Each can
be addressed by the fluidics individually or in
combination, facilitating on-chip immobiliza-
tion at each sensor position. The system can
be used with unfixed cells in suspension or
with adherent cells grown directly on the
sensor chips. Surface acoustic wave technol-
ogy is based on the ability of a wave of energy
to travel across the surface of a material. The nature of the surface, and any changes to it, can
be assessed by sensors monitoring the behavior of the wave as it propagates. Changes in mass
result in alterations to the phase of the wave, while viscoelastic and conformational characteristics
influence amplitude. The technology interprets this information to provide real-time readouts
measuring binding and conformational changes.
SAW Instruments GmbH
info@saw-instruments.de
FireWire-b Digital Cameras
Point Grey Research Inc. has added 2.8-mega pixel
models to its Grasshopper Express IEEE 1394b
(FireWire-b) digital camera series. The GX-FW-
28S5M-C (monochrome) and GX-FW-28S5C-C
(color) cameras are based on Sonys ICX674
2
3 -in.
CCD, which produces 1932 1452-pixel-resolution
images at 26 fps. EXview HAD CCD II technology
improves quantum efficiency, reduces smear and extends sensitivity into the near-infrared.
Camera features include a 32-MB frame buffer, a 14-bit analog-to-digital converter, and onboard
temperature and power sensors. The FlyCapture software development kit is a full software library
that provides a common control interface for all of the companys cameras under Windows and
Linux. The 800-Mb/s FireWire-b interface allows fast image transfer and is suited to building low-
latency, highly deterministic multiple camera networks. The cameras are used in biophotonics and
medical applications.
Point Grey Research Inc.
info@ptgrey.com
16-Channel MPPC Detectors
Hamamatsu Photonics UK Ltd. has introduced
multipixel photon counter (MPPC) detectors
for evaluation of large-area MPPC detectors.
The S11834-3388DF uses a 64-channel array
of 3 3-mm discrete detectors, with an effec-
tive area of 576 mm
2
. The C11206-0404FB uses
a 16-channel monolithic MPPC array with an
effective area of 144 mm
2
, producing maxi-
mum position resolution with minimum dead
space. Its amplifier module includes a high-
voltage supply, a temperature control circuit
and a dedicated ASIC that has an amplifier
and a digital-to-analog converter. The C11206-
0808FA uses a 64-channel MPPC array with
an effective area of 576 mm
2
. All have 3600
pixels per channel, and each pixel contains
a quenching resistor so that simultaneous
photon events can be counted separately.
Applications include scintillator readout, time-
of-flight PET and flow cytometry.
Hamamatsu Photonics UK Ltd.
europe@hamamatsu.com
Multichannel Spectrometer Engines
For detecting light energy at multiple wave-
lengths, Newport Corp. has announced the
OptoFlash miniature multichannel demulti-
plexing spectrometer engines. They are con-
figured with 10 wavelength channels, selected
from 24 standard wavelengths ranging from
200 to 900 nm. Developed for clinical chemical
analyzers, they provide high speed and high
linearity with minimal stray light, and simulta-
neous optical transmission information for
each wavelength channel, making them suit-
able for use in OEM applications that require
a small and lightweight single-package device.
They include silicon detectors, beam steering
optics and optical filters manufactured using
proprietary Stabilife optical coatings. The
40-pin dual in-line package eliminates compo-
nents that those based on a filter wheel-based
design require. The optical engines are suit-
able for spectroscopy instruments used in
immunodiagnostic testing, environmental
monitoring and colorimetry.
Newport Corp.
ken.pihl@newport.com
BREAKTHROUGHPRODUCTS
312BreakthroughProdLeads_Layout 1 3/6/12 12:48 PM Page 35

sCMOS Camera
Andor Technology plc has enhanced its Neo
camera with faster sustained frame rates, bet-
ter image quality, hardware pixel binning, flex-
ible region of interest with single-pixel gran-
ularity, accurate time stamp and improved
global snapshot exposure. The 5.5-megapixel
sCMOS sensor, with 6.5-m pixels, achieves
1 e
read noise at 30 fps, and the chips dual-

amplifier architecture produces a dynamic
range of 30,000:1. The camera delivers deep
vacuum cooling down to 40 C for maintain-
ing low noise and minimal pixel blemish in all
exposure conditions. Field-programmable gate
array intelligence produces good image qual-
ity, and 4-GB on-head image memory enables
acquisition of extended kinetic bursts at frame
rates faster than the variable hard drive write
speeds. The laboratory camera is suitable for
live-cell imaging. The sensor offers rolling and
snapshot exposure modes, the latter enabling
freeze-frame capture of fast-moving or fast-
changing objects.
