Biophotonics201210 DL

OCTOBER 2012
www.Photonics.com
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Fiber Optics Revolutionizes Neuroscience
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4 BioPhotonics October 2012
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 felds of medicine,
biology and biotechnology.
10 BIOSCAN
BioPhotonics editors curate the most signifcant headlines of
the month for photonics in the life sciences and take you
deeper inside the news. Featured stories include:
DNA-basednanoantennacaptures,emitslight
Metamaterialfocusessoundwaveslikeacameralens
OpticalmicroscopebreaksAbbeslimit

17 BUSINESSSCAN
Guidelinesneededtoadvancediagnosticaccuracy
www.photonics.com
Volume 19 Issue 8
THE COVER
Merging fber optics with neuroscience
has signifcantly increased our under-
standing of how the brain functions.
An article by News Editor Gary Boas
begins on page 20. Design by Art
Director Suzanne L. Schmidt.
20 FIBER OPTICS REVOLUTIONIZES NEUROSCIENCE
by Gary Boas, News Editor
Twoscientifcmethodsusingfberopticsoptogeneticsanda
multimodalapproachusedinconjunctionwithfMRIhavebroadened
ourunderstandingofthebrain.
24 OPTICAL MICROSCOPY QUANTIFIES LIVE CELLS WITHOUT LABELS
by Valerie C. Coffey, Freelance Science Writer
Methodssuchasspatiallightinterferencetomography,time-lapsespatial
lightinterferencemicroscopyandstimulatedRamanscatteringimagecells
livewithoutdyes.
28 FLEXIBILITY IMPROVES PHOTOACOUSTIC MICROSCOPY
by Zhun Xu and Jay Zhao, MicroPhotoAcoustics Inc.
Anewintegratedmicroscopysystemisswitchablebetweenoptical-
resolutionandacoustic-resolutionmodes,providingadditionaldata.
31 TELL-TALE COLOR CHANGES: CAMERA CAN FIND AGE OF A BRUISE
by Dr. Barbara Stam, Dr. Gerhard Holst and Ursula Buczek
Animagingsystemunderdevelopmentwilldeterminetheage
ofabruisebygaugingitscolorandtheratioofhemoglobintobilirubin.
8 EDITORIAL
35 BREAKTHROUGHPRODUCTS
40 APPOINTMENTS
Upcoming Courses and Shows
41 ADVERTISER INDEX
42 POST SCRIPTS
by Caren B. Les
Lidarrevealselephantimpact
NEWS
FEATURES
DEPARTMENTS
24
1012_Contents.indd 4 9/27/12 8:51 AM
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Group Publisher Karen A. Newman
Editorial Staff
Managing Editor Laura S. Marshall
Senior Editor Melinda A. Rose
News Editors Gary Boas, Caren B. Les, Ashley N. Rice
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Subscription Policy BioPhotonics ISSN-1081-8693 (USPS 013913) is published 10 times per year by Laurin
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www.photonics.com
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1012_LightMatters_pg7.indd 7 9/27/12 10:48 AM
Light Brings New Tools to Old Science
N
euroscience has a very long history, one that by some
measures stretches back to thousands of years B.C. Cer-
tainly, the need to understand how our brains work, why
things sometimes go wrong and, ultimately, how we can fx what
is broken makes it a compelling subject.
Some 32,000 neuroscientists are expected to gather this month
in New Orleans for the 42nd annual meeting of the Society for
Neuroscience. Attendees will have the opportunity to consider
the latest research into how the brain weighs complex decisions;
the progress being made in treating Alzheimers disease, spinal
cord and traumatic brain injuries, and much more.
Of course, biophotonics technologies will fgure into the
conversation. On the agenda is a symposium called Cracking
Neural Codes with Photons: Optogenetics as an Integral Tool for
Systems Neuroscience, chaired by Dr. Mark J. Schnitzer and
optogenetics pioneer Dr. Karl Deisseroth. Using light to activate
and deactivate neurons, optogenetics presents a powerful new
technology for brain research. Managing Editor Laura Marshall
will report from the Neuroscience meeting on our Light Matters
weekly newscast, and you can be sure that what she learns there
will inform our coverage in the coming months.
Optogenetics fgures into at least one feature in this issue of
BioPhotonics, and you can fnd a healthy selection of archived
articles on the topic at www.photonics.com.
Fiber optics, what news editor Gary Boas calls the Rodney
Dangerfeld of the photonics world, has played an integral role
in a number of techniques making signifcant contributions
to neuroscience, including BOLD fMRI (blood-oxygenation-
level-dependent functional MRI) and optogenetics. In Fiber
Optics Revolutionizes Neuroscience, beginning on page 20, he
examines the importance of fber optics in the development and
application of these two techniques.
Also in this issue, we welcome the frst BioPhotonics article
from freelance science writer Valerie C. Coffey who tells us that,
with increasing frequency, noninvasive, label-free microscopy
methods are capturing subcellular details in live cells and tissues
at ever-smaller resolutions. In her article, Optical Microscopy
Quantifes Live Cells Without Labels she writes that several
novel label-free methods help biologists to measure quantitative
properties and dynamic processes without damaging the live
cells. One approach, quantitative phase imaging, records the
phase of light as it passes through a transparent or translucent
object. Because this technique provides a quantitative measure-
ment of the optical feld, dyes and labels are not required to
enhance the image contrast. You will fnd her feature beginning
on page 24.
Zhun Xu and Jay Zhao of MicroPhotoAcoustics Inc. describe
how switching from optical resolution to acoustic resolution
allows scientists to extract more information from samples. In
their article, Flexibility Improves Photoacoustic Microscopy,
the researchers tell us that noninvasive functionality, relatively
deep penetration and multiscale spatial resolution make pho-
toacoustic imaging ideal for biomedical applications at various
scales, from centimeter-size breast tumors down to micrometer-
size red blood cells. You can fnd their article beginning on
page 28.
Finally, who hasnt watched with fascination as a bruise on the
shin changes colors, sometimes rather dramatically, in the days
after making contact with a desk or other obstacle. Scientists
have wondered whether changes in bruise color could help
doctors draw conclusions about when an injury occurred. Dr.
Barbara Stam, Dr. Gerhard Holst and Ursula Buczek are three
who believe it can. In their article, Tell-Tale Color Changes:
Camera Can Find Age of a Bruise, the authors report that a
reliable method of calculating the specifc moment of injury may
be available in the near future, thanks to development of a model
linking the color of the hematoma to its age, enabling calculation
of when the injury originally occurred. You can fnd their article
beginning on page 31.
Enjoy the issue, and let us know what you think. Write to me
at karen.newman@photonics.com.
EDITORIAL
Karen A. Newman
karen.newman@photonics.com
1012_Editorial.indd 8 9/27/12 8:53 AM
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DNA-based nanoantenna captures, emits light
PARIS A bio-inspired light nanoan-
tenna comprising two gold nanoparticles,
short DNA strands and a tiny fuorescent
molecule that can capture and emit light
could pave the way to the development of
highly effcient LEDs and ultracompact
solar cells and could even fnd use in
quantum cryptography.
Light is a wave, so it should be pos-
sible to develop optical antennas that can
amplify light signals in the same way that
televisions and mobile phones capture
radio waves. But because light oscillates
1 million times faster than radio waves,
nanoscale objects are needed to capture
the very fast light waves. Therefore, the
optical counterpart of a basic antenna (of
dipole type) is a quantum emitter sur-
rounded by two nanoparticles 1000 times
smaller than a human hair.
Scientists at CNRS and Aix Marseille
Universit, also in France, have developed
a simple, user-friendly optical antenna by
embedding a fuorescent organic cool-
ant and 36-nm-diameter gold particles
into short artifcial DNA strands. The
fuorescent molecules behave like a
quantum source, providing photons to the
antenna, while the interaction between
the light and the emitter is amplifed by
the gold nanoparticles. They produced
several billion replicas of these particle
pairs (in solution) in parallel via control
of the fuorescent molecule positions with
nanometric accuracy, thanks to the DNA
backbone.
I believe our dimers made of DNA
will fnd applications in the sensitive
monitoring of DNA or RNA which are
smaller than proteins and more diffcult
to measure, Sbastien Bidault, a CNRS
researcher at the Institut Langevins
Optical Antennas and Sensing group,
told BioPhotonics. The interesting thing
about our technique is that the antennas
are purifed in solution and therefore very
easy to handle and graft on different types
of substrates, while, with lithography, the
antennas are fxed on a given substrate.
And, because their technology does not
require cleanroom equipment or high-
temperature processes, it is cost-effective.
These characteristics extend beyond the
possibilities offered by existing lithogra-
phy techniques used to design micropro-
cessors.
Optical antennas could have wide
applications in systems where a small
piece of material absorbs or emits light:
sensing, thin solar cells or detectors,
Bidault said. For a detector, an optical
antenna will allow the photodiode to
be smaller (faster detector) and only
interact with specifc light polarizations
or colors. For a sensor, the antenna allows
strong interaction of light with a smaller
piece of matter, making the system more
sensitive.
Although it will take about fve to 10
years for sensors to be developed, Bidault
is confdent that the technology will be
useful for many applications.
Our specifc bio-templated systems
will mostly have a strong impact in
biosensing, while detectors or solar cells
will rely on lithography more than self-
assembly, he said. However, our specifc
study should have a general impact on the
feld of optical antennas as it describes the
simplest working antenna geometry.
The study appeared in Nature Commu-
nications (doi: 10.1038/ncomms1964).
BIOSCAN
A closer look at the most signifcant biophotonics research and technology headlines of the month
Schematic representation of a nanoantenna formed of two gold nanoparticles linked by a DNA double
strand and supplied by a single quantum emitter. Courtesy of Busson, Rolly, Stout, Bonod, Bidault.
Metamaterial focuses sound waves
like a camera lens
UNIVERSITY PARK, Pa. A compu-
tationally tested metamaterial that can
manipulate a variety of acoustic waves
with one simple device holds promise for
various acoustic applications, including
medical ultrasound, higher sensitivity
surface acoustic wave sensors and higher
Q factor resonators.
Man-made optical metamaterials have
been studied over the past decade for
applications including perfect lenses and
cloaking. The basic principles of optical
metamaterials apply to acoustic metama-
terials: Artifcial structures are created in
patterns that bend the acoustic wave onto
a single point and then refocus the wave
into a wider or narrower beam, depending
on the direction of travel through the pro-
posed acoustic beam aperture modifer.
The acoustic beam aperture modifer
is a brand-new application of acoustic
metamaterials that has not been built
before, Sz-Chin Steven Lin, a postdoc-
toral scholar at The Pennsylvania State
University, told BioPhotonics.
Lin and colleagues at the universitys
Materials Research Institute built the
novel device on gradient-index (GRIN)
phononic crystals in this case, an
array of steel pins embedded in epoxy
in a particular pattern. The steel pins,
or obstacles, slow the acoustic wave
speed so that they can be bent into
curved rays.
The acoustic beam aperture modifer
is built upon gradient-index phononic
crystals which are artifcially engineered
periodic structures most famous for
1012_BioScan.indd 10 9/27/12 8:58 AM
their ability to guide the propagation of
acoustic waves along curved trajectories,
known as the acoustic mirage effect,
said Lin, lead author of the report, which
appeared in the Journal of Applied Physics
(http://dx.doi.org/10.1063/1.4729803).
Although other types of acoustic
metamaterials could focus and defocus
an acoustic beam to achieve aperture
modifcation, the Penn State device is
smaller in size by at least half and offers
energy conservation of up to 83 percent
of acoustic energy after modifcation.
Compared to existing negative-
refraction-based metamaterial lenses, our
GRIN-based metamaterial lens possesses
several advantages, Lin said. First, the
GRIN lens can operate over a wide fre-
quency band, while negative-refraction-
based lenses usually operate within
a small range.
Second, a GRIN lens can be coupled
with acoustic transducers and can effec-
tively redirect paraxial incident acoustic
waves to a small focal spot the position
of this spot is determined by the adjust-
able gradient coeffcient. In contrast, with
negative-refraction-based phononic crys-
tal lenses, one must focus select diverging
waves to a long focal zone.
Lastly, GRIN lenses can be made much
smaller than negative-refraction-based
lenses and can be seamlessly integrated
with existing millimeter-scale acoustic
systems, he said.
For the past several years, Lin has
worked to apply optics concepts such as
GRIN lensing to the phononic crystals.
He has applied his GRIN concept to
various felds, including optofuidics and
nanophotonics, to obtain optical lenses.
Currently, scientists and surgeons
must have transducers of multiple sizes
to produce acoustic waves with differ-
ent apertures. With the new device, the
desired aperture can be attained easily
by changing the modifer attached to the
transducer.
The device will beneft almost all sonic
and ultrasonic applications, including
evaluations and imaging. It also could
provide more accurate and effcient high-
intensity focused ultrasound therapies, a
noninvasive heat-based technique targeted
at a variety of cancers and neurological
disorders.
The team is working on a prototype
based on this design.
The acoustic beam aperture modifer can effectively shrink or expand the aperture of an acoustic beam
with minimum energy loss and waveform distortion. With such an acoustic lens, the need for a series of
expensive transducers of various sizes is eliminated. Courtesy of Sz-Chin Steven Lin, Penn State.
Optical microscope breaks Abbes limit
AMSTERDAM, LONDON and BARCE-
LONA, Spain Combining electronic ex-
citation and optical detection has allowed
an optical microscope to break Abbes
diffraction limit. The new nanoscale
imaging method could lead to enhanced
biosensors by offering insight into how
light and complex photonic materials
interact.
Researchers at FOM Institute AMOLF
(Institute for Atomic and Molecular
Physics) in Amsterdam, Kings College
London and the Institute of Photonic Sci-
ences (ICFO) in Barcelona broke Ernst
Abbes specifcation for the resolution
limit of a diffraction-limited microscope
using a novel technique called angle-
dependent cathodoluminescence imaging
spectroscopy.
Natural photonic crystals nanostruc-
tures composed of two materials with a
different refractive index arranged in a
regular pattern with exotic optical prop-
erties are what create the iridescent
colors found in certain species of beetles,
birds, butterfies and opal gemstones.
