Biophotonics201209 DL

www.Photonics.
com
SEPTEMBER 2012
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Multimodal Label-Free Imaging
Drives Biomedical Research
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8 BIOSCAN
BioPhotonics editors curate the most significant headlines
of the month for photonics in the life sciences and take
you deeper inside the news. Featured stories include:
Scalpel-free surgery with deep-tissue imaging
Moth eyes inspire improved x-ray imaging
Metamolecules switch handedness under light
17 BUSINESSSCAN
Ophthalmic laser market growing
NEWS
28
BioPhotonics September 2012
20 MULTIMODAL LABEL-FREE IMAGING DRIVES BIOMEDICAL RESEARCH
by James Lopez and Yiwei Jia, Olympus America Inc.
Various optical techniques used in tandem can monitor disease processes
in real time without the shortcomings of fluorescence imaging.
24 THE AGE OF THE TRICORDER
by Gary Boas, Contributing Editor
This Star Trek-inspired medical diagnostic device is now a reality, and the
international Qualcomm Tricorder X PRIZE should help raise the bar even higher.
28 NEW GLASS FIBERS WIDEN RANGE OF MEDICAL LIGHTING APPLICATIONS
by Karen Holst, Schott AG
High-purity, chemically stable glass optical fibers offer increased
light transmission and the potential for new applications.
31 LIGHT SOURCE HELPS ENDOSCOPES GET SMALLER AND SMALLER
by James Hermanowski, Nathaniel Group Inc.
The weak delivery of xenon light through the small fibers used in
microendoscopes has driven the search for a new source.
FEATURES
www.photonics.com
Volume 19 Issue 7
6 EDITORIAL
35 BREAKTHROUGHPRODUCTS
40 APPOINTMENTS
Upcoming Courses and Shows
41 ADVERTISER INDEX
42 POST SCRIPTS
by Caren B. Les
Bioluminescence imaging lights up hair renewal
DEPARTMENTS
PHOTONICS
The technology of generating and harnessing light and other forms of radiant energy whose
quantum unit is the photon. The range of applications of photonics extends from energy generation
to detection to communications and information processing.
BIOPHOTONICS
The application of photonic products and techniques to solve problems for researchers,
product developers, clinical users, physicians and others in the fields of medicine,
biology and biotechnology.
THE COVER
While intrinsic fluorescence distinguishes individual
microvilli cells (green), a coherence anti-Stokes Raman
scattering signal (magenta) detects lipids within them
and nearby. An article on label-free imaging by James
Lopez and Yiwei Jia of Olympus America Inc. begins on
page 20. Design by Art Director Suzanne L. Schmidt.
Contents_Layout 1 8/30/12 2:26 PM Page 4
5 BioPhotonics September 2012
www.photonics.com
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. Paddock
Contributing Editors Hank Hogan, Marie Freebody
Copy Editors Judith E. Storie, Patricia A. Vincent,
Margaret W. Bushee
Creative Staff
Senior Art Director Lisa N. Comstock
BioPhotonics Art Director Suzanne L. Schmidt
Designer Janice R. Tynan
Director of Publishing Operations Kathleen A. Alibozek
Electronic Media Staff
Director Charley Rose
Multimedia Services & Marketing
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Masthead_Layout 1 8/30/12 9:58 AM Page 5
Biophotonics has plenty of room
for pioneers
O
ur world has lost a number of groundbreakers in recent
days, and while it will be a different place without them,
it already is a better place because of them. Neil Arm-
strong took the first walk on the moon, and Sally Ride was the
first American woman to make the trip into space. In photonics,
Elias Snitzer is considered the father of the glass laser, and Isaac
Kaplan found a purpose for the CO
2
laser.
Kaplan, who died in August at the age of 93, was a pioneer in
the creation of the first carbon dioxide laser for general surgery
and founder of the International Society for Laser Surgery and
Medicine.
While Armstrong said that circumstance gave him the role of
first man on the moon, Kaplan had a plan. In her news report on
his death for Photonics.com, senior editor Melinda Rose writes,
When it was developed in the 1960s, Kaplan said, the CO
2
laser
was without application. His goal was to research the application
of the new miracle technology while developing an apparatus
that could put the application to work in general surgery.
(http://www.photonics.com/Article.aspx?AID=51741)
Armstrong, Ride, Snitzer and Kaplan are rarely spoken of in
the same breath, for sure, but each broke new ground in his or her
area of expertise. And, while the job of pioneer is often a one-
person enterprise, each breakthrough creates new opportunities
for exploration and innovation.
Today, biophotonics innovators receive their inspiration from
many disciplines and from all kinds of places, including yester-
days view of tomorrow, Star Trek. We have so not heard the last
of the tricorder, and that could be a very good thing for all of us.
In an article in this issue, contributing editor Gary Boas says,
The Star Trek television series and movies have proved remark-
ably prescient in anticipating the future. In The Age of the Tri-
corder, beginning on page 24, Boas describes a new generation
of sensing and imaging diagnostic devices, many with origins in
smartphones with cameras and data-transmission capabilities, and
tells us to expect to see more such devices in the future.
The brilliant sparks of inspiration that mark the early careers of
so many trailblazers are game-changing, to be sure, but its the
work that continues outside of the spotlight, often for decades,
that leads to true greatness.
Neil Armstrong also said, I guess we all like to be recognized
not for one piece of fireworks, but for the ledger of our daily
work. After his walk on the moon, Armstrong worked for NASA
and taught aerospace engineering at the University of Cincinnati.
After NASA, Sally Ride taught at the University of California,
San Diego, and encouraged girls and young women to study math
and science. Snitzer and Kaplan had long careers that included
research, innovation and education. All proved that there are
many ways to affect our world and our future.
Also in this issue, James Hermanowski of Nathaniel Group
Inc. explains that xenon light sources represent the benchmark for
medical illumination but cannot couple light through the small
channels used for microendoscopes. His article, Light Source
Helps Endoscopes Get Smaller and Smaller, starts on page 31.
In Multimodal Label-Free Imaging Drives Biomedical Re-
search, James Lopez and Yiwei Jia, of Olympus America Inc.,
describe how label-free noninvasive, nondestructive optical
microscopy using multiple simultaneous techniques allows
researchers to observe diverse life processes in real time. Find
the article on page 20.
And, finally, optical fibers with higher light transmission and
longer life spans offer interesting new solutions for meeting the
growing demand for higher quality lighting in medicine, accord-
ing to Karen Holst of Schott AG in her article, New Glass Fibers
Widen Range of Medical Lighting Applications, beginning on
page 28.
Enjoy the issue.
EDITORIAL
Karen A. Newman
karen.newman@photonics.com
Editorial_Layout 1 8/31/12 10:33 AM Page 6
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BIOSCAN
A closer look at the most significant biophotonics research and technology headlines of the month
Scalpel-free surgery with deep-tissue imaging
PASADENA, Calif. A new procedure
that more than doubles the depth that light
can be focused inside biological tissues
soon could enable doctors to perform inci-
sion-free surgery or diagnose cancer by
seeing tumors inside the body.
Although the previous limit for how
deep light could be focused into tissue was
only about 1 mm, researchers at California
Institute of Technology (Caltech) now can
reach 2.5 mm. In principle, their method
could focus light as much as a few inches
into tissue.
The ability to focus high-intensity light
tightly deep within tissue has a lot of ap-
plications, said Changhuei Yang, a pro-
fessor of electrical engineering and bio-
engineering at Caltech. We hope that
with further technology improvement,
depth up to a few centimeters will be
achievable. If we can reach up to about
10 cm, it would allow us to reach most
regions of the human anatomy.
The new technique builds on a previous
method that Yang and his colleagues de-
veloped to see through a layer of biologi-
cal tissue, which is opaque because it scat-
ters light. In that study, the scientists
shone light through a tissue sample and
recorded the resulting scattered light on a
holographic plate. The recording contained
information about how the light beam
scattered, zigzagging through the tissue.
By playing the recording in reverse, they
sent the light back through the other side
of the tissue, retracing the beams path to
the original source.
In this way, they could send light through
a layer of tissue without the blurring effect
of scattering. However, to make images of
the tissues insides, they would have to be
able to focus a beam of light into it.
To precisely focus light into tissue, the
team expanded upon the recent work of
Lihong Wangs group at Washington Uni-
versity in St. Louis (WUSTL), which de-
veloped a technique to focus light using
the high-frequency vibrations of ultra-
sound and two of ultrasounds favorable
properties. First, its high-frequency sound
waves are not scattered by tissue; second,
its ultrasonic vibrations interact with light
in such a way that the lights frequency is
shifted ever so slightly. As a result of this
acousto-optic effect, light that interacts
with ultrasound changes into a slightly dif-
ferent color.
Both teams focused ultrasound waves
into a small region inside a tissue sample
during their experiments. Next, they shone
light into the sample, which scattered the
light. Any light that passed through the re-
gion with the focused ultrasound changed
color somewhat. The researchers identified
and recorded the color-shifted light.
Using Caltechs playback technique,
they sent the light back, inducing only the
color-shifted portion to retrace the path to
the small region where the ultrasound was
focused. This means that the light itself is
focused on that area, allowing an image to
be created. By moving the ultrasounds
focus, the researchers can control where
they want to focus the light.
Only a very small amount of light could
be focused in the WUSTL experiment, but
Caltechs method allows scientists to fire a
beam of light with as much power as they
need for potential applications.
This technology is still in its infancy,
Yang told BioPhotonics. We took an im-
portant step beyond Lihong Wangs origi-
nal demonstration of TRUE (time-reversed
ultrasonically encoded optical focusing)
by implementing a TRUE technique that is
effectively unlimited in terms of its ability
to deliver arbitrarily high power to the fo-
cused spot.
For this to work in living tissue, Yang
said, the team must decrease the time for
generating a focused light spot to a frac-
tion of a second, depending on the tissue
type. The ability to build a suitable sys-
tem is within our technological reach. But
it does require a significant financial in-
vestment to make it happen. If we have
the financial resources and a semiconduc-
tor foundry to help us, bringing the tech-
nology to the point of clinical imaging is
like a 10- to 20-year process.
The team demonstrated how the new
method could be used with fluorescence
imaging by embedding a patch of gel with
a fluorescent pattern that spelled out
CIT inside a tissue sample. The investi-
A new technique more than doubles the depth that light can be focused inside biological tissue. In the
experiment, Caltech researchers shone green laser light into the tissue sample seen here in the center.
Images courtesy of Caltech/Benjamin Judkewitz and Ying Min Wang.
BioScan_Layout 1 8/30/12 12:41 PM Page 8
BioPhotonics September 2012 9
gators scanned the sample with focused
light beams, which hit and excited the
fluorescent pattern, resulting in the
glowing letters emanating from inside
the tissue. They also used the technique
to take images of tumors tagged with
fluorescent dyes.
The fluorescence is used only during
the final imaging scan, Yang said, and the
technique works whether the dye is used
or not.
We can form a focused light spot [re-
gardless], he said. We chose to do fluo-
rescence imaging here because our tech-
nique is able to generate a sufficiently
strong focused spot to excite fluorophores
to provide image contrast.
Doctors also could use the technique to
treat cancer with photodynamic therapy,
which currently can be used only at the
surface of tissue because of the way light
is easily scattered. The new method should
make it possible to reach cancer cells
deeper inside tissue.
Next, Yang said he and his team would
like to combine the spatial light modulator
and image sensor into a single digital opti-
cal phase conjugation chip, but funding is
a challenge. If they could achieve this
single chip, Yang said, it would solve
several technical implementation chal-
lenges in one move and, more importantly,
allow us to deploy sensing and playback
over a far larger area. The more area we
can cover, the task of collecting and play-
ing back the conjugate light field becomes
faster and easier.
The study appeared in Nature Commu-
nications (doi:10.1038/ncomms1925).
Left, light enters the tissue sample and is scattered
(blue arrows). From above, ultrasound is focused
into a small area inside the tissue. The ultrasound
shifts the frequency of any light that passes through
that area ever so slightly, changing its color. The
color-shifted light (green) is then recorded. Right, the
recorded light is sent back to retrace its steps to the
small region where the ultrasound was focused
which means the light itself is focused on that area.
Moth eyes inspire improved x-ray imaging
NEW YORK A new class of nanoscale materials modeled after
a moths eye could improve the light-capturing efficiency of
x-ray machines and similar medical imaging devices.
As with butterflies, moths have large compound eyes com-
posed of many thousand ommatidia structures comprising a
primitive cornea and lens, connected by photoreceptor cells.
Unlike those of butterflies, however, moth eyes are extraordinar-
ily antireflective, bouncing back only a small portion of the light
that strikes them. This adaptation makes the insects less visible
to predators during their nocturnal flights. Because of this, engi-
neers have looked to the moth eye to help design more efficient
coatings for solar panels and antireflective surfaces for military
devices.
City University of New York professor Yasha Yi and col-
leagues at Tongji University in Shanghai have taken this feature
a step further: They have used the moth eye as a model for devel-
oping nanoscale materials that someday could reduce the x-ray
radiation dosages received by patients, while improving the
resolution of the resulting images.
The scientists focused their experiment on scintillation
materials compounds that, when struck by incoming particles,
absorb the energy in the form of light. Such scintillators are used
in radiographic imaging devices to convert the x-rays exiting the
body into visible light signals picked up by a detector to form
an image.
A higher x-ray dosage improves output but is not healthy for
patients. As an alternative, Yis team found that improving the
scintillators efficiency at converting x-rays to light improved
the output. Their new nanomaterial does just that.
The material consists of a 500-nm-thick thin film composed
of a cerium-doped lutetium oxyorthosilicate crystal.
We need a thin film to fabricate the light-extraction structure,
Yi told BioPhotonics. The layer was needed so as not to perturb
the scintillation materials light emission layer.
The crystals are encrusted with tiny pyramid-shaped silicon
nitride protuberances. Each protuberance, or corneal nipple, is
modeled after the structure in a moths eye and is designed to
extract more light from the film.
Within a 100 100-m square, about the same density as
the actual moth eye, the scientists can fit between 100,000 and
200,000 protuberances. They made the side walls of the device
A scanning electron microscope image of a leaf miner moths eye. Moths large
compound eyes are extraordinarily antireflective, bouncing back only a small
portion of light that strikes them; now, researchers have used the moth eye as a
model for new nanoscale materials for improved x-ray imaging. Courtesy of
Dartmouth College.
rougher, improving its ability to scatter light and enhancing the
scintillators efficiency.
The light-extraction efficiency enhancement is very sensitive
to the dimension of the protuberances, Yi said. More research is
needed to see whether there are benefits to adding more, he said.
During lab experiments, Yi discovered that adding the thin film
to the scintillator of an x-ray mammographic unit increased the
intensity of the emitted light by as much as 175 percent compared
with the output of a traditional scintillator.
The work appeared in Optics Letters (http://dx.doi.org/10.1364/
OL.37.002808) and represents a proof-of-concept evaluation of
the use of the moth eye-based nanostructures in medical imaging
materials. It also could be applied to various light-emitting
devices, Yi said.
He estimates that it will take at least another three to five years
to evaluate and perfect the film, and five years before it will
reach a clinical setting.
The team plans to continue investigations to understand and
improve the light-enhancement mechanism.
b
BIOSCAN
BERKELEY, Calif. A new technique
that uses light to change the handedness
of artificial molecules could benefit tera-
hertz technology applications from bio-
medical research to ultrahigh-speed com-
munications and homeland security.