Andor Technology plc
marketing@andor.com
Benchtop Raman Spectrometer
BaySpec Inc. has released the research-grade
benchtop RamSpec 1064-nm Raman spec-
trometer, which delivers high sensitivity and
spectral resolution at wavelengths up to 1700
nm. A lighttight sampling chamber improves
ease and accuracy of sample measurements.
Integrated deep-cooled InGaAs array detectors
and multiple volume phase gratings custom-
ized for each wavelength provide maximized
light throughput. Without any interferometric
mechanical moving parts, it is designed for
long-term stability, ruggedness and auto-
mated push-button operation. With 1064-nm
near-infrared excitation, it is suitable for use in
cell biology, forensics, materials science and
food analysis. Features include a spectral
range from 150 to 3200 cm
1
; spectral resolu-
tion of 4 cm
1
; automated wavelength calibra-
tion; a compact size for portability; and cus-
tomization with various fiber optic probes.
BaySpec Inc.
info@bayspec.com
sCMOS Image Sensor
BAE Systems Imaging Solutions has intro-
duced the Fairchild Imaging CIS1021 scientific
CMOS (sCMOS) image sensor. A high-defini-
tion component for collecting images through
a microscope or other imaging system, the
sensor chip captures single molecules by pro-
viding high sensitivity and dynamic range. Sci-
entists can capture all data in a scene, from
the faintest to the brightest target in an image.
Applications include live-cell microscopy, drug
discovery and real-time polymerase chain
reaction. Images are captured at up to 100 fps
at full resolution. During live-cell or DNA sam-
ple examination, scientists can collect weak
and strong signals from the same image,
providing greater detail from bright or dim
areas and capturing data without damaging
the sample. In cell biology and drug discovery,
the sensor helps them identify ways to pre-
vent or treat medical conditions. It is available
in monochrome and color versions.
BAE Systems Imaging Solutions
mark.christenson@baesystems.com
Packaging Submounts
Remtec Inc. provides a variety of packaging
options for laser diode, LED and photodiode
submounts and substrates, with ceramic sub-
mounts (alumina, beryllia, aluminum nitride),
metal heat sinks and enhanced plated gold
tin metallization. Plated copper on thick film
technology enables higher performance from
smaller packages. The companys laser and
photodiode submounts offer 25- to 75-m-
thick copper metallization with zero pullback
metallization from a burr-free ceramic edge,
enhancing the performance of edge-emitting
diodes. Selective gold tin plating on ceramic
submounts is used for edge-emitting and ver-
tical external-cavity surface-emitting laser
diodes, and for copper tungsten submounts
and laser bars. Selective gold, palladium and
gold tin plating finishes allow the use of gold
wire bonding, brazing and epoxy die attach.
Medical applications include blood-oxygen
sensors, transdermal delivery systems for
medications and laser imaging; cosmetic ap-
plications for skin rejuvenation and hair re-
moval; and UV curing of light-sensitive dental
materials.
Remtec Inc.
sales@remtec.com
Ultrafast Amplifier
Spectra-Physics, a Newport Corp. brand, has
unveiled a compact ultrafast amplifier with
repetition rates from 50 kHz to 1 MHz. Devel-
oped at High Q Laser (recently acquired by
Newport), the Spirit laser delivers the ad-
justable high repetition rates needed for fem-
tosecond micromachining of medical devices
and other materials, nanostructuring, pump-
probe experiments and select time-resolved
science applications. The laser provides aver-
age power of >4 W and fully automated ad-
justability via software controls. Featuring a
rugged one-box design, the laser delivers ul-
trashort 400-fs pulse widths with high energy
of 20 J per pulse. It offers good beam charac-
teristics in diffraction-limited TEM
00
mode.
Spectra-Physics
herman.chui@newport.com
Wide-Dynamic-Range Sensor
The NSC1105 manufactured by New Imag-
ing Technologies is a 1.3-megapixel wide-dy-
namic-range sensor with a 10.6-m pixel size.
It provides a dynamic range >140 dB in a sin-
gle frame. Because of its native wide-dynamic-
range technology, the sensor does not require
any setting or exposure time control, and it
produces good image quality under any illu-
mination conditions. Other features include an
extended spectral response in the infrared and
good low-light sensitivity. It is supplied in a
compact package that enables easy integration
into printed circuit board cards in socket or
surface-mount-technology mounting. Applica-
tions include laser and fluorescence imaging,
weld monitoring and spectroscopy.