These optical properties can be mim-
icked in fabricated photonic crystals,
thanks to recent advances in nanofabri-
cation techniques.
Working with 30-nm spatial resolution,
the international team explored the fner
details of photonic crystals at a resolution
more than 10 times smaller than lights
diffraction limit, providing more insight
into how light interacts with matter to
produce, for instance, the visible irides-
cence seen on butterfy wings.
We were thrilled in the lab to observe
the fner details of the photonic crystals
that were simply inaccessible before,
said Dr. Riccardo Sapienza of Kings
College. This is very important, as it
allows scientists to test optical theories to
a new level of accuracy, fully characterize
new optical materials and test new optical
devices.
The researchers fabricated a 2-D
photonic crystal by etching a hexagonal
pattern of holes in an ultrathin silicon ni-
tride membrane. The crystal inhibits light
propagation for certain colors of light,
which leads to strong refection of those
colors. By leaving out one hole, a very
small cavity can be defned where the
surrounding crystal acts as a mirror for
the light, making it possible to strongly
1012_BioScan.indd 11 9/27/12 8:58 AM
confne it within a crystal defect cavity.
Angle-dependent cathodolumines-
cence imaging spectroscopy is based on a
geological method in which visible light
is emitted by a luminescent material when
it is hit by an electron beam released
by an electron gun. The technique was
modifed by professor Albert Polmans
team at AMOLF to explore nanophotonic
materials.
Each time a single electron from the
electron gun reaches the sample surface,
it generates a burst of light, as if we
had placed a fuorescent molecule at the
impact location, Sapienza said. Scan-
ning the electron beam, we can visualize
the optical response of the nanostructure,
revealing features 10 times smaller than
ever done before.
For years, we have been struggling
with scanning near-feld probes and posi-
tioning of nanolight sources, said ICFO
professor Niek van Hulst. Now the scan-
ning e-beam provides a local broadband
dipolar light source that readily maps all
localized felds inside a photonic crystal
cavity.
This is the frst demonstration of 30-nm
instrument resolution, Polman said, but he
added that 10 nm should be achievable in
the future.
Our research provides a fundamental
insight into light at the nanoscale and, in
particular, helps in understanding how
light and matter interact, Sapienza said.
This is the key to advance nanophotonic
science, and it can be useful to design
novel optical devices like enhanced
biosensors for health care, more effcient
solar cells and displays, or novel quantum
optics and information technologies.
The instrument will be brought to mar-
ket this fall by startup company Delmic.
The development was funded by a Valori-
zation Grant from Technology Foundation
STW and the FOM Foundation.
The fndings were reported in Nature
Materials (doi: 10.1038/nmat3402).
BIOSCAN b
A dorsal view of a male butterfy. Natural photonic crystals make the iridescent colors found in
butterfies, beetles and opals, and a new nanoscale imaging method allows scientists to study
how light and complex photonic materials interact to engineer photonic crystals for biosensors and more.
Courtesy of Wikimedia Commons.
TULLAHOMA, Tenn. A
new technique harnesses
the power of femtosecond
lasers to seek, acutely map
and noninvasively destroy
cancerous tumors, and it
could especially beneft brain
cancer patients.
Developed by scientists
at the Center for Laser Ap-
plications at the University
of Tennessee Space Insti-
tute, the laser focuses on a
specifc region to fnd and
destroy tumors.
Using ultrashort light
pulses gives us the ability
to focus in a well-confned
region and the ability for in-
tense radiation, said Chris-
tian Parigger, an associate
acceptance and replace sur-
gical options that are unable
to remove all carcinogenic
tissue.
If you have a cancerous
area such as in the brain, the
notion is if you see some-
thing and take care of it, it
wont spread, Parigger said.
This treatment overcomes
diffculties in treating brain
cancer and tumors. And it
has the promise of applica-
tion to other areas as well.
The team is working with
the University of Tennes-
see Research Foundation
to bring the technology to
market.
professor of physics. This
allows us to come in and
leave a specifc area quickly
so we can diagnose and at-
tack tumorous cells fast.
After the cancerous area
is precisely targeted, the in-
tensity of the laser radiation
can be turned up to irradiate,
or burn off, the tumor. This
method has the potential to
be more exact than cur-
rent techniques and to be
performed as an outpatient
procedure.
Because the femtosecond
laser radiation can be pre-
cisely focused both spatially
and temporally, one can
avoid heating up too many
other things that you do not
want heated, Parigger said.
Using longer laser-light
pulses is similar to leav-
ing a lightbulb on, which
gets warm, and can damage
healthy tissue.
The new technology can
be especially useful for
treating brain cancer patients
because it can noninvasively
permeate thin layers of bone,
such as the skull, and help
defne a targeted treatment
strategy for persistent cancer.
It overcomes the restric-
tions posed by radiation
treatments that damage por-
tions of healthy brain tissue,
and also could overcome the
limitations of photodynamic
therapy that have limited its
Cancer-fghting laser born at university space institute
1012_BioScan.indd 12 9/27/12 8:58 AM
CAMBRIDGE, Mass. An extraordi-
narily strong negative refractive index
as large as 700 more than 100 times
larger than most previously reported has
been achieved in metamaterials using a
new technique that could one day lead to
extremely powerful microscopes and op-
tical tweezers to trap and study minuscule
particles such as viruses and individual
molecules.
In a vacuum, light travels so fast that
it can circle the Earth more than seven
times within the blink of an eye. When
light propagates through matter, however,
it slows by a factor typically less than 5.
This factor, called the refractive index, is
positive in naturally occurring materials
and causes light to bend in a particular
direction when it shines on water or glass,
for example.
Over the past 20 years, scientists
have created artifcial materials whose
refractive indices are negative, defying
normal experience by bending light in
the wrong direction. They have been
celebrated by both scientists and engi-
neers for their unusual ability to manipu-
late electromagnetic waves and for their
potential to be harnessed for technologies
such as 3-D cloaking.
Now, scientists at Harvard School
of Engineering and Applied Sciences
(SEAS), in collaboration with Weizmann
Institute of Science in Israel, have demon-
strated a drastically new way of achieving
negative refraction in metamaterials by
applying kinetic inductance, a manifes-
tation of the acceleration of electrons
subjected to electric felds, according to
Newtons second law of motion.
This work may bring the science and
technology of negative refraction into an
astoundingly miniaturized scale, confn-
ing the negatively refracting light into
an area that is 10,000 times smaller than
many previous negative-index metamate-
rials, said principal investigator Donhee
Ham, Gordon McKay Professor of Elec-
trical Engineering and Applied Physics
at SEAS.
The researchers change in strategy,
switching from using magnetic induc-
tance to using kinetic inductance, is based
on a simple shift in ideas.
Magnetic inductance represents the
tendency of the electromagnetic world
to resist change, according to Faradays
BIOSCAN b
New approach strengthens negative refraction
A negative refractive index as large as 700 was
achieved in metamaterials using a new technique
that could one day lead to extremely powerful
microscopes and optical tweezers. Here, the
chamber of the probe station where Donhee
Hams research group tests the new metamateri-
als. Images courtesy of Eliza Grinnell, Harvard
SEAS Communications.
1012_BioScan.indd 13 9/27/12 8:58 AM
law, Ham said. Kinetic inductance, on
the other hand, represents the reluctance
to change in the mechanical world, ac-
cording to Newtons law.
When electrons are confned perfectly
into two dimensions, kinetic inductance
becomes much larger than magnetic
inductance, and it is this very large two-
dimensional kinetic inductance that is
responsible for the very strong negative
refraction we achieve, said lead author
Hosang Yoon, a graduate student at
SEAS. The dimensionality profoundly
affects the condensed-matter electron
behaviors, and one of those is the kinetic
inductance.
Ham and Yoon used a 2-D electron gas
(2DEG) to obtain the large kinetic induc-
tance. The very clean 2DEG sample,
fabricated by Vladimir Umansky of Weiz-
mann Institute, forms at the interface of
two semiconductors: GaAs and AlGaAs.
Hams team sliced a sheet of 2DEG into
an array of strips and used gigahertz-fre-
quency electromagnetic waves to acceler-
ate electrons in the leftmost few strips.
The resulting movements of electrons in
these strips were felt by the neighboring
BIOSCAN b
strips to the right, where electrons were
consequently accelerated.
In this way, the device propagates an
effective wave to the right, in a direction
perpendicular to the strips, each of which
acts as a kinetic inductor because of the
electrons acceleration therein. This effec-
tive wave exhibited what the researchers
call a staggering degree of negative
refraction.
Not only can this new technology local-
ize electromagnetic waves into ultrasub-
wavelength scales, but it also is very
small in scale.
Demonstrated with microwaves, this
concept besides powerful microscopes
and optical tweezers could lead to tera-
hertz and photonic circuits that operate
far below their usual diffraction limit, and
at near feld, if extended to other regions
of the electromagnetic spectrum.
For now, the device operates at tem-
peratures of <20 K. However, similar re-
sults can be achieved at room temperature
using terahertz waves, which Hams team
is already investigating by using graphene
as an alternative 2-D conductor.
While electrons in graphene behave
like massless particles, they still possess
kinetic energy and can exhibit very large
kinetic inductance in a non-Newtonian
way, Ham said.
The fndings, supported by the US
Air Force Offce of Scientifc Research,
were reported in Nature (doi: 10.1038/
nature11297).
This experimental setup in Donhee Hams lab tests the new metamaterials, which are fabricated on
tiny chips. The metamaterials themselves are inside the probing chamber at the bottom right. Imaged
through the black microscope, they appear on the screen at the top of this image.
Diagnosis is in the eyes, thanks to color-coded markers
SAN DIEGO New fuorescent probes
that change color when they encounter
brain disease markers found in the eye
could offer a simpler way to identify
neurodegenerative disease and distinguish
between closely related disorders such as
Parkinsons, Alzheimers and Creutzfeldt-
Jakob.
Amyloids sticky plaques of protein
mark several different but related brain
diseases with overlapping symptoms.
Methods for diagnosing and monitoring
these disorders are not very advanced.
Among the few available diagnostics
for Alzheimers disease are radioactive
molecules that target amyloid, which can
be detected in the brain using PET scans.
This test shows whether amyloid has
formed in the brain, but does not distin-
guish between the various diseases.
To overcome this obstacle, scientists at
the University of California, San Diego,
have created several fuorescent probes
that change color depending on the type
of amyloid they encounter. Because amy-
loids accumulate in the eyes as well as the
brain, it is possible that neurodegenerative
diseases could be differentially diagnosed
with simple eye drops or ointment and an
eye exam.
The key trick here is that the small
differences in the proteins that make up
different forms of amyloid interact differ-
ently with our fuorescent probes to result
in measurably different colors of the
emitted light, said Jerry Yang, co-leader
of the project with Emmanuel Theodora-
kis; both are professors of chemistry and
biochemistry at the university. Christina
Sigurdson from the department of pathol-
ogy at UCSDs School of Medicine was a
key collaborator.
The physical properties of the pockets
in the various amyloid proteins determine
the color change in the fuorescent probes.
The team showed that one of the probes
glows yellow when marking amyloid
deposits associated with prion disease,
whereas the same probe glows green when
it binds to tissue samples with Alzheim-
ers disease.
We think that our approach represents
a signifcant step toward developing diag-
nostics to distinguish between different,
1012_BioScan.indd 14 9/27/12 8:58 AM
BioPhotonics October 2012
but closely related, diseases where symptoms and pathological
characteristics show many similarities, Yang said. Such capa-
bility might prove to be very important for deciding on effective
treatment strategies for specifc diseases.
The team is expanding its catalog of markers by creating
probes that can discriminate between other amyloid forms. The
technology has been licensed for commercial development of
diagnostic tests for human neural disease.
The study appeared online in the Journal of the American
Chemical Society (doi: 10.1021/ja3063698).
BIOSCAN b
Glowing molecules turn on,
off to visualize cell activity
CORAL GABLES, Fla. Using UV light to switch fuorescent
molecules on and off in aqueous environments could help scien-
tists develop better fuorescent probes for biomedical research.
The molecules frst must be strategically trapped inside water-
soluble particles, which isnt new; water-soluble particles have
been used in previous studies to bring organic molecules into
water. What is new in this system, developed by scientists at
the University of Miami, is the addition of the photoswitching
mechanism.
Finding a way to switch fuorescence inside cells is one of
the main challenges in the development of fuorescent probes for
bioimaging applications, said chemistry professor Francisco
Raymo. Our fuorescent switches can be operated in water ef-
fciently, offering the opportunity to image biological samples
with resolution at the nanometer level.
Because fuorescent molecules are not water soluble, Raymo
and his team created their system by embedding them in synthet-
ic water-soluble polymer nanoparticles, which serve as transport
vehicles into living cells. Once inside cells, the fuorescence of
the molecules trapped inside the nanoparticles can be turned on
and off under optical control.
The polymers can preserve the properties of the fuores-
cent molecules and at the same time assist the transfer of the
UV light now can switch fuorescent molecules on and off in aqueous envi-
ronments. Here, live cells have been incubated with the polymer nanoparti-
cles. The green color is the fuorescence coming from the molecules trapped
within the nanoparticles. Images courtesy of Francisco Raymo, University of
Miami.
1012_BioScan.indd 15 9/27/12 8:58 AM
molecules into water, Raymo said. Its
a bit like having a fsh in a bowl, so the
fsh can carry on with its activities in the
bowl, and the whole bowl can be trans-
ferred into a different environment.
The new system is faster and more sta-
ble than current methods. The fuorescent
molecules glow when exposed simultane-
ously to UV and visible light and revert
to their original nonluminous state in less
than 10 s after UV light is removed.
Using synthetic molecules enables the
system to overcome the natural wear that
organic molecules endure from overexpo-
sure to UV light.
The system can be switched back and
forth between the fuorescent and non-
fuorescent states for hundreds of cycles,
without sign of degradation, Raymo said.
The systems surface can be customized
to help it attach to specifc molecules of
interest, enabling researchers to visual-
ize structures and activity within cells, in
real time, with unprecedented resolution.