Using a light beam, the chirality of arti-
ficial molecules has been switched from a
right-handed orientation to a left-handed
one for the first time. Chirality is the dis-
tinct left or right orientation, or handed-
ness, of some types of molecules mean-
ing it can take one of two mirror-image
forms. Called enantiomers, the right- and
left-handed forms of such molecules can
exhibit strikingly different properties; for
example, one enantiomer of the chiral
molecule limonene has a lemon scent,
while the other smells of orange.
The ability to observe or switch a mole-
cules chirality using terahertz electromag-
netic radiation is a coveted asset in high
technology.
In electromagnetism, chirality or opti-
cal activity arises from the coupling be-
tween the electric and magnetic responses
of the materials, said Xiang Zhang, one
of the leaders of the research and a princi-
pal investigator with the US Department
of Energys Lawrence Berkeley National
Laboratorys Materials Sciences Div.
However, in natural materials, the mag-
netic response is extremely weak at THz
and optical frequencies, and as a result,
the chirality is also very weak.
Using terahertz metamaterials engi-
neered from nanometer-size gold strips
with air as the dielectric, Zhang and a
multi-institutional team of colleagues from
Los Alamos National Lab and the Univer-
sity of Birmingham in the UK fashioned a
delicate artificial chiral molecule that they
incorporated with a photoactive silicon
medium. By performing photoexcitation of
their metamolecules with an external light
beam, they observed dynamically con-
trolled handedness flipping in the form of
circularly polarized emitted terahertz light.
Under strong optical irradiation, the
handedness of the metamolecule is
switched to its opposite handedness,
Zhang told BioPhotonics. This state is
temporary; it relaxes back to its original
handedness in a time scale of 1 millisec-
ond. The process is repeatable.
The optically switchable chiral terahertz
metamolecules consisted of a pair of 3-D
meta-atoms of opposite chirality made
from precisely structured gold strips. Each
meta-atom serves as a resonator with a
coupling between electric and magnetic
responses that produces strong chirality
and large circular dichroism at the reso-
nance frequency.
When two chiral meta-atoms of the
same shape but opposite chirality are put
together, they form a metamolecule, and
their symmetry is preserved, resulting in
vanishing optical activity. Essentially,
the optical activity that arises from the
opposite meta-atoms cancels each other
out, he said.
To break the mirror symmetry and in-
duce chirality for the combined metamole-
cule, the researchers introduced silicon
pads to each chiral meta-atom in the meta-
molecule. In one meta-atom, the silicon
pad bridged two gold strips, while the sili-
con pad replaced part of the gold strip in
the other meta-atom. The silicon pads
functioned as the optoelectronic switches
that flipped the chirality of the metamole-
cule under photoexcitation.
Terahertz electromagnetic radiation falls
within the frequency range of molecular
vibrations, making it a suitable noninva-
sive tool for analyzing the chemical con-
stituents of organic and nonorganic mate-
rials. By having the ability to flip the
handedness of metamolecules and control
the circular polarization of terahertz light,
scientists could use the technology to de-
Metamolecules switch handedness under light
Controlling the chirality of artificial molecules could
enable advances in communications and biomedical
imaging. Top, a scanning electron microscope image
of optically switchable chiral terahertz metamole-
cules. Bottom, the purple, blue and tan colors
represent the gold meta-atom structures at different
layers; two silicon pads are shown in green. Images
courtesy of Xiang Zhang et al, Berkeley Lab.
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BIOSCAN
In this schematic, the chirality-switching metamolecule consists of four chiral resonators with fourfold
rotational symmetry. An external beam of light instantly reverses the metamolecules chirality from
right-handed to left-handed.
tect toxic or explosive chemicals, or use it
in high-speed data processing systems and
wireless communications.
Terahertz-based polarimetric devices
also could benefit medical researchers and
developers of pharmaceutical drugs be-
cause most biological molecules, includ-
ing DNA, RNA and proteins, are chiral.
In THz, most of the biological mole-
cules show circular dichroism, Zhang said.
However, there is a lack of spectroscopy
tools to accurately measure the circular
dichroism of biomolecules at THz in com-
parison with the visible range. The sensitive
detection of circular dichroism requires dy-
namic modulation of the electromagnetic
waves between the two circular polariza-
tions. The chirality-switching metamaterial
we demonstrated may bridge this gap.
Their design principle for optically
switchable chiral terahertz metamolecules
is not limited to just handedness switching;
it also could be applied to dynamic revers-
ing of other electromagnetic properties.
Dynamically reversing other electro-
magnetic properties would enable us com-
plete control of electromagnetic waves, not
only in polarization, but also in phase, in-
tensity and propagation directions, Zhang
said. For example, we can use a similar
design principle to make a meta-surface
with dynamically switchable high and low
impedance. For a THz wave reflected by
the meta-surface, the phase can be dynami-
cally switched between 0 and 180 degrees.
The metamaterials we demonstrated so
far still have some drawbacks: Chirality is
not strong enough to completely convert
the THz waves into purely circular polar-
izations. We will work on the perfection of
the metamaterial design to achieve a
stronger chirality switching effect.
The work was published in Nature Com-
munications (doi:10.1038/ncomms 1908).
LOS ANGELES A new optical micro-
scope easily detects rare cells in real time
and could help doctors diagnose diseases
earlier or monitor treatments. The ability
to distinguish and isolate rare cells such
as circulating cancer tumor cells and stem
cells from a large population of assorted
cells has become increasingly important
for disease detection. Typically, there are
only a handful of these rogue cells
among a billion healthy ones, but because
they are precursors to metastasis the
spread of cancer that causes about 90 per-
cent of cancer mortalities it is important
to be able to find them.
To detect such cells requires an auto-
mated high-throughput instrument that can
examine millions of cells in a reasonably
short time. Currently, microscopes
equipped with digital cameras are used to
analyze cells, but they are too slow to be
useful for this application.
Now, Bahram Jalali and Dino Di Carlo
from the University of California, Los An-
geles, have devised a high-throughput
flow-through optical microscope that can
detect rare cells with sensitivity of one
part per million in real time. The instru-
ment is equipped with photonic time-
stretch camera technology developed by
Jalalis group in 2009 to create the quick-
est continuous-running camera in the
world.
To catch these elusive cells, the camera
must be able to capture and digitally pro-
cess millions of images continuously
at a very high frame rate, said Jalali, who
holds the Northrop Grumman Endowed
Opto-Electronic Chair in Electrical Engi-
neering at the UCLA Henry Samueli
School of Engineering and Applied Sci-
ence. Conventional CCD and CMOS
cameras are not fast and sensitive enough.
It takes time to read the data from the
array of pixels, and they become less sen-
sitive to light at high speed.
The team described how it integrated
the camera with real-time image process-
ing and advanced microfluidics for the
classification of cells in blood samples in
Proceedings of the National Academy of
Sciences (doi 10.1073/pnas.1204718109).
The new blood-screening technology de-
livers throughput of 100,000 cells per sec-
ond, roughly a hundredfold increase in
rate when compared with conventional im-
aging-based blood analyzers.
This study illustrates the detection of
rare breast cancer cells in blood in real
time with an unprecedented low false-pos-
itive rate of one cell in a million. Initial re-
sults show that this method can quickly
detect rare circulating tumor cells from
large volumes of blood samples, opening
the door for statistically accurate early
cancer detection and for monitoring the ef-
ficacy of drug and radiation therapies. The
results were obtained by mixing cancer
cells grown in a laboratory with various
proportions of blood to emulate real pa-
tient blood.
The team is conducting clinical trials to
assess the efficacy of the technology,
which can significantly reduce errors and
costs in medical diagnosis. It also could be
used for water-quality monitoring and
urine analysis.
The research was funded by the US
Congressionally Directed Medical Re-
search Programs, the Burroughs Wellcome
Fund and NantWorks LLC.
b
BIOSCAN
For more on the camera technology de-
veloped by Bahram Jalalis group, see
Full Steam Ahead with the Fastest
Camera in the World, www.photonics.
com/a38998.
Optical microscope detects rare cancer cells
Optical microscope with worlds fastest camera. Courtesy of UCLA.
Photonic crystals help fish see in the murk
LEIPZIG, Germany The elephantnose
fish has light-reflecting cups lined with
photonic crystals in its retinas that help it
navigate its dark, murky environment, sci-
entists have found. This unusual eye struc-
ture might aid future sensors that filter sig-
nal noise or peform detection in turbid
fluids.
These freshwater fish, found in the
cloudy depths of African rivers, use elec-
trosensing to navigate their dark environ-
ment, but they also depend somewhat on
vision. Until recently, these weakly elec-
tric fish were thought to be blind, or al-
most blind, University of Leipzig neuro-
physiologist Andreas Reichenbach said in
a podcast.
The visual capabilities of this fish are
pretty poor, he said. Its color-blind. It
cannot see anything that is not bigger than
six times the size of a full moon. But sur-
prisingly, its optimal for its environment.
Vertebrate eyes have rod photorecep-
tors, which are very sensitive to light but
do not detect color or fine details, and
cone photoreceptors, which are less sensi-
tive to light but can distinguish color and
details. Most vertebrate eyes optimize pri-
marily either rods or cones, but an interna-
tional team of scientists has discovered
that the retina of the elephantnose fish is
structured so that both types of receptors
work simultaneously.
The researchers observed that the cones
are grouped together within larger, light-
reflecting cups lined with photonic crys-
tals. The rods are positioned behind these
reflectors. This unusual arrangement
works because the mirrorlike surfaces of
the cups propagate the light in a way that
delivers just the right wavelength to both
the rods and cones.
Behind the eye in the so-called retina
pigment epithelium, there are huge cells,
which form kind of parabola mirrors re-
flecting the light, Reichenbach said.
From outside, you can see that light is re-
flected, like in the cats eye, but it is fo-
cused on a certain level in this case. The
astonishing thing is that within such
parabola mirrors, there are about 30 cone
photoreceptors, which are responsible for
high-acuity vision in our case, but not in
this case, and a couple hundred rod pho-
toreceptors.
Each photoreceptor sees the same part
of an image because all the rods and cones
are illuminated by the same structure,
meaning that the visual acuity is very bad,
he said. The fish are at an advantage be-
cause they are not able to see or get dis-
tracted by the small particles, such as dead
worms and bubbles or air moving around
them, but they can see the big predators
moving.
The special structure of the retina
of the fish enables the fish to see large
moving objects more reliably than any
other fish, and this makes him thrive
under these [turbid water] conditions,
he said.
While this vision proves advantageous
for the fish in dark, dim, muddy waters,
its detrimental in aquarium settings
with other fish.
If the fish swims in an aquarium
together with other fish under normal
laboratory conditions, its almost blind,
Reichenbach said. This was the reason
why the fish had been considered blind
for many years.
The study appeared in Science (doi:
10.1126/science.336.6089.1617-c).
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b
BIOSCAN
Scientists had long thought the elephantnose fish (Gnathonemus petersii) to be blind, but it turns out to have
light-reflecting cups lined with photonic crystals in its retinas that help it navigate in dark waters. Courtesy of
Gerhard von der Emde.
Light amplification by photonic-crystal light collector
onto photoreceptor cells in the retina of the ele-
phantnose fish helps it to see. Courtesy of Moritz
Kreysing.
LEUVEN, Belgium A new nanoscale
light-manipulation method that optically
detects single molecules could be used in
a variety of photochemistry applications
and help advance technologies for visual-
izing single molecules and multiple-mole-
cule interactions.
Progress in optically detecting single
molecules has been hindered by their weak
optical response. Currently, researchers use
metal nanostructures to focus light into
tiny zones called hot spots, which excite
electrons on the surface, causing them to
oscillate coherently. When shone on a mol-
ecule, and with the help of these oscillating
electrons, the focused light can increase a
molecules optical signal to 100 billion
times its normal strength, a level detectable
by optical microscopes.
The current method, however, has two
limitations: The first is that hot spots can
become too hot; the second is that they are
very small. This means that the heat from
hot spots can melt the nanostructure, de-
stroying its ability to channel light effec-
tively. And hot spots produce only a very
small cross section in which interaction
with molecules can take place. For a sin-
gle molecule to become detectable, it
must find the hot spot.
To overcome these drawbacks, Dr.
Ventsislav Valev and colleagues at
Katholieke Universiteit Leuven sought to
nanoengineer larger spots. The interna-
tional team began by shining circularly
polarized light on nanostructures and
found that this could increase the useful
area. When they shone light on square-
ring-shaped gold nanostructures, the scien-
tists observed that the entire surface of the
nanostructures was successfully activated.
Essentially, light is constituted of elec-
tric and magnetic fields moving through
space, Valev said. While with linearly
polarized light the fields move in a linear,
forward direction, with circularly polar-
ized light, they rotate in a spiral-like
motion.
The circularly polarized light imparts a
sense of rotation on the electron density in
ring-shaped gold nanostructures, thus trap-
ping the light in the rings and forming
loops of light. The loops cause excited
electrons to oscillate coherently on the full
surface of the square-ringed nanostruc-
tures, rather than in a few concentrated hot
spots. This increases the opportunity for
interaction with molecules.
The trick is to try to activate the whole
surface of the nanostructure so that when-
ever a molecule attaches, we will be able
to see it, Valev said. That is precisely
what we did.
The study appeared online in Advanced
Materials (doi: 10.1002/adma.201201151).
b
BIOSCAN
Shining circularly polarized light on ring-shaped nanostructures increases the opportunity for interaction with
molecules. Courtesy of Katholieke Universiteit Leuven.
Loops of light optically detect single molecules
Antennas capture, upconvert weak IR light
GRONINGEN, Netherlands A new tech-
nique that uses special molecules as light
antennas to harvest the energy from weak
infrared light and amplify the process
3300 times could lead to improved med-
ical imaging methods.
Materials scientists and chemists from
the University of Groningen and from the
FOM Foundation harvested infrared light
which has too little energy to release
electrons in solar cells more efficiently
by modifying an organic dye that acts as
light antennas to transmit the energy to the
nanoparticles to which they are attached.
These particles subsequently convert
two weak captured photons into a
single strong, energy-rich photon in a
Inspiration from nature: (left) a natural photosynthesis system with light-harvesting (LH) molecules and a reac-
tive center (RC); (right) a schematic representation of the nanocrystal that realizes the upconversion (UC) with
the attached antennas in green. Courtesy of University of Groningen.
process called upconversion.
There are inorganic materials made
from rare-earth metals that can facilitate
this upconversion process, said Jan C.
Kees Hummelen, a University of
Groningen professor of organic chemistry
and leader of the FOM focus group on
next-generation organic photovoltaics.
However, these materials absorb very
few infrared photons. We have therefore
attached organic molecules to them [as an-
tennas] that can capture these photons and
transmit the energy to the upconversion
material.
Because of this, the entire infrared ab-
sorption process, upconversion and the
emission of visible light is increased by a
factor of 3300, Hummelen said.
Even with the antennas, his group can
capture only a limited amount of infrared
light. He predicts that an even better yield
can be obtained, but because the upcon-
version process inside the nanocrystal is
still inefficient, it is not yet possible to
achieve.
Two photons must come together in
the material within a short space of time,
he said. In practice, the efficiency of this
process is still very low. However the har-
vest is already much better, so step one
has been achieved.
The upconversion system could be ap-
plicable for medical imaging techniques.
Infrared light penetrates further into
biological tissues than visible light, he
said. If you allow compounds that carry
out upconversion to bind to specific cells
in tissues, then you can make images
using infrared light.
The scientists work also is applicable
to solar cells, as about half of all the solar
energy reaching Earths surface consists of
infrared light.
