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8 • BIOSCANBioPhotonics editors curate the most significant headlinesof the month for photonics in the life sciences – and takeyou 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 • BUSINESSSCANOphthalmic laser market growing

NEWS

28

BioPhotonics • September 2012

20 • MULTIMODAL LABEL-FREE IMAGING DRIVES BIOMEDICAL RESEARCHby 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 TRICORDERby Gary Boas, Contributing EditorThis 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 APPLICATIONSby 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 SMALLERby 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

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Volume 19 • Issue 7

6 • EDITORIAL

35 • BREAKTHROUGHPRODUCTS

40 • APPOINTMENTSUpcoming Courses and Shows

41 • ADVERTISER INDEX

42 • POST SCRIPTSby Caren B. LesBioluminescence imaging lights up hair renewal

DEPARTMENTS

PHOTONICSThe 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.

BIOPHOTONICSThe 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 Ramanscattering signal (magenta) detects lipids within themand nearby. An article on label-free imaging by JamesLopez and Yiwei Jia of Olympus America Inc. begins onpage 20. Design by Art Director Suzanne L. Schmidt.

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5BioPhotonics • September 2012

www.photonics.com

Group Publisher Karen A. Newman

Editorial StaffManaging Editor Laura S. Marshall

Senior Editor Melinda A. RoseNews 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 StaffSenior Art Director Lisa N. Comstock

BioPhotonics Art Director Suzanne L. SchmidtDesigner Janice R. Tynan

Director of Publishing Operations Kathleen A. Alibozek

Electronic Media StaffDirector Charley Rose

Multimedia Services & Marketing

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Subscription Policy BioPhotonics ISSN-1081-8693 (USPS 013913) is published 10 times per year by LaurinPublishing Co. Inc., 2 South Street, 3rd floor/Berkshire Common, Pittsfield, MA 01201. TITLE reg. in US Libraryof Congress. The issues will be as follows: January, February, March, April, May/June, July/August, Sep-tember, October, November and December. Copyright © 2012 by Laurin Publishing Co. Inc. All rights reserved.POSTMASTER: Periodicals postage paid at Pittsfield, MA, and at additional mailing offices. Postmaster: Sendform 3579 to BioPhotonics, Berkshire Common, PO Box 4949, Pittsfield, MA 01202-4949, +1 (413) 499-0514. CIR-CULATION POLICY: BioPhotonics is distributed without charge to qualified researchers, engineers, practi-tioners, technicians and management personnel working with the fields of medicine or biotechnology.Eligibility requests must be returned with your business card or organization’s letterhead. Rates for others asfollows: $45 domestic and $56.25 outside US per year prepaid. Overseas postage: $30 airmail per year. Pub-lisher reserves the right to refuse nonqualified subscriptions. ARTICLES FOR PUBLICATION: Individuals wish-ing to submit an article for possible publication in BioPhotonics should contact Laurin Publishing Co. Inc.,Berkshire Common, PO Box 4949, Pittsfield, MA 01202-4949; phone: +1 (413) 499-0514; fax: +1 (413) 442-3180;email: editorial@ photonics.com. Contributed statements and opinions expressed in BioPhotonics are thoseof the contributors — the publisher assumes no responsibility for them.

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Biophotonics has plenty of room for pioneersO 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 thefirst American woman to make the trip into space. In photonics,Elias Snitzer is considered the father of the glass laser, and IsaacKaplan found a purpose for the CO2 laser.

Kaplan, who died in August at the age of 93, was a pioneer inthe creation of the first carbon dioxide laser for general surgeryand founder of the International Society for Laser Surgery andMedicine.

While Armstrong said that circumstance gave him the role offirst man on the moon, Kaplan had a plan. In her news report onhis death for Photonics.com, senior editor Melinda Rose writes,“When it was developed in the 1960s, Kaplan said, the CO2 laserwas without application. His goal was to research the applicationof the new ‘miracle technology’ while developing an apparatusthat 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 inthe same breath, for sure, but each broke new ground in his or herarea of expertise. And, while the job of “pioneer” is often a one-person enterprise, each breakthrough creates new opportunitiesfor exploration and innovation.

Today, biophotonics innovators receive their inspiration frommany disciplines and from all kinds of places, including yester-day’s view of tomorrow, Star Trek. We have so not heard the lastof 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 generationof sensing and imaging diagnostic devices, many with origins insmartphones with cameras and data-transmission capabilities, andtells us to expect to see more such devices in the future.

The brilliant sparks of inspiration that mark the early careers ofso many trailblazers are game-changing, to be sure, but it’s thework 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 recognizednot for one piece of fireworks, but for the ledger of our dailywork.” After his walk on the moon, Armstrong worked for NASAand 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 mathand science. Snitzer and Kaplan had long careers that included research, innovation and education. All proved that there aremany ways to affect our world and our future.

Also in this issue, James Hermanowski of Nathaniel GroupInc. explains that xenon light sources represent the benchmark formedical illumination but cannot couple light through the smallchannels used for microendoscopes. His article, “Light SourceHelps 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 andlonger life spans offer interesting new solutions for meeting thegrowing demand for higher quality lighting in medicine, accord-ing to Karen Holst of Schott AG in her article, “New Glass FibersWiden Range of Medical Lighting Applications,” beginning onpage 28.

Enjoy the issue.

6 BioPhotonics • September 2012

EDITORIAL

Karen A. Newmankaren.newman@photonics.com

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BIOSCAN

8 BioPhotonics • September 2012

A closer look at the most significant biophotonics research and technology headlines of the month

Scalpel-free surgery with deep-tissue imagingPASADENA, Calif. – A new procedurethat more than doubles the depth that lightcan be focused inside biological tissuessoon could enable doctors to perform inci-sion-free surgery or diagnose cancer byseeing tumors inside the body.

Although the previous limit for howdeep light could be focused into tissue wasonly about 1 mm, researchers at CaliforniaInstitute of Technology (Caltech) now canreach 2.5 mm. In principle, their methodcould focus light as much as a few inchesinto tissue.

“The ability to focus high-intensity lighttightly 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 thatwith further technology improvement,depth up to a few centimeters will beachievable. 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 previousmethod 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 scientistsshone light through a tissue sample andrecorded the resulting scattered light on aholographic plate. The recording containedinformation about how the light beamscattered, zigzagging through the tissue.By playing the recording in reverse, theysent the light back through the other sideof the tissue, retracing the beam’s path tothe original source.

In this way, they could send light througha layer of tissue without the blurring effectof scattering. However, to make images ofthe tissue’s insides, they would have to beable to focus a beam of light into it.

To precisely focus light into tissue, theteam expanded upon the recent work ofLihong Wang’s group at Washington Uni-versity in St. Louis (WUSTL), which de-veloped a technique to focus light usingthe high-frequency vibrations of ultra-sound and two of ultrasound’s favorableproperties. First, its high-frequency soundwaves are not scattered by tissue; second,its ultrasonic vibrations interact with lightin such a way that the light’s frequency is

shifted ever so slightly. As a result of thisacousto-optic effect, light that interactswith ultrasound changes into a slightly dif-ferent color.

Both teams focused ultrasound wavesinto a small region inside a tissue sampleduring their experiments. Next, they shonelight into the sample, which scattered thelight. Any light that passed through the re-gion with the focused ultrasound changedcolor somewhat. The researchers identifiedand recorded the color-shifted light.

Using Caltech’s playback technique,they sent the light back, inducing only thecolor-shifted portion to retrace the path tothe small region where the ultrasound wasfocused. This means that the light itself isfocused on that area, allowing an image tobe created. By moving the ultrasound’sfocus, the researchers can control wherethey want to focus the light.

Only a very small amount of light couldbe focused in the WUSTL experiment, butCaltech’s method allows scientists to fire abeam of light with as much power as theyneed for potential applications.

“This technology is still in its infancy,”Yang told BioPhotonics. “We took an im-portant step beyond Lihong Wang’s origi-nal demonstration of TRUE (time-reversedultrasonically encoded optical focusing)by implementing a TRUE technique that iseffectively unlimited in terms of its abilityto deliver arbitrarily high power to the fo-cused spot.”

For this to work in living tissue, Yangsaid, the team must decrease the time forgenerating a focused light spot to a frac-tion of a second, depending on the tissuetype. “The ability to build a suitable sys-tem is within our technological reach. Butit does require a significant financial in-vestment to make it happen. If we havethe financial resources and a semiconduc-tor foundry to help us, bringing the tech-nology to the point of clinical imaging islike a 10- to 20-year process.”

The team demonstrated how the newmethod could be used with fluorescenceimaging by embedding a patch of gel witha 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.

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BioPhotonics • September 2012 9

gators scanned the sample with focusedlight beams, which hit and excited thefluorescent 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 duringthe final imaging scan, Yang said, and thetechnique works whether the dye is usedor 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 sufficientlystrong focused spot to excite fluorophoresto provide image contrast.”

Doctors also could use the technique totreat cancer with photodynamic therapy,which currently can be used only at the

surface of tissue because of the way lightis easily scattered. The new method shouldmake it possible to reach cancer cellsdeeper inside tissue.

Next, Yang said he and his team wouldlike to combine the spatial light modulatorand image sensor into a single digital opti-cal phase conjugation chip, but funding isa challenge. If they could achieve this single chip, Yang said, it would “solveseveral technical implementation chal-lenges in one move and, more importantly,allow us to deploy sensing and playbackover a far larger area. The more area wecan cover, the task of collecting and play-ing back the conjugate light field becomesfaster 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 focusedinto a small area inside the tissue. The ultrasoundshifts the frequency of any light that passes throughthat area ever so slightly, changing its color. Thecolor-shifted light (green) is then recorded. Right, therecorded light is sent back to retrace its steps to thesmall region where the ultrasound was focused –which means the light itself is focused on that area.

Moth eyes inspire improved x-ray imagingNEW YORK – A new class of nanoscale materials modeled aftera moth’s 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 aprimitive 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 lightthat 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 efficientcoatings for solar panels and antireflective surfaces for militarydevices.

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-rayradiation 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 usedin radiographic imaging devices to convert the x-rays exiting thebody into visible light signals picked up by a detector to form an image.

A higher x-ray dosage improves output but is not healthy forpatients. As an alternative, Yi’s team found that improving thescintillator’s 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 perturbthe scintillation material’s light emission layer.

The crystals are encrusted with tiny pyramid-shaped silicon nitride protuberances. Each protuberance, or corneal nipple, ismodeled after the structure in a moth’s eye and is designed to extract more light from the film.