The fndings were reported online
by Chemistry-A European Journal (doi:
10.1002/chem.201201184).
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typical reflection curve
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CVIMG_DeepUV_hph_PS.indd 1 3/30/2012 10:13:48 AM
BIOSCAN b
Ashley N. Rice
ashley.rice@photonics.com
Francisco Raymo, a professor of chemistry at the University of Miami, has developed a way to switch fuo-
rescent molecules on and off within aqueous environments. The technique could help scientists develop
better fuorescent probes for biomedical research.
1012_BioScan.indd 16 9/27/12 2:47 PM
Guidelines needed to advance diagnostic accuracy
NEW YORK Tiny mechanical micro-
scopes those that can see inside single
living cells increasingly are being
used to diagnose illness in hard-to-reach
areas of the body, but specialists say that
improved, standardized guidelines are
needed to advance diagnostic accuracy.
The little probes often are threaded into
the narrow bile duct that connects the
liver to the small intestine to search for
cancer or are used to minutely explore the
pancreatic duct, said Dr. Michel Kahaleh
of New York-Presbyterian Hospital/Weill
Cornell Medical Center.
But because the groundbreaking tech-
nology is comparatively new, Kahaleh
suspects that specialists using the probes
may be interpreting what they see in dif-
ferent ways.
This was precisely what he found when
he and his research team sent six gastro-
enterologists at fve medical institutions
some videos taken by probe-based confo-
cal laser endomicroscopy (pCLE). The
specialists were asked to analyze seven
variables in the approximately 1-min
videos recorded deep inside 25 patients
with abnormally narrowed bile ducts.
Bile, secreted by the liver to aid digestion,
is transported to the small intestine by
the bile duct. Infammatory disease, the
passing of gallstones or tumors, however,
can cause the duct to constrict, resulting
in a blockage that can lead to cirrhosis,
jaundice or other serious conditions.
In the study, diagnostic agreement was
poor to fair, depending on the variable, as
was the fnal diagnosis.
Physicians need to come up with a
standard way of interpreting what the
videos reveal in order to properly use this
amazing technology, said Kahaleh,
who is chief of endoscopy at the Cen-
ter for Advanced Digestive Care at the
hospital and medical director of the
Pancreas Program at Weill Cornell. We
can see detail that was just unimaginable
a decade ago this breakthrough is born
for the bile duct and those tiny tubes and
complicated organ structures that no one
has ever been able to visualize before.
And when physicians are certain of
what they are seeing, we will be able
to greatly improve patient treatment,
avoiding unnecessary surgery whenever
possible.
The pCLE diagnostic system was
approved by the FDA two years ago for
use in the bile duct and pancreas. The
device is a tiny microscopic probe that is
threaded inside a larger spyglass probe
to image blood vessels, mucosal struc-
tures and epithelial tissue in real time,
broadcasting the images on a large moni-
tor for physicians to examine.
Most institutions, however, still use hit-
or-miss techniques to determine whether
a bile duct is cancerous. In the traditional
technique, a probe is threaded inside the
duct to where it is abnormally narrowed,
and then tiny forceps or a small brush is
used to gather a cell sample that can be
biopsied in the lab.
We still miss 20 to 30 percent of bile
duct cancer or other tumors in this way,
and that is unacceptable, Kahaleh said.
It is clear physicians need a standard
by which to understand what they see,
which will also need to involve more
training, he noted. This is increasingly
important, as these minimally invasive
systems are proposed for use in diagnos-
ing other health issues in the gastrointes-
tinal tract, including ulcerative colitis and
Barretts esophagus.
We can now see inside these tiny
organs, but we just need to know exactly
what we are looking at.
The study was published in Diges-
tive Diseases and Sciences (doi: 10.1007/
s10620-012-2338-6).
BUSINESSSCAN
Tiny microscopes that can see inside single living cells could help gastroenterologists diagnose
conditions as long as guidelines are developed, according to a recent study.
1012_BusinessScan.indd 17 9/27/12 9:01 AM
Quantum cascade laser (QCL) manufacturer
Block Engineering LLC of Marlborough,
Mass., has added SKAE Associates of Lex-
ington and Pembroke Instruments of San
Francisco to its family of sales representatives.
SKAE Associates will cover the New England
states as an exclusive representative for Block
Engineerings line of QCL-based products.
Pembroke Instruments serves emerging mar-
kets within life sciences, semiconductor, R&D
and academic research. It will be the exclusive
representative for California. Block Engineer-
ing added the representatives as a step in its
strategy to increase its focus on industrial and
academic markets and enhance its presence in
commercially critical US locations.
The modular objective assembly in Hamilton
Thorne Ltd.s Lykos and Xyrcos lasers will be
granted a patent, according to a notice of in-
tention that the Beverly, Mass.-based company
received from the European Patent Offce.
Upon approval, the patent can be fled in more
than 30 European countries. The patent on
the modular objective assembly utilized in the
Lykos and Xyrcos lasers is extremely valuable,
as this patent broadly covers the concept of
building a laser into a microscope objective,
said President and CEO David Wolf. The com-
pany said the assembly is a signifcant advance
in integrated laser optics, providing increased
resolution and compatibility with all major
microscope models.
Imaging and analysis systems company FEI Co.
of Hillsboro, Ore., has purchased Visualiza-
tion Sciences Group (VSG) of Bordeaux,
France, for e44.8 million (about $55 million).
The acquisition is expected to expand FEIs
image analysis capability across all of its
markets. FEI funded the purchase with euros
from its European operations, which otherwise
would be subject to US taxation if repatriated.
The acquisition is expected to have a neutral
impact on the companys earnings for the sec-
ond half of 2012 and to be accretive in 2013,
it said. VSG provides high-performance 3-D
visualization software products for the life and
materials sciences, industrial inspection and
other industries.
Dr. Eric Chandler has joined Halma plc sub-
sidiary Ocean Thin Films as an electro-optical
scientist focused on multispectral imaging and
sensing applications. He will provide technical
support to OEM sensing and imaging product
customers using PixelTec multispectral sub-
systems. The proprietary technology enables
micron-scale patterning of multiple thin-flm
optical coatings on a single substrate, provid-
ing compact devices for defense, medical and
industrial applications. Chandler graduated
from the applied physics doctoral program
at the Colorado School of Mines, where his
research efforts focused on nonlinear optical
characterization of silicon nanostructured
materials for bioimaging and photovoltaic
applications.
Pacifc Biosciences of California Inc. of
Menlo Park, and imec, a nanoelectronics
research center in Louvain, Belgium, have
announced a multiyear research collabora-
tion focused on the development of advanced
microchips for highly multiplexed single-mol-
ecule genetic analysis. The research will build
on Pacifc Biosciences zero-mode waveguide
(ZMW) technology and imecs experience in
nanophotonics, CMOS sensors, technology
integration and fabrication. Pacifc Biosciences
said it is committed to exploiting the potential
of the capabilities of its ZMW-based single-
molecule, real-time (SMRT) analysis technology
to drive innovation in the life sciences. The
goal is to harness the power of microchips to
scale the capacity and throughput of the SMRT
technology.
CVI Laser of Albuquerque, N.M., is marking
its 40th anniversary of providing thin-flm-
enabled optical components and subsystems
to the semiconductor, life sciences, industrial,
aerospace and scientifc markets. The company
was founded in 1972 to support high-energy
laser development at Sandia and Los Alamos
national laboratories. In June 2011, CVI was
acquired by Idex Corp., where it joined the
new Idex Optics & Photonics platform. CVI op-
erates manufacturing facilities in Albuquerque;
Carlsbad, Calif.; Rochester, N.Y.; the Isle of
Man and Leicester in the UK; Saitama, Japan;
and Seoul, South Korea.
Medical device industry veteran William M.
Moore will serve as interim president and CEO
of laser-based medical systems maker Iridex
of Mountain View, Calif. He replaces Dominik
Beck, whose employment with the company
ended in August. Moore will continue to serve
as chairman of the board; he has served as
a company director since September 2007.
Moore co-founded Natus Medical Inc., a
provider of health care screening products,
in 1990 and served as CEO until 1993. He
still serves on the companys board. He also
worked as a consultant to BlueLine Partners
LLC, a private equity frm and investor in Iridex.
Rapid growth in Europe and Asia has spurred
nanoanalytical microscopy systems maker
WiTec GmbH of Ulm, Germany, to open
regional offces in Spain and Japan. Head of
the Japan offce, which is in Kanagawa Science
Park, is Dr. Keiichi Nakamoto, a scanning
probe microscopy veteran of more than 20
years. The Spain offce, in Barcelona, will pri-
marily serve the Spanish and Portuguese mar-
kets. Area manager and offce head Dr. Elena
Bailo is a former member of the WiTec service
and support team. Both offces will provide
sales operations, pre- and post-sales technical
support and product demonstrations.
Jenoptiks Lasers & Material Processing
Div. has appointed Stephen Hypsh as vice
president of its North American lasers business
unit. He has more than 15 years of experience
in the laser sector, most recently as head of
business development at femtosecond laser
maker Raydiance. He also has served as a
North American sales manager at Trumpf Inc.
Based in Jena, Germany, Jenoptik manufac-
tures high-power diode lasers, and disk and f-
ber lasers used mainly in industry and medical
technology. The North American unit is based
in Jupiter, Fla.
Samsung Venture Investment Group, the
investment arm of Samsung Group, and
other companies have invested $20 million in
ultrafast laser solutions company Raydiance
Inc.s latest growth fnancing round. The
funds will be used to accelerate the Petaluma,
Calif.-based companys consumer electronics
efforts and to ramp up manufacturing to meet
the demand for its medical device, automotive
and other manufacturing customers. Others
included in the fnancing round are existing
Raydiance investors Draper Fisher Jurvetson,
DFJ-Growth and Greenstreet Partners.
To leverage emerging opportunities in North
America and Europe, laser diode module and
LED systems manufacturer ProPhotonix Ltd.
of Salem, N.H., has hired fve people to join
its global sales team. Patric Geubbelmans will
serve as regional sales manager for Benelux,
Western Germany, France and Switzerland.
David Richards will manage the UK, Ireland,
Spain, Italy and the Nordics. In North America,
Kevin Finn will manage sales for the West,
Nazih Moussawee for the Midwest and George
Minott for the East regions. The companys
products have applications in the industrial,
medical, and security and defense markets.
InfniLED, a spinout of Tyndall National
Institute of Cork, Ireland, and a portfolio
company of London-based ScienceWorks
Ventures plc, has announced an access
agreement with Tyndall National Institute
allowing InfniLED engineers to work within
the institutes ISO 9001-certifed compound
semiconductor cleanrooms to fabricate its LED
technology. InfniLED develops LED light source
modules based on its patented LED technol-
ogy. By the end of this year, it aims to bring to
market its frst LED-based products, which
are suitable for diagnostic testing devices and
consumer products.
ON Semiconductor Corp. of Phoenix and
Donald Colvin, its executive vice president
and chief fnancial offcer, have mutually
agreed to Colvins resignation as an offcer
of the company. The company said he would
continue at the frm for up to 90 days while a
replacement is sought. The search process for
a new CFO has been launched by the board.
ON Semiconductor supplies silicon solutions
for energy-effcient electronics. Its power and
signal management, logic, discrete and custom
devices help customers solve design challenges
in automotive, computing, LED lighting, medi-
cal, military, aerospace, consumer and power
applications.
eMagin Corp. of Bellevue, Wash., has re-
ceived a $2.4 million US Navy contract for the
research and development of a high-brightness
BUSINESSSCAN b
BUSINESSBRIEFS
2000 2000-pixel OLED microdisplay. The
$1.1 million Phase I of the project was sched-
uled to run through September 2012, when
the $1.3 million Phase II option period was
scheduled to begin; the second phase will run
an additional 12 months. The proposed work
for this program will leverage the accomplish-
ments of prior Night Vision and Electronic
Sensors Directorate OLED programs and
further improve OLED performance. eMagin
manufactures OLED microdisplays for military,
industrial, medical and consumer OEMs.
Rochester Institute of Technology in New
York has been awarded $1.2 million by the
National Science Foundation to develop,
fabricate and test a family of detectors grown
on silicon wafer substrates by Raytheon Vi-
sion Systems of Waltham, Mass. Cheaper,
larger and better infrared detectors grown on
silicon wafers could give more scientists access
to infrared astronomy and further spur the
hunt for exoplanets and the study of the uni-
verses acceleration. Closer to home, the same
technology could advance remote sensing and
medical imaging.
Volpi AG of Schlieren, Switzerland, has been
named a certifed solution partner of LED
technologies provider Luminus Devices of
Billerica, Mass. With its new partner, Luminus
wants to support customers better and provide
shorter development times in the case of
complex lighting solutions. With access to new
LED technologies, Volpi can further expand its
technological lead in high-end applications in
medical technology, life sciences and industrial
image processing. Luminus also has opened
a sales and support offce in Taoyuan County,
Taiwan, in response to the growing demand in
the Asian market.
Michael Volpe has been named a senior ad-
viser for the investor relations program at
Laser Energetics Inc. of Mercerville, N.J. He
will coordinate with Ray Dirks and Michael
Little to expand the companys shareholder
base and to elicit investor interest. He brings
to the new role more than 25 years of Wall
Street experience and was a senior-level
branch manager at Josepthal & Co. and
Oppenheimer & Co. He oversaw sales, re-
cruiting and fnancial advising on a daily basis.
Laser Energetics develops laser products that
address applications in industry, science, medi-
cine, homeland security and the military.
Dr. Farzan Bob Roohparvar has been
replaced as president of DigitalOptics Corp.
(DOC) by Chief Operations Offcer Logan
Saverimuthu. The company announced the
departure and interim appointment in Septem-
ber. Roohparvar came to DOC from Flextron-
ics, which he joined in 2006 as president of its
power supply business FlexPower and where
he served as president and CEO of Vista
Point Technologies. Saverimuthu, who joined
DOC in April 2011, manages DOC plants and
production facilities. DOC, of San Jose, Calif.,
makes miniaturized camera modules for con-
sumer electronics and the automotive, medical
and security markets. It is a wholly owned
subsidiary of Tessera Technologies Inc.