The research was published online in
Nature Photonics (doi: 10.1038/npho
ton.2012.158).
b
BIOSCAN
Nanohole-based sensors ideal for medical diagnostics
SINGAPORE Novel molecular sensors
based on thin metallic films with nano -
holes hold promise for applications that
require detection of small quantities of
molecules, such as gas biomedical diag-
nostics and gas sensing.
The majority of these applications call
for inexpensive disposable sensors, but
they must be sensitive enough to detect
single molecules.
Ping Bai and colleagues at A*Star Insti-
tute of High Performance Computing and
the Institute of Materials Research and En-
gineering have studied the properties of
thin-film metallic films with holes in them
that show promise for molecular sensing
applications.
Metallic thin films with nanometer-size
holes are known to transmit light of partic-
ular wavelengths efficiently because of
surface plasmon polaritons (SPPs), the
collective movement of electrons on a
metal surface that focus light into tiny
spots much smaller than the wavelength of
light used.
SPPs can detect molecules through the
fluorescence of tracer molecules attached
to them. The SPPs enhance the fluores-
cence, which is easily detectable by a mi-
croscope, even for small quantities of mol-
ecules.
The whole setup is ultracompact to
support a point-of-care sensing system,
Bai said.
The team studied two sensing arrange-
ments: In the first, light was directed at a
film with nanoholes at an oblique angle
from the same side as the sample. The
film in the second arrangement was illu-
minated from the back so that light trav-
eled through the holes first. The re-
searchers observed that both arrangements
had advantages.
In the reflection scheme, the SPP ef-
fect is stronger because the light is aimed
directly at the sample and does not have to
cross the metal film. However, a thicker
film is needed so that the light does not
pass through. The intensity of the light
emitted by the molecules is weaker in the
transmission scheme, but filters and
other sensors could be included with the
metal film, and the film could be much
thinner.
There is therefore no clear advantage
for either sensing mode of such films,
Bai said. One thing that is clear from the
study, however, is the clear benefits of
using metal films with nanoholes as a
molecular sensing platform.
This is only a snapshot of the entire
project, Bai said.
Ultimately, our sensing technology
will be utilized in hospitals and test cen-
ters; for example, in prostate cancer
screening, or even used at home just like
glucose test kits.
The research appeared in IEEE Photon-
ics Journal (doi: 10.1109/jphot.2011.217
7652).
b
BIOSCAN
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Non-Magnetic Linear Motors
In surface plasmon polariton (SPP) sensing, nanohole films can be used in two configurations to sense
molecules in a water solution. In the reflection mode (top), light is directed at the sample from the water side.
In the transmission mode (bottom), it is directed at the sample from the back, leading to different SPP proper-
ties. The SPP field intensity is represented by the color plot; the optical fields on the top and bottom are
calculated for different resonance frequencies. 2012 IEEE.
Ashley N. Paddock
ashley.paddock@photonics.com
BUSINESSSCAN
As the population of the world ages, asso-
ciated eye problems will mean significant
growth for the ophthalmic laser market.
The number of people 60 and older has
tripled in the past 50 years. As of 2000,
there were 606 million people over the age
of 60 worldwide, according to a United
Nations report, and that global population
is projected to reach nearly 2 billion in
2050.
In the US alone, the 90-and-older popu-
lation nearly tripled over the past three
decades, reaching 1.9 million in 2010, ac-
cording to a November 2011 report by the
US Census Bureau and supported by the
National Institute on Aging. Over the next
four decades, this population is projected
to more than quadruple.
The aging population is subject to
unique eye conditions, such as cataracts,
which are a clouding of the eyes natural
lens. More than 15 million cataract surger-
ies are performed worldwide each year to
surgically replace the damaged lens with
an intraocular lens.
Besides the aging population, other fac-
tors driving the global ophthalmic laser
market, which is expected to reach $804
million by 2015, are increasing accessibil-
ity to advanced laser eye treatment; the in-
creasing proportion of people needing vi-
sion correction, especially in Asia; and an
increase in patients opting for eye surgery,
said Global Industry Analysts (GIA) Inc.
in an ophthalmic lasers report released in
January.
Although demand for certain major
ophthalmic laser treatments declined dur-
ing the economic recession as people post-
poned elective surgeries, technological de-
velopments continued, GIA said,
providing the stimulus needed to drive fu-
ture growth.
Certain new technological develop-
ments in laser surgery are believed to offer
benefits beyond vision correction and at-
tract significant demand in the future,
GIA said. Application of laser technology
in early diagnosis, and the detection of
certain eye disorders in conjunction with
imaging technologies, such as OCT, is an-
other factor that would boost growth of
the laser eye correction market in the fu-
ture.
On Aug. 6, New York-based eye health
company Bausch + Lomb and ophthalmic
laser maker Technolas Perfect Vision of
Munich announced that their Victus fem-
tosecond laser designed for cataract and
corneal surgery had received clearance
from the FDA.
Femtosecond lasers, with their ultra-
short pulses, do not transfer heat or shock
to the material being cut and can make
surgical incisions with extreme precision.
The technology was introduced commer-
cially in 2002 for creating thin, hinged
flaps during lasik surgery.
Companies that make femtosecond
lasers commercially for ophthalmic appli-
cations include Calmar Laser, Advanced
Medical Optics and Carl Zeiss Meditec.
Carl Zeiss Meditec announced in April
that it will begin a US clinical trial of its
ReLEx smile procedure for correcting my-
opia, or nearsightedness, after receiving
FDA approval.
In lasik procedures, the excimer laser
vaporizes tissue, but the ReLEx smile
method generates a refractive lenticule in
the intact cornea with a femtosecond laser.
The surgeon then removes the lenticule
through a small incision less than 4 mm
without having to move the patient to an
excimer laser, the company said.
The introduction of femtosecond laser
technology is the most significant ad-
vancement in cataract surgery in recent
history, said Dr. Steven J. Dell of Dell
Laser Consultants in Austin, Texas, in the
press release announcing the Victus ap-
proval.
The Victus is the first femtosecond laser
that can support both surgical procedures
on a single platform, the companies say,
and it is designed to provide greater preci-
sion compared with manual cataract sur-
gery techniques. The laser received CE
mark approval in Europe in November
2011 and has been used in more than 2000
cataract or refractive procedures world-
wide, the companies say. They are work-
ing to gain approval in the US for addi-
tional applications.
In June, Iridex Corp. announced the
first use of its MicroPulse laser therapy
(MPLT) through an intraocular fiber optic
endoprobe during ophthalmic surgery.
Expanding MPLT applications from
physicians offices into the operating room
and surgery centers will continue to drive
growth in our laser systems, said Iridex
President and CEO Dominik Beck.
MicroPulse works by electronically
chopping a continuous-wave laser emis-
sion into trains of microsecond pulses, en-
hancing the physicians ability to more
precisely control the laser effects on target
tissues. It is more effective for very thin
retinas, allowing more tissue to be pre-
served than in conventional continuous-
wave laser photocoagulation, the company
said.
Iridex is working to accelerate adoption
of MicroPulse for treating diabetic macu-
lar edema (DME), Beck said in an early
August statement announcing the com-
Ophthalmic laser market growing
BussinessScan_Layout 1 8/30/12 9:59 AM Page 17
panys second-quarter financial results.
Our experiences in DME have led us
to explore opportunities for MicroPulse in
the treatment of glaucoma, he said,
adding that the company is working with
key opinion leaders in glaucoma on how
its product can improve the current stan-
dard of care for treating the disease.
The new glaucoma therapy, a tissue-
sparing, repeatable technique called Mi-
croPulse Laser Trabeculoplasty, was intro-
duced by Iridex at the recent American
Society of Cataract and Refractive Surgery
meeting.
If the results of these initiatives indi-
cate an equivalent or better outcome than
currently available options, we could see a
significant impact to our revenues, as this
is a large market opportunity, Beck said.
The companys revenue from ophthal-
mology was $8.4 million for the quarter,
up from slightly over the prior quarter and
the prior year.
Dental laser maker Biolase also is see-
ing opportunity in the ophthalmic market.
We continue to seek the most efficient
route to market for our laser technology as
it relates to ophthalmology and other sur-
gical specialties, said Federico Pignatelli,
chairman and CEO, during an earnings
call on Aug. 8. We are currently in early
discussions with a leading ophthalmic
company to develop a relationship to
jointly deliver our first product to that
marketplace.
b
BUSINESSSCAN
Melinda A. Rose
melinda.rose@photonics.com
BUSINESSBRIEFS
ON Semiconductor Corp. of Phoenix and
Donald Colvin, its executive vice president and
chief financial officer, have mutually agreed to
Colvins resignation as an officer of the com-
pany. It was expected at the time of the an-
nouncement in August that he would continue
at the firm for up to 90 days while the board
sought a replacement. ON Semiconductor sup-
plies silicon solutions for energy-efficient elec-
tronics. Its power and signal management,
logic, discrete and custom devices help cus-
tomers solve their design challenges in automo-
tive, computing, LED lighting, medical, military,
aerospace, consumer and power applications.
Laser-sintering systems manufacturer EOS of
Krailling, Germany, filed a patent lawsuit March
5 against Phenix Systems of Riom, France, for
infringing two US patents for its dental product
lines. The lawsuit alleges infringement of US
Patent Nos. 5,753,274 and 6,042,774 through
the manufacture, sale and use of the PXL, PXM,
PXS and PXS Dental product lines from Phenix in
the US. During the second half of 2011, Phenix
announced publicly the commercial manufac-
ture, sale and use of exactly these product lines,
even though, EOS said, it had apprised Phenix
of its patent portfolio several times.
To honor professor Michael S. Felds fundamen-
tal contributions in the fields of laser science
and applied physics for solving biomedical
problems, The Optical Society (OSA) and the
OSA Foundation, both in Washington, have
established the Michael S. Feld Biophotonics
Award to be given annually beginning in 2013.
It will recognize individuals for innovative and
influential contributions to the field of biopho-
tonics, regardless of their career stage. Feld,
who passed away in 2010, founded the Laser
Biomedical Research Center at MIT in 1985
with the support of the National Institutes of
Health. Nominations for the award are now
being accepted from OSA members.
Shimadzu Scientific Instruments of Colum-
bia, Md., has opened the Shimadzu Center
for Advanced Analytical Chemistry at the
University of Texas at Arlington to give re-
searchers there access to enhanced capabilities
for trace qualitative and quantitative analysis.
The center contains $6 million worth of chro-
matography, mass spectrometry and spec-
troscopy equipment. The instruments will be
used to research illnesses such as cancer and
malaria, and to develop nanofabrication
materials for industry. Kevin Schug has been
named the Shimadzu Distinguished Professor
of Analytical Chemistry. An associate professor
of chemistry and biochemistry, he will oversee
the new laboratory.
DigitalOptics Corp. of San Jose, Calif., a
subsidiary of Tessera Technologies Inc., and
MMD Monitors and Displays Taiwan Ltd., a
subsidiary of TPV Technology Ltd., have part-
nered to deliver a computer monitor manufac-
tured by MMD with a built-in ergonomic sensor
to help users correct posture. TPV owns part of
Philips monitor and entry-level flat-screen TV
business, and DigitalOptics developed the soft-
ware used in Philips ErgoSensor detection tech-
nology. The technology uses the distance be-
tween a users pupils to determine whether he
or she is sitting within the optimal ergonomic
zone and, if not, determines how the user can
adjust seating position or posture to avoid risk
of injury. In addition, the device offers energy
savings by powering down when no user is
present.
Genia Photonics of Laval, Quebec, Canada,
has received $300,000 in financial assistance
from the Canadian government to acquire
state-of-the-art production equipment and labo-
ratory materials. The repayable funding was
awarded under the Canada Economic Devel-
opments business and regional growth pro-
gram and could result in the creation of 22 jobs
by 2014. The new equipment and laboratory fa-
cilities will enable the company to meet growing
customer demand and to accelerate research
and development work it has initiated over
the past two years. Genia Photonics develops
and manufactures pulse-programmable and
multifunctional fiber-based lasers for security,
biomedical, pharmaceutical and chemical
applications.
Three photonics companies have received the
Queens Award for Enterprise, the UKs most
coveted award for business success. Edinburgh
Instruments of Livingston, a photonics and
electro-optical scientific instrumentation manu-
facturer, received the honor for its sustained
international growth. Laser Quantum of
Cheshire was recognized for providing laser
technology equipment and services to the
aerospace, medicine, research and biomedical
sectors. Fianium of Southampton received the
award in the innovation category for its devel-
opment of the WhiteLase supercontinuum fiber
laser. The awards are made each year by the
queen on the advice of the prime minister and
an advisory committee.
Raptor Photonics Ltd. of Larne, Northern Ire-
land, has named Laser 2000 GmbH of Munich
as its scientific camera distributor for Germany
and Austria. Laser 2000 supplies lasers and
light sources, optics and optomechanics, optical
instrumentation and optical detectors for the
machine vision and scientific and instrumenta-
tion markets. Raptor Photonics manufactures
industrial-grade low-light digital and analog
cameras.
Given Imaging Ltd.s patent infringement
lawsuit against Intromedic Co. Ltd. of Seoul,
South Korea, has been upheld by the Intellec-
tual Property Tribunal of the Korean Intellectual
Property Office (KIPO). Given Imaging of
Yokneam, Israel, alleges that Intromedics cap-
sule endoscope, marketed under the brand
name MiroCam, has infringed two of its Korean
patents. In response to the accusation, In-
tromedic brought proceedings before KIPO to
invalidate the two patents asserted by Given
Imaging. KIPOs decision rejects Intromedics
invalidity arguments and cripples one of its
main defenses against Given Imagings patent
infringement action. The decisions may be
appealed by Intromedic.
Olympus America Inc. of Center Valley, Pa.,
and Carl Zeiss Microscopy GmbH of Jena,
Germany, have signed a nonexclusive world-
wide licensing agreement allowing the German
company to access Olympus portfolio of digital
pathology and virtual microscopy patents. The
patents in the licensing deal cover methods and
equipment for creating, storing and delivering
virtual microscopy slides. The technology en-
ables individuals to view and share high-resolu-
tion virtual microscopy images over the Internet.
Specific terms and conditions of the agreement
will not be made public. The microscopy busi-
ness group at Carl Zeiss manufactures light and
electron microscopes for the life and materials
sciences.
To increase its presence in the Middle East, Im-
aging Diagnostic Systems Inc. of Fort Laud-
erdale, Fla., has signed a distribution agree-
ment with Mareen Group Co. to market and
sell its computed tomography laser mammogra-
phy system in Jordan. Mareen Group is a med-
ical and pharmaceutical distribution company
based in Kuwait. The noninvasive optical breast
imaging system uses patented continuous-wave
laser technology and computed algorithms to
create 3-D images of the breast.
Medical device company SpectraScience Inc.
of San Diego has signed an exclusive five-year
agreement with Pentax Europe GmbH of
Hamburg, Germany, to distribute its WavSTAT
optical biopsy system for colorectal cancer
screening and diagnosis. Pentax provides mini-
mally invasive surgical devices, including flexible
endoscopes that are used with the WavSTAT
system. The agreement, which includes the
companys new WavSTAT4 mobile console and
disposable optical biopsy forceps, covers Eu-
rope, Turkey, Saudi Arabia and South Africa. It
also provides for minimum purchase quantities
in specified countries and gives Pentax a right
of first refusal option for all other countries in
the Middle East and Africa.
Laser-based medical systems provider Iridex
Corp. of Mountain View, Calif., has announced
the success of its MicroPulse laser therapy in
surgery using an IQ 577 laser coupled with
EndoProbe instrumentation. This is the first time
that tissue-sparing laser therapy has been deliv-
ered through an intraocular fiber optic probe in
a surgical setting, the company said. Endo-Mi-
croPulse is effective in cases of very thin retinas
because it preserves tissue rather than destroy-
ing it, as conventional laser therapy does. Dr.