Within a 100 � 100-μm square, about the same density as the actual moth eye, the scientists can fit between 100,000 and200,000 protuberances. They made the side walls of the device

A scanning electron microscope image of a leaf miner moth’s eye. Moths’ largecompound eyes are extraordinarily antireflective, bouncing back only a smallportion of light that strikes them; now, researchers have used the moth eye as amodel for new nanoscale materials for improved x-ray imaging. Courtesy ofDartmouth College.

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rougher, improving its ability to scatter light and enhancing thescintillator’s efficiency.

“The light-extraction efficiency enhancement is very sensitiveto the dimension of the protuberances,” Yi said. More research isneeded to see whether there are benefits to adding more, he said.

During lab experiments, Yi discovered that adding the thin filmto the scintillator of an x-ray mammographic unit increased theintensity of the emitted light by as much as 175 percent comparedwith 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 ofthe use of the moth eye-based nanostructures in medical imagingmaterials. It also could be applied to various light-emitting devices, Yi said.

He estimates that it will take at least another three to five yearsto evaluate and perfect the film, and five years before it willreach a clinical setting.

The team plans to continue investigations to understand andimprove the light-enhancement mechanism.

10 BioPhotonics • September 2012

b BIOSCAN

BERKELEY, Calif. – A new techniquethat 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 aright-handed orientation to a left-handedone 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-imageforms. Called enantiomers, the right- andleft-handed forms of such molecules canexhibit strikingly different properties; forexample, one enantiomer of the chiralmolecule limonene has a lemon scent,while the other smells of orange.

The ability to observe or switch a mole-cule’s chirality using terahertz electromag-netic radiation is a coveted asset in hightechnology.

“In electromagnetism, chirality or opti-cal activity arises from the coupling be-tween the electric and magnetic responsesof the materials,” said Xiang Zhang, oneof the leaders of the research and a princi-pal investigator with the US Departmentof Energy’s Lawrence Berkeley NationalLaboratory’s Materials Sciences Div.“However, in natural materials, the mag-netic response is extremely weak at THzand optical frequencies, and as a result,the chirality is also very weak.”

Using terahertz metamaterials engi-neered from nanometer-size gold stripswith air as the dielectric, Zhang and amulti-institutional team of colleagues fromLos Alamos National Lab and the Univer-sity of Birmingham in the UK fashioned adelicate artificial chiral molecule that theyincorporated with a photoactive siliconmedium. By performing photoexcitation oftheir metamolecules with an external lightbeam, they observed dynamically con-

trolled handedness flipping in the form ofcircularly polarized emitted terahertz light.

“Under strong optical irradiation, thehandedness of the metamolecule isswitched to its opposite handedness,”Zhang told BioPhotonics. “This state istemporary; it relaxes back to its originalhandedness in a time scale of 1 millisec-ond.” The process is repeatable.

The optically switchable chiral terahertzmetamolecules consisted of a pair of 3-Dmeta-atoms of opposite chirality madefrom precisely structured gold strips. Eachmeta-atom serves as a resonator with acoupling between electric and magneticresponses that produces strong chiralityand large circular dichroism at the reso-nance frequency.

When two chiral meta-atoms of thesame shape but opposite chirality are puttogether, they form a metamolecule, andtheir symmetry is preserved, resulting invanishing optical activity. Essentially, the optical activity that arises from the opposite meta-atoms cancels each otherout, he said.

To break the mirror symmetry and in-duce chirality for the combined metamole-cule, the researchers introduced siliconpads to each chiral meta-atom in the meta-molecule. In one meta-atom, the siliconpad bridged two gold strips, while the sili-con pad replaced part of the gold strip inthe other meta-atom. The silicon padsfunctioned as the optoelectronic switchesthat flipped the chirality of the metamole-cule under photoexcitation.

Terahertz electromagnetic radiation fallswithin the frequency range of molecularvibrations, 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 thehandedness of metamolecules and controlthe circular polarization of terahertz light,scientists could use the technology to de-

Metamolecules switch handedness under light

Controlling the chirality of artificial molecules couldenable advances in communications and biomedicalimaging. Top, a scanning electron microscope imageof optically switchable chiral terahertz metamole-cules. Bottom, the purple, blue and tan colors represent the gold meta-atom structures at differentlayers; two silicon pads are shown in green. Imagescourtesy of Xiang Zhang et al, Berkeley Lab.

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In this schematic, the chirality-switching metamolecule consists of four chiral resonators with fourfold rotational symmetry. An external beam of light instantly reverses the metamolecule’s chirality from right-handed to left-handed.

tect toxic or explosive chemicals, or use itin high-speed data processing systems andwireless communications.

Terahertz-based polarimetric devicesalso could benefit medical researchers anddevelopers 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 spectroscopytools to accurately measure the circulardichroism of biomolecules at THz in com-parison with the visible range. The sensitivedetection of circular dichroism requires dy-namic modulation of the electromagneticwaves between the two circular polariza-tions. The chirality-switching metamaterialwe demonstrated may bridge this gap.”

Their design principle for opticallyswitchable chiral terahertz metamoleculesis 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, notonly in polarization, but also in phase, in-tensity and propagation directions,” Zhangsaid. “For example, we can use a similardesign principle to make a meta-surfacewith dynamically switchable high and lowimpedance. For a THz wave reflected bythe meta-surface, the phase can be dynami-cally switched between 0 and 180 degrees.

“The metamaterials we demonstrated sofar still have some drawbacks: Chirality isnot strong enough to completely convertthe THz waves into purely circular polar-izations. We will work on the perfection ofthe metamaterial design to achieve astronger chirality switching effect.”

The work was published in Nature Com-munications (doi:10.1038/ncomms 1908).

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LOS ANGELES – A new optical micro-scope easily detects rare cells in real timeand could help doctors diagnose diseasesearlier or monitor treatments. The abilityto distinguish and isolate rare cells – suchas circulating cancer tumor cells and stemcells – from a large population of assortedcells has become increasingly importantfor disease detection. Typically, there areonly a handful of these “rogue” cellsamong a billion healthy ones, but becausethey are precursors to metastasis – thespread of cancer that causes about 90 per-cent of cancer mortalities – it is importantto be able to find them.

To detect such cells requires an auto-mated high-throughput instrument that canexamine millions of cells in a reasonablyshort time. Currently, microscopesequipped with digital cameras are used toanalyze cells, but they are too slow to beuseful for this application.

Now, Bahram Jalali and Dino Di Carlofrom the University of California, Los An-geles, have devised a high-throughputflow-through optical microscope that candetect rare cells with sensitivity of onepart per million in real time. The instru-ment is equipped with photonic time-stretch camera technology developed byJalali’s group in 2009 to create the quick-est continuous-running camera in theworld.

“To catch these elusive cells, the cameramust be able to capture and digitally pro-cess millions of images continuously at a very high frame rate,” said Jalali, whoholds the Northrop Grumman EndowedOpto-Electronic Chair in Electrical Engi-neering at the UCLA Henry SamueliSchool 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 thearray of pixels, and they become less sen-sitive to light at high speed.”

The team described how it integratedthe camera with real-time image process-ing and advanced microfluidics for theclassification of cells in blood samples inProceedings of the National Academy ofSciences (doi 10.1073/pnas.1204718109).The new blood-screening technology de-livers throughput of 100,000 cells per sec-ond, roughly a hundredfold increase inrate when compared with conventional im-aging-based blood analyzers.

This study illustrates the detection ofrare breast cancer cells in blood in realtime with an unprecedented low false-pos-itive rate of one cell in a million. Initial re-sults show that this method can quicklydetect rare circulating tumor cells fromlarge volumes of blood samples, openingthe door for statistically accurate early

cancer detection and for monitoring the ef-ficacy of drug and radiation therapies. Theresults were obtained by mixing cancercells grown in a laboratory with variousproportions of blood to emulate real pa-tient blood.

The team is conducting clinical trials toassess the efficacy of the technology,which can significantly reduce errors andcosts in medical diagnosis. It also could beused for water-quality monitoring andurine analysis.

The research was funded by the USCongressionally Directed Medical Re-search Programs, the Burroughs WellcomeFund and NantWorks LLC.

12 BioPhotonics • September 2012

b BIOSCAN

For more on the camera technology de-veloped by Bahram Jalali’s group, see“Full Steam Ahead with the FastestCamera in the World,” www.photonics.com/a38998.

Optical microscope detects rare cancer cells

Optical microscope with world’s fastest camera. Courtesy of UCLA.

Photonic crystals help fish see in the murk

LEIPZIG, Germany – The elephantnosefish has light-reflecting cups lined withphotonic crystals in its retinas that help itnavigate 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 turbidfluids.

These freshwater fish, found in thecloudy depths of African rivers, use elec-

trosensing to navigate their dark environ-ment, but they also depend somewhat onvision. Until recently, these weakly elec-tric fish were thought to be blind, or al-most blind, University of Leipzig neuro-physiologist Andreas Reichenbach said ina podcast.

“The visual capabilities of this fish arepretty poor,” he said. “It’s color-blind. Itcannot see anything that is not bigger than

six times the size of a full moon. But sur-prisingly, it’s optimal for its environment.”

Vertebrate eyes have rod photorecep-tors, which are very sensitive to light butdo not detect color or fine details, andcone photoreceptors, which are less sensi-tive to light but can distinguish color anddetails. Most vertebrate eyes optimize pri-marily either rods or cones, but an interna-tional team of scientists has discovered

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that the retina of the elephantnose fish isstructured so that both types of receptorswork simultaneously.

The researchers observed that the conesare grouped together within larger, light-reflecting cups lined with photonic crys-tals. The rods are positioned behind thesereflectors. This unusual arrangementworks because the mirrorlike surfaces ofthe cups propagate the light in a way thatdelivers just the right wavelength to boththe rods and cones.

“Behind the eye in the so-called retinapigment 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 cat’s eye, but it is fo-cused on a certain level in this case. Theastonishing thing is that within suchparabola mirrors, there are about 30 conephotoreceptors, which are responsible forhigh-acuity vision in our case, but not inthis case, and a couple hundred rod pho-toreceptors.”

Each photoreceptor sees the same partof an image because all the rods and conesare 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 deadworms and bubbles or air moving around

them, but they can see the big predatorsmoving.

“The special structure of the retina of the fish enables the fish to see largemoving objects more reliably than anyother fish, and this makes him thriveunder these [turbid water] conditions,” he said.

While this vision proves advantageousfor the fish in dark, dim, muddy waters,

it’s detrimental in aquarium settings with other fish.