Matthijs Glastra has been hired as group
president of GSI Group Inc.s Laser Products
Div. A longtime Philips executive, he was ex-
pected to join GSI in the fourth quarter and to
be based at the companys Santa Clara, Calif.,
site. The company also announced the depar-
ture of corporate offcer Dave Clarke, effective
Sept. 28. Clarke spent 18 years with GSI,
including 14 years as president of Synrad,
its industrial CO
2
laser business. GSI Group,
of Bedford, Mass., designs and manufactures
laser-based products, and precision motion
and optical technologies for the industrial,
electronics, medical and scientifc markets.
Kentek Corp. of Pittsfeld, N.H., has acquired
fellow laser safety products maker Laser-
Professionals Inc. Financial terms of the deal
were not disclosed. Kentek also provides laser
components and accessories for end users in
various sectors, including medicine. With the
acquisition, Kentek launched Laser Smart
Services, which includes laser safety audits,
training and consulting.
PicoQuant GmbH
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Tel.: +1-413-562-6161
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BUSINESSSCAN b
Fiber Optics Revolutionizes Neuroscience
An occasionally overlooked technology leads to major advances in the feld
F
iber optics might just be the Rodney
Dangerfeld of the photonics world:
Despite being a workhorse technol-
ogy that has contributed to countless
studies over the years, it doesnt always
get the respect it deserves. But, in fact, it
is integral in a broad spectrum of imaging
and monitoring techniques.
Here, we look at the importance of fber
optics in the development and application
of two techniques that have made and
continue to make signifcant contribu-
tions in the feld of neuroscience.
Untangling BOLD fMRI signal
Blood oxygen level-dependent (BOLD)
functional MRI (fMRI) is widely used in
neuroscience studies, but it is an indirect
and imprecise measure of neural activity;
the relationship between the changes in
blood fow and oxygenation it measures
and the neural activity that spurs those
changes is still not entirely clear, so
researchers dont necessarily know how
accurately the BOLD signal refects what
is happening at the neural level.
One way to tease out this relationship
BY GARY BOAS, NEWS EDITOR
Feat FiberNeuro.indd 20 9/27/12 10:15 AM
is to measure the BOLD signal and the
underlying neural activity simultaneously,
the latter with conventional electrophysi-
ological recordings. But this technique is
really challenging because the magnetic
feld of the MR scanner heavily interferes
with the electrical signal and vice versa,
said Kristina Schulz, a researcher with
the Brain Research Institute at the Uni-
versity of Zurich.
In a recent Nature Methods paper,
Schulz and colleagues from Fritjof Helm-
chens group and Markus Rudins group
at the university reported a study in which
they combined fMRI recordings of the
BOLD signal with fber optic recordings
of fuorescent calcium indicator signals
to probe the relationship between the two
in a rat somatosensory cortex. Calcium
indicators offer a suitable alternative to
electrophysiological recordings, they
wrote, because they can measure several
aspects of cortical dynamics including
neuronal network activations and glial
signaling in vivo, using single-photon
excitation delivered through a conven-
tional optical fber.
Was there anything particularly
complicated anything fancy about the
use of fber optics in the study? It was
actually pretty straightforward, Schulz
said, and I guess it could have been done
even earlier. She noted that the novelty
of the study, at least in the early stages,
lay simply in the idea to combine the two
measures.
Using this multimodal approach with
BOLD fMRI and calcium recordings
the investigators found that they could
measure signals that have not been acces-
sible with electrophysiological record-
ings. They could show, for example, how
astrocytic activity relates to the BOLD
signal.
By using astrocyte-specifc calcium
indicator labeling, we discovered that
our stimulation paradigm in some cases
induced strong astrocytic activation,
Schulz said. We could further show a
relation of these astrocytic calcium waves
to prolonged and increased BOLD signals.
This relation could only be uncovered by
simultaneous measurements.
The unsung hero of optogenetics
Fiber optic technology is leaving its
fngerprint everywhere, it seems. In
recent years, it has played an integral
role in another cutting-edge neuroscience
technique optogenetics by enabling
Researchers have developed and are beginning to perform implants of 3-D multiwaveguide
probes. Courtesy of Ed Boyden.
MITs Ed Boyden and colleagues are working to expand their multiwave-
guide approach into three dimensions, designing probes that enable light
delivery to thousands of individual sites in the brain in full 3-D patterns.
In this way, we can try to simulate complex patterns of stimulating the
brain, important for testing theories of how the brain encodes for infor-
mation, Boyden said.
New probes, new data
Hoping to better understand the relationship between the blood oxygen level-dependent (BOLD) func-
tional MRI (fMRI) signal and the underlying neural activity, researchers performed multimodal imaging
of the rat somatosensory cortex with BOLD fMRI recordings and fber optic recordings of fuorescent
calcium indicator signals. Shown here is the MR scanner used in the study. The optical setup was kept
outside the electromagnetically shielded MR scanner area and connected to the probe with an optical
fber more than 7 m in length. Courtesy of Kristina Schulz, Group Helmchen, University of Zurich.
delivery of light to deep regions of the brain that might not be
accessible otherwise.
Optogenetics seeks to elucidate the role of neural circuits in
certain behaviors by silencing or driving particular neural activ-
ity patterns. Stanford Universitys Karl Deisseroth, a pioneer
of the technique, recalls how important fber optics was to its
development. When he and colleagues reported an in vitro,
proof-of-principle study in Nature Neuroscience in 2005, he said,
other researchers questioned how the method would work in liv-
ing animals light would scatter before it reached the targeted
tissue, they argued.
That was a good criticism, Deisseroth continued, and it
was a couple of years before we fgured it out.
The researchers tried a variety of approaches. They tried
surface illumination; they tried opposing LEDs; they considered
strategies to make cells generate their own light. Other groups
also sought to tackle the problem. But the basic question of how
to deliver light to deep regions of the brain remained unan-
swered.
Finally, the Stanford group coupled laser diodes to optical
fbers and, in 2007, reported the frst fber optics-based neuroin-
terface. The fbers were off the shelf, Deisseroth said, nothing
fancy. The method worked, though, and today it is a fundamental
part of optogenetics studies.
And there is no shortage of these. In 2010, Science hailed op-
togenetics as one of the breakthroughs of the decade, noting that,
within a few short years, thousands of scientists in hundreds of
labs were using the technique to explore how the brain works.
The questions it can help to answer are myriad, ranging from
how cocaine use affects the brains reward pathway to a universe
of questions in the area of psychiatry. And fber optics is at the
center of it all.
Ed Boyden, a researcher in the MIT Media Lab and another
pioneer in the feld he was frst author on the 2005 Nature
Neuroscience paper and is recognized with Deisseroth as a co-
inventor of optogenetics emphasizes the importance of fber
optics to the success of the technique.
For the in vivo, live-brain case, he said, it would have been
much, much harder without fber optics or waveguides. (In vitro,
of course, you can just use a microscope to illuminate the cells
through the objective lens.)
Basically, you have two choices for illuminating a deep
target: implant a light source in the brain or use a waveguide or
fber to serve as a conduit to get light into the brain. Implanting
Fiber Optics
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Fiber optics plays an integral role in optogenetics. Here, an example of in
vivo manipulation of neurons using fber optics, as reported by Karl Deis-
seroths group at Stanford University. ChR2(C 128S)-EYFP was expressed
in hippocampal CA1 neurons using the aCaMKII-tTa line. Blue light pulses
transmitted through an optical fber inserted into the brain illuminated the
dorsal left hippocampus, and neuronal activity was measured. Courtesy of
Cell Reports.
a light source into the brain is tricky because it can rapidly result
in prohibitive heat. This essentially leaves use of a waveguide
or fber as the only viable option.
As successful as fber optic technology has proved already,
however, scientists are looking at how they can use it to advance
their research still further.
At Stanford, Deisseroths group is looking at the possibility
of having extremely dense arrays of independently addressable
sources and using the fber bundle as a collimator coupled to im-
age information on either end.
Also, Boyden and colleagues have demonstrated a multiwave-
guide probe that offers optical control over sets of targets in the
brain by independently delivering light to targets along the probe
axis. The probe consists of many waveguides running in paral-
lel to one another and thus enables systematic manipulation of
neural activity in different parts of brain circuits, with minimal
damage to the brain.
The researchers are now applying the probe to map such cir-
cuits; for example, using it to stimulate a number of individual
sites in the brain in rapid succession to see which most strongly
connect to a downstream target. This could help to determine
whether the functional connections between different parts of
the brain change over time.
Also, Boyden said, by stimulating multiple sites in temporal
registration to one another, they can play back activity to the
brain. One of my hopes is that we can use this technology to
test detailed theories of the neural codes utilized by the brain.
Say that we could stimulate a set of neurons with a realistic pat-
tern of activity: We could try to fgure out whether that realistic
pattern of activity actually drives a particular perception, action
or behavior.
gary.boas@photonics.com
Fiber Optics
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Optical Microscopy Quantifes
Live Cells Without Labels
With increasing frequency, noninvasive, label-free microscopy
methods are capturing subcellular details in live cells and tissues
at ever-smaller resolutions.
BY VALERIE C. COFFEY
FREELANCE SCIENCE WRITER
U
nderstanding the complex behavior
and dynamics within live cells
is key to exploring biological
processes. Researchers have increas-
ingly employed novel optical microscopy
techniques and devices to conduct live-
cell imaging, which allows the study of
dynamic processes such as cell division
and protein formation in real time.
1
One
challenge to live-cell imaging is that live
cells exhibit low contrast and an often
transparent internal structure. To address
this, optical microscopy relies heavily
upon staining the cell with fuorescent
dyes and labels, which can interfere with
long-term biological dynamics. Fluores-
cent dyes also tend to photobleach, which
limits imaging time.
Several novel label-free methods help
biologists to measure quantitative proper-
ties and dynamic processes without dam-
aging the live cells. One approach, quanti-
tative phase imaging, records the phase of
light as it passes through a transparent or
translucent object. Because this technique
provides a quantitative measurement of
the optical feld, dyes and labels are not
required to enhance the image contrast.
Last year, a team of researchers led by
professor Gabriel Popescu at the Beck-
man Institute at the University of Illinois
at Urbana-Champaign successfully mea-
sured 3-D complex felds on live neurons
and photonic crystal structures, using a
new optical technique called spatial light
interference tomography (SLIT).
2
The
method, a variation of quantitative phase
imaging, uses a combination of micros-
copy and interferometry to measure the
mass density of a cell in 3-D.
The 3-D capabilities of SLIT were fur-
ther extended recently when the research-
ers added advanced image processing and
a novel computational technique that uses
a 3-D feld deconvolution algorithm called
deconvolution spatial light interference
tomography (dSLIT) to obtain subdiffrac-
tion-limited resolution of live E. coli cells
(Figure 1).
3

This is the frst time this kind of imag-
ing has been done, said Mustafa Mir,
frst author on the paper and a member
of Popescus Quantitative Light Imaging
Laboratory at Beckman. We imaged sub-
cellular structures in E. coli smaller than
the diffraction-limited resolution of the
microscope in 3-D for the frst time, using
only the intrinsic contrast of the sample.
Leaving the cell free of labels, stains
or other contrast agents allows us to
image the live cells indefnitely. Our tech-
nique doesnt kill them with chemicals or
phototoxicity; the cells are happy.
People thought E. coli was an amor-
Figure 1a. Label-free, noninvasive microscopy methods can capture subcellular details in vivo at
ever-smaller resolutions. Here, the deconvolution spatial light interference tomography (dSLIT) optical
microscopy technique resolves a subdiffraction-limited helical structure in live E. coli cells 0.5 m across,
an improvement on the spatial light interference microscopy (SLIM) technique. Both techniques enable
subcellular imaging of live cells without contrast stains or fuorescent dyes, which can affect cellular life
cycles and dynamics. Courtesy of Mustafa Mir, Gabriel Popescu and Derin Babacan.
Figure 1b. A surface map representation of E.
coli cells shows the enhanced subcellular detail
obtained using dSLIT processing on SLIM optical
microscopy techniques. Courtesy of Mustafa Mir,
Gabriel Popescu and Derin Babacan, University
of Illinois at Urbana-Champaign.
Micro Deep Feat.indd 24 9/27/12 9:03 AM
phous blob, Mir said, but it really has a
cytoskeletal structure that was previously
thought to exist only in eukaryotic cells.
We found two coiled, subcellular struc-
tures: one that retains a constant period as
the cell grows, and one with a period of
approximately half the length of the cell.
The practical, noninvasive dSLIT
imaging technique should foster quicker
turnaround times for experiments study-
ing the basic physiology of cells such
as E. coli. The research team designed a
white-light quantitative-phase-imaging
add-on device that can be used with many
existing phase-contrast microscopes.
Our imaging method works with any
brand of microscope, Popescu said. He
used the Zeiss AxioObserver Z1 phase-
contrast microscope. We put a lot of
work into making this into an add-on
device so many people can use it (see
Figure 2).
The add-on device is in development at
Phi Optics, a startup company founded by
Popescu in 2009 and located in the Uni-
versity of Illinois at Urbana-Champaigns
Research Park. Phi Optics is currently
co-developing the add-on device with a
commercial partner.
Live-cell video imaging
Live-cell phase-based imaging can also
lend itself to 4-D video. Popescus team
has used spatial light interference micros-
copy (SLIM) for time-lapse (video) mea-
surements for several applications; it has
even developed a method that measures
temporal fuctuations to characterize mass
transport in living cells.
4
Such fast movies
enable investigation of phenomena such
as membrane dynamics; movies over
longer periods (up to two weeks) make it
possible to study cell growth, motility and
neural network formation, among many
other applications.
Another recent development in live cell
imaging is called interferometric phase
microscopy (IPM). Researchers at Tel
Aviv University in Israel recently used
IPM to record the phase of transparent
samples without labeling at a rate of up to
thousands of frames per second (a submil-
lisecond rate).