Sam Mansour, who performed the surgery at
George Washington University School of
Medicine and Health Sciences, is medical di-
rector of the Virginia Retina Center and clini-
cal professor of ophthalmology at the university.
LensAR Inc. of Orlando, Fla., has received
510(k) clearance from the FDA for its next-gen-
eration LensAR Laser System for use in anterior
capsulotomy, with and without laser phacofrag-
mentation during cataract surgery. The regula-
tory action covers the new system, which is in
final preparation for commercial launch in the
US. The system combines the latest laser tech-
nology with product features intended to im-
prove surgeon and patient interactions with it.
Enhancements include 3-D imaging measure-
ment and beam-guided delivery that generates
a personalized surgical treatment plan.
Roger H. Brggemann has been hired as head
of marketing and sales at diode-pumped solid-
state laser manufacturer Crystal Laser Sys-
tems GmbH of Berlin. He brings to the role
more than 12 years of international experience
in sales and marketing of solid-state lasers and
optical components. Prior to joining the com-
pany, he worked at Luceo Technologies
GmbH and, before that, at Klastech Laser
Technologies GmbH. Crystal Laser Systems
products have applications in the life sciences,
optical metrology, research and development,
and original equipment manufacturing.
Idex Corp. of Lake Forest, Ill., has acquired
Matcon Group Ltd. of Evesham, UK, a supplier
of materials processing solutions for high-value
powders used in food, pharmaceuticals, plastics
and fine-chemicals manufacturing. Matcons
products include the original cone valve powder
discharge system and filling, mixing and pack-
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reliable and repeatable formulations of
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lean, agile manufacturing. With annual rev-
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$34.2 million), Matcon will operate within Idexs
Health and Science Technologies Div. in the
materials processing technologies platform.
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b
O
ptical microscopy is a power-
ful tool in bioscience research,
allowing researchers to ob-
serve multiple complex physi-
ological processes in real time. Fluores-
cence imaging a major technique used
with optical microscope systems pres-
ents many challenges, however. Achieving
sufficient concentration of a fluorescent
probe within a tissue can be difficult. Photo-
toxicity caused by singlet oxygen forma-
tion is damaging to living cells. And, in
live animal and animal tissue imaging, the
probe is likely to be recognized as a for-
eign entity by the animals immune
system.
Multimodal label-free imaging includ-
ing second-harmonic generation (SHG),
coherent anti-Stokes Raman scattering
(CARS) and intrinsic two-photon excita-
tion fluorescence offers a technique to
monitor disease processes over time with-
out perturbing physiological processes
by incision, adding foreign reagents or
encountering artifacts caused by fixation,
permeabilization or biochemical extraction
protocols. There is also an advantage in
using label-free imaging techniques based
on harmonics or Raman scattering because
electrons are not excited in the same man-
ner as in regular fluorescence excitation.
In both harmonics and Raman scattering
imaging, the formation of reactive oxygen
and its subsequent toxicity are signifi-
cantly reduced.
Multimodal imaging
Multimodal label-free imaging exploits
the properties of molecules when they in-
teract with photons from the short-pulsed
lasers used in multiphoton microscope
systems. These two-photon or multiphoton
imaging systems typically are optimized
for observation of fluorescent molecules
several hundred microns deep in tissue,
exploiting the improved penetration and
reduced scattering of longer infrared
wavelengths. To achieve the two-photon
effect, these lasers produce an intense flux
of photons in femtosecond pulses. The
total energy is kept low to avoid overheat-
ing the sample.
The only position where the photon flux
is strong enough for two or more photons
to combine their energies is at the exact
focal point. Because there is no excitation
outside that spot, fluorescence is confined
to molecules in one optical section as the
laser scans over the field of view. This in-
herent optical sectioning also works with
Drives Biomedical Research
Label-free noninvasive, nondestructive optical microscopy
using multiple simultaneous techniques allows researchers
to observe diverse life processes in real time.
Figure 1. Multimodal imaging of macromolecules in C. elegans. Using multiphoton excitation at 800 nm,
a second-harmonic generation signal was collected at 375 to 405 nm in both the reflected (top left) and
forward (top right) external nondescanned detectors. Intrinsic two-photon excitation fluorescence (autofluores-
cence) was simultaneously collected at 520 to 560 nm in the reflected external nondescanned detectors with
800-nm excitation (bottom left, with overlay at bottom right). Maximum intensity projections of 139 Z-series
slices acquired at 0.4 m per optical slice. Scale bar 50 m. Courtesy of Delong Zhang, Purdue University.
BY JAMES LOPEZ AND YIWEI JIA, OLYMPUS AMERICA INC.
Feat Olympus_Layout 1 8/30/12 10:00 AM Page 20
other photonic techniques that depend on
these photon interactions, including har-
monic generation and CARS.
Multimodal imaging is the combination
of two-photon techniques such as two-
photon excitation fluorescence of intrinsi-
cally fluorescent molecules, SHG and
CARS in a single experiment. When com-
bined, these techniques create a more
complete image of life processes without
additional labels.
Most cells and tissues exhibit a complex
mixture of spectra from autofluorescence
(also called intrinsic fluorescence). It is
possible to attribute intrinsic fluorescence
of a particular wavelength to molecules
such as nicotine adenine dinucleotide
(NADH), lipofuscin or elastin. The peak
emission for these molecules is in the blue
range due to their component aromatic
amino acids, so intrinsic fluorescence is
often imaged using multiphoton excitation
rather than a blue or UV-emitting laser to
avoid the photodamage with the higher-
energy (shorter wavelength) photons.
SHG occurs when two photons are scat-
tered simultaneously by an orderly array
of molecules that all point in the same di-
rection. Known as inversion asymmetry,
this type of molecular structure is found
in various tissue structures including colla-
gen fibers, myofilaments and microtubules
of the mitotic spindle. The second-har-
monic signal is emitted coherently in
the direction of the incident beam, with
exactly twice the incoming energy and
therefore half the wavelength.
In CARS, the three photons that interact
originate with two different wavelengths.
The difference in frequency gives rise to a
signal because of resonance with specific
chemical bonds, notably the C-H bond
stretch that predominates in lipids.
Methodology
A laser-scanning microscope equipped
for multiphoton excitation can be used to
image both fluorescence and SHG through
the selection of appropriate excitation
wavelengths and filters. Intrinsic fluores-
cence is a hundredfold weaker than most
exogenous fluorophores, so the detection
path must be optimized by using high-
numerical-aperture objective lenses and
nondescanned detectors.
SHG signals typically are stronger in
the forward direction, so a transmitted
nondescanned fluorescence detector and
high-numerical-aperture condenser with an
oil-top lens is preferred. Forward-directed
SHG detection tends to favor large, bright
structures, while the reflected direction is
often more sensitive to finer, dimmer
structures. This is also generally true for
CARS imaging. Muscle fibers can be vi-
sualized without the use of any labels in
Caenorhabditis elegans, a commonly used
model organism in biological research,
using SHG. SHG and intrinsic two-photon
excitation fluorescence (autofluorescence)
signals can be collected simultaneously in
both the forward and reflected directions,
and then can be combined into a single
multimodal imaging data set (Figure 1).
There are several ways to generate the
two beams that combine to produce the
CARS signal: Researchers have often used
two picosecond-pulsed IR lasers tuned to
Figure 2. Green fluorescent protein expressing tumor growing in liver, imaged
using simultaneous multimodal imaging. Collagen fibers (white) are visualized
with second-harmonic generation. Lipids are imaged using femto-CARS (red).
The GFP-labeled tumor mass and the intrinsic fluorescence are co-observed in
the green channel. Maximum intensity projection of a stack of 12 Z-planes
spaced at 2.42 m. Courtesy of Teng-Leong Chew, Northwestern University.
Figure 3. Lipids exterior to and within cells after mice were gavaged with 200 l
of oleic acid. The CARS signal (magenta) from lipids and intrinsic fluorescence
(green) delineates individual cells of the microvillus. Maximum intensity projec-
tion, 511 Z-planes, 0.5 m apart, scale bar 100 m. Courtesy of Mikhail
Slipchenko, Purdue University.
different frequencies to serve as pump and
Stokes beams, with the difference in fre-
quency tuned to match the resonant fre-
quency of a specific chemical bond. Re-
cently, however, Adrian Pegoraro et al
have developed a femto-CARS system
that uses the same femtosecond-pulsed IR
laser that is used for multiphoton excita-
tion and splits the beam into two compo-
nents. One component passes through a
photonic crystal fiber to produce a red-
shifted Stokes beam, which then recom-
bines with the unaltered beam using preci-
sion alignments and stage delay.
The CARS signal can be collected in ei-
ther the reflected or forward direction with
qualitatively different patterns, adding in-
formation for expert interpretation. In all
detection modes, the IR wavelengths of
the imaging beams are blocked, and filters
are chosen to separate different signals ac-
cording to wavelength range. For example,
the Olympus femto-CARS system uses
two excitation wavelengths for imaging:
800 and 1040 nm. The 800-nm wave-
length serves as the imaging wavelength
for intrinsic fluorescence and SHG, and is
one of the wavelengths for CARS imag-
ing; 1040 nm functions as the second nec-
essary wavelength for CARS imaging. The
SHG signal from the 800-nm beam occurs
at 400 nm, and the CARS signal is col-
lected at 650 nm.
Depending upon the sample, these three
signals (SHG, CARS and intrinsic fluores-
cence) can be collected simultaneously
using either reflected or forward detection.
Additional wavelengths may be used for
a fourth signal. A four-channel filter set
for the reflected detector might have filters
that collect narrow bands for simultaneous
imaging of SHG; green fluorescent protein
or intrinsic fluorescence; yellow fluores-
cent protein or the DiI fluorescent indica-
tor; and CARS. Because these imaging
modalities are not as specific as antibody-
or nucleic-acid-sequence-recognizing
probes, most experiments are comparative.
For example, the collagen distribution
around a tumor may be compared to unaf-
fected stromal tissue or to the pattern ob-
served in a control animal. Researchers
might, for example, do a comparison be-
tween the intrinsic fluorescence of NADH
under normoxic and hypoxic conditions.
Metabolism may also be expressed as a
ratio of NADH (or NADPH) with another
member of the electron transport chain,
such as flavin adenine dinucleotide. Simi-
larly, the CARS signal indicates lipids in
general but cannot distinguish sphin-
gomyelin from phosphatidylcholine or any
other molecule with a long chain of C-H
bonds.
SHG imaging of collagen
Collagen deposition around tumors has
been recognized by pathologists for
decades. Paolo Provenzano et al have pro-
posed a classification of tumor-associated
collagen signatures that have potential for
clinical staging. These changes in collagen
structure can be observed using SHG im-
aging. Degradation of collagen resulting
from extracellular protease activity, as
well as changes in fibril composition, may
be helpful in identifying changes in tissue
that indicate tumor initiation or progres-
sion.
Combined with collagen imaging,
CARS imaging of lipids has the potential
to help investigate the role of fat-contain-
ing adipocytes in the tumor microenviron-
ment. The observation that cancers appear
to have an association with fat cells might
suggest that adipokines (hormones se-
creted from adipocytes) promote tumori-
genesis by inducing the expression of
genes regulating cancer cell proliferation,
invasion, survival and angiogenesis (Fig-
ure 2). Longitudinal studies may reveal
changes in lipid content and fibrosis as the
tumor progresses.
Intrinsic fluorescence and CARS
The impact of dietary fats on lipid ab-
sorption can be studied using CARS. Indi-
vidual cells in intestinal microvilli are
visualized by their intrinsic fluorescence
in the green wavelengths, while the CARS
signal, detected in the red wavelengths,
highlights lipids both in the lumen of the
gut and in microvillus cells (Figures 3 and
4). Such experiments may help in the de-
sign of therapeutic interventions for meta-
bolic syndrome and other lipid absorption
abnormalities.
More applications
of multimodal imaging
In cancer research, recognizing the im-
portance of the tumor cell microenviron-
ment has led to an increase in studies in
living animals and animal tissue. Multi-
modal imaging provides a way to eluci-
date the relationship between obesity and
cancer using CARS imaging of lipids, the
mechanisms of invasion and metastasis
using SHG, and altered metabolism using
intrinsic fluorescence. Epidemiological
studies reveal a correlation between cer-
tain cancers and obesity, but finding a di-
rect cause-and-effect relationship has
proved elusive.
In a series of studies using CARS, Ji-
Xin Cheng, Thuc T. Le and colleagues ap-
proached this question using CARS imag-
ing of lipids in cells and in animal models.
They observed increased lung metastasis
and circulating tumor cells in animals fed
a high-fat diet. Microscopic imaging of
these cells showed increased lipid deposi-
tion compared to tumor cells from animals
fed a low-fat diet.
In neuroscience, significant research is
being conducted with the ultimate goal of
alleviating myelin degradation in spinal
cord injury and demyelinating diseases
such as multiple sclerosis. CARS imaging
of myelin sheath, SHG imaging of as-
troglial processes and two-photon excita-
tion fluorescence imaging of calcium ion
distribution in live spinal tissues may help
researchers identify opportunities for inter-
vention.
In animal models of cardiovascular dis-
ease, the stability of atherosclerotic plaque
can be assessed using multimodal label-
free imaging. Lipid-rich macrophages
known as foam cells are increased in un-
stable plaque, while underlying collagen
and elastin are disrupted. CARS can iden-
tify the lipid content of the accumulated
macrophages, while SHG indicates disor-
Figure 4. Imaging of lipids within cells of the
microvillus, with CARS signal (magenta) from
lipids and intrinsic fluorescence (green) delineating
individual cells of the microvillus. Maximum intensity
projection, 495 Z-planes, 0.3 m apart with
calculated orthogonal slices. Courtesy of Mikhail
Slipchenko, Purdue University.
ganized collagen fibrils; the intrinsic fluo-
rescence of elastin can highlight the vul-
nerability of the lesion.
Multimodal label-free imaging offers a
way to monitor disease processes over
time with less physiological perturbation.
Now that there are turnkey multimodal
systems available, biomedical researchers
can combine these methodologies for a
more thorough understanding of disease
processes. Moreover, these microscopic
imaging techniques can pave the way for
developing specific molecular imaging
techniques that offer greater tissue depth
and even the potential for clinical utility.
Meet the authors
James Lopez is the confocal and multiphoton
sales application specialist at Olympus America
Inc. in Chicago; email: james.lopez@olympus.
com. Yiwei Jia is marketing manager of confo-
cal laser scanning microscopes at Olympus
America Inc. in Center Valley, Pa.; email:
yiwei.jia@olympus.com.
References
K.A. Kasischke et al (July 2, 2004). Neural ac-
tivity triggers neuronal oxidative metabolism
followed by astrocytic glycolysis. Science,
pp. 99-103.
T.T. Le et al (January 2009). Coherent anti-
Stokes Raman scattering imaging of lipids
in cancer metastasis. BMC Cancer, Vol. 9,
p. 42.
T.T. Le et al (2010). Shedding new light on
lipid biology with coherent anti-Stokes
Raman scattering microscopy. J Lipid Res,
Vol. 51, p. 3091.
A.F. Pegoraro et al (February 2009). Optimally
chirped multimodal CARS microscopy based
on a single Ti:sapphire oscillator. Opt Ex-
press, Vol. 17, p. 2984.
P.P. Provenzano et al (December 2006). Colla-
gen reorganization at the tumor-stromal in-
terface facilitates local invasion. BMC Med,
Vol. 4, p. 38.