“If the fish swims in an aquarium together with other fish under normal laboratory conditions, it’s almost blind,”Reichenbach said. “This was the reasonwhy 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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BioPhotonics • September 2012 13

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Scientists had long thought the elephantnose fish (Gnathonemus petersii) to be blind, but it turns out to havelight-reflecting cups lined with photonic crystals in its retinas that help it navigate in dark waters. Courtesy ofGerhard von der Emde.

Light amplification by photonic-crystal light collectoronto photoreceptor cells in the retina of the ele-phantnose fish helps it to see. Courtesy of MoritzKreysing.

BioScan_Layout 1 8/30/12 2:28 PM Page 13

LEUVEN, Belgium – A new nanoscalelight-manipulation method that opticallydetects single molecules could be used ina variety of photochemistry applicationsand help advance technologies for visual-izing single molecules and multiple-mole-cule interactions.

Progress in optically detecting singlemolecules has been hindered by their weakoptical response. Currently, researchers usemetal nanostructures to focus light intotiny zones called “hot spots,” which exciteelectrons on the surface, causing them tooscillate coherently. When shone on a mol-ecule, and with the help of these oscillatingelectrons, the focused light can increase amolecule’s optical signal to 100 billiontimes its normal strength, a level detectableby optical microscopes.

The current method, however, has twolimitations: The first is that hot spots canbecome too hot; the second is that they arevery small. This means that the heat fromhot spots can melt the nanostructure, de-stroying its ability to channel light effec-tively. And hot spots produce only a verysmall cross section in which interactionwith 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 atKatholieke Universiteit Leuven sought tonanoengineer larger spots. The interna-tional team began by shining circularly

polarized light on nanostructures andfound that this could increase the usefularea. When they shone light on square-ring-shaped gold nanostructures, the scien-tists observed that the entire surface of thenanostructures was successfully activated.

“Essentially, light is constituted of elec-tric and magnetic fields moving throughspace,” Valev said. “While with linearlypolarized 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 asense 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 excitedelectrons to oscillate coherently on the fullsurface of the square-ringed nanostruc-tures, rather than in a few concentrated hotspots. This increases the opportunity forinteraction with molecules.

“The trick is to try to activate the wholesurface of the nanostructure so that when-ever a molecule attaches, we will be ableto see it,” Valev said. “That is preciselywhat we did.”

The study appeared online in AdvancedMaterials (doi: 10.1002/adma.201201151).

14 BioPhotonics • September 2012

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Shining circularly polarized light on ring-shaped nanostructures increases the opportunity for interaction withmolecules. 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 lightantennas to harvest the energy from weakinfrared light and amplify the process3300 times could lead to improved med-ical imaging methods.

Materials scientists and chemists fromthe University of Groningen and from theFOM Foundation harvested infrared light– which has too little energy to releaseelectrons in solar cells – more efficientlyby modifying an organic dye that acts aslight antennas to transmit the energy to thenanoparticles 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) withthe attached antennas in green. Courtesy of University of Groningen.

BioScan_Layout 1 8/30/12 12:42 PM Page 14

process called upconversion.“There are inorganic materials made

from rare-earth metals that can facilitatethis upconversion process,” said Jan C.“Kees” Hummelen, a University ofGroningen professor of organic chemistryand leader of the FOM focus group onnext-generation organic photovoltaics.“However, these materials absorb veryfew infrared photons. We have thereforeattached organic molecules to them [as an-tennas] that can capture these photons andtransmit the energy to the upconversionmaterial.”

Because of this, the entire infrared ab-sorption process, upconversion and the

emission of visible light is increased by afactor of 3300, Hummelen said.

Even with the antennas, his group cancapture only a limited amount of infraredlight. He predicts that an even better yieldcan be obtained, but because the upcon-version process inside the nanocrystal isstill inefficient, it is not yet possible toachieve.

“Two photons must come together inthe material within a short space of time,”he said. “In practice, the efficiency of thisprocess is still very low. However the har-vest is already much better, so step onehas been achieved.”

The upconversion system could be ap-

plicable for medical imaging techniques.“Infrared light penetrates further into

biological tissues than visible light,” hesaid. “If you allow compounds that carryout upconversion to bind to specific cellsin tissues, then you can make imagesusing infrared light.”

The scientists’ work also is applicableto solar cells, as about half of all the solarenergy reaching Earth’s surface consists ofinfrared light.

The research was published online inNature Photonics (doi: 10.1038/nphoton.2012.158).

BioPhotonics • September 2012 15

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Nanohole-based sensors ideal for medical diagnosticsSINGAPORE – Novel molecular sensorsbased on thin metallic films with nano -holes hold promise for applications thatrequire detection of small quantities ofmolecules, such as gas biomedical diag-nostics and gas sensing.

The majority of these applications call

for inexpensive disposable sensors, butthey must be sensitive enough to detectsingle molecules.

Ping Bai and colleagues at A*Star Insti-tute of High Performance Computing andthe Institute of Materials Research and En-gineering have studied the properties of

thin-film metallic films with holes in themthat show promise for molecular sensingapplications.

Metallic thin films with nanometer-sizeholes are known to transmit light of partic-ular wavelengths efficiently because ofsurface plasmon polaritons (SPPs), the

BioScan_Layout 1 8/30/12 12:42 PM Page 15

collective movement of electrons on ametal surface that focus light into tinyspots much smaller than the wavelength oflight used.

SPPs can detect molecules through thefluorescence of tracer molecules attachedto 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 tosupport a point-of-care sensing system,”Bai said.

The team studied two sensing arrange-

ments: In the first, light was directed at afilm with nanoholes at an oblique anglefrom the same side as the sample. Thefilm 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 arrangementshad advantages.

In the “reflection” scheme, the SPP ef-fect is stronger because the light is aimeddirectly at the sample and does not have tocross the metal film. However, a thickerfilm is needed so that the light does notpass through. The intensity of the lightemitted by the molecules is weaker in the“transmission” scheme, but filters andother sensors could be included with themetal film, and the film could be muchthinner.

“There is therefore no clear advantagefor either sensing mode of such films,”Bai said. “One thing that is clear from thestudy, however, is the clear benefits ofusing metal films with nanoholes as a molecular sensing platform.”

This is only a snapshot of the entireproject, Bai said.

“Ultimately, our sensing technologywill be utilized in hospitals and test cen-ters; for example, in prostate cancerscreening, or even used at home just likeglucose test kits.”

The research appeared in IEEE Photon-ics Journal (doi: 10.1109/jphot.2011.2177652).

16 BioPhotonics • September 2012

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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. Paddockashley.paddock@photonics.com

BioScan_Layout 1 8/30/12 12:42 PM Page 16

BUSINESSSCAN

As the population of the world ages, asso-ciated eye problems will mean significantgrowth for the ophthalmic laser market.

The number of people 60 and older hastripled in the past 50 years. As of 2000,there were 606 million people over the ageof 60 worldwide, according to a UnitedNations report, and that global populationis projected to reach nearly 2 billion in2050.

In the US alone, the 90-and-older popu-lation nearly tripled over the past threedecades, reaching 1.9 million in 2010, ac-cording to a November 2011 report by theUS Census Bureau and supported by theNational Institute on Aging. Over the nextfour decades, this population is projectedto more than quadruple.

The aging population is subject tounique eye conditions, such as cataracts,which are a clouding of the eye’s naturallens. More than 15 million cataract surger-ies are performed worldwide each year tosurgically replace the damaged lens withan intraocular lens.

Besides the aging population, other fac-tors driving the global ophthalmic lasermarket, which is expected to reach $804million 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 anincrease in patients opting for eye surgery,said Global Industry Analysts (GIA) Inc.in an ophthalmic lasers report released inJanuary.

Although demand for certain majorophthalmic 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 offerbenefits beyond vision correction and at-tract significant demand in the future,”GIA said. “Application of laser technologyin early diagnosis, and the detection ofcertain eye disorders in conjunction withimaging technologies, such as OCT, is an-other factor that would boost growth ofthe laser eye correction market in the fu-ture.”

On Aug. 6, New York-based eye healthcompany Bausch + Lomb and ophthalmiclaser maker Technolas Perfect Vision of

Munich announced that their Victus fem-tosecond laser designed for cataract andcorneal surgery had received clearancefrom the FDA.

Femtosecond lasers, with their ultra-short pulses, do not transfer heat or shockto the material being cut and can makesurgical incisions with extreme precision.The technology was introduced commer-cially in 2002 for creating thin, hingedflaps during lasik surgery.

Companies that make femtosecondlasers commercially for ophthalmic appli-cations include Calmar Laser, AdvancedMedical Optics and Carl Zeiss Meditec.

Carl Zeiss Meditec announced in Aprilthat it will begin a US clinical trial of itsReLEx smile procedure for correcting my-opia, or nearsightedness, after receivingFDA approval.

In lasik procedures, the excimer laservaporizes tissue, but the ReLEx smilemethod generates a refractive lenticule inthe intact cornea with a femtosecond laser.The surgeon then removes the lenticulethrough a small incision – less than 4 mm– without having to move the patient to anexcimer laser, the company said.

“The introduction of femtosecond lasertechnology is the most significant ad-vancement in cataract surgery in recenthistory,” said Dr. Steven J. Dell of DellLaser Consultants in Austin, Texas, in thepress release announcing the Victus’ ap-proval.

The Victus is the first femtosecond laserthat can support both surgical procedureson 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 CEmark approval in Europe in November2011 and has been used in more than 2000cataract 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 thefirst use of its MicroPulse laser therapy(MPLT) through an intraocular fiber opticendoprobe during ophthalmic surgery.

“Expanding MPLT applications fromphysicians’ offices into the operating roomand surgery centers will continue to drivegrowth in our laser systems,” said IridexPresident and CEO Dominik Beck.

MicroPulse works by electronically“chopping” a continuous-wave laser emis-sion into trains of microsecond pulses, en-hancing the physician’s ability to moreprecisely control the laser effects on targettissues. It is more effective for very thinretinas, allowing more tissue to be pre-served than in conventional continuous-wave laser photocoagulation, the companysaid.

Iridex is working to accelerate adoptionof MicroPulse for treating diabetic macu-lar edema (DME), Beck said in an earlyAugust statement announcing the com-

Ophthalmic laser market growing

BioPhotonics • September 2012 17

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pany’s second-quarter financial results.“Our experiences in DME have led us

to explore opportunities for MicroPulse inthe treatment of glaucoma,” he said,adding that the company is working with“key opinion leaders” in glaucoma on howits 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 AmericanSociety of Cataract and Refractive Surgerymeeting.

“If the results of these initiatives indi-cate an equivalent or better outcome thancurrently available options, we could see asignificant impact to our revenues, as thisis a large market opportunity,” Beck said.