5

Professor Natan Shaked and col-
leagues in the department of biomedical
engineering used live video to quantita-
tively image a monolayer of transparent
HeLa human cervical cancer cells with
subnanometer accuracy (albeit laterally
diffraction-limited at a resolution of 600
nm) without labeling or physical contact
with the sample (Figure 3).
The team demonstrated that optical
thickness values of a cell can be used for
quantitative microscopy to identify the
various cell life-cycle stages and sub-
stages, growth rates, controlled or linear
growth, and more with no fuorescent
dyes or special sample preparation.
6

By directly measuring the quantitative
phase measurements of nucleated cells,
Shaked said, we were able to describe
unique life-cycle stages and substages of
the HeLa cancer cells.
Current commercial availability of
portable interferometric microscopes is
Figure 2. The optical microscopy setup of the dSLIT technique at the University of Illinois at Urbana-
Champaign incorporates the Zeiss AxioObserver Z1 phase-contrast microscope; the add-on device can
be used with many existing phase-contrast microscopes, however. Courtesy of Mustafa Mir, Gabriel
Popescu and Derin Babacan.
Figure 3. Without using fuorescent dyes or other sample preparations, wide-feld interferometric phase
microscopy can map the dynamic quantitative optical thickness of a HeLa human cervical cancer cell
during its full life cycle (19 hours) with subnanometer sensitivity. The cycle starts with the division of the
mother cell (G1 phase) and continues through DNA replication (S phase), the premitotic stage (G2 phase)
and new cell division (M phase). The feld of view is 180 3 143 m. Courtesy of The Optical Society,
Natan Shaked and Pinhas Girshovitz.
limited because obtaining high-quality,
stable interference patterns with mod-
est equipment is diffcult. To solve this
problem, Shaked and colleagues designed
the interferometer, an inexpensive
portable device that can be attached to
the output of an inverted microscope to
obtain spatial interferograms of micro-
scopic biological samples.
7
It can do this
without the strict stability and highly
coherent illumination usually required for
interferometric microscopy setups. Built
using off-the-shelf optical elements and
operable with low-coherence illumina-
tion, the interferometer measures the
optical thickness profle with temporal
stability of 0.18 nm and spatial stability
of 0.42 nm.
Optical Microscopy
Figure 4. Stimulated Raman scattering (SRS)
microscopy can image cells live. (a) Raman spec-
trum of an HEK-293 cell pellet. (bf) Stimulated
Raman scattering images of HEK-293 cells at: (b)
2845 cm
21
, primarily lipid; (c) 1004 cm
21
, phe-
nylalanine; (d) 785 cm
21
, nucleic acid; (e) 1090
cm
21
, primarily nucleic acid. (f) Multicolor overlay
of (b) (d). Scale: 20 mm. Courtesy of Wiley-VCH
Verlag GmbH & Co. KGaA, Weinheim, Germany.
We believe that the simplicity of connecting the device to a
microscope and ease of operation will make wide-feld IPM [in-
terferometric phase microscopy] more accessible and affordable
for biologists and clinicians, signifcantly broadening its range of
applications, Shaked said.
We are now working on better setups with higher resolution
and portability, and on solving fundamental problems associated
with IPM setups, he added. We are also working on vari-
ous new and exciting biological and medical applications that
become possible using this technology, such as cancer detection
and blood screening. Further, the group has patented the inter-
ferometer and is working toward commercialization.

SRS microscopy
Another method of live-cell imaging without labels or dyes
comes from X. Sunney Xie and colleagues at Harvard University
in Cambridge, Mass. The group used a microscopy technique
based on stimulated Raman scattering (SRS) to image the chemi-
cal composition of live cells.
8
The team measured the Raman vi-
brational signatures of nucleic acids, lipids and proteins to reveal
subcellular details of human embryonic kidney cells (HEK-293),
breast cancer cells (MCF-7) and chromosomes within the sali-
vary glands of fruit fy larvae (Figure 4).
We are moving toward in vivo imaging in living animals to
decipher some scientifc problems involving cell-division-related
disease models, said Xu Zhang, frst author and PhD candidate
in Xies lab. We next plan to focus on histopathological studies
and further development of this technique as an intraoperative
diagnostic tool.
The technology, which offers diffraction-limited resolution
of 400 nm, has commercial potential for academic research and
for medical diagnostics. The team expects to reduce costs and
improve portability by developing a fber-based system.
Meet the author
Freelance science and technology writer and editor Valerie C. Coffey is
the founder of Stellar Editorial Services in Boxborough, Mass.; email:
stellaredit@gmail.com.
References
1. Live Cell Imaging Techniques, http://www.leica-microsystems.com.
2. S. McGaughey (June 28, 2012). Stealthy microscopy method visual-
izes E. coli sub-cellular structure in 3-D. http://www.beckman.
illinois.edu/news.
3. M. Mir et al (June 28, 2012). Visualizing Escherichia coli sub-cellular
structure using sparse deconvolution spatial light interference tomog-
raphy. PLoS One 7(6), e39816.
4. Z. Wang et al (Feb. 28, 2011). Label-free intracellular transport mea-
sured by spatial light interference microscopy. J. Biomed. Opt. Vol.
16, 026019.
5. N.T. Shaked (2012). Visualizing transparent biology with sub-nano-
meter accuracy. SPIE Newsroom online, http://spie.org/x87885.xml.
6. P. Girshovitz, N.T. Shaked (Aug. 1, 2012). Generalized cell morpho-
logical parameters based on interferometric phase microscopy and
their application to cell life cycle characterization. Biomed. Opt.
Express, pp. 1757-1773.
7. N.T. Shaked (2012). Quantitative phase microscopy of biological
samples using a portable interferometer. Optics Letters, Vol. 37, pp.
2016-2018.
8. X. Zhang et al (2012). Label-Free Live-Cell Imaging of Nucleic Acids
Using Stimulated Raman Scattering Microscopy. ChemPhysChem,
Vol. 13, pp. 1054-1059.
Optical Microscopy
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Flexibility Improves Photoacoustic Microscopy
Switching from optical resolution to acoustic resolution
allows scientists to extract more information from samples.
BY ZHUN XU AND JAY ZHAO
MICROPHOTOACOUSTICS INC.
O
ptical imaging offers the pros-
pect of visualizing anatomical
structures and detecting func-
tional characteristics with nonionizing
radiation,
1
but the predominant optical
scattering in tissue limits penetration at
high spatial resolution to depths within
one transport mean-free path (typically,
~1 mm in tissue).
1,2
Also, traditional opti-
cal microscopy fails to provide in vivo
physiological information such as blood
oxygenation and fow rate in vasculature,
which is required by clinical and research
studies.
2-6
Photoacoustic imaging, emerging as a
promising biomedical imaging technol-
ogy, combines the advantages of optical
imaging (high sensitivity) and ultrasonic
imaging (low scattering). With ultrasonic
detection of optical absorption in biologi-
cal tissues, photoacoustic imaging yields
a relatively large depth-to-resolution ratio
among all the optical imaging technolo-
gies.
1-7
During the imaging process, the
target is irradiated by a pulsed laser beam,
and the ultrasonic waves are generated
through thermoelastic conversion and
detected by an ultrasonic transducer.
The attributes of multiscale spatial
resolution, noninvasive functionality and
relatively large penetration depth render
photoacoustic imaging well suited for var-
ious biomedical applications across a wide
range of length scales, from centimeter-
size breast tumors to micrometer-size
single red blood cells. Many optical ab-
sorbers have proved useful in photoacous-
tic imaging as well, such as hemoglobin,
7

melanoma,
8
water,
9,10
lipids,
11
and various
natural and articial contrast agents.
12-15
A new integrated rapid-scanning PAM
(photoacoustic microscopy) system
(Figure 1) is switchable between optical-
resolution PAM (OR-PAM) and acoustic-
resolution PAM (AR-PAM), which can
provide biological functional information
in tissue with high resolution and depth.
In the system, two Q-switched ber
lasers (for OR- and AR-PAM, respec-
tively) provide photoacoustic irradiation
at a wavelength of 532 nm. By replacing
a single-mode ber with a multimode one
congured with a different collimator
lens, keeping all other parts unchanged,
it is easy to switch between OR-PAM
and AR-PAM modes. The B-scan rate for
OR-PAM across a 2-mm line is ~5 Hz
(0.625-m step size), and for AR-PAM,
~50 Hz (6.25-m step size).
By using nanotubes as targets, the
lateral resolution of the OR-PAM was
measured as 2.56 m, in good agreement
with the theoretical resolution, calculated
as 0.61/NA 2.55 m.
Several in vivo mouse images obtained
Figure 1. A new photoacoustic microscopy (PAM) system is switchable between optical-resolution PAM
and acoustic-resolution PAM. This fexibility can provide functional information in tissue with high
resolution and depth. Images courtesy of MicroPhotoAcoustics Inc.
Pai Feat.indd 28 9/27/12 9:05 AM
by the system are shown in Figure 2.
Figures 2a and 2b are mouse ear and
brain OR-PAM images. During the brain
imaging process, the scalp was removed,
but the skull was kept intact (Figure 2b).
Taking advantage of the high lateral reso-
lution, OR-PAM resolves capillaries very
well. Figure 2c is an AR-PAM image of
the mouses back. Vasculature structure
lying ~400 nm to 1.2 mm beneath the
surface is revealed.
One special application of PAM is in
revealing the use of oxygen by tissues;
i.e., the blood oxygen saturation (sO
2
),
especially the sO
2
distributions in capil-
laries.
5,16
This is achieved by using the
spectral difference between oxy- and
deoxyhemoglobin. In this work, two
lasers at wavelengths of 532 and 560 nm
were triggered sequentially to irradiate
the imaging target at each point (A line)
in B-scans. A photodiode monitored
the fuctuation in laser intensity. The max-
imum-amplitude-projection (MAP) image
at 532 nm and the sO
2
image are shown in
Figures 3a and 3b, respectively.
PAM also is a promising imaging
modality for clinical studies. Figure 4
shows its potential in imaging the human
vascular structure within ~1 mm beneath
the surface of the skin. The photoacoustic
signal from above the epidermal-dermal
junction was removed during the con-
struction of the MAP images. Signifcant
vascular differences among skin from
different regions were visualized; here,
PAM demonstrates its feasibility to assess
microvascular functioning in humans.
Examining the microvascular networks in
human skin in vivo can aid the study and
understanding of microcirculation. The
potential uses of PAM include diagnosis
of many cardiovascular disorders such as
diabetes, hypertension, renal and vascular
diseases as well as monitoring of heman-
giomas and angiogenesis of tumors.
17
The combination selectively provides
high-resolution images of relatively shal-
low features and useful images, albeit at
lower resolution, of deeper structures and
targets. It effectively bridges the scales
of microscopic research and clinical
practice.
More applications of this technol-
ogy including testing of drug re-
sponse, biomarkers and gene activities
are expected with the help of organic
dyes, reporter genes and nanoparticles.
Melanoma imaging, gastrointestinal tract
endoscopy, intravascular catheter imag-
ing, neonatal brain imaging, breast cancer
imaging and sentinel lymph node needle
biopsy for cancer staging are anticipated
in our future clinical applications.
16
Meet the authors
Zhun Xu is a biomedical researcher at Micro-
PhotoAcoustics (MPA) Inc.; email: johnxz@
biompa.com. Jay Zhao is a research scientist at
MicroPhotoAcoustics; email: jay@a-optowave.
com.
MPA is a spinoff from Advanced Optowave
Corp., founded in 2010 with the inventors of
3-D PAM. Multiple patents have been licensed
from Dr. Lihong Wangs Optical Imaging Lab-
oratory at Washington University in St. Louis.
This project was sponsored by the National
Institutes of Health Small Business Innovation
Research grant 1R43HL106855-01.
References
1. L.V. Wang and H.-i Wu (2007). Biomedical
Optics: Principles and Imaging. Wiley-
Interscience.
2. K. Maslov et al (2005). In vivo dark-feld
refection-mode photoacoustic microscopy.
Optics Letters, Vol. 30, Issue 6, pp. 625-627.
3. E.Z. Zhang et al (2009). In vivo high-resolu-
tion 3D photoacoustic imaging of superfcial
vascular anatomy. Physics in Medicine and
Figure 2. In vivo images of a mouse: (a) mouse ear and (b) brain imaged by optical-resolution PAM;
(c) mouse back imaged by acoustic-resolution PAM. The photographs are shown in the left column.
The photoacoustic amplitude in each image in the right column was normalized.
Figure 3. Revealing blood oxygen saturation is
one application of PAM. Here, in vivo mouse ear
blood-oxygen-saturation images: (a) maximum-
amplitude-projection image at 532 nm; (b) sO
2

image.
Biology, Vol. 54, Issue 4, pp. 1035-1046.
4. J. Yao et al (2010). In vivo photoacoustic
imaging of transverse blood fow by using
Doppler broadening of bandwidth. Optics
Letters, Vol. 35, Issue 9, pp. 1419-1421.
5. S. Hu et al (2011). Second-generation
optical-resolution photoacoustic microscopy
with improved sensitivity and speed. Optics
Letters, Vol. 36, Issue 7, pp. 1134-1136.
6. H.F. Zhang et al (2006). Functional pho-
toacoustic microscopy for high-resolution
and noninvasive in vivo imaging. Nature
Biotechnology, Vol. 24, pp. 848-851.
7. X.D. Wang et al (2003). Noninvasive laser-
induced photoacoustic tomography for
structural and functional in vivo imaging
of the brain. Nature Biotechnology, Vol. 21,
Issue 7, 803-806.
8. Jung-Taek Oh et al (2006). Three-dimen-
sional imaging of skin melanoma in vivo by
dual-wavelength photoacoustic microscopy.
Journal of Biomedical Optics, Vol. 11, Issue
3, p. 034032.
9. Z. Xu et al (2011). In vivo photoacoustic to-
mography of mouse cerebral edema induced
by cold injury. Journal of Biomedical Optics,
Vol. 16, Issue 6, p. 066020.
10. Z. Xu et al (2010). Photoacoustic tomog-
raphy of water in phantoms and tissue.
Journal of Biomedical Optics, Vol. 15, Issue
3, p. 036019.