New Imaging Technologies
info@new-imaging-technologies.com
Fiber Optic Raman Probe
The BAC200 from B&W Tek Inc. is a micro-
lensed fiber optic Raman probe that delivers
the performance of a larger Raman probe in a
diameter <4 mm with enhanced optical collec-
tion power. Its design provides immersion and
direct contact measurements, enabling appli-
cations and measurements previously not pos-
sible with standard Raman probes. The fused
silica tip is housed in a stainless steel needle
tube, resulting in a scratch-resistant, easy-to-
clean probe. The optical elements are perma-
nently fixed in alignment, with no possibility
of movement caused by impact or vibrations.
p BREAKTHROUGHPRODUCTS
312_Breakthrough Prods_Layout 1 3/6/12 12:49 PM Page 36
Its small size, flexibility and durability make it
suitable for analysis in biological and biomedical
applications with small sample sizes. Scientists
performing molecular-level spectroscopic analy-
sis can perform in vivo analyses of specimens
without creating apertures any larger than 4
mm.
B&W Tek Inc.
sales@bwtek.com
USB 3.0 Cameras
Imaging Development Systems GmbH has un-
veiled the uEye CP family of USB 3.0 cameras.
Three sensors ranging from VGA to 5-mega-
pixel are available. Measuring 29 29 29
mm, the cameras feature a magnesium casing
housing. The USB 3.0, or SuperSpeed, inter-
face delivers a data rate of up to 400 MB/s. It
offers trigger, flash, pulse width modulation
and two general-purpose input/outputs that
can be changed into an RS-232 serial interface
for trigger or control of peripheral devices.
Brightness correction is achieved by a 12-bit
look-up table and hardware gamma. A field-
programmable gate array performs de-bayer-
ing and allows the cameras to output RGB or
YUV data. It also performs color correction,
rendering true-to-life color quality. A software
package for Microsoft Windows and Linux in-
cludes 32- and 64-bit drivers, demo programs,
and source code in C++, C# and Visual Basic.
Vision applications include medical and bio-
metrics.
Imaging Development Systems GmbH
usasales@ids-imaging.com
Near-IR VCSELs
Princeton Optronics Inc. has announced the
availability of single-mode near-infrared verti-
cal-cavity surface-emitting lasers (VCSELs)
with output power up to 100 mW, useful
for applications including sensing, machine
vision, bioinstrumentation and Raman detec-
tion systems. They are single-transverse and
single-longitudinal-mode emitters and can be
provided in a variety of packages, including
TO can, chip-on-submount and custom plat-
forms. An increased signal-to-noise ratio,
lower detection limits and increased measure-
ment speed are some of the benefits that
high-power single-mode VCSELs provide.
VCSEL technology is suited to the demands
of rigorous operating conditions. The new
VCSELs are designed to replace the complex
and costly amplified systems that previously
were the only means to achieve these single-
mode power levels.
Princeton Optronics Inc.
sales@princetonoptronics.com
640 512 InGaAs Camera
The PIoNIR:640 from Princeton Instruments is
a scientific-grade camera designed for low-
light near-infrared or short-wavelength in-
frared imaging and spectroscopy applications
that require sensitivity from 0.9 to 1.7 m,
including nanotube fluorescence imaging and
photovoltaic inspection. The camera is thermo-
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electrically cooled down to 90 C, minimizing
thermal noise. It performs singlet oxygen im-
aging, photoluminescence imaging of photo-
voltaic materials, near-infrared fluorescence
and absorbance, and deep-tissue imaging.
Built-in air or liquid cooling, or a combination
of the two, enables use in thermal- and vibra-
tion-sensitive environments. The Gigabit Eth-
ernet interface enables remote operation and
delivers a maximum rate of 110 fps at full res-
olution. Proprietary LightField data acquisition
software provides automatic defect correction,
exposure control up to minutes, and functions
for easy capture and export of imaging and
spectral data.
Princeton Instruments
info@princetoninstruments.com
Surface-Mount IR LED Light
Larson Electronics LLCs magnalight.com has
introduced an explosion-proof surface-mount
infrared LED light that provides illumination in
the 1145-nm range applied in spectroscopic
testing and analysis. The EPL-SMLED-20W-
1445 produces infrared light without lenses or
filters. Cool running and portable, it operates
from 9 to 48 VDC. Designed for infrared spec-
troscopy, it is suitable for testing and obser-
vation of molecular structures and chemical
composition. The aluminum body is water-
tight-tested to resist corrosion from exposure
to saltwater and wet environments. A flat base
with preformed mounting slots provides per-
manent mounting to flat surfaces, and an alu-
minum alloy yoke allows the light head to be
adjusted through 135 of vertical movement.