The company’s revenue from ophthal-mology was $8.4 million for the quarter,up from slightly over the prior quarter andthe prior year.

Dental laser maker Biolase also is see-ing opportunity in the ophthalmic market.

“We continue to seek the most efficientroute to market for our laser technology asit relates to ophthalmology and other sur-

gical specialties,” said Federico Pignatelli,chairman and CEO, during an earningscall on Aug. 8. “We are currently in earlydiscussions with a leading ophthalmiccompany to develop a relationship tojointly deliver our first product to thatmarketplace.”

18 BioPhotonics • September 2012

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Melinda A. Rosemelinda.rose@photonics.com

BUSINESSBRIEFS

ON Semiconductor Corp. of Phoenix and Donald Colvin, its executive vice president andchief financial officer, have mutually agreed toColvin’s resignation as an officer of the com-pany. It was expected at the time of the an-nouncement in August that he would continueat the firm for up to 90 days while the boardsought 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 ofKrailling, Germany, filed a patent lawsuit March5 against Phenix Systems of Riom, France, forinfringing two US patents for its dental productlines. The lawsuit alleges infringement of USPatent Nos. 5,753,274 and 6,042,774 throughthe manufacture, sale and use of the PXL, PXM,PXS and PXS Dental product lines from Phenix inthe US. During the second half of 2011, Phenixannounced publicly the commercial manufac-ture, sale and use of exactly these product lines,even though, EOS said, it had apprised Phenixof its patent portfolio several times.

To honor professor Michael S. Feld’s fundamen-tal contributions in the fields of laser scienceand applied physics for solving biomedicalproblems, The Optical Society (OSA) and theOSA Foundation, both in Washington, haveestablished the Michael S. Feld BiophotonicsAward to be given annually beginning in 2013.It will recognize individuals for innovative andinfluential contributions to the field of biopho-tonics, regardless of their career stage. Feld,who passed away in 2010, founded the LaserBiomedical Research Center at MIT in 1985with the support of the National Institutes ofHealth. Nominations for the award are nowbeing accepted from OSA members.

Shimadzu Scientific Instruments of Colum-bia, Md., has opened the Shimadzu Centerfor Advanced Analytical Chemistry at theUniversity of Texas at Arlington to give re-searchers there access to enhanced capabilitiesfor trace qualitative and quantitative analysis.

The center contains $6 million worth of chro-matography, mass spectrometry and spec-troscopy equipment. The instruments will beused to research illnesses such as cancer andmalaria, and to develop nanofabrication materials for industry. Kevin Schug has beennamed the Shimadzu Distinguished Professor of Analytical Chemistry. An associate professorof chemistry and biochemistry, he will oversee the new laboratory.

DigitalOptics Corp. of San Jose, Calif., a subsidiary of Tessera Technologies Inc., andMMD Monitors and Displays Taiwan Ltd., asubsidiary of TPV Technology Ltd., have part-nered to deliver a computer monitor manufac-tured by MMD with a built-in ergonomic sensorto help users correct posture. TPV owns part ofPhilips’ monitor and entry-level flat-screen TVbusiness, and DigitalOptics developed the soft-ware used in Philips’ ErgoSensor detection tech-nology. The technology uses the distance be-tween a user’s pupils to determine whether heor she is sitting within the optimal ergonomiczone and, if not, determines how the user canadjust seating position or posture to avoid riskof injury. In addition, the device offers energysavings by powering down when no user ispresent.

Genia Photonics of Laval, Quebec, Canada,has received $300,000 in financial assistancefrom the Canadian government to acquirestate-of-the-art production equipment and labo-ratory materials. The repayable funding wasawarded under the Canada Economic Devel-opment’s business and regional growth pro-gram and could result in the creation of 22 jobsby 2014. The new equipment and laboratory fa-cilities will enable the company to meet growingcustomer demand and to accelerate researchand development work it has initiated over the past two years. Genia Photonics developsand manufactures pulse-programmable andmultifunctional fiber-based lasers for security,biomedical, pharmaceutical and chemical applications.

Three photonics companies have received theQueen’s Award for Enterprise, the UK’s mostcoveted award for business success. Edinburgh

Instruments of Livingston, a photonics andelectro-optical scientific instrumentation manu-facturer, received the honor for its sustained international growth. Laser Quantum ofCheshire was recognized for providing lasertechnology equipment and services to the aerospace, medicine, research and biomedicalsectors. Fianium of Southampton received theaward in the innovation category for its devel-opment of the WhiteLase supercontinuum fiberlaser. The awards are made each year by thequeen on the advice of the prime minister andan advisory committee.

Raptor Photonics Ltd. of Larne, Northern Ire-land, has named Laser 2000 GmbH of Munichas its scientific camera distributor for Germanyand Austria. Laser 2000 supplies lasers andlight sources, optics and optomechanics, opticalinstrumentation and optical detectors for themachine vision and scientific and instrumenta-tion markets. Raptor Photonics manufactures industrial-grade low-light digital and analogcameras.

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 IntellectualProperty Office (KIPO). Given Imaging ofYokneam, Israel, alleges that Intromedic’s cap-sule endoscope, marketed under the brandname MiroCam, has infringed two of its Koreanpatents. In response to the accusation, In-tromedic brought proceedings before KIPO toinvalidate the two patents asserted by Given Imaging. KIPO’s decision rejects Intromedic’s invalidity arguments and cripples one of itsmain defenses against Given Imaging’s patentinfringement 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 Germancompany to access Olympus’ portfolio of digitalpathology and virtual microscopy patents. Thepatents in the licensing deal cover methods andequipment for creating, storing and deliveringvirtual microscopy slides. The technology en-

BussinessScan_Layout 1 8/30/12 9:59 AM Page 18

ables individuals to view and share high-resolu-tion virtual microscopy images over the Internet.Specific terms and conditions of the agreementwill not be made public. The microscopy busi-ness group at Carl Zeiss manufactures light andelectron microscopes for the life and materialssciences.

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 andsell its computed tomography laser mammogra-phy system in Jordan. Mareen Group is a med-ical and pharmaceutical distribution companybased in Kuwait. The noninvasive optical breastimaging system uses patented continuous-wavelaser technology and computed algorithms tocreate 3-D images of the breast.

Medical device company SpectraScience Inc.of San Diego has signed an exclusive five-yearagreement with Pentax Europe GmbH ofHamburg, Germany, to distribute its WavSTAToptical biopsy system for colorectal cancerscreening and diagnosis. Pentax provides mini-mally invasive surgical devices, including flexibleendoscopes that are used with the WavSTATsystem. The agreement, which includes thecompany’s new WavSTAT4 mobile console anddisposable optical biopsy forceps, covers Eu-rope, Turkey, Saudi Arabia and South Africa. Italso provides for minimum purchase quantitiesin specified countries and gives Pentax a “rightof first refusal” option for all other countries inthe Middle East and Africa.

Laser-based medical systems provider IridexCorp. of Mountain View, Calif., has announcedthe success of its MicroPulse laser therapy insurgery using an IQ 577 laser coupled with EndoProbe instrumentation. This is the first timethat tissue-sparing laser therapy has been deliv-ered through an intraocular fiber optic probe ina surgical setting, the company said. Endo-Mi-croPulse is effective in cases of very thin retinasbecause it preserves tissue rather than destroy-ing it, as conventional laser therapy does. Dr.Sam Mansour, who performed the surgery atGeorge Washington University School ofMedicine 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 received510(k) clearance from the FDA for its next-gen-eration LensAR Laser System for use in anteriorcapsulotomy, with and without laser phacofrag-mentation during cataract surgery. The regula-tory action covers the new system, which is infinal preparation for commercial launch in theUS. 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 generatesa personalized surgical treatment plan.

Roger H. Brüggemann has been hired as headof marketing and sales at diode-pumped solid-state laser manufacturer Crystal Laser Sys-tems GmbH of Berlin. He brings to the rolemore than 12 years of international experience

in sales and marketing of solid-state lasers andoptical components. Prior to joining the com-pany, he worked at Luceo TechnologiesGmbH and, before that, at Klastech LaserTechnologies 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 acquiredMatcon Group Ltd. of Evesham, UK, a supplierof materials processing solutions for high-value

powders used in food, pharmaceuticals, plasticsand fine-chemicals manufacturing. Matcon’sproducts include the original cone valve powderdischarge system and filling, mixing and pack-aging systems, all of which maintain clean, reliable and repeatable formulations ofprepackaged foods and pharmaceuticals forlean, agile manufacturing. With annual rev-enues of approximately £22 million (about$34.2 million), Matcon will operate within Idex’sHealth and Science Technologies Div. in thematerials processing technologies platform.

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Optical 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 usedwith optical microscope systems – pres-

ents many challenges, however. Achievingsufficient concentration of a fluorescentprobe within a tissue can be difficult. Photo-toxicity caused by singlet oxygen forma-tion is damaging to living cells. And, inlive animal and animal tissue imaging, theprobe is likely to be recognized as a for-

eign entity by the animal’s 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 tomonitor disease processes over time with-out perturbing physiological processes by incision, adding foreign reagents or encountering artifacts caused by fixation,permeabilization or biochemical extractionprotocols. There is also an advantage inusing label-free imaging techniques basedon harmonics or Raman scattering becauseelectrons are not excited in the same man-ner as in regular fluorescence excitation.In both harmonics and Raman scatteringimaging, the formation of reactive oxygenand its subsequent toxicity are signifi-cantly reduced.

Multimodal imagingMultimodal label-free imaging exploits

the properties of molecules when they in-teract with photons from the short-pulsedlasers used in multiphoton microscopesystems. These two-photon or multiphotonimaging systems typically are optimizedfor observation of fluorescent moleculesseveral hundred microns deep in tissue,exploiting the improved penetration andreduced scattering of longer infraredwavelengths. To achieve the “two-photon”effect, these lasers produce an intense fluxof photons in femtosecond pulses. Thetotal energy is kept low to avoid overheat-ing the sample.

The only position where the photon fluxis strong enough for two or more photonsto combine their energies is at the exactfocal point. Because there is no excitationoutside that spot, fluorescence is confinedto molecules in one optical section as thelaser scans over the field of view. This in-herent optical sectioning also works with

Multimodal Label-Free Imaging Drives Biomedical Research

20 BioPhotonics • September 2012

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 with800-nm excitation (bottom left, with overlay at bottom right). Maximum intensity projections of 139 Z-seriesslices acquired at 0.4 µm per optical slice. Scale bar 50 µm. 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 onthese photon interactions, including har-monic generation and CARS.