P.P. Provenzano et al (2009). Multiphoton mi-
croscopy and fluorescence lifetime imaging
microscopy (FLIM) to monitor metastasis
and the tumor microenvironment. Clin Exp
Metastasis, Vol. 26, pp. 357-370.
P.P. Provenzano et al (November 2009). Shin-
ing new light on 3D cell motility and the
metastatic process. Trends Cell Biology,
Vol. 19, pp. 638-648.
P.P. Provenzano et al (December 2009). Matrix
density-induced mechanoregulation of breast
cell phenotype, signaling and gene expres-
sion through a FAK-ERK linkage. Onco-
gene, Vol. 28, pp. 4326-4343.
M. Skala and N. Ramanujam (2010). Multipho-
ton redox ratio imaging for metabolic moni-
toring in vivo. Methods Mol Biol, Vol. 594,
pp. 155-162.
M.C. Skala et al (December 2007). In vivo
multiphoton microscopy of NADH and
FAD redox states, fluorescence lifetimes,
and cellular morphology in precancerous
epithelia. Proc Natl Acad Sci, Vol. 104, pp.
19494-19499.
This article is the final installment in
a series. The first three articles in this
series are:
Adrian Pegoraro et al (October 2009).
CARS Microscopy Made Simple.
BioPhotonics.
Angela Goodacre et al (October 2010).
Combining Second-Harmonic Generation
with Multiphoton Imaging. BioPhotonics.
Angela Goodacre and Dennis Donley
(September 2011). Intrinsic Fluorescence
Lights Up Cellular Components.
BioPhotonics.
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T
he Star Trek television series and
movies have proved remarkably
prescient in anticipating future tech-
nologies from flip phones to
iPads decades before they appeared in
everyday life. Now, nearly half a century
after the debut of the original series, the
science fiction classic featuring Captain
Kirk and the alien Mr. Spock, we are be-
ginning to see modern-day equivalents of
another iconic Star Trek device: the tri-
corder.
In the series, tricorders are handheld
medical instruments used to detect, diag-
nose and treat any number of injuries or
maladies, either terrestrial or alien. The
design has evolved over the decades, but
in all cases the device is portable, requires
no external power source and provides
some sort of sensing capability.
This description also can be applied to a
new generation of sensing and imaging
devices in our own time. Recent advances
enabling miniaturization of the technolo-
gies, the advent of smartphones with cam-
eras and data-transmission capabilities,
and other factors have led to the develop-
ment of a host of instruments that might
be described as tricorders, or at least as
tricorder-like. And theres undoubtedly
more to come.
Early this year, the X PRIZE and Qual-
comm foundations announced the launch
of the $10 million Qualcomm Tricorder X
PRIZE, a global competition in which
teams will leverage innovative technolo-
gies such as wireless sensing to develop a
mobile platform that can make medical di-
agnoses independently of a physician or
The Age of the Tricorder
The medical device of the future is already here.
Researchers at the Beckman Laser Institute at the University of California, Irvine, have developed a handheld laser scanner to distinguish between potentially
malignant and benign tumors in the breast. The device uses diffuse optical spectroscopy imaging and a new analysis method called self-referencing differential
spectroscopy analysis. A recent Cancer Research study demonstrated the potential benefit of this method. Courtesy of Paul Kennedy.
BY GARY BOAS, CONTRIBUTING EDITOR
Feat Tricorder_Layout 1 8/30/12 10:07 AM Page 24
health care provider. The top prize will go
to the team whose platform most accu-
rately diagnoses a set of 15 diseases in-
volving 30 consumers in three days, while
also providing a compelling consumer ex-
perience.
Theres no telling what the winning de-
sign will look like, or what technology it
will employ the only constraint is that
the system and its components together
cant weigh more than 5 lb but many as-
sume it will involve a smartphone running
custom-developed apps, in no small part
because smartphones already carry sophis-
ticated cameras and displays as well as
other technology essential to the sort of
home health monitoring envisioned by the
sponsors of the competition.
Importantly, from a technology stand-
point, such a platform is possible today. A
variety of research groups and companies
have already taken advantage of advances
in imaging technology to turn smartphones
into microscopes and sensor systems. One
example: Philips offers an iPhone and
iPad app called Vital Signs Camera, which
can measure heart rate from a distance, ex-
trapolating heartbeats from a slight flush-
ing of the skin.
Where does the Qualcomm Tricorder X
PRIZE fit in, then? The competition is
about technology development, said Bruce
Tromberg, director of the Beckman Laser
Institute and Medical Clinic at the Univer-
sity of California, Irvine, but it is just as
much about determining what information
people need to make a diagnosis, to know
when to see a doctor, when to take medi-
cine, and so on, and determining how best
to obtain and use that information.
As the health care landscape continues
to change, he said, activities like screening
and follow-up monitoring, generally
will move into the home, into the hands of
the patient.
One possible scenario: Sensors on a
smartphone or some other device will
monitor a patients physiological parame-
ters and send the data to a server for analy-
sis. The results will be considered in the
context of the patients overall health (his
or her entire medical history will also be
stored there), and if any further action is
needed call the doctor, pick up a pre-
scription an email or text will be sent.
The tricorder competition will help us
envision what all this will look like.
Home testing is only one potential use
for tricorder-like devices, however. Such
instruments could help to advance a range
of additional applications, both within and
beyond traditional clinical settings.
Point of care
In the clinic, Tromberg and colleagues
are developing devices for physicians that
can impact patient care and even change
clinical outcomes: for example, a hand-
held laser scanner for use in detection, di-
agnosis and treatment of breast cancer. By
measuring parameters such as hemoglobin
concentrations and fat and water content,
Innovation and
entrepreneurship
F
ew would argue the importance
of developing optics-based and
other medical devices for global
health applications, but sustain-
ability of the model can still prove
challenging. At the end of the day
there has to be a market, said
Utkan Demirci, director of the Bio-
Acoustic-MEMS in Medicine
(BAMM) Laboratory at Brigham
and Womens Hospital in Boston,
and an assistant professor there
as well as at Harvard Medical
School and Harvard-MIT Health
Sciences and Technology. The lab
develops microfluidics for CD4
counts and viral load for HIV in
resource-limited and other set-
tings. These technologies also
have been adapted for isolating
and detecting bacterial pathogens
in produce (e.g., milk, spinach),
and for primary care blood sens-
ing applications; they have poten-
tial military applications as well.
Additionally, as a part of his
educational efforts in the field,
Demirci developed and taught a
course at Harvard-MIT Health and
Sciences Technology titled De-
signing and Sustaining Technology
Innovation for Global Health Prac-
tice. The course which has been
offered several times in the past
five years is based on the prem-
ise that innovation in this area re-
quires leaders to think and act like
entrepreneurs. Theres been con-
siderable interest in the course,
Demirci said. Its amazing how
people are motivated to help.
Cell phone-based technologies such as this recently announced device developed by researchers at
UCLA can help to address a range of global health needs. Courtesy of Ozcan Research Group at UCLA.
the device can help distinguish between
potentially malignant and benign tumors.
It can also be used to evaluate the effec-
tiveness of chemotherapy at bedside and
during the course of treatment allowing
the oncologist to adjust the therapy based
on how the patient responds.
Tricorder-like devices could help to
advance care in other settings as well,
including any number of sites where
advanced diagnostic devices wouldnt
normally be found.
Chris Myatt is founder and CEO of
MBio Diagnostics, which develops optics-
based solutions for disease diagnosis and
research. In an article in the February
2011 issue of BioPhotonics (Not Your
Fathers Microscope, pp. 21-23), he said,
We look at point-of-care, home testing
and world health together as resource-
limited settings, where users are not for-
mally trained medical technicians and the
lab facilities are not sophisticated. This
is true of a clinic in Mozambique, a mo-
bile STD van in San Diego, or in a home
in New York.
Point of care refers to testing or mon-
itoring performed at or near the site of
care, although it is more commonly used
today to describe clinical services pro-
vided in nontraditional settings. For exam-
ple, especially with the shifting health care
landscape in the US, we will see an in-
creasing demand for long-term monitoring
of chronic diseases including cardiovas-
cular and autoimmune in pharmacies
and other retail outlets (both CVS and
Wal-Mart have explored the possibility of
keeping diagnostic kiosks in their stores)
as well as in community clinics and out-
reach centers.
Also consider point-of-care HIV testing.
Testing is already done in nontraditional
settings including the mobile STD vans in
San Diego and elsewhere and, with a new
program in Washington, testing sites in
grocery stores and high schools and even
at the Department of Motor Vehicles. And
demand for this point-of-care application
continues to increase.
Optics-based technologies are well
suited to meet this demand. The technolo-
gies may not look exactly like the tri-
corders in Star Trek devices roughly the
size of an electric razor that you operate
by waving them around in the air some-
where near the patient but they meet all
the criteria that matter: portable, rugged
and reliable.
Since April of last year, the Antiviral
Research Center at the University of Cali-
fornia, San Diego, has been evaluating the
performance of an MBio system designed
to deliver absolute CD4 counts at the point
of care in minutes; CD4 count is essential
to monitoring disease progression in HIV
patients. The system a fluorescence im-
aging cytometer with single-use dispos-
able cartridges offers a rapid read time
of 3.5 min and a simple design, with pas-
sive fluid handling (no pumps or valves)
Tricorder
MBio Diagnostics has developed a multiplexed
fluorescence immunoassay system for rapid
diagnosis of complex infectious diseases like HIV
and hepatitis. Among the applications the company
is exploring: antenatal screening for HIV/syphilis
in Kenya. Courtesy of MBio Diagnostics.
The MBio Diagnostics system combines single-use disposable array cartridges with a simple reader instrument
a USB peripheral device that connects to and draws power from a laptop computer to provide simultane-
ous measurement of multiple analytes from a single sample. Illumination and imaging of fluorescence
immunoassays is achieved using a multimode planar waveguide technology developed by the company.
Courtesy of the Journal of Clinical Microbiology.
and minimal biohazard (all waste stays
onboard). The system weighs about 2 kg,
with dimensions of 12 8 20 cm.
Preliminary findings from the study,
presented at the 2012 Conference on
Retroviruses and Opportunistic Infections
held in Seattle in March, showed that the
system had minimal bias relative to the
gold standard, flow cytometry thus un-
derscoring the potential of the system for
point-of-care applications.
Imaging in the developing world
Tricorder-like devices particularly op-
tics-based ones can also contribute to a
host of global health applications. There
is little access in developing nations to
the sophisticated lab tests and the training
needed to run them that can be common-
place in the developed world.
Health care workers use a variety of in-
expensive, portable tests to meet the many
global health demands they face, but these
can have limited efficacy. In recent years,
researchers and medical device companies
have shown that optics-based technologies
can bridge this gap.
Take, for example, rapid diagnostic
tests (RDTs) assays designed to detect
target analytes in blood or fluid samples.
Using RDTs, and with only minimal train-
ing, health care workers have been able to
detect a range of diseases including
HIV, malaria, tuberculosis and syphilis
leading to better management of disease
and more efficient surveillance of out-
breaks.
Conventional RDTs have their limita-
tions, though. Because they are read man-
ually, there is potential for error, especially
as the workers often administer a variety
of different tests at the same time. Cell-
phone-based, tricorder-like devices could
help to eliminate this potential for error by
offering automated readings of the diag-
nostic tests.
At the annual conference of the Ameri-
can Association for Clinical Chemistry
held in Los Angeles in July, Holomic LLC
a company launched in 2011 to commer-
cialize the biophotonic technologies in-
vented in Aydogan Ozcans lab at UCLA
introduced its cell-phone-based rapid
diagnostic test reader, the HRDT-1.
Weighing only about 65 g, the device
mechanically attaches to the existing camera
unit of a cell phone. An app on the phone
digitally processes captured images within
0.2 s per image then provides a reading of
the diagnosis, and finally sends the image
and accompanying data to a central server.
Uploading images to the server offers a
means to store them; the color changes in
RDTs dont last more than a few hours in
the field. But it has other advantages too.
The cloud angle and the Google Maps-
based interface could especially help over
the long run to study the data that accumu-
lates, Ozcan said. In the shorter term, it
can also help manage epidemics or get
prepared for them.
HIV/AIDs is, of course, another health
concern in the developing world, espe-
cially in sub-Saharan Africa. In 2009, an
estimated 33.3 million people worldwide
were living with AIDS, according to the
UNAIDS Report on the Global AIDS Epi-
demic 2010. Of those, an estimated 22.5
million were in sub-Saharan Africa. The
number of new infections is dropping, but
there is still a considerable need for
screening and monitoring of the disease.
MBio is also seeking to tackle HIV in
Africa and other parts of the developing
world. In addition to the CD4 test for stag-
ing of the disease and ongoing monitoring
of therapy, the company is developing
tests for co-infections, and panels of tests
for applications such as antenatal screen-
ing. We have an HIV/syphilis combina-
tion test currently in a study in rural
Kenya, testing pregnant moms for these
diseases where intervention can prevent
the transmission to the child, Myatt said.
The latter application, in particular, has
been in the spotlight recently. In July, in a
keynote address at the biennial conference
of the International AIDS Society, Secre-
tary of State Hillary Clinton called for
elimination of mother-to-child transmis-
sion of HIV, worldwide, by 2015.
Currently, HIV/syphilis screening in
resource-limited areas uses an HIV rapid
test and the RPR (rapid plasma reagin)
syphilis test. The latter, though, requires a
skilled operator with laboratory facilities
and a cold chain for the reagents (where
reagents are shipped and stored cold
throughout the supply chain), and it gener-
ates many false positives, particularly in
pregnant women. While inexpensive,
Myatt said, the RPR tests complications
limit its use.
gary.boas@photonics.com
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N
ew glass optical fibers offer
longer lifetimes and higher
light transmission, and experi-
ence only minimal changes in
color and dispersion, and these character-
istics enable them to answer the call for
higher quality medical lighting. Whats
more, a newly developed environmentally
friendly process allows these high-purity
multicomponent glass fibers to be manu-
factured without using lead, arsenic or
antimony.
In medicine in particular, glass optical
fibers have conquered a wide range of ap-
plications, mostly in endoscopy and surgi-
cal microscopy, but fibers also are used in
dental treatment and light therapy.
Improved high-purity, multimode step
index fibers will pave the way for new
ideas that extend well beyond existing ap-
plications. This can be attributed to the
progress that has been made in the compo-
sition and preparation of the special glass
from which these fibers are drawn at high
temperatures. Multicomponent glass also
offers an outstanding price-to-performance
ratio compared with quartz glass. Com-
pared to existing fiber products, this
means significant performance improve-
ments that are certain to offer major bene-
fits in actual applications.
For example, it is now possible to in-
crease the transmission of white light by
up to 10 percent (Figure 1). High-purity
raw materials for manufacturing the glass
are instrumental in achieving this goal. Of
course, many years of experience in melt-
ing and manufacturing glass in the area
of refining, for instance (driving bubbles
out of molten glass) reveal other ways to
avoid glass defects.
The fibers high purity limits shifts in
color caused mainly by impurities in the
glass. Thus, the illuminated objects retain
their natural colors even when longer
lightguides are used.
New Glass Fibers
Widen Range of Medical Lighting Applications
Optical fibers with higher light transmission and longer life spans
offer interesting new solutions for meeting the growing demand for higher quality lighting in medicine.
BY KAREN HOLST, SCHOTT AG
Figure 1. Puravis multicomponent glass fibers transmit wavelengths in the visible range better than
conventional Schott glass optical fibers. Images courtesy of Schott AG.