Consisting of two 10-W infrared LEDs in the
lamp head, the assembly is sealed within the
housing with a thermal shock- and impact-
resistant glass lens.
Larson Electronics LLC
sales@magnalight.com
Femtosecond Fiber Laser
The Femtolite HX-150 femtosecond fiber laser
manufactured by Imra America Inc. emits at
1620 and 810 nm, allowing adjustment of the
average power at one of these wavelengths,
with 200 mW at 1620 nm or 150 mW at 810
nm, or simultaneous emission at both wave-
lengths. A slider bar enables continuous ad-
justment of the two signals average power.
Applications include multiphoton fluorescence
microscopy, second-harmonic imaging, tera-
hertz wave generation and detection, laser
lithography and ultrafast spectroscopy. With
dimensions of 23 19.3 7.6 cm and a con-
troller size of 30.7 20.7 13.5 cm, the HX-
150 is easy to integrate. It operates directly
from the front panel controls or remotely via
an RS-232 interface. The fiber-based design
ensures that no adjustment, alignment or
optical tweaking is required.
Imra America Inc.
lasers@imra.com
HD LCD Digital Cameras
The BLC-200 high-definition (HD) LCD cameras
for microscopy manufactured by Bestscope In-
ternational Ltd. include a tablet PC. They pre-
view, take snapshots and videos, and save
them. They offer wireless transmission and
3-G Internet surfing and have an aluminum
C-mount that connects to monocular, binocu-
lar, trinocular, stereo and dissecting micro-
scopes and telescopes. The cameras include a
2-megapixel
1
3-in. CMOS sensor that delivers
1600 1200-pixel resolution. They produce
high-quality true-color images and operate at
15 fps at full resolution and at temperatures
from 30 to 70 C. Accessories include a
5-VDC, 2500-mA power adapter and a USB
cable. The 7-in. LED backlight HD LCD screen
has a four-point capacitance touch screen and
a gravity sensor. The cameras are used in bio-
logical, medical, pharmaceutical, geologic,
mineral, metallurgical and chemical research.
Bestscope International Ltd.
info@bestscope.net
Blue Lasers
Modulight Inc. has extended its LimeLight pro-
duct family with the introduction of 465-nm
single-emitter blue lasers for acne treatment
and teeth whitening. The 1-W lasers are sup-
plied with an SMA-905 connector, an inte-
grated driver and a cooling controller. They
can be controlled through a USB port with a
standard PC user interface or directly by an
analog/digital control signal. Operating in both
continuous-wave and pulsed modes, they
measure 140 56 41 mm. Other package
types, as well as an OEM version with varying
wavelengths and power configurations, are
available upon request. The following wave-
lengths and maximum power outputs are
offered as standard configurations: 465 nm
(1 W), 635 nm (400 mW), 650 nm (750 mW),
808 nm (1.5 W), 1470 nm (700 mW) and
1550 nm (500 mW).
Modulight Inc.
sales@modulight.com
Lithography System
The Archetto 3 from Parian Technologies is an
interference lithography system for use in ma-
terials science and biology. Using newly avail-
able blue laser diodes and a patent-pending
spatial filtering approach, the optical tabletop
system enables users to produce controlled
1- and 2-D periodic nanostructures with pitches
ranging from 230 nm to 1 m, over a 1-cm
2
area. It measures 30.48 60.96 30.48 cm and
weighs 9.07 kg. The system does not require a
vibration isolation table and can produce peri-
odic nanostructures within minutes of assem-
bly. It uses interfering light beams to expose
a standing wave in photoresist. Output power
is ~1 mW, required line voltage is from 90 to
264 VAC, and frequency is from 50 to 60 Hz.
Parian Technologies
sales@pariantech.com
25Objective Lens
Olympus Europa Holding GmbH has released
the XLPLN25XSVMP ScaleView, a 25 objec-
tive lens with a numerical aperture of 1.0 for
deep imaging of thick biological samples.
Researchers can create 3-D structural repre-
sentations of brain tissue. To counter the ef-
fects of tissue opacity and light scattering, the
objective has a working distance of 4 mm and
works with Olympus ScaleView-A2 clearing
agent, rendering samples nearly translucent
while preserving fluorescent signals. When
it is used as part of an Olympus FluoView
FV1000MPE multiphoton system, the objective
enables peering deeper into samples, allowing
the user to generate insightful results from in-
tact specimens. By clearing formalin-fixed tis-
sues and allowing light to pass through the
sample, the reagent minimizes the need for
sectioning, allowing the user to generate data
that reflects the internal structure of a complex
specimen. True 3-D representations are cre-
ated, without requiring complex interpolation
or predictive algorithms.