Multimodal imaging is the combinationof two-photon techniques such as two-photon excitation fluorescence of intrinsi-cally fluorescent molecules, SHG andCARS in a single experiment. When com-bined, these techniques create a morecomplete image of life processes withoutadditional labels.

Most cells and tissues exhibit a complexmixture of spectra from autofluorescence(also called intrinsic fluorescence). It ispossible to attribute intrinsic fluorescenceof a particular wavelength to moleculessuch as nicotine adenine dinucleotide(NADH), lipofuscin or elastin. The peakemission for these molecules is in the bluerange due to their component aromaticamino acids, so intrinsic fluorescence isoften imaged using multiphoton excitationrather than a blue or UV-emitting laser toavoid the photodamage with the higher-energy (shorter wavelength) photons.

SHG occurs when two photons are scat-

tered simultaneously by an orderly arrayof 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 microtubulesof the mitotic spindle. The second-har-monic signal is emitted coherently – in the direction of the incident beam, withexactly twice the incoming energy andtherefore half the wavelength.

In CARS, the three photons that interactoriginate with two different wavelengths.The difference in frequency gives rise to asignal because of resonance with specificchemical bonds, notably the C-H bondstretch that predominates in lipids.

MethodologyA laser-scanning microscope equipped

for multiphoton excitation can be used toimage both fluorescence and SHG throughthe selection of appropriate excitationwavelengths and filters. Intrinsic fluores-cence is a hundredfold weaker than mostexogenous fluorophores, so the detection

path must be optimized by using high-numerical-aperture objective lenses andnondescanned detectors.

SHG signals typically are stronger inthe forward direction, so a transmittednondescanned fluorescence detector andhigh-numerical-aperture condenser with anoil-top lens is preferred. Forward-directedSHG detection tends to favor large, brightstructures, while the reflected direction isoften more sensitive to finer, dimmerstructures. This is also generally true forCARS imaging. Muscle fibers can be vi-sualized without the use of any labels inCaenorhabditis elegans, a commonly usedmodel organism in biological research,using SHG. SHG and intrinsic two-photonexcitation fluorescence (autofluorescence)signals can be collected simultaneously inboth the forward and reflected directions,and then can be combined into a singlemultimodal imaging data set (Figure 1).

There are several ways to generate thetwo beams that combine to produce theCARS signal: Researchers have often usedtwo picosecond-pulsed IR lasers tuned to

BioPhotonics • September 2012 21

Figure 2. Green fluorescent protein expressing tumor growing in liver, imagedusing simultaneous multimodal imaging. Collagen fibers (white) are visualizedwith second-harmonic generation. Lipids are imaged using femto-CARS (red).The GFP-labeled tumor mass and the intrinsic fluorescence are co-observed inthe green channel. Maximum intensity projection of a stack of 12 Z-planesspaced at 2.42 µm. Courtesy of Teng-Leong Chew, Northwestern University.

Figure 3. Lipids exterior to and within cells after mice were gavaged with 200 µlof 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 µm apart, scale bar 100 µm. Courtesy of MikhailSlipchenko, Purdue University.

Feat Olympus_Layout 1 8/30/12 10:00 AM Page 21

different frequencies to serve as pump andStokes 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 alhave developed a femto-CARS systemthat uses the same femtosecond-pulsed IRlaser that is used for multiphoton excita-tion and splits the beam into two compo-nents. One component passes through aphotonic 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 withqualitatively different patterns, adding in-formation for expert interpretation. In alldetection modes, the IR wavelengths ofthe imaging beams are blocked, and filtersare chosen to separate different signals ac-cording to wavelength range. For example,the Olympus femto-CARS system usestwo excitation wavelengths for imaging:800 and 1040 nm. The 800-nm wave-length serves as the imaging wavelengthfor intrinsic fluorescence and SHG, and isone of the wavelengths for CARS imag-ing; 1040 nm functions as the second nec-essary wavelength for CARS imaging. TheSHG signal from the 800-nm beam occursat 400 nm, and the CARS signal is col-lected at 650 nm.

Depending upon the sample, these threesignals (SHG, CARS and intrinsic fluores-cence) can be collected simultaneouslyusing either reflected or forward detection.

Additional wavelengths may be used fora fourth signal. A four-channel filter setfor the reflected detector might have filtersthat collect narrow bands for simultaneousimaging of SHG; green fluorescent proteinor intrinsic fluorescence; yellow fluores-cent protein or the DiI fluorescent indica-tor; and CARS. Because these imagingmodalities are not as specific as antibody-or nucleic-acid-sequence-recognizingprobes, most experiments are comparative.For example, the collagen distributionaround a tumor may be compared to unaf-fected stromal tissue or to the pattern ob-served in a control animal. Researchersmight, for example, do a comparison be-tween the intrinsic fluorescence of NADHunder normoxic and hypoxic conditions.Metabolism may also be expressed as aratio of NADH (or NADPH) with anothermember 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 anyother molecule with a long chain of C-Hbonds.

SHG imaging of collagenCollagen deposition around tumors has

been recognized by pathologists fordecades. Paolo Provenzano et al have pro-posed a classification of tumor-associatedcollagen signatures that have potential forclinical staging. These changes in collagenstructure can be observed using SHG im-aging. Degradation of collagen resultingfrom extracellular protease activity, aswell as changes in fibril composition, maybe helpful in identifying changes in tissuethat indicate tumor initiation or progres-sion.

Combined with collagen imaging,CARS imaging of lipids has the potentialto help investigate the role of fat-contain-ing adipocytes in the tumor microenviron-ment. The observation that cancers appearto have an association with fat cells mightsuggest that adipokines (hormones se-creted from adipocytes) promote tumori-genesis by inducing the expression ofgenes regulating cancer cell proliferation,invasion, survival and angiogenesis (Fig-ure 2). Longitudinal studies may revealchanges in lipid content and fibrosis as thetumor progresses.

Intrinsic fluorescence and CARSThe impact of dietary fats on lipid ab-

sorption can be studied using CARS. Indi-vidual cells in intestinal microvilli are visualized by their intrinsic fluorescencein the green wavelengths, while the CARSsignal, detected in the red wavelengths,highlights lipids both in the lumen of thegut and in microvillus cells (Figures 3 and4). Such experiments may help in the de-sign of therapeutic interventions for meta-bolic syndrome and other lipid absorptionabnormalities.

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 inliving animals and animal tissue. Multi-modal imaging provides a way to eluci-date the relationship between obesity andcancer using CARS imaging of lipids, themechanisms of invasion and metastasisusing SHG, and altered metabolism usingintrinsic fluorescence. Epidemiologicalstudies reveal a correlation between cer-tain cancers and obesity, but finding a di-rect cause-and-effect relationship hasproved 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 metastasisand circulating tumor cells in animals feda high-fat diet. Microscopic imaging ofthese cells showed increased lipid deposi-tion compared to tumor cells from animalsfed a low-fat diet.

In neuroscience, significant research isbeing conducted with the ultimate goal ofalleviating myelin degradation in spinalcord injury and demyelinating diseasessuch as multiple sclerosis. CARS imagingof myelin sheath, SHG imaging of as-troglial processes and two-photon excita-tion fluorescence imaging of calcium iondistribution in live spinal tissues may helpresearchers identify opportunities for inter-vention.

In animal models of cardiovascular dis-ease, the stability of atherosclerotic plaquecan be assessed using multimodal label-free imaging. Lipid-rich macrophagesknown as foam cells are increased in un-stable plaque, while underlying collagenand elastin are disrupted. CARS can iden-tify the lipid content of the accumulatedmacrophages, while SHG indicates disor-

22 BioPhotonics • September 2012

Multimodal Label-Free Imaging

Figure 4. Imaging of lipids within cells of the microvillus, with CARS signal (magenta) from lipids and intrinsic fluorescence (green) delineatingindividual cells of the microvillus. Maximum intensityprojection, 495 Z-planes, 0.3 µm apart with calculated orthogonal slices. Courtesy of MikhailSlipchenko, Purdue University.

Feat Olympus_Layout 1 8/30/12 10:00 AM Page 22

ganized collagen fibrils; the intrinsic fluo-rescence of elastin can highlight the vul-nerability of the lesion.

Multimodal label-free imaging offers away to monitor disease processes overtime with less physiological perturbation.Now that there are turnkey multimodalsystems available, biomedical researcherscan combine these methodologies for amore thorough understanding of diseaseprocesses. Moreover, these microscopicimaging techniques can pave the way fordeveloping specific molecular imagingtechniques that offer greater tissue depthand even the potential for clinical utility.

Meet the authorsJames Lopez is the confocal and multiphotonsales application specialist at Olympus AmericaInc. in Chicago; email: james.lopez@olympus.com. Yiwei Jia is marketing manager of confo-cal laser scanning microscopes at OlympusAmerica Inc. in Center Valley, Pa.; email:yiwei.jia@olympus.com.

ReferencesK.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 onlipid biology with coherent anti-StokesRaman scattering microscopy. J Lipid Res,Vol. 51, p. 3091.

A.F. Pegoraro et al (February 2009). Optimallychirped multimodal CARS microscopy basedon 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 imagingmicroscopy (FLIM) to monitor metastasisand the tumor microenvironment. Clin ExpMetastasis, Vol. 26, pp. 357-370.

P.P. Provenzano et al (November 2009). Shin-ing new light on 3D cell motility and themetastatic process. Trends Cell Biology, Vol. 19, pp. 638-648.

P.P. Provenzano et al (December 2009). Matrixdensity-induced mechanoregulation of breastcell 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 Generationwith Multiphoton Imaging. BioPhotonics.

Angela Goodacre and Dennis Donley(September 2011). Intrinsic FluorescenceLights Up Cellular Components. BioPhotonics.

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The Star Trek television series andmovies have proved remarkablyprescient in anticipating future tech-nologies – from flip phones to

iPads – decades before they appeared ineveryday life. Now, nearly half a centuryafter the debut of the original series, thescience fiction classic featuring CaptainKirk and the alien Mr. Spock, we are be-ginning to see modern-day equivalents ofanother 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 ormaladies, either terrestrial or alien. Thedesign has evolved over the decades, butin all cases the device is portable, requiresno external power source and providessome sort of sensing capability.

This description also can be applied to anew generation of sensing and imagingdevices in our own time. Recent advancesenabling 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 mightbe described as tricorders, or at least as tricorder-like. And there’s undoubtedlymore to come.

Early this year, the X PRIZE and Qual-comm foundations announced the launchof the $10 million Qualcomm Tricorder XPRIZE, a global competition in whichteams will leverage innovative technolo-gies such as wireless sensing to develop amobile platform that can make medical di-agnoses independently of a physician or

The Age of the Tricorder

24 BioPhotonics • September 2012

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 goto the team whose platform most accu-rately diagnoses a set of 15 diseases in-volving 30 consumers in three days, whilealso providing a compelling consumer ex-perience.