Figure 2. The new glass fibers (shown here are the data for the GOF85 product, as opposed to A2) minimize
shifts in color, even when long lightguides are used. This can be important for medical and other applications.
Feat Schott_Layout 1 8/30/12 10:08 AM Page 28
Applications such as endoscopy and
surgical microscopy are certain to benefit.
Ever-thinner optical lightguides, brighter
light and smoother true-color illumination
are needed to distinguish between certain
types of tissue.
Comparative measurements on fibers
used in the past clearly show this (Figure
2). When used in the standardized light
source A, which equates to halogen light
that has a color temperature of 2856 K
and that is emitted directly, Puravis
GOF85 glass fibers from Schott AG ex-
hibit hardly any deviation over a distance
of 10 m. A conventional glass fiber (A2)
experiences shifts of close to 200 K that
can be seen even with the naked eye as the
distance increases. This difference be-
comes even clearer in comparison to nor-
mal light (6500 K) from a xenon lamp
D65, where a color shift of around 800 K
occurs at GOF85, which is significantly
lower than that of A2. The effect of disper-
sion that causes distorted colors along the
light field edges in existing fibers (Figure
3) is also less significant when the new
fibers are used.
Lightguides made from the new fibers
can be of great benefit here, thanks to their
improved numerical aperture that allows
them to capture more light. Their low at-
tenuation in the visible range results in
even higher light output at the end of the
fiber bundle for instance, 28 percent
more light at 400 nm using a 2-m light-
guide. Smaller bundle diameters that put
out the same amount of light are another
alternative, making it easier to construct or
install these in thinner endoscopes that
support wound healing after minimally
invasive surgery.
Improved chemical properties
These optical properties are not
achieved at the expense of chemical stabil-
ity in fact, the opposite is true. Puravis
fibers have achieved the highest rankings
in all four chemical resistance glasses
based on the respective ISO standards.
This means that they are resistant to acids
(resistance class SR 1.0 as described by
ISO 8424), alkalis (AR 1.0 as described
by ISO 10629), climatic influences (CR
1.0 as described by ISO/CD13384) and
staining (FR 0). Optical glasses obviously
react extremely sensitively to these types
of effects because their optical quality de-
clines or is completely lost when chemical
damages occur, or the surface of the glass
or the glass material changes.
While developing the new fiber, Schott
improved its chemical stability the pro-
prietary raw materials used yield better
chemical stability and optical properties
than traditional materials, increasing the
life span of the fibers. This is particularly
important when it comes to reprocessing
and sterilizing medical instruments by
cleaning or autoclaving. Tests have shown
that transmission losses after 100 auto-
claving cycles can be reduced by up to
70 percent in the new fibers as compared
with other fibers. The new fibers therefore
also support the growing hygiene require-
ments in medicine.
Optical durability is also ensured by
Figure 3. Lighting with Puravis fibers reduces dispersion effects (left), whereas existing glass fibers produce
distorted color along the edges of the light field (right).
Figure 4. Investigation of solarization at 365 nm. GOF70 and GOF80 show a very fast initial solarization at
365 nm, which stabilizes at a transmission level higher than that of the B3 fiber. The B3 fiber shows solariza-
tion at this wavelength as well. The effect is very slow and gradual over a long period of time, stabilizing at a
low level. Note: The lightguides investigated were fairly long (3 m). Shorter lightguides would result in higher
transmission levels.
minimizing possible solarization effects.
This was achieved by developing a suit-
able glass formula that does without the
heavy metal lead. The new and environ-
mentally friendly manufacturing process
also avoids using arsenic or antimony
as refining agents. Thus, any product
equipped with these fibers already com-
plies with the European Union directives
RoHS and REACH, and is therefore al-
ready capable of meeting future environ-
mental requirements.
Trendsetting applications
Thanks to their improved light transmis-
sion in the near-UV range between 350
and 400 nm (Figure 4), these high-tech
glass fibers are certain to open up interest-
ing new fields. In this respect, the fibers
exhibit significantly higher transmission
than conventional products: Because the
fibers are lead-free, Schott had to reduce
the solarization effects. The solarization
effects of the new fiber are minimized in
comparison with the standard leaded
Schott B3 fiber, so the overall absolute
transmission level after solarization is two
times higher than that of GOF85 and three
times higher (GOF70) than that of the B3
fiber. This paves the way for innovative
fluorescence applications in clinical diag-
nostics involving tissue or tooth decay,
and in fluorescence microscopy.
The glass fibers also can be used for
industrial purposes such as UV curing of
adhesives. They are also suited for use as
lightguides for lighting and image trans-
mission solutions in industrial image pro-
cessing for instance, in the area of mi-
croscopy or to monitor and perform quality
assurance on manufacturing processes.
Security-oriented industries like avia-
tion and vehicle construction also stand to
benefit. Glass fibers are chemically inert
and offer extremely high thermal stability.
In contrast to conductive (metal) cables,
they transmit light without causing any
sparks. Fire safety is therefore not an
issue. This, coupled with ease of mainte-
nance and a long service life, is but one of
the compelling reasons why this fiber is
equally suited for medical applications and
for illuminating aircraft cabins and vehicle
interiors.
The new multimode-stage index glass
fibers are made of extremely pure, select
raw materials and are processed in an en-
vironmentally compatible manner. This
contributes significantly to increased per-
formance with respect to light yield, trans-
mission, color shifting, attenuation and
dispersion. It is now possible to realize
more sophisticated and innovative new
lighting applications in medicine, and the
glass fibers support the trend toward
miniaturization of medical technology, as
in endoscopy.
Meet the author
Karen Holst has been the product manager re-
sponsible for fibers for the Lighting and Imaging
Business Unit of Schott AG in Mainz, Germany,
since 2007; email: karen.holst@schott.com.
$3,800* ScopeLite 200 Microscope Illuminator
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Glass Fibers
Figure 5. High-purity Puravis glass fibers are manufactured using an environmentally friendly process that does
not use lead, arsenic or antimony.
S
ignificant research has been under-
taken to improve imaging sensors
for endoscopy, but little work has
been done to maximize the per-
formance of the light sources and the light
delivery system required to support them.
Xenon light systems suffer from weak
light delivery through small fibers in spite
of continuous sensitivity improvements to
image sensors. A new endoscopic illumi-
nation system can significantly reduce the
size of traditional video endoscopes.
Physical space constraints continue to
affect advanced procedures such as single-
incision laparoscopic surgery, robot-
assisted surgery and other minimally
invasive surgical procedures. More func-
tionality and instruments are desired and
are being squeezed through the smallest
possible incisions. Space continues to
tighten with the migration of larger-diame-
ter 3-D, high-definition endoscopic imag-
ing systems into minimally invasive pro-
cedures. Fortunately, a significant portion
of the endoscope, the light delivery chan-
nel, can be reduced in size to allow the
space to be used for other purposes or
to allow the shrinking of the endoscope
itself.
1
For many years, illumination systems
have teamed with endoscopic imaging
systems for medical applications to help
image inside body cavities (colon,
abdomen, heart, throat, nose, ear, eye); to
assist in the placement of internal medical
devices such as gastric bands; and even to
perform work such as ablation of un-
wanted or diseased tissue as in laser eye
surgery or laser atrial fibrillation treat-
ment. The use of in vivo illumination
sources for medical applications has ex-
panded recently to even more revolution-
ary technologies, including spectropho-
tometry, fluorescence analysis,
2
near-
infrared lipid core plaque detection and
optical coherence tomography.
Functions of light
Viewing tissues using white light alone
is effective in detecting many lesions and
in determining the general health of the
tissue. In contrast, some bacterial infec-
tions, lipid plaque, and precancerous and
subtle inflammatory conditions are diffi-
cult to visualize under white light. Further-
more, it can be challenging to position an
illumination and imaging system in the
vicinity of the organ to be viewed. Once
there, it is desirable and advantageous to
use light to do more than illuminate the
object: Radiation in the form of visible
light, infrared or ultraviolet wavelengths
can be used to do work.
3
The delivered ra-
diation can be used to assist in the diagno-
sis of disease using fluorescence or spec-
troscopy, to cut diseased
4
tissue for
removal, to ablate stones, to initiate a re-
action between a therapeutic molecule and
its target reaction site, or to provide physi-
cally based phototherapy.
Fluorescence imaging techniques use a
generally nondestructive property exhib-
ited by some materials. Fluorescence oc-
curs when a material absorbs radiation of
one wavelength, converts some portion of
that radiation to a slightly different and
usually longer wavelength, and then re-
emits it. For example, when normal oral
cavity tissues are illuminated with violet
light (405 nm), they have a fluorescence
emission that appears light blue. The
Light Source Helps Endoscopes
Get Smaller and Smaller
Xenon light sources represent the benchmark for medical illumination,
but they cannot couple light through the small channels used for microendoscopes.
Figure 1. The new Hyperion 300 submillimeter optical fiber illumination system enables smaller
instruments for endoscopy, microsurgery and other applications. Images courtesy of Nathaniel Group Inc.
Hyperion Competitor
Output Output
(lm) (lm)
0.170-mm
Plastic Fiber 19 1
0.500-mm
Plastic Fiber 300 14
Number of
Output Channels 2 1
Intensity
Improvement ~40
BY JAMES HERMANOWSKI, NATHANIEL GROUP INC.
Table 1. Measured optical output from Hyperion
300 small optical fiber illuminator (output from each
of two channels) compared with standard fiber
illumination source.
Feat Endo_Layout 1 8/30/12 10:09 AM Page 31
effect is small but can be noticeable and
help discriminate between healthy tissue
and tissue with underlying problems.
5
Fluorescence can be the result of tissue
labeling using fluorophores or the result
of autofluorescence, where the specimen
naturally exhibits the property.
For endoscopic diagnostic tests, narrow-
band illumination can provide a sharper
image or better contrast. Hemoglobin has
peak absorption at specific wavelengths in
the blue and green bands, so illumination
using these wavelengths improves visibil-
ity and identification of blood vessels and
capillaries. Additionally, the different light
absorption of hemoglobin bound with oxy-
gen versus hemoglobin without oxygen
can be used to calculate oxygen saturation
when absorption is measured at two differ-
ent wavelengths. Narrowband illumination
has also been helpful in identifying Bar-
retts esophagus
6,7
and atypical dysplastic
colon cells, and in differentiating between
malignant and benign cells of the urinary
bladder.
Photochemotherapy or photodynamic
therapy involves the administration of a
sensitizing agent followed by the action of
light on tissues where the photosensitizer is
localized.
8
The need for ample illumination
through small optical fibers is one limiting
factor of this promising technique.
Physical phototherapy normally in-
volves using infrared radiation to penetrate
deep within tissue to deliver heat and
stimulate blood vessel expansion. Often
infrared radiation is used because it can
penetrate through tissues easily. Infrared
lasers are a preferred embodiment, allow-
ing large doses to be delivered in short
times under controlled positioning of the
therapy.
Optical fibers and imaging systems
A new approach couples radiation from
a variety of sources into individual sub-
millimeter optical fibers or fiber bundles
for medical and industrial applications.
The Hyperion 300s patent-pending tech-
nology from Nathaniel Group Inc. allows
integration and mixing of multiple sources
into an optical fiber, including infrared,
white-light, ultraviolet and solid-state
sources. The flexibility of the system al-
lows the optimum source or sources to be
selected for each application. For example,
a xenon source for general illumination
can be combined with the stable UV out-
put from a deuterium lamp for semiquanti-
tative spectroscopy; or solid-state LED
sources can be combined for general illu-
mination and fluorescence imaging with
an infrared laser source for ablation,
allowing the visualization,
9
analysis and
removal of diseased tissues.
A primary use for the new device is re-
ducing the size of the light channel in en-
doscopic imaging systems for both tradi-
tional endoscopes and the latest generation
of millimeter-dimensioned medical camera
systems such as the Awaiba sensor.
Table 1 compares the measured radio-
metric output of a Hyperion 300 small
optical fiber illumination system to other
fiber illumination sources on the market.
The data was measured for white light in
lumens at the distal end of a 1-m fiber
connected to the source. The new device
was in a configuration with two output
channels optimized for coupling radiation
into optical fibers 0.5 mm. The data
demonstrates exceptional performance for
fiber diameters down to 170 m.
Figure 2 is a photograph of a traditional
endoscope tip showing the imaging area,
light-emitting area and protective exterior
wall. Significant space is consumed by the
lighting function. The figure shows at
scale the amount of space required for
the new device to deliver suitable illumi-
nation. The light source consumes only
0.43 to 3 percent of the endoscope area,
depending upon implementation (see
Table 2). Switching to the new source
reduces the standard endoscope size by
up to 6.5 mm
2
, enough to make space for
an instrument.
Figure 3 shows a side-by-side color ren-
dering comparison of an endoscope setup
using the new source and a standard xenon
source, considered to be the benchmark
for medical illumination. The image
clearly demonstrates that both sources
provide comparable color matching, while
the Hyperion source shows improved
color saturation.
There is a continuous drive to reduce
the size of imaging systems for medical
applications. Smaller imaging systems
Endoscopy
Figure 2. A traditional endoscope tip showing the
imaging area, light-emitting area and protective
exterior wall. Significant space is consumed by
the lighting function.
Table 2. Comparison of endoscope sizes using Hyperion as light source; here, a microendoscope uses an Awaiba NanEye 2B video camera. The Hyperion
reduces the standard endoscope size by up to 6.5 mm
2
, enough to make space for another instrument.
Standard Hyperion Micro Micro
Endoscope Enabled Endoscope Endoscope
Endoscope Without Hyperion With Hyperion
Imaging Area (mm
2
) 10.3 10.3 1 1
Light-Delivery Area (mm
2
) 6.55 0.02 0.20 0.39 1.0 0.02 0.20
Light Channel Area Savings up to 32 smaller up to 19 smaller
Total Endoscope
Area Savings ~32% smaller ~40% smaller
Area Savings (mm
2
) 6.3 6.5 ~1
allow exploration of ever-smaller cavities and reduce the impact
on living organisms. A new small fiber illumination light source
was studied to determine its capabilities as a light source enabling
microendoscopic imaging systems.
Radiometric measurements of the new light source showed
performance up to 40 times better than that of other systems.
The light source was coupled with two imaging systems. The
first imager was a NanEye ultrasmall 1 1-mm, 250 250-
pixel sensor from Awaiba. The second camera consisted of a
three-sensor high-definition camera illuminated through a 500-
m fiber. In both cases, the new light source allowed for a signif-
icant reduction in endoscope size without deteriorating function.
Meet the author
James Hermanowski is vice president of business development at
Nathaniel Group Inc. in Vergennes, Vt.; email: jhermanowski@
nathaniel.com. The author thanks Jeff Cogger at Nathaniel Group Inc.
for mechanical designs and data collection, and the staff of Awaiba
GmbH for support relating to its imaging system.
References
1. J. Hermanowski (August 2011). High Intensity Illumination from Small
Fibers for In-Vivo Medical Lighting, www.nathaniel.com.
2. R. Schwarz et al (April 2009). Noninvasive evaluation of oral lesions
using depth-sensitive optical spectroscopy. Cancer, Vol. 115, pp.
1669-1679.
3. A. Mendez (Jan. 1, 2011). Medical applications of fiber optics: Optical
fiber sees growth as medical sensors, OptoIQ.
4. D. Roblyer and R. Richards-Kortum (January 2010). Optical diagnosis
for early detection of oral cancer, American Dental Hygienists Associ-
ation Access, pp. 22-25.
5. Q. Nguyen (October 2011). Color-Coded Surgery, TEDMED Confer-
ence.