Olympus Europa Holding GmbH
microscopy@olympus-europa.com
VBG-Stabilized Benchtop Lasers
PD-LD Inc. has announced its turnkey Lab-
Source series benchtop lasers. The LS-1
features a single volume Bragg grating (VBG)
stabilized laser, and the LS-2 offers dual lasers
that enable it to perform dual-wavelength light
therapy and specialized analytics. Both offer a
variety of wavelength options and include in-
tegrated drive circuitry and software, facilitat-
ing integration into existing laboratory instru-
ments. They include a user-friendly interface
and an ergonomic design. The LS-2s dual
lasers enable it to analyze and identify fluores-
cent substances that traditional single-source
Raman spectroscopy cannot. The dual-source
technique, known as shifted-excitation Raman
differential spectroscopy, or SERDS, repre-
sents a significant development in Raman
spectroscopy, particularly in field-based set-
tings and in the analysis of organic and/or
biological samples.
PD-LD Inc.
info@pd-ld.com
Cooled Scientific CMOS Camera
Raptor Photonics Ltd. has introduced a 4.2-
megapixel cooled scientific CMOS camera.
The Osprey OS4MPc-CL features a 2k 2k
low-noise 2048 2048-pixel scientific CMOS
sensor that produces high sensitivity, high
resolution, high speed and good quantum
efficiency. It is Peltier-cooled to 20 C, uses
a 12-bit analog-to-digital converter and offers
standard Camera Link output. The camera
is suitable for low-light applications, such as
fluorescence, live-cell and hyperspectral imag-
ing; biochemiluminescence; and electrophore-
sis. Features include an active pixel size of
5.5 5.5 m, up to 37.5-Hz full-frame 12-bit
Camera Link output, and a compact size of 86
65 61 mm.
Raptor Photonics Ltd.
info@raptorphotonics.com
DPSS Lasers
The Archimed series diode-pumped solid-state
(DPSS) lasers manufactured by RPMC Lasers
Inc. offer 45 to 150 mJ of pulse energy at 1064
nm, with pulse widths from 9 to 12 ns and
repetition rates up to 50 Hz. The compact air-
cooled devices also are available with second-,
third- and fourth-harmonic-generation options.
They can be equipped with an optical para-
metric oscillator to generate the eye-safe
wavelength of 1.5 m, which produces 10 mJ
of pulse energy with pulse widths from 7 to
9 ns and repetition rates of up to 25 Hz. All
lasers in the series have multimode beam pro-
files and a polarization ratio of 100:1. They are
suitable for use in light detection and ranging,
rangefinding and laser-induced breakdown
spectroscopy, and are rugged enough for
limited field use.
RPMC Lasers Inc.
info@rpmclasers.com
Optical Fiber Stripper
Vytran LLC has unveiled the SAS-400 optical
fiber stripper, which uses hot sulfuric acid to
remove the protective coating from a fiber
while maintaining the fibers intrinsic strength.
The company built it on the concept of its
predecessor, the SAS-200, but with an in-
creased emphasis on manufacturing use.
Improvements include greater ease of use and
enhanced robustness. The new model features
an intuitive graphical user interface and im-
proved operator protection. The automated
system is intended for sensing, medical, tele-
communications, aerospace and research ap-
plications. It can remove a variety of coating
types, including acrylate and polyimide. It can
strip a fiber section up to 40 mm long and can
be used to center strip a fiber, making it useful
for fiber Bragg grating manufacture and for
metallizing fiber sections.
Vytran LLC
info@vytran.com
BREAKTHROUGHPRODUCTS p
Shine the spotlight on your Breakthrough
Product in a display ad in BioPhotonics.
Contact Kristina Laurin at (413) 499-0514
or at advertising@photonics.com
Contact your sales representative or:
sales@photonics.com (413) 499-0514
Advertise in BioPhotonics
Lasers, optics, imaging, lighting, microscopy
and spectroscopy covered in every issue,
in addition to our special content focus.
May
Content Focus: Medical Imaging
June
Clinical Spectroscopy, Ultrafast Imaging,
Laser-Illuminated Microscopy,
Optics for Microscopy
Ad close: April 9
July/August
Content Focus: Medical Devices
Lasers in Medicine, Microscopy on the Go,
In Vivo Imaging, Data Storage & Analysis
Ad close: May 29
APPOINTMENTS
APRIL
Focus on Microscopy 2012 (April 1-4) Singa-
pore. Contact Fred Brakenhoff, Swammerdam
Institute for Life Sciences, University of Am-
sterdam, +31 20 525 5189; info2012@focuson
microscopy.org; www.focusonmicroscopy.org.