There’s no telling what the winning de-sign will look like, or what technology itwill employ – the only constraint is thatthe system and its components togethercan’t weigh more than 5 lb – but many as-sume it will involve a smartphone runningcustom-developed apps, in no small partbecause smartphones already carry sophis-ticated cameras and displays as well asother technology essential to the sort ofhome health monitoring envisioned by thesponsors of the competition.

Importantly, from a technology stand-point, such a platform is possible today. Avariety of research groups and companieshave already taken advantage of advancesin imaging technology to turn smartphonesinto microscopes and sensor systems. Oneexample: Philips offers an iPhone andiPad app called Vital Signs Camera, whichcan 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 isabout technology development, said BruceTromberg, director of the Beckman LaserInstitute and Medical Clinic at the Univer-sity of California, Irvine, but it is just asmuch about determining what informationpeople need to make a diagnosis, to knowwhen to see a doctor, when to take medi-cine, and so on, and determining how bestto obtain and use that information.

As the health care landscape continuesto change, he said, activities like screeningand follow-up – monitoring, generally –will move into the home, into the hands ofthe patient.

One possible scenario: Sensors on asmartphone or some other device willmonitor a patient’s physiological parame-ters and send the data to a server for analy-sis. The results will be considered in thecontext of the patient’s overall health (hisor her entire medical history will also bestored there), and if any further action isneeded – “call the doctor,” “pick up a pre-scription” – an email or text will be sent.

The tricorder competition will help usenvision what all this will look like.

Home testing is only one potential usefor tricorder-like devices, however. Suchinstruments could help to advance a range

of additional applications, both within andbeyond traditional clinical settings.

Point of careIn the clinic, Tromberg and colleagues

are developing devices for physicians thatcan impact patient care and even changeclinical outcomes: for example, a hand-held laser scanner for use in detection, di-agnosis and treatment of breast cancer. Bymeasuring parameters such as hemoglobinconcentrations and fat and water content,

BioPhotonics • September 2012 25

Innovation and entrepreneurshipFew would argue the importance

of developing optics-based andother medical devices for globalhealth applications, but sustain-ability of the model can still provechallenging. “At the end of the daythere has to be a market,” saidUtkan Demirci, director of the Bio-Acoustic-MEMS in Medicine(BAMM) Laboratory at Brighamand Women’s Hospital in Boston,and an assistant professor thereas well as at Harvard MedicalSchool and Harvard-MIT HealthSciences and Technology. The labdevelops microfluidics for CD4counts and viral load for HIV inresource-limited and other set-tings. These technologies alsohave been adapted for isolatingand detecting bacterial pathogensin 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 acourse at Harvard-MIT Health andSciences Technology titled “De-signing and Sustaining TechnologyInnovation for Global Health Prac-tice.” The course – which has beenoffered several times in the pastfive years – is based on the prem-ise that innovation in this area re-quires leaders to think and act likeentrepreneurs. There’s been con-siderable interest in the course,Demirci said. “It’s amazing howpeople 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.

Feat Tricorder_Layout 1 8/30/12 10:07 AM Page 25

the device can help distinguish betweenpotentially malignant and benign tumors.It can also be used to evaluate the effec-tiveness of chemotherapy – at bedside andduring the course of treatment – allowingthe oncologist to adjust the therapy basedon 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 wouldn’t normally be found.

Chris Myatt is founder and CEO ofMBio Diagnostics, which develops optics-based solutions for disease diagnosis andresearch. In an article in the February2011 issue of BioPhotonics (“Not YourFather’s Microscope,” pp. 21-23), he said,“We look at point-of-care, home testingand 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 homein New York.”

“Point of care” refers to testing or mon-itoring performed at or near the site ofcare, although it is more commonly usedtoday to describe clinical services pro-vided in nontraditional settings. For exam-ple, especially with the shifting health carelandscape in the US, we will see an in-creasing demand for long-term monitoringof chronic diseases – including cardiovas-cular and autoimmune – in pharmaciesand other retail outlets (both CVS andWal-Mart have explored the possibility ofkeeping 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 nontraditionalsettings including the mobile STD vans inSan Diego and elsewhere and, with a newprogram in Washington, testing sites ingrocery stores and high schools and evenat the Department of Motor Vehicles. Anddemand for this point-of-care applicationcontinues to increase.

Optics-based technologies are wellsuited to meet this demand. The technolo-gies may not look exactly like the tri-corders in Star Trek – devices roughly thesize of an electric razor that you operateby waving them around in the air some-

where near the patient – but they meet allthe criteria that matter: portable, ruggedand reliable.

Since April of last year, the AntiviralResearch Center at the University of Cali-fornia, San Diego, has been evaluating theperformance of an MBio system designedto deliver absolute CD4 counts at the pointof care in minutes; CD4 count is essentialto monitoring disease progression in HIVpatients. The system – a fluorescence im-aging cytometer with single-use dispos-able cartridges – offers a rapid read timeof 3.5 min and a simple design, with pas-sive fluid handling (no pumps or valves)

26 BioPhotonics • September 2012

Tricorder

MBio Diagnostics has developed a multiplexed fluorescence immunoassay system for rapid diagnosis of complex infectious diseases like HIVand hepatitis. Among the applications the companyis 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.

Feat Tricorder_Layout 1 8/30/12 10:07 AM Page 26

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 onRetroviruses and Opportunistic Infectionsheld in Seattle in March, showed that thesystem had “minimal bias” relative to thegold standard, flow cytometry – thus un-derscoring the potential of the system forpoint-of-care applications.

Imaging in the developing worldTricorder-like devices – particularly op-

tics-based ones – can also contribute to ahost of global health applications. There is little access in developing nations to the sophisticated lab tests and the trainingneeded 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 manyglobal health demands they face, but thesecan have limited efficacy. In recent years,researchers and medical device companieshave shown that optics-based technologiescan bridge this gap.

Take, for example, rapid diagnostictests (RDTs) – assays designed to detecttarget analytes in blood or fluid samples.Using RDTs, and with only minimal train-ing, health care workers have been able todetect a range of diseases – includingHIV, malaria, tuberculosis and syphilis –leading to better management of diseaseand more efficient surveillance of out-breaks.

Conventional RDTs have their limita-tions, though. Because they are read man-ually, there is potential for error, especiallyas the workers often administer a varietyof different tests at the same time. Cell-phone-based, tricorder-like devices couldhelp to eliminate this potential for error byoffering automated readings of the diag-nostic tests.

At the annual conference of the Ameri-can Association for Clinical Chemistryheld in Los Angeles in July, Holomic LLC– a company launched in 2011 to commer-cialize the biophotonic technologies in-vented in Aydogan Ozcan’s lab at UCLA –introduced its cell-phone-based rapid diagnostic test reader, the HRDT-1.

Weighing only about 65 g, the devicemechanically attaches to the existing cameraunit of a cell phone. An app on the phonedigitally processes captured images – within0.2 s per image – then provides a reading ofthe 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 inRDTs don’t last more than a few hours inthe field. But it has other advantages too.“The cloud angle and the Google Maps-based interface could especially help overthe long run to study the data that accumu-lates,” Ozcan said. “In the shorter term, itcan also help manage epidemics or getprepared for them.”

HIV/AIDs is, of course, another healthconcern in the developing world, espe-cially in sub-Saharan Africa. In 2009, anestimated 33.3 million people worldwidewere living with AIDS, according to theUNAIDS Report on the Global AIDS Epi-demic 2010. Of those, an estimated 22.5million were in sub-Saharan Africa. Thenumber of new infections is dropping, butthere is still a considerable need forscreening and monitoring of the disease.

MBio is also seeking to tackle HIV inAfrica and other parts of the developingworld. In addition to the CD4 test for stag-ing of the disease and ongoing monitoringof therapy, the company is developing

tests for co-infections, and panels of testsfor applications such as antenatal screen-ing. “We have an HIV/syphilis combina-tion test currently in a study in ruralKenya, testing pregnant moms for thesediseases where intervention can preventthe transmission to the child,” Myatt said.

The latter application, in particular, hasbeen in the spotlight recently. In July, in akeynote address at the biennial conferenceof the International AIDS Society, Secre-tary of State Hillary Clinton called forelimination of mother-to-child transmis-sion of HIV, worldwide, by 2015.

Currently, HIV/syphilis screening in resource-limited areas uses an HIV rapidtest and the RPR (rapid plasma reagin)syphilis test. The latter, though, requires askilled operator with laboratory facilitiesand a “cold chain” for the reagents (wherereagents are shipped and stored coldthroughout the supply chain), and it gener-ates many false positives, particularly inpregnant women. “While inexpensive,”Myatt said, “the RPR test’s complicationslimit its use.”

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New glass optical fibers offerlonger lifetimes and higherlight transmission, and experi-ence only minimal changes in

color and dispersion, and these character-istics enable them to answer the call forhigher quality medical lighting. What’smore, a newly developed environmentallyfriendly process allows these high-puritymulticomponent glass fibers to be manu-factured without using lead, arsenic or antimony.

In medicine in particular, glass opticalfibers have conquered a wide range of ap-plications, mostly in endoscopy and surgi-cal microscopy, but fibers also are used indental treatment and light therapy.

Improved high-purity, multimode stepindex fibers will pave the way for newideas that extend well beyond existing ap-plications. This can be attributed to theprogress that has been made in the compo-sition and preparation of the special glassfrom which these fibers are drawn at hightemperatures. Multicomponent glass alsooffers an outstanding price-to-performanceratio compared with quartz glass. Com-pared to existing fiber products, thismeans 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 byup to 10 percent (Figure 1). High-purityraw materials for manufacturing the glassare instrumental in achieving this goal. Ofcourse, many years of experience in melt-ing and manufacturing glass – in the areaof refining, for instance (driving bubblesout of molten glass) – reveal other ways toavoid glass defects.

The fibers’ high purity limits shifts incolor caused mainly by impurities in theglass. Thus, the illuminated objects retaintheir natural colors even when longerlightguides are used.

New Glass Fibers Widen Range of Medical Lighting Applications

28 BioPhotonics • September 2012

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) minimizeshifts 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 andsurgical microscopy are certain to benefit.Ever-thinner optical lightguides, brighterlight and smoother true-color illuminationare needed to distinguish between certaintypes of tissue.