11. Bo Wang et al (2010). Detection of lipid in
atherosclerotic vessels using ultrasound-
guided spectroscopic intravascular photo-
acoustic imaging. Optics Express, Vol. 18,
pp. 4889-4897.
12. J. Yao et al (2009). Evans blue dye-en-
hanced capillary-resolution photoacoustic
microscopy in vivo. Journal of Biomedical
Optics, Vol. 14, p. 054049.
13. K.H. Song et al (2009). Near-infrared gold
nanocages as a new class of tracers for
photoacoustic sentinel lymph node mapping
on a rat model. Nano Letters, Vol. 9, Issue 1,
pp. 183-188.
14. C. Kim et al (2010). Sentinel lymph
nodes and lymphatic vessels: noninvasive
dual-modality in vivo mapping by using
indocyanine green in rats volumetric spec-
troscopic photoacoustic imaging and planar
fuorescence imaging. Radiology, Vol. 255,
pp. 442-450.
15. M.L. Li et al (2008). Simultaneous molecu-
lar and hypoxia imaging of brain tumors
in vivo using spectroscopic photoacoustic
tomography. Proc IEEE, Vol. 96, Issue 3,
pp. 481-489.
16. L.V. Wang and S. Hu (2012). Photoacoustic
tomography: in vivo imaging from organ-
elles to organs. Science, Vol. 335, No. 6075,
pp. 1458-1462.
17. C.P. Favazza et al (2011). In vivo photo-
acoustic microscopy of human cutaneous
microvasculature and a nevus. Journal
of Biomedical Optics, Vol. 16, Issue 1, p.
016015.
Photoacoustic Microscopy
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Figure 4. Human images (all at 532 nm): (a) cuticle image by optical-resolution PAM; (b) palm image;
(c) inner forearm by acoustic-resolution PAM. Regions of interest are indicated by black rectangles. The
photoacoustic amplitude in each subfgure was normalized.
Tell-Tale Color Changes:
Camera Can Find Age of a Bruise
Changes in bruise color allow doctors to draw conclusions
about when an injury occurred.
BY DR. BARBARA STAM, DR. GERHARD HOLST
AND URSULA BUCZEK
T
o determine physical abuse of a
child, several warning signs must be
considered: Is the child scared? Are
bruises present, and if so, where? What
do the parents say happened to the child?
Although a physician can pick up on most
of these signals, a conviction based on
this information alone can be difcult.
One reason is the uncertainty as to ex-
actly when the injury happened a bruise
or hematoma bears no time stamp. If it
were possible to determine the precise
time that the child got hurt, even days
later, physicians and courts would
have an effective weapon against child
abusers.
A reliable method of calculating that
specic moment may be available in the
near future, thanks largely to the work
of Dr. Barbara Stam (co-author of this
article), a medical physicist at the Aca-
demic Medical Center of the University of
Amsterdam. In her doctoral thesis, Stam
laid the groundwork for reliably deter-
mining the age of hematomas based on
their color. This has been tried in the past,
but dating injuries by using color tables is
an imprecise method that cannot be used
in court. Even technical processes have
brought no advances up to now.
Stam built on work carried out by a
colleague, Lise Lyngsnes Randeberg of
the Norwegian University of Science and
Technology in Trondheim, who developed
a model linking the color of the hematoma
to its age, enabling calculation of when
the injury originally occurred. Stam,
meanwhile, has succeeded in developing
a method based on this model that doctors
should be able to use in several years
without undue expense or effort.
In the case of a hematoma, the clock
starts ticking as soon as the the skin re-
ceives the blow. Blood from damaged ves-
sels spreads throughout the surrounding
tissue, creating a dark reddish-blue mark,
which expands slightly over the next 24
hours. This is caused by hemoglobin,
the red blood pigment. At the same time,
a larger yellow area of bilirubin forms
around the mark, a result of enzymatic
conversion of the hemoglobin. The biliru-
bin is eventually cleared by the lymphatic
system, one of whose tasks as part of the
immune system is to lter waste products
from the body.
Dr. Barbara Stam of the
Academic Medical Center of
the University of Amsterdam
and colleagues have developed
a system that uses the color of
a bruise to determine its age.
Here, the ring of LED lights they
developed for the system.
Images courtesy of PCO.
Feat PCO.indd 31 9/27/12 9:07 AM
Key to establishing a bruises age is the
fact that the two substances increase and
disappear at different rates, resulting in
an inhomogeneous distribution of color
beneath the skin. The dark hemoglobin
mark usually reaches its maximum size
after just a day; after that, it begins to
shrink as it is converted into bilirubin. On
average, this mark completely disappears
after about a week. In contrast, the yellow
area continues to expand for an average
period of four days before slowly begin-
ning to disappear.
The presence of the bilirubin is a
delicate balance between formation of
bilirubin from the breakdown of hemo-
globin and clearance of bilirubin into the
lymphatic system. This mark also disap-
pears after 10 days. Information about the
age of a hematoma is obtained from the
ratios between the sizes of the two marks,
rather than from the absolute quantity of
both, and in particular from the change in
these ratios over time.
Bruises, up close and personal
Stams apparatus can automatically
measure this color distribution. She posi-
tions a pixelfy qe camera system from
PCO of Germany above the damaged
tissue. A liquid crystal tunable flter that
allows only certain wavelengths of visible
light to pass through it is mounted in front
of the camera. The flter can be opened
and closed in 2-nm steps within the
visible light spectrum between 440 and
700 nm. In the course of a full measure-
ment, 131 images are recorded, each of
which is for only a narrow 2-nm band of
wavelength. The fnal result is a 3-D data
record that shows the light intensities for
each point on the surface of the skin, and
for each of the wavelength windows.
The recordings measure the intensity
of light refected by the skin. Stam il-
luminates the hematoma with a ring of
white, blue and cyan-colored LEDs, and
the recording apparatus adjusts sensitiv-
ity fuctuations. One portion of the light
is absorbed by the tissue, while another
portion is refected; the refected por-
tion changes according to whether more
hemoglobin or more bilirubin is present
in the tissue. Some wavelengths yield es-
pecially striking results: Hemoglobin, for
example, absorbs mainly at wavelengths
of 430, 540 and 575 nm, while bilirubin
absorbs at 470 nm. Making the distinc-
tion, however, is not easy. The cameras
sensitivity ensures the quality of the
recordings.
The entire measurement takes roughly
90 seconds, the limiting factor being the
slowness of the electronic flters currently
available the camera alone would be
Imaging Bruises
www.optojena.de
efhcient optical signal switching
optical hberswitch from piezosystem jena
switching time in milliseconds
wavelength independent and effcient
signal transmission
specifcally designed for metrology and spectroscopy
custom confgurations upon request
RSWRMHQD
The system uses a tunable acoustic flter (the

gray device with the FTS sticker) and a CCD
camera from PCO (the blue device). Everything is
mounted on a camera stand. Here, the system is
shown measuring bloodstains, an alternative use
developed by Stam and colleagues.
much faster. Stam therefore takes a dif-
ferent approach to speed up the process:
If the initial results are confrmed, and
just four or fve wavelengths of visible
light are actually enough to obtain clear
fngerprints of hemoglobin and biliru-
bin, fewer recordings are taken, reducing
measuring time to several seconds.
Small, portable, cheap
The measuring system is mounted
on a small trolley, but the camera, flter
and laptop could also ft into a bag; the
aim is to make the measuring device
cheap enough so that every hospital can
afford one. Stam expects that four more
years of research will be needed before
the measuring technology is suffciently
developed for hospital use.
The process would also be a great help
in forensic medicine to uncover cases
of child abuse. The results Stam has
achieved on hematomas on voluntary test
subjects have been very promising. With
a bruise that is 24 hours old, Stam can ac-
curately determine the time of the injury
to within half an hour. The uncertainty
period for 5-day-old bruises that already
have turned a clear yellow is still just
under 16 hours.
Meet the authors
Dr. Barbara Stam studied medical natural
sciences and achieved her masters degree in
medical physics in 2006 at the Free University
in Amsterdam. Dr. Gerhard Holst is head of
research at PCO in Germany. Ursula Buczek is
a public relations consultant and account man-
ager at Storymaker PR in Tbingen, Germany;
email: u.buczek@storymaker.de.
Imaging Bruises
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Changing colors in a bruise: At 4 hours (h), only redness is visible. At 24 h, the predominant color is blue,
whereas a day later, yellow is also apparent. After 74 h, yellow is the predominant color, but blue is still
visible. After 121 h, only yellow is present. At 218 h, a small amount of yellow is still visible. At 264 h, no
yellowness is still visible (not shown). The bruise, resulting from a strike with a small cane, is located on
the upper arm of a 27-year-old woman.
New! Smallest Thermal GigE Camera
Accurate temperature measurement of life tissue can now be performed
with an ultracompact Gobi-640-GigE thermal camera, featuring GigE Vision
and Power over Ethernet (PoE). The thermal camera is based on a fully
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New Image Analysis Software
New Image-Pro Premier scientifc image analysis software offers intuitive
tools that make it easy to capture, process, measure, analyze and share
your images and valuable data. Image-Pro Premier offers 64-bit support, a
user-friendly interface, intuitive macros and app building tools as well as
new ways to automatically segment, classify and measure objects. Request
a free 14-day trial version at www.mediacy.com.
(301) 495-3305
info@mediacy.com
www.mediacy.com
The Next Microscopy Revolution Is Here
The DeltaVision OMX
(featuring the Blaze SIM module for live-cell

superresolution imaging) is a multimode, superresolution microscope
system. The OMX offers advanced microscope resolution and imaging
using fast 3-D structured illumination microscopy (3D-SIM), wide-feld
microscopy and localization microscopy techniques. The system comes
in various confgurations to meet budgetary and research needs.
Visit Neuroscience 2012, Booth 1623.
(425) 557-1000
deltavision@ge.com
www.super-resolution.com
New sCMOS Camera
The new Zyla 5.5 megapixel scientifc CMOS (sCMOS) camera is ideal for
research and OEM usage. Zyla sCMOS offers a 100 fps rate, rolling and
snapshot (global) shutter modes and ultra-low noise performance in a light,
compact and cost-effective design. Zyla achieves down to 1.2 electron rms
read noise and can read out the 5.5 megapixel sensor at a sustained 100 fps
through a 10-tap Camera Link interface. A highly cost-effective 3-tap
version is also available, offering up to 30 fps.
(800) 296-1579
info@andor.com
Andor.com/zyla
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1012_Spotlight.indd 34 9/27/12 10:09 AM
b Multispectral Optical Filter Assemblies
Deposition Sciences Inc. has expanded its optical components line. The new multispectral
optical flter assemblies (MOFAs) combine individually coated multispectral flter substrates
into an array assembly. The assemblies range from two- to eight-flter stacks, or more. The
MOFAs can employ a variety of adhesives, including space-qualifed ones. The durable,
complex MOFAs are used in linear- and planar-array CMOS detectors, and in medical instru-
mentation. They can be customized using a variety of substrate sizes. By combining numer-
ous complex flters into one device, the flters, once assembled, provide distinct capabilities
on each multispectral array. The company also can incorporate stops and apertures on the
part surface by using patterned coating technology.
Deposition Sciences Inc.
solutions@depsci.com
BREAKTHROUGHPRODUCTS
Surface-Mount Photodiode m
Opto Diode Corp. has released a surface-mount
photodiode with high sensitivity and short switching
time. The low-capacitance ODD-900-002 is suit-
able for use in medical diagnostic applications. The
surface-mount packaging facilitates integration into
new or existing systems. The device operates from
400 to 1100 nm, with peak sensitivity of 940 nm. Typi-
cal responsivity is 0.44 A/ W, with typical reverse dark
current of 5 nA and total capacitance of 25 pF. Robust
and fexible, the ODD-900-002 operating temperature
ranges from 225 to 85 C. Power dissipation is 150
mW at 25 C free air temperature. Soldering tempera-
ture is 260 C, with maximum soldering time of 5 s.
Opto Diode Corp.
sales@optodiode.com
LED Microscope System
Leica Microsystems DM4000 B LED microscope with
LED illumination for biomedical and research appli-
cations has the LED transmitted light illumination in-
tegrated into the microscope automation to produce
constant color temperature without heat buildup.
With a 50,000-h lifetime, frequent bulb changes are
not necessary. The microscope sets parameters
for transmitted light and fuorescence illumination
according to the users selection of contrast method
and magnifcation. The automated fuorescence
axis with apochromatic light path provides bright
images with high contrast. The instrument is suited
for clinical pathology applications with H&E- or IHC-
stained slides. The Leica Application Suite software
integrates the microscope and digital camera into a
system for visualization, storage and documentation
of microscope images.
Leica Microsystems
news@leica-microsystems.com
SEM Upgrade
JEOL USA Inc.s NeoScope benchtop scan-
ning electron microscope (SEM) is used for
pharmaceutical inspection, imaging insects
for student projects, and in conjunction with
optical microscopes and traditional SEMs in
the lab. Now available with higher magnifca-
tion and multitouch screen control, the high-
resolution SEM produces images with a large
depth of feld at magnifcations from 103 to
60,0003. It features high- and low-vacuum
operation, three selectable accelerating volt-
ages, and secondary electron and backscattered electron imaging. Conductive and
nonconductive samples can be examined. Sample loading to imaging in vacuum
takes less than 3 min.
JEOL USA Inc.
salesinfo@jeol.com
Ultraviolet Multispectral Camera c
The SpectroCam-UV, an ultraviolet multispec-
tral camera from Ocean Thin Films, provides
sensitive detection from the UV across the
visible and into the near-IR. Suitable for
high-level research, the confgurable video-
speed instrument has eight interchangeable
customer-defned flters. Users can test many
flter options in combination with the image
processing software. To accommodate a wider
scope of applications, the sensor range has
been extended into the UV and can be paired
with flters available throughout the UVA, UVB
and UVC wavelengths. The company also of-
fers turnkey UV imaging packages that include
UV-compatible optics and light sources. With
a full range of standard flter wavelengths and
custom optical flters, the camera supports
biomedical applications.