Photonix 2012 Expo & Conference (April 11-
13) Tokyo. Contact Mitsuru Takazawa, Reed
Exhibitions Japan Ltd., +81 3 3349 8549; photonix
@reedexpo.co.jp; www.photonix-expo.jp/en.
SPIE Photonics Europe (April 16-20) Brussels.
Contact SPIE, +1 (360) 676-3290; customer
service@spie.org; spie.org.
Photonics.World of Lasers and Optics 2012
(April 17-20) Moscow. Contact Liudmila V.
Bedniakova, Laser Association (LAS), +7 495
333 0022; laser@tsr.ru; www.photonics-expo.
ru/en.
2012 ASLMS Annual Conference (April 18-22)
Kissimmee, Fla. Contact American Society for
Laser Medicine & Surgery, +1 (715) 845-9283;
information@aslms.org; www.aslms.org.
META12, Third International Conference on
Metamaterials, Photonic Crystals and Plas-
monics (April 19-22) Paris. Contact META12
Secretariat, +33 1 69 85 16 60; meta12@meta
conferences.org; metaconferences.org.
Experimental Biology 2012 (April 21-25)
San Diego. Contact Yvette Clark, Federation
of American Societies for Experimental Biol-
ogy, +1 (301) 634-7016; yclark@faseb.org;
experimentalbiology.org.
Bio-IT World Conference & Expo 12 (April 24-
26) Boston. Contact Cindy Crowninshield,
Cambridge Healthtech Institute, +1 (781) 354-
0120; ccrowninshield@healthtech.com;
www.bio-itworldexpo.com.
Biomedical Optics and 3-D Imaging:
OSA Optics and Photonics Congress
(April 29-May 2) Miami. Contact Optical
Society of America, +1 (202) 223-8130;
info@osa.org; www.osa.org.
Eighth Annual PEGS: The Essential Protein
Engineering Summit (April 30-May 4) Boston.
Contact Cambridge Healthtech Institute,
+1 (781) 972-5400; reg@healthtech.com;
pegsummit.com.
MAY
Laser Safety Officer Training Course (May 1-4)
Cincinnati. Contact Rockwell Laser Industries,
+1 (513) 272-9900; training@rli.com; www.
rli.com.
ISBI 2012: IEEE International Symposium
on Biomedical Imaging (May 2-5) Barcelona,
Spain. Contact contact@biomedicalimaging.
org; www.biomedicalimaging.org.
CLEO: 2012 (May 6-11) San Jose, Calif. Confer-
ence on Lasers and Electro-Optics. Contact
Optical Society of America Customer Service
CLEO Management, +1 (202) 416-1907; custserv
@osa.org; www.cleoconference.org.
SME Mfg4 Conference & Exposition
(May 8-10) Hartford, Conn. Contact Society
of Manufacturing Engineers, +1 (313) 425-3000
or +1 (800) 733-4763; service@sme.org; www.
sme.org.
OSAV 2012: Third International Topical
Meeting on Optical Sensing and Artificial
Vision (May 14-17) St. Petersburg, Russia.
Contact Igor Gurov, St. Petersburg National
Research University of Information Technolo-
gies, Mechanics and Optics, +7 812 571 6532;
gurov@mail.ifmo.ru; osav.spb.ru.
E-MRS 2012 Spring Meeting (May 14-18)
Strasbourg, France. A European Materials
Research Society event. Contact EMRS, +33
3 88 10 63 72; emrs@emrs-strasbourg.com;
www.emrs-strasbourg.com.
Biomarker World Congress 2012 (May 21-23)
Philadelphia. Contact Cambridge Healthtech
Institute, +1 (781) 972-5400; reg@health
tech.com; biomarkerworldcongress.com.
Symposium on Photonics and Optoelectronics
(SOPO 2012) (May 21-23) Shanghai. Contact
Conference Secretary, +86 130 1803 5105;
sopo@scirp.org; www.sopoconf.org.
ICNP 2012: Sixth International Conference on
Nanophotonics (May 27-30) Beijing. Contact
Peking University, icnp2012@pku.edu.cn;
icnp2012.pku.edu.cn.
JUNE
Principles of Fluorescence Techniques Course
(June 4-6) Urbana, Ill. Contact Samantha
Redes, +1 (217) 359-8681; coordinator@
fluorescence-foundation.org; www.fluores
cence-foundation.org.
Molecular Imaging in Drug Discovery and
Development Conference (June 6-7) Philadel-
phia. Contact Marina Filshtinsky, Cambridge
Healthtech Institute, +1 (781) 972-5455;
mfilshtinsky@healthtech.com; www.world
pharmacongress.com/img.