Comparative measurements on fibersused in the past clearly show this (Figure2). When used in the standardized lightsource A, which equates to halogen lightthat has a color temperature of 2856 K and that is emitted directly, PuravisGOF85 glass fibers from Schott AG ex-hibit hardly any deviation over a distanceof 10 m. A conventional glass fiber (A2)experiences shifts of close to 200 K thatcan be seen even with the naked eye as thedistance increases. This difference be-comes even clearer in comparison to nor-mal light (6500 K) from a xenon lampD65, where a color shift of around 800 Koccurs at GOF85, which is significantlylower than that of A2. The effect of disper-sion that causes distorted colors along thelight field edges in existing fibers (Figure3) is also less significant when the newfibers are used.

Lightguides made from the new fiberscan be of great benefit here, thanks to theirimproved numerical aperture that allowsthem to capture more light. Their low at-tenuation in the visible range results ineven higher light output at the end of thefiber bundle – for instance, 28 percentmore light at 400 nm using a 2-m light-guide. Smaller bundle diameters that putout the same amount of light are anotheralternative, making it easier to construct orinstall these in thinner endoscopes thatsupport wound healing after minimally invasive surgery.

Improved chemical propertiesThese optical properties are not

achieved at the expense of chemical stabil-ity – in fact, the opposite is true. Puravisfibers have achieved the highest rankingsin all four chemical resistance glassesbased on the respective ISO standards.This means that they are resistant to acids(resistance class SR 1.0 as described byISO 8424), alkalis (AR 1.0 as describedby ISO 10629), climatic influences (CR1.0 as described by ISO/CD13384) andstaining (FR 0). Optical glasses obviouslyreact extremely sensitively to these typesof effects because their optical quality de-clines or is completely lost when chemicaldamages occur, or the surface of the glassor the glass material changes.

While developing the new fiber, Schottimproved its chemical stability – the pro-prietary raw materials used yield betterchemical stability and optical propertiesthan traditional materials, increasing thelife span of the fibers. This is particularlyimportant when it comes to reprocessingand sterilizing medical instruments by

cleaning or autoclaving. Tests have shownthat transmission losses after 100 auto-claving cycles can be reduced by up to 70 percent in the new fibers as comparedwith other fibers. The new fibers thereforealso support the growing hygiene require-ments in medicine.

Optical durability is also ensured by

BioPhotonics • September 2012 29

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 at365 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 alow level. Note: The lightguides investigated were fairly long (3 m). Shorter lightguides would result in highertransmission levels.

Feat Schott_Layout 1 8/30/12 10:08 AM Page 29

minimizing possible solarization effects.This was achieved by developing a suit-able glass formula that does without theheavy metal lead. The new and environ-mentally friendly manufacturing processalso avoids using arsenic or antimony

as refining agents. Thus, any productequipped with these fibers already com-plies with the European Union directivesRoHS 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 350and 400 nm (Figure 4), these high-techglass fibers are certain to open up interest-ing new fields. In this respect, the fibersexhibit significantly higher transmissionthan conventional products: Because thefibers are lead-free, Schott had to reducethe solarization effects. The solarizationeffects of the new fiber are minimized incomparison with the standard leadedSchott B3 fiber, so the overall absolutetransmission level after solarization is twotimes higher than that of GOF85 and threetimes higher (GOF70) than that of the B3fiber. This paves the way for innovativefluorescence 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 ofadhesives. They are also suited for use aslightguides 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 qualityassurance on manufacturing processes.

Security-oriented industries like avia-tion and vehicle construction also stand tobenefit. Glass fibers are chemically inertand offer extremely high thermal stability.In contrast to conductive (metal) cables,they transmit light without causing anysparks. Fire safety is therefore not anissue. This, coupled with ease of mainte-nance and a long service life, is but one ofthe compelling reasons why this fiber isequally suited for medical applications andfor illuminating aircraft cabins and vehicleinteriors.

The new multimode-stage index glassfibers are made of extremely pure, selectraw materials and are processed in an en-vironmentally compatible manner. Thiscontributes significantly to increased per-formance with respect to light yield, trans-mission, color shifting, attenuation anddispersion. It is now possible to realizemore sophisticated and innovative newlighting applications in medicine, and theglass fibers support the trend towardminiaturization of medical technology, asin endoscopy.

Meet the authorKaren Holst has been the product manager re-sponsible for fibers for the Lighting and ImagingBusiness Unit of Schott AG in Mainz, Germany,since 2007; email: karen.holst@schott.com.

$3,800* ScopeLite 200™ Microscope Illuminator

OPTICAL BUILDING BLOCKS CORPORATION

Metal Halide Microscope Illuminator

ScopeLite 200™ unique benefits

Requires no lamp focus adjustments to

maintain throughput or uniformity

200 W metal halide lamp

Excellent stability

2,000 hour lamp

Adapters for all fluorescence

microscopes

TTL shutter

The ScopeLite 200™ delivers high intensity illumination in a small package at a very reasonable cost. It is an excellent alternative to a traditional mercury arc lamp microscope illuminator because it requires no dealer maintenance contract or continual focus adjustments to ensure optimal throughput and uniformity of illumination. In addition it is a very cost effective alternative due to the significantly longer lamp life. With a new global price of just $3,800 there is no reason not to upgrade your older fluorescence microscope illuminator to the new ScopeLite 200™.

www.obbcorp.com

ScopeLite 200™

* Price includes ScopeLite 200™ illuminator with liquid light guide (microscope adapter not included).

30 BioPhotonics • September 2012

Glass Fibers

Figure 5. High-purity Puravis glass fibers are manufactured using an environmentally friendly process that doesnot use lead, arsenic or antimony.

Feat Schott_Layout 1 8/30/12 10:08 AM Page 30

Significant research has been under-taken to improve imaging sensorsfor endoscopy, but little work hasbeen done to maximize the per-

formance of the light sources and the lightdelivery system required to support them.Xenon light systems suffer from weaklight delivery through small fibers in spiteof continuous sensitivity improvements toimage sensors. A new endoscopic illumi-nation system can significantly reduce thesize of traditional video endoscopes.

Physical space constraints continue toaffect advanced procedures such as single-incision laparoscopic surgery, robot-assisted surgery and other minimally invasive surgical procedures. More func-tionality and instruments are desired andare being squeezed through the smallestpossible incisions. Space continues totighten with the migration of larger-diame-ter 3-D, high-definition endoscopic imag-ing systems into minimally invasive pro-cedures. Fortunately, a significant portionof the endoscope, the light delivery chan-nel, can be reduced in size to allow thespace to be used for other purposes or to allow the shrinking of the endoscope itself.1

For many years, illumination systemshave teamed with endoscopic imaging systems for medical applications to helpimage inside body cavities (colon, abdomen, heart, throat, nose, ear, eye); toassist in the placement of internal medicaldevices such as gastric bands; and even toperform work such as ablation of un-wanted or diseased tissue as in laser eyesurgery or laser atrial fibrillation treat-ment. The use of in vivo illuminationsources 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 andoptical coherence tomography.

Functions of lightViewing tissues using white light alone

is effective in detecting many lesions andin determining the general health of thetissue. In contrast, some bacterial infec-tions, lipid plaque, and precancerous andsubtle inflammatory conditions are diffi-cult to visualize under white light. Further-more, it can be challenging to position anillumination and imaging system in thevicinity of the organ to be viewed. Oncethere, it is desirable and advantageous touse light to do more than illuminate theobject: Radiation in the form of visiblelight, infrared or ultraviolet wavelengthscan 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 diseased4 tissue forremoval, to ablate stones, to initiate a re-action between a therapeutic molecule andits target reaction site, or to provide physi-cally based phototherapy.

Fluorescence imaging techniques use agenerally nondestructive property exhib-ited by some materials. Fluorescence oc-curs when a material absorbs radiation of

one wavelength, converts some portion ofthat radiation to a slightly different andusually longer wavelength, and then re-emits it. For example, when normal oralcavity tissues are illuminated with violetlight (405 nm), they have a fluorescenceemission that appears light blue. The

Light Source Helps Endoscopes Get Smaller and Smaller

BioPhotonics • September 2012 31

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 smallerinstruments for endoscopy, microsurgery and other applications. Images courtesy of Nathaniel Group Inc.

Hyperion CompetitorOutput Output

(lm) (lm)

0.170-mmPlastic Fiber 19 1

0.500-mmPlastic Fiber 300 14

Number ofOutput Channels 2 1

IntensityImprovement ~40� –

BY JAMES HERMANOWSKI, NATHANIEL GROUP INC.

Table 1. Measured optical output from Hyperion300 small optical fiber illuminator (output from eachof 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 andhelp discriminate between healthy tissueand tissue with underlying problems.5Fluorescence can be the result of tissue labeling using fluorophores or the result of autofluorescence, where the specimennaturally exhibits the property.

For endoscopic diagnostic tests, narrow-band illumination can provide a sharperimage or better contrast. Hemoglobin haspeak absorption at specific wavelengths inthe blue and green bands, so illuminationusing these wavelengths improves visibil-ity and identification of blood vessels andcapillaries. Additionally, the different lightabsorption of hemoglobin bound with oxy-gen versus hemoglobin without oxygencan be used to calculate oxygen saturationwhen absorption is measured at two differ-ent wavelengths. Narrowband illuminationhas also been helpful in identifying Bar-rett’s esophagus6,7 and atypical dysplasticcolon cells, and in differentiating betweenmalignant and benign cells of the urinarybladder.

Photochemotherapy or photodynamictherapy involves the administration of asensitizing agent followed by the action oflight on tissues where the photosensitizer islocalized.8 The need for ample illuminationthrough small optical fibers is one limitingfactor of this promising technique.

Physical phototherapy normally in-volves using infrared radiation to penetratedeep within tissue to deliver heat andstimulate blood vessel expansion. Ofteninfrared radiation is used because it canpenetrate through tissues easily. Infraredlasers are a preferred embodiment, allow-ing large doses to be delivered in shorttimes under controlled positioning of thetherapy.

Optical fibers and imaging systemsA new approach couples radiation from

a variety of sources into individual sub-millimeter optical fibers or fiber bundlesfor medical and industrial applications.The Hyperion 300’s patent-pending tech-nology from Nathaniel Group Inc. allowsintegration and mixing of multiple sourcesinto an optical fiber, including infrared,white-light, ultraviolet and solid-statesources. The flexibility of the system al-lows the optimum source or sources to beselected for each application. For example,a xenon source for general illuminationcan be combined with the stable UV out-put from a deuterium lamp for semiquanti-tative spectroscopy; or solid-state LEDsources can be combined for general illu-mination and fluorescence imaging withan infrared laser source for ablation, allowing the visualization,9 analysis andremoval 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 generationof millimeter-dimensioned medical camerasystems such as the Awaiba sensor.