Ocean Thin Films
info@oceanthinflms.com
LED Fiber Optic Illuminator
Dolan-Jenner Industries has announced
the Fiber-Lite model LMI-6000 LED, a
fber optic illuminator that supports
microscopy, medical research and
laboratory studies. It incorporates
long-life bright-white LEDs with a color
temperature of 6000 K and up to 780
lm at the fber interface. The illumina-
tor is offered with a linear, 15-step
light-intensity control and universal
voltage input of 100 to 240 VAC, with
available UK-, mainland Europe- and
North America-compatible line cords. It
supports and illuminates gooseneck and annular ringlight fber optic lightguides, and
features an integrated handle, stackable housing and a small footprint. The device is
RoHS-compliant and CE-certifed.
Dolan-Jenner Industries
sales@dolan-jenner.com
m
m
m
New Prod Leads.indd 35 9/27/12 9:16 AM
TCSPC Module
Aurea Technology is launching the SPD_AT,
its new near-infrared time-correlated
single-photon-counting (TCSPC) module.
The ultralow-noise and high-quantum-
effciency 900- to 1700-nm device includes
a Geiger-mode InGaAs avalanche photodi-
ode and thermoelectric coolers that ensure
high detection effciency of up to 25%. Two
versions are available: the SPD_AT_M1 with
one channel and the SPD_AT_M2 with two
channels. Applications include near-infrared
fuorescence spectroscopy and photolumi-
nescence.
Aurea Technology
info@aureatechnology.com
Laser Remote
Coherent Inc. has expanded its OBIS
plug-and-play smart laser modules and
accessories with the OBIS 6-Laser Remote,
which integrates the power supply and
control of up to six lasers in a stand-alone
Center for Devices and Radiological Health
(CDRH)-compliant format. It incorporates
a CDRH-requisite on/off master key switch
and color-coded fip switches to power on/
off up to six lasers. The remote is offered as
a package with a 12-V power supply module,
color-coded labels and six color-coded
cables to identify various-wavelength lasers.
The addition of a remote interface enables
the modules use as stand-alone lasers for
laboratory applications, R&D or instrumenta-
tion/system integration. Applications include
fuorescence-based techniques such as fow
cytometry, confocal microscopy and array
readers for drug discovery. The wide choice
of wavelengths enables optimum excitation
of target fuorophores.
Coherent Inc.
tech.sales@coherent.com
Digital CMOS Optocoupler
Avago Technologies GmbHs ACNW261L
10-MBd digital CMOS optocoupler consumes
<18 mW and features 5-kV reinforced insula-
tion voltage. In medical and electrical equip-
ment, and industrial and renewable energy
generation systems used in harsh environ-
ments, applications may require internal
system communication speed of 10 MBd with
low power consumption and high insulation
voltage. The supply current is <1.5 mA over
the 240 to 105 C range. Both 3.3- and 5-V
applications are supported. The input LED
current is 4 mA. Input-to-output insulation
voltage is 5000 V rms. The optocoupler
meets the IEC 607475-5-5 working voltage
requirement of 1414 volts peak, internal clear-
ance of 1 mm, external creepage of 10 mm
and external clearance of 9.6 mm. By using
an internal Faraday shield, it delivers com-
mon mode transient rejection performance
of 20 kV/s minimum, 35 kV/s typical, at
1000-V common mode voltage.
Avago Technologies
support@avagotech.com
Scientifc-Grade Spectrometer
Ocean Optics QE65 Pro scientifc-grade
modular spectrometer features high sensitiv-
ity and low stray light for fuorescence,
Raman and DNA sequencing spectroscopy.
Its optical bench components manipulate light
for high throughput and sensitivity. A ther-
mally robust design promotes spectrometer
wavelength stability over a wide temperature
range, and ultralow jitter triggering synchro-
nizes timing with other devices. New grat-
ings optimize wavelength range and stray
light performance. Replaceable slits can be
reconfgured in the feld. By changing the
slit, the user can balance optical resolution
and throughput to achieve accurate results
with a single multipurpose instrument. The
Hamamatsu FFT-CCD back-thinned detector
produces 90% maximum quantum effciency,
low etalon characteristics, a >1000:1 signal-
to-noise ratio and high signal processing
speeds. The spectrometer performs low-
light-level detection and offers integration
times from 8 ms to 15 min, with virtually no
spectral distortion.
Ocean Optics
info@oceanoptics.com
Ultra-Absorbing Black Coating
Acktar Advanced Coatings is prepared for
industrial-scale production of foils coated
with its Metal Velvet ultra-absorbing black
coating for the extreme-UV through the
far-IR. With specular absorbance of 99.99%
and wide-band performance, the Metal
BREAKTHROUGHPRODUCTS p
New Prods.indd 36 9/27/12 9:17 AM
Velvet-coated light-absorbing foil is a stray-
and scattered-light-absorbing/suppressing
material that can be supplied with or without
self-adhesive backing and in roll or cut-sheet
formats. Metal Velvet is an inorganic material
with hemispherical refectance <1%. The
high-emissivity coating features ultrahigh-
vacuum compatibility, low outgassing and
high thermal stability at temperatures from
4 to 623 K, rendering it suitable for medical
devices. The coated foil is easily applied to
metals, glass, ceramics and polymers.
Acktar Advanced Coatings
customer-support@acktar.com
Atomic Force Microscope
Bruker Corp.s Dimension FastScan Bio
atomic force microscope enables high-
resolution microscopy research in biological
dynamics. It allows temporal investigation
under physiological operating environments
in fuid, while exceeding the diffraction
limits of optical microscopy, and it provides
temporal resolution in frames per second
for live biological sample observations. Ap-
plications include studies of the dynamics
behind protein, DNA, RNA, membrane, cell
and tissue interactions, and spatiotemporal
nanometer-scale research. Features include
an X-Y-Z scanner that operates at high
speeds while producing low drift and low
noise, a small-volume fuid sample cell, auto-
mated laser and detector alignment, an easy
sample engaging process, and the ability to
investigate samples in a droplet of solution
or its 60-l sample cell.
Bruker Corp.
steve.hopkins@bruker-nano.com
671-nm Laser
Laser Quantum Ltd. has launched tau, a
671-nm laser with a compact mono-block
design that makes it suitable for OEM
integration. It outputs up to 50 mW with a
stable TEM
00
diffraction-limited beam. The
single-transverse-mode continuous-wave
red laser is used in Raman and fuorescence
spectroscopy, and in DNA sequencing. Fea-
tures of the hermetically sealed laser include
a permanently aligned cavity, noise <1% rms,
RS-232 control, an ~100-GHz bandwidth,
beam divergence <1 mrad, M
2
<1.2, pointing
stability <10 rad and a polarization ratio
>100:1. Polarization direction is horizontal,
coherence length is ~3 mm, beam angle is
<2 mrad, and operating temperature is from
22 to 37 C.
Laser Quantum Ltd.
sales@laserquantum.com
Micromachined Probes
The photoacoustic tomographic (PAT) imag-
ing modality for minimally invasive cancer
detection and diagnosis is getting closer to
clinical realization with Leeoat Co.s laser
micromachined miniature photoacoustic
tomographic imaging sensor (PATIS) probes
based on micromachined 2-D ultrasound
phase array transducer sensors, combined
with fber optic illuminators. The waterproof
probes, with up to 1024 transducer elements,
are custom-tailored to accommodate specifc
PAT imaging requirements; namely, sensing
of weak photoacoustic signals above the
noisy environment at broadband frequencies
of 5 to 50 MHz, while achieving symmetric
computerized uniform architecture for beam-
forming optimization. The company has
demonstrated 98% yield in the fabrication of
PATIS probes, with elements interdistances
of 50 to 750 m, which are individually Z-
interconnected with separate coaxial cables
for high-speed tomographic imaging.
Leeoat Co.
leeoat@leeoat.com
Autofocus Lenses
Varioptic SA has announced a series of
imaging products based on its electrowetting
technology. Dedicated to imaging systems
integrators, Caspian is a family of autofocus
lens modules that combine a fxed objec-
tive lens, a proprietary liquid lens and a fex
cable in a single lens barrel. The modules are
designed according to standard mounts to
enable integration into most camera boards.
The Caspian M12-316-9.6, based on an Arctic
316 liquid lens and a Sunex DSL935 fxed
lens, is compatible with M1230.5 mounts
(S-mount) and off-the-shelf FPC connectors.
With a 9.6-mm focal length and compatibil-
ity with up to 1/1.8-in. sensors, it is suitable
for applications where focus speed and
industrial-grade robustness are a must, such
as biometrics and medical imaging.
Varioptic SA
contact@varioptic.com
1-Megapixel Camera
Vision Research Inc. extends its Phantom
1-megapixel v-Series digital high-speed
cameras with the v411. It delivers 4 gigapixels
per second, and top speed at full resolution
is 4200 fps. It features high-defnition, wide-
screen 1280 3 800 CMOS sensors and has
20-m pixels that allow shooting in low light.
It offers Phantom CineMag compatibility for
on-camera storage and long-record-time
applications, image-based autotrigger, an
extreme dynamic range and an internal cap-
ping shutter for hands-free and remote black
references. Applications include scientifc re-
search and product development. The latest
Phantom v-Series cameras offer additional
connectivity and on-camera controls that
improve signaling and provide users with
more options for enhancing their research.
The cameras offer 8, 16 and 32 GB of internal
high-speed memory and a Gigabit Ethernet
interface.
Vision Research Inc.
phantom@visionresearch.com
Spectral Contamination
Identifer Software
Los Gatos Research has formally document-
ed and independently validated a software
analysis package that enables the companys
water isotope analyzers to simultaneously
measure multiple isotopic ratios directly
from contaminated samples without treat-
ment or purifcation. The Spectral Contami-
nation Identifer software measures isotope
ratios from water samples contaminated with
methanol and ethanol. Scientists can analyze
samples obtained from soils, plants or other
complex water sources. The effectiveness
of the software results from the companys
method of recording fully resolved high-
resolution laser absorption spectra, which
are viewable in real time and archived by its
isotopic water analyzers. Using rugged and
portable laser-based analyzers for direct
isotope analysis eliminates the complexity,
cost and time associated with traditional
lab-bound instrumentation, i.e., isotope ratio
mass spectrometry.
Los Gatos Research
sales@lgrinc.com
LED Illuminators
CoolLED Ltd. has launched its pE-200 and pE-
300 series LED light sources for life sciences
applications. The illuminators deliver high
intensity and a compact footprint. Two- (pE-
200) and three-wavelength (pE-300) confgu-
rations are available. These additions to the
companys existing products offer the user a
wide choice of LED illumination to meet indi-
vidual needs. Common clinical, tissue culture
and confocal confgurations are available in
both light sources. An intuitive control pod
facilitates on/off and independent intensity
control. The units are available as a direct
ft to replace the redundant mercury source.
Lifetime is >10,000 h.
CoolLED Ltd.
sales@coolled.com
Miniature Microscope Module
IVO Associates KeepLoop miniature micro-
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scope module turns an ordinary mobile
phone (or iPad, laptop) into a good-quality
microscope by attaching a thin magnetic mi-
croscope module in front of the phones lens.
It is accurate to 0.01 mm. The user attaches
the module to the mobile device, turns on the
LED light source, starts the phone camera,
previews the image and clicks. The micro-
scope module fts in the users pocket. The
KeepLoop is used in the life sciences sector.
Users can quickly examine samples and
then transmit microscope images with their
mobile phones to anywhere in the world. Ex-
amples include imaging of skin and medical
samples.
IVO Associates
info@ivo-associates.co.uk
Laser-Line Cleanup Filters
Edmund Optics has announced TechSpec OD
6 laser-line cleanup flters for use with solid-
state and gas lasers. They provide the high
transmission and deep rejection necessary
to isolate narrow spectral regions. The band-
pass flters are fabricated using hard-coated
plasma deposition technology for durabil-
ity. They achieve >90% transmission at
their specifed design laser wavelength and
offer blocking of >6 optical density at 1.5%
of the laser wavelength. With steep edges,
they provide maximum transmission of
stimulated emission while eliminating noisy
spontaneous emission. They can be used in
laser-based fuorescence instrumentation, in
Raman spectroscopy, and in analytical and
medical laser systems. They are available
with center wavelengths of 325, 355, 488,
514, 532, 632, 785, 808, 830, 980 and 1064 nm,
with diameters of 12.5 and 25 mm.
Edmund Optics
sales@edmundoptics.com
High Performance
Lasers by Cobolt.
www.cobolt.se
Cobolt Headoffce, Sweden
Phone +46 8 545 912 30, E-mail info@cobolt.se
04-01 Series
Compact SLM DPSSLs
457, 473, 491, 515, 532, 561, 594 nm
CW power up to 300 mW, rms<0.25%
05-01 Series
High power single frequency DPSSLs
355, 491, 532, 561, 660, 1064 nm
MLD Series
Compact diode laser modules
405 - 660nm
Fast and deep direct modulation
Fully integrated control electronics
Fluorescence imaging
and analysis
Raman spectroscopy
Interferometry
HTCure manufacturing
for ultra-robust lasers and
ensured reliability!
Semiconductor metrology
CW power up to 3000 mW, rms <0.1%
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
New Bench-Top Fluorometer
OPTICAL BUILDING BLOCKS CORPORATION
The worlds fastest and most sensitive integrated bench-
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of these unique benets, let alone all four. Now, with the introduction of the all-new Quattro
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much more, in a compact, easy-to-use and very aordable system.
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Quattro
Unmatched speed.
This 3-D matrix of wavelength vs s decay was
acquired in just 15 seconds!
NOVEMBER
Fifth International Photonics and OptoElec-
tronics Meetings (POEM 2012) (Nov. 1-2) Wu-
han, China. Contact Wuhan National Labora-
tory for Optoelectronics, +86 27 877 92 227;
poem@mail.hust.edu.cn; poem.wnlo.cn.
SPIE/COS Photonics Asia (Nov. 4-7) Beijing.
Sponsored by SPIE and the Chinese Optical
Society. Contact SPIE, +1 (360) 676-3290;
customerservice@spie.org; spie.org.