3D Microscopy of Living Cells Course
(June 9-21) and 3D Image Processing
Post-course Workshop (June 23-25) Vancou-
ver, British Columbia, Canada. Contact James
Pawley, University of Wisconsin-Madison,
+1 (608) 238-3953; jbpawley@wisc.edu;
www.3dcourse.ubc.ca/2012.
BIO International Convention (June 18-21)
Boston. Contact Biotechnology Industry
Organization, +1 (202) 962-9200; reg2012@
bio.org; www.convention.bio.org.
Third International Congress on Biophotonics
(ICOB 2012) (June 19-21) Jena, Germany.
Contact IPHT Jena: Institute of Photonic
Technology, icob2012@ipht-jena.de; www.
icob2012.org.
Imaging and Applied Optics: OSA Optics &
Photonics Congress (June 24-28) Monterey,
Calif. Includes Applied Industrial Optics:
Spectroscopy, Imaging and Metrology (AIO);
Computational Optical Sensing and Imaging
(COSI); Imaging Systems Applications (IS);
Optical Remote Sensing of the Environment
(ORS); and Optical Sensors (SENSORS).
Contact Optical Society of America, +1 (202)
223-8130; info@osa.org; www.osa.org.
WMIC 2012 September 5-8
Deadline: Abstracts, April 17, 11:50 p.m. PT
Dublin. The World Molecular Imaging Society encourages submissions for its annual meeting,
the 2012 World Molecular Imaging Congress. Areas to be addressed include optical imaging, MRI,
positron emission tomography/single-photon emission computed tomography, ultrasound and
photoacoustic imaging, and hybrid multimodality technology. Categories include the preclinical
cell and tissue, preclinical in vivo, and translational and clinical levels.
Contact: World Molecular Imaging Society +1 (310) 215-9730
meverett@wmis.org www.wmicmeeting.org
BMES 2012 Annual Meeting October 24-27
Deadline: Abstracts, April 18
Atlanta. The Biomedical Engineering Society is accepting papers for its 2012 annual meeting.
Among the areas to be considered are biomedical imaging and optics, including multimodality
imaging, lasers in medicine, novel imaging probes, image-guided therapy and novel imaging
contrast agents. Other topics to be discussed include functional, physiological and molecular
imaging; optical diagnostics, sensing and devices; and imaging applications in cardiovascular
medicine, regenerative medicine, cancer and neuroengineering.
Contact: Biomedical Engineering Society +1 (301) 459-1999, Ext. 104
meetings@bmes.org www.bmes.org
EOS Annual Meeting 2012 September 25-28
Deadline: Abstracts, May 7
Aberdeen, Scotland. The European Optical Society invites papers for EOSAM 2012. Contributions
will be accepted for oral and poster presentation. The event will encompass seven topical meet-
ings, including one on biophotonics that will cover optogenetics, photoporation, biomarkers for
optical techniques, lab-on-a-chip optofluidic devices, and OCT technical advances.
Contact: EOS Events & Services GmbH +49 511 2788 115
aberdeen@myeos.org www.myeos.org
For complete listings, visit
www.photonics.com/calendar
CALL FOR PAPERS
312Appointments_Layout 1 3/6/12 12:50 PM Page 40
41
ADVERTISERINDEX
Photonics Media Advertising Contacts
Please visit our client service
website Photonics.com for all
your marketing needs.