6. R. Singh et al (Oct. 14, 2011). Advanced endoscopic imaging in Bar-
retts oesophagus: A review on current practice. World Journal of
Gastroenterology, pp. 42714276.
7. S. Tanaka and Y. Sano (May 23, 2011). Aim to unify the narrow band
imaging (NBI) magnifying classification for colorectal tumors: Current
status in Japan from a summary of the Consensus Symposium in the
79th Annual Meeting of the Japan Gastroenterological Endoscopy
Society. Digestive Endoscopy, pp. 131139.
8. A. Dietze (November 2004). Preclinical evaluation of photochemical
treatment on rheumatoid arthritis and soft tissue sarcomas, Institute for
Cancer Research at the Norwegian Radium Hospital.
9. S. Park et al (January/February 2008). Automated image analysis of
digital colposcopy for the detection of cervical neoplasia. Journal of
Biomedical Optics, Vol. 13, 014029.
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Endoscopy
Figure 3. A comparison of Hyperion 300 endoscopic light source (left) to a
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saturation. Color comparison was carried out using an X-Rite color card,
a Weck endoscope and a Richard Wolf HD three-chip camera system.
Fluorescence Microscope
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Spotlight_Layout 1 8/30/12 3:47 PM Page 34
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White Chip-on-Board LED
Excelitas Technologies ACULED chip-
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(CCT), high color rendering index (CRI),
and high R9 value and output needed
for applications such as surgical oper -
ating room and examination lights, and
dental operatory lighting. It contains
four separately addressable chips to provide tunable CCTs from 3500 to 5500 K. CRIs
greater than 95 and R9 values above 90 are achievable. Benefits of the new LED include
good heat transfer from the chips to the substrate and heat sink, and a compact design
with chips that are closely spaced, enabling improved color mixing and compact optics.
The company offers a standard four-chip chip-on-board package (Model R3C6) that is
supplied with warm-white, cool-white, red and cyan LED dice.
Excelitas Technologies
media@excelitas.com
Continuous-Wave Integrated Lasers
Spectra-Physics has launched the Excelsior
One continuous-wave lasers. The plug-and-
play ultraviolet, visible and near-infrared de-
vices are available in free-space and fiber-
coupled configurations, include 11
wavelengths and deliver up to 500 mW of
average power. They are suitable for flow
cytometry, confocal microscopy, DNA se-
quencing and fluorescence-based bioinstru-
mentation applications. The line includes di-
rect-diode and diode-pumped solid-state (DPSS) technology in a consistent footprint with
a common electronics interface. The new platform is based on the proprietary Its In the
Box design, where the laser cavity and control electronics are integrated into a single
housing. All lasers deliver TEM
00
-mode beam quality and low optical noise for a high
signal-to-noise ratio. The DPSS models are available in single- or multilongitudinal-mode
versions. The direct-diode models include high-speed modulation (transistor-transistor-
logic and analog) and an RS-232 interface.
Spectra-Physics
jurgen.niederhofer@newport.com
VLWIR Filters
Deposition Sciences Inc.s line of very long wavelength infrared (VLWIR) filters provides high trans-
mittance from the 12- to beyond the 22-m-wavelength region. Fabricated using a proprietary and
precise physical vapor deposition process, the coatings pass all environmental tests and can be re-
peatedly cycled between ambient and cryogenic temperatures without degradation. They are avail-
able with antireflection coatings in narrow- and wide-bandpass, and in long- and short-wave-pass
types. They can be applied to a variety of substrates, including germanium, zinc selenide, silicon and
indium antimonide. Edge placement, transmission blocking ranges and levels, and operating temper-
atures and angles can be customized per specifications. Applications include remote sensing, chemi-
cal analysis, astrophysics/astronomy and horizon sensors.
Deposition Sciences Inc.
solutions@depsci.com
Solid-State Lasers
InnoLas Laser GmbHs picolo AOT series electro-op-
tical Q-switched lasers are compact high-repetition-
rate, short-pulse solid-state devices operating with
high energy in the UV, visible and near-infrared.
Proprietary high-speed switching technology allows
them to deliver kilohertz pulses below 1-ns duration
that are synchronizable to external events with sub-
nanosecond accuracy. The lasers comprise master
oscillator power amplifier units and operate with a
pulse rate from 0 to 100 kHz, pulse energy >100 J
and peak power >100 kW. Used in R&D applications,
their short, intense pulses provide many advan-
tages. In precision processing and marking, the
short interaction time reduces workpiece heating ef-
fects and improves quality. In ranging applications
and in excite-and-probe studies, short pulses in-
crease temporal resolution. In nonlinear harmonic
and parametric processes, the high intensity of the
short pulses leads to high conversion efficiency.
InnoLas Laser GmbH
franziska.koelbl@innolas.com
Blue Laser Diode
The PL TB450 blue laser
diode from Osram Opto
Semiconductors is
mounted in a compact
TO-56 package and fea-
tures optical power of
1.4 W, making it suitable
for professional projec-
tors with a luminous flux
of more than 1000 lm for
use in offices, confer-
ence rooms and home
cinemas. Built on an
InGaN substrate, it is
suited for medical appli-
cations and for laser
systems for stage and decoration illumination. At
450 nm, the diode produces the blue laser light de-
sired and, with 1.4 W at room temperature and a
current of 1.2 A, the required high optical power. Ef-
ficiency is 27%, so the temperature of the laser will
rise only slightly when in use, giving it a service life
of up to 10,000 h at 40 C in continuous operation.
Osram Opto Semiconductors
support@osram-os.com
BREAKTHROUGHPRODUCTS
New Prod Leads_Layout 1 8/30/12 10:10 AM Page 35

Objective Lenses
Olympus Europa Holding GmbH has released
its MicroProbe Objective lenses for studying
the internal biology of living organisms. The
27 magnification IV-OB35F22W20 and the
20 IV-OB13F20W20 water-immersion lenses
have a needlelike design and are housed in
tips measuring 3.5 and 1.3 mm in diameter,
respectively. They can be inserted into small
surgical excisions, facilitating in vivo imaging
without disrupting the natural state of the tis-
sue or organ being investigated, and can be
combined with patch clamping to produce
multifluorescence images. Working with laser
scanning microscopes or multiphoton sys-
tems, the lenses provide a means of investi-
gating biological processes as they occur in
a living animal. Because of built-in chromatic
color correction, they can be used for multi-
color fluorescence studies.
Olympus Europa Holding GmbH
microscopy@olympus-europa.com
LED Illuminator
Prior Scientific Inc.s Brightfield LED illumina-
tor provides the advantages of LED illumina-
tion in a flexible package that can be fitted to
most modern upright and inverted microscope
systems. With 10,000 h of operating lifetime,
the LED replaces the standard lamp house
and is easily fitted to the microscope. Control
of the unit is a choice of manual, transistor-
transistor logic or on/off, eliminating the need
for shutter mechanisms. The intensity can be
regulated manually via a controller for precise
adjustment of illumination. The intensity is
sufficient for techniques such as phase con-
trast and differential interference contrast im-
aging. Illumination is even across the field of
view, and constant color temperature is en-
sured at all intensities. The LED can be pow-
ered directly from the companys ProScan and
OptiScan controllers via the shutter connec-
tions or as a stand-alone light source with a
separate power cable.
Prior Scientific Inc.
ddoherty@prior.com
Mini CCD Spectrometer
Horiba Scientifics VS-7000 mini CCD spec-
trometer outperforms front- and back-illumi-
nated CCDs, making it suitable for industrial
low-light applications such as fluorescence,
emission, absorbance and reflectance. It offers
coverage for three spectral ranges: ultraviolet-
visible, visible and ultraviolet-near-infrared. It
also provides the highest signal-to-noise ratio
of any uncooled CCD mini-spectrometer, the
company says. The UV-VIS, VIS and VIS-NIR
ultracompact spectrograph features a back-
thinned CCD with a deep full well, two height
options (300 and 1000 m) and a USB 2.0 in-
terface. Its sturdy single-optic design with a
concave grating offers light purity, and with
no moving parts or shutter, it is reliable for
original equipment manufacturer integration.
Horiba Scientific
joanne.lowy@horiba.com
Hyperspectral Imager
Bodkin Design & Engineering LLC has
launched the VNIR-90 snapshot hyperspectral
imager. Based on proprietary and patented
HyperPixel Array technology, it has an optical
processor that instantly captures the full hy-
perspectral data cube in each video frame.
The system can be mounted on moving plat-
forms or used as a handheld device for captur-
ing transient events or moving objects. Cover-
ing the spectral range from 500 to 910 nm, it
produces a data cube of 55 44 spatial pixels
90 spectral bins. Average spectral resolution
is 4.56 nm per bin. Interchangeable C-mount
lenses enable variable fields of view. The sys-
tem is supplied with a USB interface, a laptop
PC and software to produce environment for
visualizing images (ENVI)-compatible data
cubes. It is used to characterize skin lesions
and to develop cosmetic products.
Bodkin Design & Engineering LLC
sales@bodkindesign.com
Laser Beam Steering Correction
A laser beam steering correction system
from New Focus, a Newport Corp. brand, the
Picomotor mirror-mount-based GuideStar II
delivers precise control of laser pointing and
position drift. It includes two independent
Picomotor-actuated mirror mounts to provide
manual and active four-axis control. Two
miniature CMOS cameras provide position
sensing and continuous tracking of laser
beam positions and profiles. A patented con-
trol algorithm ensures correct alignment of the
laser beam in X and Y, and in the near and
far fields. The controller can be connected to
cameras and to a Windows computer via
USB ports to position and shape data in real
time, or, alternatively, data can be tracked,
stored and analyzed later. The DVD software
and setup menu guide users through installa-
tion. Intuitive settings menus permit user
control over a variety of camera and beam
stabilization parameters. The system offers
complete position, pointing and beam profile
tracking, and it is suitable for research and
laboratory applications.
New Focus
milan.zeman@newport.com
Vibration Isolation Workstations
Newport Corp.s Vision IsoStation vibration
isolation workstation includes scientific-grade
optical breadboards from 24 24 to 36 72
in. to accommodate applications from small
bioinstrumentation isolation up to medium-
size optical investigations. The breadboards
are stable and rigid, with steel triple-core-in-
terface honeycomb construction. The design
increases point-loading capability while mini-
mizing static deflection, providing a light-
weight work surface for research applications.
The breadboards provide a
3
16-in. ferromag-
netic stainless steel working surface, enhanced
damping, sealed holes and a surface flatness
better than 0.1 mm over 600 mm. The inter-
face features float-height indicators and frame
p BREAKTHROUGHPRODUCTS
New Prods_Layout 1 8/30/12 12:43 PM Page 36
bubble levels. Integrated leveling feet and
casters are standard, rendering the system
easy and safe to transport and install. The
platforms are compatible with the companys
line of Vision IsoStation accessories, which
have been designed for modern scientific and
biological investigations.
Newport Corp.
warren.booth@newport.com
Near-Infrared Camera
Dage-MTI has launched the IR-1000, a near-in-
frared CCD camera featuring automatic con-
trast and real-time edge enhancement. It in-
cludes electronics that automatically readjust
when a scene changes. The user has continu-
ous access to the manual gain and also may
engage the cameras black-level control to
achieve specific gray-scale contrast. Real-time
edge enhancement sharpens the edges and
delivers a clearer picture by resolving fine de-
tails in the image. With sensitivity across the
visible and infrared spectral wavelengths, the
-in. sensor can detect cells in low-light condi-
tions and penetrate more deeply into tissue
sections such as brain slices. The high gain
enables the user to detect images in real time
at 30 fps. With a C-mount, the IR-1000 is used
in live mode, connected directly to a moni-
tor. Applications include microscopy, electro-
physiology, infrared differential interference
contrast, failure analysis and forensics.
Dage-MTI
info@dagemti.com
Cooled CCD Camera
The Bigeye G-283B actively cooled, low-noise
CCD manufactured by Allied Vision Technolo-
gies GmbH delivers 14-bit images with long
exposure times in low-light conditions. The
digital camera features a GigE Vision-compli-
ant interface and is equipped with a Sony
ICX674 monochrome CCD sensor chip with
2.8-megapixel resolution, good quantum effi-
ciency and a high dynamic range. It operates
at 6 fps at full resolution in 14-bit mode, fea-
tures Peltier cooling down to 10 C and
achieves a good signal-to-noise ratio. It is suit-
able for scientific imaging applications, fluo-
rescence microscopy, low-light imaging and
nondestructive evaluation of photosensitive
objects. The Gigabit Ethernet interface mod-
ules 20-pin serial modular receiver decoder
interface provides four inputs and four out-
puts, and two RS-232 connectors are available.
Allied Vision Technologies GmbH
info@alliedvisiontec.com
Imaging Computer
Matrox Imaging has announced the Matrox
4Sight GP industrial computer for medical im-
aging and machine vision applications. Pow-
ered by an Intel Core processor, the computer
offers desktop-level performance including
SMARTSHUTTER
Stepper-motor driven shutter

FEATURES
s Robust design
s Life tested to 100 million cycles
s Modular repairable design
s Stand-alone or use with Sutter lter wheel
s Microprocessor-based controller
s Soft action mode provides minimum vibration
s Serial, USB and TTL interfaces
PHONE: 415. 883. 0128 | FAX: 415. 883. 0572
EMAI L: I NFO@SUTTER. COM | WWW. SUTTER. COM
The SmartShutter

is designed to complement our growing line of optical products
and sets a new standard for shutter performance and reliability. In the traditional
shutter design there are two or more leaves that rub against each other.
The SmartShutter is designed with only one moving part,
which virtually eliminates the effects of wear and
markedly improves performance.
BREAKTHROUGHPRODUCTS p
real-time high-definition H.264 encoding off -
load in a small, rugged enclosure. The plat-
form accommodates full-height, half-length
PCIe boards, enabling developers to insert
standard add-in cards, such as Matrox frame
grabbers, for analog, Camera Link, CoaXPress,
DVI or SDI video capture. It integrates Gigabit
Ethernet and USB 3.0 interfaces, which pro-
vide native support for capturing from GigE
Vision and USB3 Vision cameras. The com-
puter is preloaded with Microsoft Windows
Embedded Standard 7 software. Applications
are created using standard Microsoft develop-
ment tools and the Matrox Imaging Library
(MIL). MIL features programming functions for
image capture, processing, analysis, annota-
tion, display and archiving.
Matrox Imaging
imaging.info@matrox.com
Analytical Field-Emission SEM
With JEOL USA Inc.s JSM-7800F field-emis-
sion scanning electron microscope (SEM) for
nanotechnology imaging and analysis, users
can observe fine structural morphology of
nanomaterials at 1,000,000 magnification
with sub-1-nm resolution; perform low-
kilovolt imaging and analysis of magnetic
samples; collect large-area electron backscat-
ter diffraction maps at low magnifications
without distortion; and image thin, electron-
transparent samples with sub-0.8-nm resolu-
tion. The superhybrid lens design and in-col-
umn detectors with filtering capabilities allow
observation of any specimen, especially at
accelerating voltages down to 10 V. The SEM
performs x-ray spectroscopy and cathodolumi-
nescence, combining large beam currents with
a small interaction volume and increasing
analytical resolution to the sub-100-nm scale.
Beam deceleration in gentle-beam mode de-
creases charging on nonconductive samples
and reduces lens aberration effects for high-
resolution imaging. Applications include cryo-
microscopy and electron-beam lithography.