MiCom 2012: Third International Conference
on Microbial Communication (Nov. 5-8) Jena,
Germany. Contact Jena School for Microbial
Communication, +49 3641 930 421; micom@
uni-jena.de; micom-conference.de.
Clinical Application of Adaptive Optics
Retinal Imaging Incubator Meeting (Nov. 6-8)
Washington. Contact The Optical Society, +1
(202) 223-8130; info@osa.org; www.osa.org.
Asia Communications and Photonics Confer-
ence (ACP) (Nov. 7-10) Guangzhou, China.
Contact The Optical Society, +1 (202) 223-
8130; info@osa.org; www.acp-conf.org.
Laser Florence 2012 (Nov. 9-10) Florence,
Italy. Contact IALMS International Academy
for Laser Medicine and Surgery, +39 055 234
2330; info@laserforence.org; www.laser
forence.org.
2012 International Conference on Image
Analysis and Signal Processing (IASP) (Nov.
9-11) Hangzhou, China. Contact Linda Sun,
+1 (770) 973-8732; asppress@yahoo.com;
iasp2012.zjicm.edu.cn.
Latin America Optics & Photonics Confer-
ence (LAOP) (Nov. 11-13) So Sebastio,
Brazil. Contact The Optical Society, +1 (202)
223-8130; info@osa.org; www.osa.org.
Renewable Energy and the Environment:
OSA Optics and Photonics Congress (Nov.
11-15) Eindhoven, Netherlands. Includes
Optical Instrumentation for Energy and
Environmental Applications (E2); Optical
Nanostructures and Advanced Materials for
Photovoltaics (PV); Optics for Solar Energy
(SOLAR); and Solid State and Organic Light-
ing (SOLED). Contact The Optical Society, +1
(202) 223-8130; info@osa.org; www.osa.org.
CIC 20: Twentieth Color and Imaging Con-
ference (Nov. 12-16) Los Angeles. Contact
Society for Imaging Science and Technology,
+1 (703) 642-9090; www.imaging.org/ist/
conferences/cic.
DECEMBER
MSSA 2012: 50th Annual Conference of the
Microscopy Society of Southern Africa (Dec.
4-7) Cape Town, South Africa. Contact Sala-
mander Conferences, +27 21 556 0653; info
@mssa2012.co.za; www.mssa2012.co.za.
First International Biophotonics Meeting
in Israel (Dec. 9-11) Tel Aviv, Israel. Contact
SPIE, +1 (360) 676-3290; customerservice
@spie.org; spie.org.
International Conference on Fiber Optics
and Photonics (Photonics 2012) (Dec. 9-12)
Chennai, India. Contact The Optical Society,
+1 (202) 223-8130; info@osa.org; www.
photonics2012.in.
Photonics Global Conference (PGC 2012)
(Dec. 13-16) Singapore. Contact Director,
Optimus-Photonics Centre of Excellence,
Nanyang Technological University, +65 6790
4685; d-optimus@ntu.edu.sg; www.photon
icsglobal.org.
2012 American Society for Cell Biology
Annual Meeting (Dec. 15-19) San Francisco.
Contact ASCB, +1 (301) 347-9300; www.ascb.
org/meetings.
Sixth International Conference on Sens-
ing Technology (ICST 2012) (Dec. 18-21)
Calcutta, India. Contact Subhas Mukhopad-
hyay, Massey University, +64 63 505 799;
s.c.mukhopadhyay@massey.ac.nz; seat.
massey.ac.nz/conferences/icst2012.
Cairo International Biomedical Engineering
Conference (CIBEC 2012) (Dec. 20-22) Giza,
Egypt. Contact Dina S. Elkholy, Cairo Univer-
sity, +201 222 608 698; cibec@k-space.org;
www.cibec2012.org.
JANUARY
Nanometa 2013: Fourth International Topical
Meeting on Nanophotonics and Metamateri-
als (Jan. 3-6) Tirol, Austria. Contact European
Physical Society, +33 3 89 32 94 42; confer
ences@eps.org; www.nanometa.org.
Advanced Photonics Techniques in Soft
Matter and Biology (Jan. 14) London. Contact
Jenny Bremner, Institute of Physics, jenny.
bremner@iop.org; www.iop.org.
PepTalk: The Protein Science Week (Jan. 21-
25) Palm Springs, Calif. Contact Cambridge
Healthtech Institute, +1 (781) 972-5400; chi@
healthtech.com; www.chi-peptalk.com.
OnSite Analysis Conference & Exposition
(Jan. 23-25) Baltimore. Contact Julie Kovach,
+1 (847) 543-6800; info@ifpacnet.org; www.
ifpacpat.org/onsite.
2013 North American Association for Laser
Therapy (NAALT) Conference (Jan. 31-Feb.
2) Palm Beach Gardens, Fla. Contact Jennifer
Anderson, jennifer@naalt.org; www.naalt.
org.
FEBRUARY
Biophysical Societys 57th Annual Meeting
(Feb. 2-6) Philadelphia. Contact Biophysical
Society, +1 (240) 290-5600; society@biophys
ics.org; www.biophysics.org.
Photonics West (Feb. 2-7) San Francisco.
Includes the conferences BiOS, LASE, OPTO,
MOEMS-MEMS and Green Photonics. Con-
tact SPIE, +1 (360) 676-3290; customer
service@spie.org; spie.org.
IS&T/SPIE Electronic Imaging (Feb. 3-7)
Burlingame, Calif. Contact SPIE, +1 (360) 676-
3290; customerservice@spie.org; spie.org.
ALD 20th Anniversary Conference (Feb. 7-9)
Palm Springs, Calif. Contact Academy of
Laser Dentistry, +1 (954) 346-3776; www.
laserdentistry.org.
APPOINTMENTS
Experimental Biology 2013 April 20-24
Deadline: Abstracts, November 8, 11:59 p.m. EST
Boston. Organizers of the annual meeting Experimental Biology 2013
invite papers for oral and poster sessions in anatomy, physiology,
biochemistry, pathology, nutrition and pharmacology. Topics to be
addressed include imaging informatics, functional imaging, imaging
technology and methods, imaging live tissue, novel 3-D imaging
with microcomputed tomography and microimaging in biological
anthropology.
Contact: EB Management Offce +1 (301) 634-7010
eb@faseb.org www.experimentalbiology.org
Blue Photonics 3 Optics in the Sea March 18-20
Deadline: Abstracts, November 16
Texel, Netherlands. The European Optical Society is accepting papers
for the Third EOS Topical Meeting on Blue Photonics Optics in the
Sea. Areas to be considered include fuorometry, ocean color, radia-
tive transfer and modeling, marine bio-optics and remote sensing,
2-D and 3-D underwater imaging, and innovative subsea optical
techniques and instrumentation. Environmental monitoring, including
crowdsourcing and the use of apps, also will be addressed.
Contact: Julia Dalichow, EOS Events and Services GmbH
bluephotonics3@myeos.org www.myeos.org
Optics in the Life Sciences April 14-18
Deadline: Submissions, December 10, noon EST (17:00 GMT)
Waikoloa, Hawaii. Papers are encouraged for this OSA Optics and
Photonics Congress, which encompasses the conferences Optical
Trapping Applications (OTA); Novel Techniques in Microscopy (NTM);
Bio-Optics: Design and Application (BODA); and Optical Molecular
Probes, Imaging and Drug Delivery (OMP).
Contact: The Optical Society +1 (202) 223-8130
info@osa.org www.osa.org
CALL FOR PAPERS
For complete listing, visit
www.photonics.com/calendar.
1012_Appointments.indd 40 9/27/12 9:19 AM
a
Andor Technology plc .................................................................................................................................................................... 34
www.andor.com
Applied Precision Inc. ................................................................................................................................................................... 34
www.appliedprecision.com
Applied Scientifc Instrumentation Inc. ........................................................................................................................................ 6
www.asiimaging.com
b
B&W Tek Inc. .................................................................................................................................................................................... 3
www.bwtek.com
Blue Sky Research .......................................................................................................................................................................... 13
www.blueskyresearch.com
c
Cobolt AB ......................................................................................................................................................................................... 39
www.cobolt.se
CVI Melles Griot .............................................................................................................................................................................. 16
www.cvimellesgriot.com
e
Edmund Optics ................................................................................................................................................................................. 9
www.edmundoptics.com
h
Hamamatsu ..................................................................................................................................................................................... 22
www.sales.hamamatsu.com
l
Lumencor Inc. ................................................................................................................................................................................ 37
www.lumencor.com
m
Mad City Labs Inc. ......................................................................................................................................................................... 38
www.madcitylabs.com
Media Cybernetics Inc. ................................................................................................................................................................. 34
www.mediacy.com
Mightex Systems ............................................................................................................................................................................ 32
www.mightexsystems.com
Mobius Photonics Inc. ................................................................................................................................................................... 26
www.mobiusphotonics.com
n
NKT Photonics A/S ...................................................................................................................................................................... CV2
www.nktphotonics.com
o
Ocean Thin Films ............................................................................................................................................................................ 15
www.oceanthinflms.com
OFS Specialty Photonics Division ................................................................................................................................................ 27
www.specialtyphotonics.com
Optical Building Blocks Corp. ................................................................................................................................................30, 39
www.obbcorp.com
p
PCO-TECH Inc. ............................................................................................................................................................................. CV3
www.pco-tech.com
Photonics Media ............................................................................................................................................................... 5, 7, 34, 38
www.photonics.com
PHOTONIS USA Inc. ................................................................................................................................................................... CV4
www.photonis.com
PicoQuant GmbH ............................................................................................................................................................................ 19
www.picoquant.com
piezosystem jena GmbH ................................................................................................................................................................ 32
www.piezojena.com
s
Siskiyou Corporation ..................................................................................................................................................................... 36
www.siskiyou.com
Spectra-Physics, A Newport Corporation Brand ....................................................................................................................... 23
www.newport.com
SPIE International Society for Optical Engineering................................................................................................................... 33
www.spie.org/aboutpw
Sutter Instrument ........................................................................................................................................................................... 26
www.sutter.com
x
Xenics ............................................................................................................................................................................................... 34
www.xenics.com
Photonics Media Advertising Contacts
Please visit our website Photonics.
com/mediakit for all
our marketing opportunities.
Ken Tyburski
Director of Sales
Voice: +1 (413) 499-0514, Ext. 101
Fax: +1 (413) 443-0472
ken.tyburski@photonics.com
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Rocky Mountains, AZ, NM & Midwest
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Associate Director
Voice: +1 (413) 499-0514, Ext. 112
Fax: +1 (413) 443-0472
becky.pontier@photonics.com
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Timothy A. Dupree
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tim.dupree@photonics.com
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joanne.gagnon@photonics.com
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Tracy L. Reynolds
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tracy.reynolds@photonics.com
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Maureen Riley Moriarty
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riley.moriarty@photonics.com
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Owen Broch
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Voice: +81 3 5225 6614
Fax: +81 3 5229 7253
s_shiba@optronics.co.jp
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advertising@photonics.com
ADVERTISERINDEX
1012_Ad Index.indd 41 9/27/12 10:14 AM
Lidar reveals elephant impact
S
cientists and conservation managers
have long suspected that elephants
browsing for food are the main
culprits behind toppled trees in the South
African savannas and airborne lidar and
3-D mapping have helped prove this.
Widespread tree loss is a concern to
wildlife managers because it is known
to have a negative effect on the habitat
for many other species. To gain a better
understanding of the problem, scientists
from the Washington-based Carnegie
Institution for Science collaborated with
managers of South Africas Kruger Na-
tional Park to produce a detailed analysis
of treefall in the park.
They mounted the lidar equipment on
the fxed-wing Carnegie Airborne Obser-
vatory so that its laser pulses could sweep
across the savannas to provide detailed
3-D images of the vegetation canopy at
tree-level resolution. The observatorys
vast coverage far surpasses previous feld-
based and aerial photographic evalua-
tions, the scientists say.
In 2008 and 2010, the researchers iden-
tifed and monitored 58,000 trees from
the air, inside and outside of the exclo-
sures and across the landscape. The lidar
can detect even small changes in a trees
height, and the scientists found that nearly
9 percent of the trees decreased in height
in two years. They also found that the
mapped changes in treefall were linked to
different climate and terrain conditions.
The trees that elephants prefer found
in lowland areas with more moisture and
high-nutrient soils experienced most of
the loss, they noted.
The study, published in Ecology Let-
ters, showed conclusively that elephants,
rather than other herbivores and fre, were
the major contributors to tree loss over
the two-year period. The lidar-acquired
data showed that trees were toppled at a
rate averaging six times higher than were
those in elephant-free areas. The scien-
tists also determined that elephants prefer
trampling trees in the 16- to 30-ft range,
with annual losses of up to 20 percent in
this range.
Our maps show that elephants clearly
toppled medium-size trees, creating an
elephant trap for the vegetation. These
elephant-driven tree losses have a ripple
effect across the ecosystem, including
how much carbon is sequestered from
the atmosphere, said researcher Gregory
Asner. Previous feld studies gave us
important clues that elephants are a key
driver of tree losses, but our airborne 3-D
mapping approach was the only way to
fully understand the impacts of elephants
across a wide range of environmental con-
ditions found in savannas.
Park offcials now can use the data to
help preserve trees and wildlife.
Knowing where increasing elephant
impacts occur in sensitive landscapes
allows park managers to take appropriate
and focused action, said Danie Pienaar,
head of scientifc services of the South
African National Parks.
POSTSCRIPTS
Caren B. Les
caren.les@photonics.com
Lidar and 3-D mapping data in South Africas savannas have revealed that elephants browsing for food
trample trees, with possibly negative consequences for other species in the habitat. Courtesy of Gregory
Asner, Carnegie Institution for Science.
1012_Postscripts.indd 42 9/27/12 9:20 AM
1012_PCOTech_PgCVR3.indd 3 9/27/12 9:21 AM
1012_Photonics_PgCVR4.indd 4 9/27/12 9:22 AM

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to deliver short pulses to the sample

The system uses a tunable acoustic flter (the

(featuring the Blaze SIM module for live-cell

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