Ken Tyburski
Director of Sales
Voice: +1 (413) 499-0514, Ext. 101
Fax: +1 (413) 443-0472
ken.tyburski@photonics.com
New England, Southeastern US, FL,
Rocky Mountains, AZ, NM & Midwest
Rebecca L. Pontier
Associate Director
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
Joanne C. Gagnon
Regional Manager
Voice: +1 (413) 499-0514, Ext. 226
Fax: +1 (413) 443-0472
joanne.gagnon@photonics.com
Southern CA, Central CA & HI
Tracy L. Reynolds
Regional Manager
Voice: +1 (413) 499-0514, Ext. 104
Fax: +1 (413) 443-0472
tracy.reynolds@photonics.com
Eastern Canada
Maureen Riley Moriarty
Regional Manager
Voice: +1 (413) 499-0514, Ext. 229
Fax: +1 (413) 443-0472
riley.moriarty@photonics.com
Europe, Israel & South Central US
Owen Broch
Regional Manager
Voice: +1 (413) 499-0514, Ext. 108
Fax: +1 (413) 443-0472
owen.broch@photonics.com
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Voice: +49 2241 1684777
Fax: +49 2241 1684776
olaf.kortenhoff@photonics.com
Asia (except Japan)
Hans Zhong
Voice: +86 755 2872 6973
Fax: +86 755 8474 4362
hans.zhong@yahoo.com.cn
Japan
Scott Shibasaki
Voice: +81 3 5225 6614
Fax: +81 3 5229 7253
s_shiba@optronics.co.jp
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and advertising copy to:
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Voice: +1 (413) 499-0514
Fax: +1 (413) 442-3180
advertising@photonics.com
a
Andor Technology..........................................................................................................CV2, 34
www.andor.com
Applied Scientific Instrumentation........................................................................................10
www.asiimaging.com
b
Bayspec Inc. ...........................................................................................................................33
www.bayspec.com
Blue Sky Research ..................................................................................................................26
www.blueskyresearch.com
c
Cargille Laboratories ..............................................................................................................37
www.cargille.com
Coherent Inc. ...................................................................................................................3, CV4
www.coherent.com
CVI Melles Griot ......................................................................................................................23
www.cvimellesgriot.com
e
Edmund Optics........................................................................................................................13
www.edmundoptics.com
89 North...................................................................................................................................15
www.89north.com
h
Hamamatsu .............................................................................................................................27
www.sales.hamamatsu.com
i
Iridian Spectral Technologies ..................................................................................................5
www.iridian.ca
l
Lumencor Inc. ........................................................................................................................16
www.lumencor.com
m
Mad City Labs .........................................................................................................................39
www.madcitylabs.com
p
Photonics Media..........................................................................................19, 34, 37, 39, CV3
www.photonics.com
Piezosystem Jena GmbH.......................................................................................................32
www.piezojena.com
Prior Scientific Inc. .................................................................................................................12
www.prior.com
r
Raptor Photonics Ltd. ......................................................................................................32, 34
www.raptorphotonics.com
t
Toptica Photonics Inc. ..............................................................................................................7
www.toptica.com
312_Ad Index_Layout 1 3/6/12 12:51 PM Page 41
This microscopic image of trichomes
on the skin of an immature cucumber
under 800 magnification received an
honorable mention in the photography
category. The trichomes help cucumbers
protect themselves against most herbivores.
Courtesy of Dr. Robert Rock Belliveau.
POSTSCRIPTS
S
eeing science actually seeing it, instead of reading or talk-
ing about it can lead to deeper understanding of the forces,
processes and phenomena that govern our universe. And
science can be just as beautiful hanging on a wall as any Monet
or van Gogh print.
The 2011 International Science and Engineering Visualization
Challenge honored recipients who use visual media specifically
to promote understanding of scientific research; the winning en-
tries appeared in the Feb. 3 issue of Science, which held the com-
petition in conjunction with the US National Science Foundation.
The annual event, now in its ninth year, showcases spectacular
photographs, illustrations, graphics, videos and interactive games
that engage viewers by conveying the complex substance of sci-
ence through arts. Judging criteria for the 212 entries, which
came from 33 countries, included visual impact, effective com-
munication, freshness and originality.
The competition moved online this year: Participants could
enter online, and judges could view materials electronically. The
general public got involved in the voting process, with the fan
favorite photo receiving the Peoples Choice award. Entries also
could be shared and promoted on Facebook and Twitter.
The winning images for 2011 spanned the realm of science,
including a computer illustration depicting the emergence of
structure in the universe over 240 million light years; Foldit, a
multiplayer online computer game puzzle that allows users to
bend and fold amino acids into realistic proteins and solve the
problem of protein folding; and a movie that shows a novel 3-D
model view of a whole cell in minute detail and presents complex
biological data visually for a general audience.
The talent of these award winners is remarkable, said Mon-
ica M. Bradford, the journals executive editor. Science is pub-
lished by AAAS, the nonprofit international science society.
These winners communicate science in a manner that not only
captures your attention but in many instances strives to look at
different ways to solve scientific problems through their varied
art forms.
The art of science
To see the winners, visit www.nsf.gov/news/scivis.
Laura S. Marshall
312_Postscripts_Layout 1 3/6/12 12:52 PM Page 42
Coming in July
Medicine & Health
SEPTEMBER Solar
NOVEMBER Space
2 0 1 2 W E B I N A R S E R I E S
Expert Briefings
In-depth presentations and interactive
Q&A featuring top industry experts.
For more information, visit:
www.Photonics.com/Webinars
To become a sponsor, contact your sales
representative at (413) 499-0514, or email
advertising@photonics.com.
Photonic applications in medical imaging.
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read noise at 30 fps, and the chips dual-

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