JEOL USA Inc.
salesinfo@jeol.com
29-Megapixel Camera
Imperx Inc. has introduced its four-tap Bobcat
camera series. Led by the 29-megapixel ICL-
B6640 Bobcat, the cameras operate over a
temperature range of 40 to 85 C and offer
a mean time between failures of >660,000 h
at 40 C. The B6640 produces 6600 4400-
pixel resolution and operates at 5 fps at full
resolution. Available in monochrome, color
and Truesense color with 8-, 10- and 12-bit
output, it consumes 7.8 W and can operate
without fail in harsh environments. It meas-
ures 60 60 53 mm, is lightweight and is
enclosed in a rugged housing. It is suitable for
medical and scientific applications. Standard
features include Base or Medium Camera Link,
binning of up to eight pixels horizontally and
vertically, a Truesense Imaging KAI-29050 sen-
sor, eight independent areas of interest and
five triggering modes.
Imperx Inc.
sales@imperx.com
Q-Switched DPSS Laser
The Starlase AO40 UV is the newest addition
to the Starlase series from Powerlase Photon-
ics and is available from RPMC Lasers.
The high-power Q-switched diode-pumped
solid-state laser emits at 355 nm and operates
from 10 to 50 kHz. At the low end of the repeti-
tion rate range, it produces 40 W of output
power and, at the high end, 5 W. Because
an acousto-optic Q-switch is used, the pulse
width changes with the repetition rate. At 10
kHz, the laser will have pulse widths of 60 ns,
and at 50 kHz, the pulse width grows to 200
ns. Applications include the photovoltaic,
medical and display industries.
RPMC Lasers
info@rpmclasers.com
Motorized Microscope X-Y Stage
Manufactured by PI (Physik Instrumente) L.P.,
the compact M-687 motorized X-Y stage for
inverted microscopes is stable because of the
self-clamping miniature ceramic/ceramic linear
motors that drive it. Once the motors are in
place, they consume no energy to hold posi-
tion and have no leadscrews, and there is no
creep caused by lubricant flow in the drive
mechanism. Integrated 100-nm-resolution lin-
ear encoders provide direct position feedback
to the controller, enabling closed-loop opera-
tion. Accessories include slide, petri dish and
multiwell plate holders, and Piezo-Z nanoposi-
tioning stages for 3-D microscopy, image stack
acquisition and fast autofocus. The low-profile
X-Y stage has a large aperture and maintains
constant velocity, even at speeds down to
10 m/s. Travel range is up to 135 85 mm,
and speeds are up to 120 mm/s.
PI (Physik Instrumente) L.P.
info@pi-usa.us
Image Analysis Software
Media Cybernetics Image-Pro Premier image
processing and analysis software is for life sci-
ences research. Tools facilitate capture, pro-
cessing, enhancement, measurement, compar-
ison, analysis, automation and sharing of
images and data. The software includes 64-
and 32-bit support; intuitive macros and app-
building tools; ways to automatically segment,
classify and measure objects; and tools for
customizing work flow. Users can analyze
rapid events or experiments that last for long
periods. It can stream multigigabyte movies
directly to the hard drive, and multiresolution
files are supported. The code-based editing
tools can be used to test, edit and debug
scripts. Users can download apps from the
companys Solutions Zone website, or develop
and package their own. Applications include
bright-field microscopy, cell and marine biol-
ogy, pharmaceutical development and fluores-
cence imaging.
Media Cybernetics
customerservice@mediacy.com
Instrumentation Imaging Lenses
Edmund Optics TechSpec compact instru-
mentation lenses provide high-quality images
with low lens-to-lens variation and feature a
broadband antireflection coating for maximum
light transmission. They are designed for vol-
ume integration into applications such as ana-
lytical medical devices, including benchtop-
based blood analyzers. Their adjustable,
lockable focus enables the user to set the best
position before the lens is integrated into in-
strumentation, eliminating the need for future
adjustments. A variety of fixed-aperture op-
tions allow maximum flexibility of resolution,
throughput and depth of field, and each focal
length is offered in a range of f/number op-
tions. Seventeen aperture stop versions, from
f/1.4 to f/8 in 16-, 25- and 35-mm focal lengths,
are available. Customized f/number versions
also are offered.
Edmund Optics
sales@edmundoptics.com
Imaging Spectrograph
The IsoPlane SCT-320, an imaging spectro-
graph from Princeton Instruments, eliminates
the aberrations present in traditional imaging
spectrographs. It produces clearer and sharper
images across the focal plane, enabling more
photons to end up in spectral peaks and in-
creasing the signal-to-noise ratio. The spectro-
graph reduces coma, preserving spectral
resolution at all wavelengths. There is no
astigmatism, allowing many more fibers in
a bundle to be resolved and eliminating
crosstalk in multichannel spectroscopy. The
mirror-based device combines high-quality
imaging with an f/4.6 aperture, a motorized
triple-grating turret and an ultrastable me-
chanical design. Applications include multi-
channel spectroscopy, microspectroscopy,
Raman scattering, fluorescence, photolumi-
nescence, laser-induced breakdown spec-
troscopy, Fourier-domain spectroscopy
and biomedical imaging.
Princeton Instruments
info@princetoninstruments.com
Gel Imager
UVP LLCs GelMax Imager images precast and
mini gels for illumination, capture and analy-
sis. Gels can be illuminated with multiple trans -
illumination light sources for maximizing fluo-
rophore stain excitation. Midrange 302-nm UV
is built into the unit to view ethidium bro-
mides and other stains. The Visi-Blue sample
plate converts the UV to 460- to 470-nm blue
light for viewing stains such as SYBR Green,
SYBR Safe and GelGreen. The white light sam-
ple plate enables white light transillumination.
Long-wave 365-nm UV can be achieved via the
long-wave sample plate, which reduces photo -
nicking of gels. A black sample plate enables
placement of samples not requiring transillu-
mination. Intuitive work-flow-based software
controls the color camera. Researchers can
BREAKTHROUGHPRODUCTS p
Shine the spotlight on your Breakthrough
Product in a display ad in BioPhotonics.
Contact Kristina Laurin at (413) 499-0514
or at advertising@photonics.com.
generate quantitative analysis results using
molecular weight, histograms and lane profile
graphs. Data can be exported to Excel for
documentation and publication.
UVP LLC
info@uvp.com
Contact your sales representative or:
sales@photonics.com (413) 499-0514
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APPOINTMENTS
OCTOBER
2012 IEEE Third International Conference on
Photonics (ICP) (Oct. 1-3) Pulau, Pinang,
Malaysia. Contact ICP2012 Secretariat, Multi-
media University. +603 8318 3029; info.icp2012
@gmail.com; www.icp2012.org.
NLO 50: 50 Years of Nonlinear Optics Interna-
tional Symposium (Oct. 7-10) Barcelona,
Spain. Contact ICFO-The Institute of Photonic
Sciences, nlo50@icfo.es; www.nlo50.icfo.es.
Bio-IT World Europe Conference and Expo
2012 (Oct. 9-11) Vienna. Contact Ming Guo,
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5439; mguo@healthtech.com; www.bio-it-
worldexpoeurope.com.
Neuroscience 2012 (Oct. 13-17) New Orleans.
Contact Society for Neuroscience, +1 (202)
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2012 IEEE Symposium on Biological Data Vi-
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tact Maria Velez, +1 (732) 535-1523; mariacv@
gmail.com; visweek.org.
Conference on Coherent Raman Scattering
Microscopy (microCARS2012) (Oct. 14-16)
Wiesbaden, Germany. Contact Andreas Volk-
mer, andreas.volkmer@physics.org; www.pi3.
uni-stuttgart.de.
Frontiers in Optics 2012/Laser Science XXVIII
(Oct. 14-18) Rochester, N.Y. Annual meetings
of OSA and American Physical Society/Div. of
Laser Science, respectively. Contact The Opti-
cal Society, +1 (202) 416-1907; custserv@osa.
org; www.frontiersinoptics.com.
2012 IEEE Visualization Conference (VisWeek
2012) (Oct. 14-19) Seattle. Contact Maria C.
Velez-Rojas, +1 (732) 535-1523; mariacv@
gmail.com; visweek.org.
22nd International Conference on Optical
Fiber Sensors (OFS-22) (Oct. 15-19) Beijing.
Contact general@ofs-22.org; www.ofs-22.org.
2012 Fifth International Conference on Bio-
medical Engineering and Informatics (BMEI)
(Oct. 16-18) Chongqing, China. Contact Qian-
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Telecommunications, +86 23 6246 1195; cisp
bmei@cqupt.edu.cn; cisp-bmei.cqupt.edu.cn.
Photonex 2012 (Oct. 17-18) Coventry, UK.
Contact Clare Roberts, Xmark Media Ltd.,
+44 1372 750 555; info@xmarkmedia.com;
www.photonex.org.
OPTO (Oct. 23-25) Paris. Contact Nadege Venet,
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venet@gl-events.com; www.optoexpo. com.
BMES 2012 Annual Meeting (Oct. 24-27) At-
lanta. Contact Biomedical Engineering Society,
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bmes.org.
IEEE Sensors 2012 (Oct. 28-31) Taipei, Taiwan.
Contact Chris Dyer, Conference Catalysts LLC,
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SPIE Asia-Pacific Remote Sensing (Oct. 29-
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NOVEMBER
Fifth International Photonics and OptoElec-
tronics Meetings (POEM 2012) (Nov. 1-2)
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SPIE/COS Photonics Asia (Nov. 4-7) Beijing.
Sponsored by SPIE and the Chinese Optical
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MiCom 2012: Third International Conference
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micom-conference.de.
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Laser Florence 2012 (Nov. 9-10) Florence,
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florence. org.
2012 International Conference on Image
Analysis and Signal Processing (IASP) (Nov.
9-11) Hangzhou, China. Contact Linda Sun,
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Latin America Optics & Photonics Conference
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Renewable Energy and the Environment: OSA
Optics and Photonics Congress (Nov. 11-15)
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strumentation for Energy and Environmental
Applications (E2); Optical Nanostructures and
Advanced Materials for Photovoltaics (PV); Op-
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and Organic Lighting (SOLED). Contact The
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Photonics Global Conference (PGC 2012)
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meetings.
CALL FOR PAPERS
Biophysical Society 57th Annual Meeting February 2-6
Deadline: Abstracts, October 1
Philadelphia. The Biophysical Society invites submissions for platform
and poster sessions at its annual meeting. Among the abstract cate-
gories are biophysical methods, including biomolecular nuclear mag-
netic resonance spectroscopy, imaging and optical microscopy, fluores-
cence and luminescence spectroscopies, atomic force microscopy,
optogenetics, biosensors, single-molecule techniques, micro- and
nano technology, and molecular mechanics and force spectroscopy.
Contact: Biophysical Society +1 (240) 290-5600
society@biophysics.org www.biophysics.org
33rd ASLMS Annual Conference April 3-7
Deadline: Abstracts, October 22
Boston. The American Society for Laser Medicine and Surgery encour-
ages abstract submissions for its 2013 annual conference. The society
promotes excellence in patient care by advancing biomedical applica-
tions of lasers and other technologies worldwide. The conference is
suitable for those who work with medical lasers in a clinical, research or
business environment. Last years conference addressed topics such as
photobiomodulation, photodynamic therapy, cutaneous laser surgery,
and head and neck optical diagnostics.
Contact: ASLMS +1 (715) 845-9283
information@aslms.org www.aslms.org
AACR Annual Meeting 2013 April 6-10
Deadline: Abstract submissions, November 15
Washington. The American Association for Cancer Research is accept-
ing abstracts for its annual meeting. Session categories for the 2012
meeting included molecular and cellular biology, with a poster session
on imaging and cytometry. Other categories will include cancer chem-
istry, carcinogenesis, clinical research, endocrinology, epidemiology,
immunology, tumor biology, and experimental and molecular thera -
peutics.
Contact: AACR +1 (215) 440-9300
aacr@aacr.org www.aacr.org
For complete listings, visit
www.photonics.com/calendar
Appointments_Layout 1 8/30/12 10:11 AM Page 40
41
ADVERTISERINDEX
Photonics Media Advertising Contacts
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riley.moriarty@photonics.com
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Japan
Scott Shibasaki
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Fax: +81 3 5229 7253
s_shiba@optronics.co.jp
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Voice: +1 (413) 499-0514
Fax: +1 (413) 442-3180
advertising@photonics.com
a
Andor Technology plc. .................................................................................................CV2, 34
www.andor.com
Applied Scientific Instrumentation Inc. .................................................................................5
www.asiimaging.com
c
Coherent Inc. .......................................................................................................................CV4
www.coherent.com
CVI Melles Griot ......................................................................................................................11
www.cvimellesgriot.com
e
Edmund Optics........................................................................................................................19
www.edmundoptics.com
Esco Products Inc. ..................................................................................................................37
www.escoproducts.com
i
Iridian Spectral Technologies Ltd. ..........................................................................................7
www.iridian.ca
l
Lumencor Inc. ........................................................................................................................23
www.lumencor.com
m
Mad City Labs Inc. .................................................................................................................15
www.madcitylabs.com
n
NKT Photonics A/S ...................................................................................................................3
www.nktphotonics.com
o
Optical Building Blocks Corp. .........................................................................................27, 30
www.obbcorp.com
p
Photonics Media......................................................................................................34, 39, CV3
www.photonics.com
PI (Physik Instrumente) L.P. ...................................................................................................16
www.pi.ws
Prior Scientific Inc. .................................................................................................................13
www.prior.com
r
Raptor Photonics Ltd. ............................................................................................................15
www.raptorphotonics.com
s
Sutter Instrument....................................................................................................................37
www.sutter.com
u
UVP LLC...................................................................................................................................34
www.uvp.com
x
Xmark Media Ltd. ..................................................................................................................33
www.photonex.org
Ad Index_Layout 1 8/31/12 8:31 AM Page 41
POSTSCRIPTS
S
tem cell therapy could be the wave of the future for hair regeneration, and biolumi-
nescence imaging could help doctors monitor treatment.
The therapy has been shown to produce hair growth where other methods, includ-
ing various creams and drugs, have proved less than successful.
Hair regeneration using hair stem cells is a promising therapeutic option
emerging for hair loss, and molecular imaging can speed up the devel-
opment of this therapy, said Byeong-Cheol Ahn, professor and di-
rector of the department of nuclear medicine at Kyungpook Na-
tional University School of Medicine and Hospital in Daegu,
South Korea.
Ahns recent study on animal models shows that the mo-
lecular imaging technique can be used to effectively track
hair regeneration by stem cell therapy.
Researchers currently are grafting hair stem cells in
animal models to determine whether these cells can
grow and multiply the way normal cells do.
In this study, Ahn and colleagues conducted bio-
luminescence imaging using firefly luciferase to-
gether with D-luciferin on hair follicle stem cells
implanted in mice to track the cells viability and
their development into hair follicles. They per-
formed the imaging technique on the implanted
cells five times over the course of 21 days.
The key finding was that molecular imaging
techniques can noninvasively visualize what hap-
pens to the transplanted hair stem cells in terms of
survival, death and proliferation during the forma-
tion of new hair follicles in mice.
Perhaps more importantly for potential human
patients, the scientists found new hair follicles on the
surface of the skin samples when they examined them
under the microscope.
This study is the first study of hair follicle regenera-
tion using an in vivo molecular imaging technique, Ahn
said which means that more studies must be conducted be-
fore clinical trials can be put in place to determine whether the
therapy could work to regenerate human hair.
The research was presented at the Society of Nuclear Medicines
2012 annual meeting and published in the Journal of Nuclear Medicine.
Caren B. Les
caren.les@photonics.com
Bioluminescence imaging
lights up hair renewal
Postscripts_Layout 1 8/30/12 10:11 AM Page 42
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