Table 1 compares the measured radio-metric output of a Hyperion 300 small optical fiber illumination system to otherfiber illumination sources on the market.The data was measured for white light inlumens at the distal end of a 1-m fiberconnected to the source. The new devicewas in a configuration with two outputchannels optimized for coupling radiationinto optical fibers ≤0.5 mm. The datademonstrates exceptional performance forfiber diameters down to 170 μm.

Figure 2 is a photograph of a traditionalendoscope tip showing the imaging area,light-emitting area and protective exteriorwall. Significant space is consumed by thelighting function. The figure shows atscale the amount of space required for the new device to deliver suitable illumi-nation. The light source consumes only0.43 to 3 percent of the endoscope area,depending upon implementation (seeTable 2). Switching to the new source reduces the standard endoscope size by up to 6.5 mm2, enough to make space foran instrument.

Figure 3 shows a side-by-side color ren-dering comparison of an endoscope setupusing the new source and a standard xenonsource, considered to be the benchmarkfor medical illumination. The imageclearly demonstrates that both sources provide comparable color matching, whilethe Hyperion source shows improvedcolor saturation.

There is a continuous drive to reducethe size of imaging systems for medicalapplications. Smaller imaging systems

32 BioPhotonics • September 2012

Endoscopy

Figure 2. A traditional endoscope tip showing theimaging 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 mm2, enough to make space for another instrument.

Standard Hyperion Micro MicroEndoscope Enabled Endoscope Endoscope

Endoscope Without Hyperion With Hyperion

Imaging Area (mm2) 10.3 10.3 1 1

Light-Delivery Area (mm2) 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 EndoscopeArea Savings – ~32% smaller – ~40% smaller

Area Savings (mm2) – 6.3 – 6.5 – ~1

Feat Endo_Layout 1 8/30/12 10:09 AM Page 32

allow exploration of ever-smaller cavities and reduce the impacton living organisms. A new small fiber illumination light sourcewas studied to determine its capabilities as a light source enablingmicroendoscopic imaging systems.

Radiometric measurements of the new light source showedperformance up to 40 times better than that of other systems.

The light source was coupled with two imaging systems. Thefirst imager was a NanEye ultrasmall 1 � 1-mm, 250 � 250-pixel sensor from Awaiba. The second camera consisted of athree-sensor high-definition camera illuminated through a 500-μm fiber. In both cases, the new light source allowed for a signif-icant reduction in endoscope size without deteriorating function.

Meet the authorJames Hermanowski is vice president of business development atNathaniel 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 AwaibaGmbH for support relating to its imaging system.

References1. 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: Opticalfiber sees growth as medical sensors, OptoIQ.

4. D. Roblyer and R. Richards-Kortum (January 2010). Optical diagnosisfor 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-rett’s oesophagus: A review on current practice. World Journal of Gastroenterology, pp. 4271–4276.

7. S. Tanaka and Y. Sano (May 23, 2011). Aim to unify the narrow bandimaging (NBI) magnifying classification for colorectal tumors: Currentstatus in Japan from a summary of the Consensus Symposium in the79th Annual Meeting of the Japan Gastroenterological Endoscopy Society. Digestive Endoscopy, pp. 131–139.

8. A. Dietze (November 2004). Preclinical evaluation of photochemicaltreatment on rheumatoid arthritis and soft tissue sarcomas, Institute forCancer Research at the Norwegian Radium Hospital.

9. S. Park et al (January/February 2008). Automated image analysis ofdigital colposcopy for the detection of cervical neoplasia. Journal ofBiomedical Optics, Vol. 13, 014029.

PLAN TO VISITThe UK’s Premier

Event forVision & Imaging

WEDNESDAY 17 & THURSDAY 18 OCTOBER 2012RICOH ARENA · COVENTRY

Don’t miss theopportunity to meetwith the exhibitingcompanies

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Biomedical Sensing2012

BioPhotonics • September 2012 33

Endoscopy

Figure 3. A comparison of Hyperion 300 endoscopic light source (left) to a commercial xenon source shows good color matching and improved color saturation. Color comparison was carried out using an X-Rite color card, a Weck endoscope and a Richard Wolf HD three-chip camera system.

Feat Endo_Layout 1 8/30/12 10:09 AM Page 33

Fluorescence MicroscopeThe iBox Explorer™ Fluorescence Microscope enables visible to NIR

detection for in vivo imaging applications. The iBox Explorer monitors

tumor progression and tracks distribution of fluorescent markers. The

system utilizes a BioLite™ xenon multispectral light source and tailored

filter sets to allow for deeper detection of a broad spectrum of fluorophores.

Xenon is a very powerful light source to maximize illumination of samples.

(909) 946-3197

info@uvp.com

www.uvp.com

New sCMOS CameraThe new Zyla 5.5 megapixel scientific CMOS (sCMOS) camera is ideal for

research and OEM usage. Zyla sCMOS offers a 100 fps rate, rolling and

snapshot (global) shutter modes and ultra-low noise performance in a light,

compact and cost-effective design. Zyla achieves down to 1.2 electron rms

read noise and can read out the 5.5 megapixel sensor at a sustained 100 fps

through a “10-tap” Camera Link interface. A highly cost-effective “3-tap”

version is also available, offering up to 30 fps.

(800) 296-1579

info@andor.com

Andor.com/zyla

Spotlight_Layout 1 8/30/12 3:47 PM Page 34

BioPhotonics • September 2012 35

6-Megapixel Cameras �Point Grey Research Inc. has added

6-megapixel models to its Grass -

hopper Express FireWire-b digital

camera series. The GX-FW-60S6

uses the Sony ICX694 to deliver

high resolution and sensitivity,

and the ICX694 applies EXview

HAD technology to high-resolution multitap image sensors. Known for high quantum effi-

ciency, reduced smear and increased NIR sensitivity, ICX694 is a 1-in. CCD that produces

2736 � 2192-pixel images at 11 fps. The cameras have a tripod mounting bracket and on-

board temperature and power sensors. The FlyCapture software development kit library

provides a common control interface for all of the company’s cameras under Windows

and Linux. The 800-Mb/s bandwidth delivers low-latency, deterministic image transfer

without CPU loading. Applications include machine vision and bioscience. The GX-FW-

60S6M-C (monochrome) and GX-FW-60S6C-C (color) models offer high sensitivity, short

exposure times that eliminate motion blur, and postcapture gain.

Point Grey Research Inc.info@ptgrey.com

White Chip-on-Board LEDExcelitas Technologies’ ACULED chip-

on-board white LED delivers a combina-

tion of correlated color temperature

(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 Technologiesmedia@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 It’s In the

Box design, where the laser cavity and control electronics are integrated into a single

housing. All lasers deliver TEM00

-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-Physicsjurgen.niederhofer@newport.com

� VLWIR FiltersDeposition Sciences Inc.’s line of very long wavelength infrared (VLWIR) filters provides high trans-

mittance from the 12- to beyond the 22-µm-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 GmbH’s 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 µJ

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 GmbHfranziska.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 Semiconductorssupport@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 GmbHmicroscopy@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 company’s 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 Scientific’s 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 µm) 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 Scientificjoanne.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 LLCsales@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 Focusmilan.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

36 BioPhotonics • September 2012

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 company’s

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 camera’s 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

½-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-MTIinfo@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-

ule’s 20-pin serial modular receiver decoder

interface provides four inputs and four out-

puts, and two RS-232 connectors are available.

Allied Vision Technologies GmbHinfo@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 Robust design Life tested to 100 million cycles Modular repairable design Stand-alone or use with Sutter fi lter wheel Microprocessor-based controller “Soft” action mode provides minimum vibration Serial, USB and TTL interfaces

PHONE: 415.883.0128 | FAX: 415.883.0572 EMAIL: INFO@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.

BioPhotonics • September 2012 37

BREAKTHROUGHPRODUCTS p

New Prods_Layout 1 8/30/12 2:29 PM Page 37

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 Imagingimaging.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 CameraImperx 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 Lasersinfo@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 µm/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

company’s 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 Cyberneticscustomerservice@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

38 BioPhotonics • September 2012

p BREAKTHROUGHPRODUCTS

New Prods_Layout 1 8/30/12 12:43 PM Page 38

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 Opticssales@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 Instrumentsinfo@princetoninstruments.com

Gel Imager UVP LLC’s 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

BioPhotonics • September 2012 39

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.

p BREAKTHROUGHPRODUCTS

generate quantitative analysis results using

molecular weight, histograms and lane profile

graphs. Data can be exported to Excel for

documentation and publication.

UVP LLCinfo@uvp.com

Contact your sales representative or: sales@photonics.com • (413) 499-0514

Advertise in BioPhotonicsBiophotonics Technologies have a

bright future in global health.

You’ve put your heart into developing great technologies and devices for cardiovascular

applications. Now get them in front of BioPhotonics magazine’s 27,500 subscribers.

NovemberContent Focus: Cardiovascular ApplicationsLasers for Angioplasty, Imaging the Heart, Micro-Optics, Fiber Optics for Cardiology

Ad Close: Oct. 16

DecemberContent Focus: Trends

Optical Tweezers, Choosing a Microscopy System,Lighting in Bio Research

Ad Close: Nov. 13

New Prods_Layout 1 8/30/12 3:23 PM Page 39

APPOINTMENTS

OCTOBER2012 IEEE Third International Conference onPhotonics (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 Expo2012 (Oct. 9-11) Vienna. Contact Ming Guo,

Cambridge Healthtech Institute, +1 (781) 972-

5439; mguo@healthtech.com; www.bio-it-

worldexpoeurope.com.

Neuroscience 2012 (Oct. 13-17) New Orleans.

Contact Society for Neuroscience, +1 (202)

962-4000; info@sfn.org; www.sfn.org.

2012 IEEE Symposium on Biological Data Vi-sualization (BioVis) (Oct. 14-15) Seattle. Con-

tact Maria Velez, +1 (732) 535-1523; mariacv@

gmail.com; visweek.org.

Conference on Coherent Raman ScatteringMicroscopy (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 (VisWeek2012) (Oct. 14-19) Seattle. Contact Maria C.

Velez-Rojas, +1 (732) 535-1523; mariacv@

gmail.com; visweek.org.

22nd International Conference on OpticalFiber 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-

bin Chen, Chongqing University of Posts and

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,

GL events Exhibitions, +33 1 44 31 82 57; nadege.

venet@gl-events.com; www.optoexpo. com.

BMES 2012 Annual Meeting (Oct. 24-27) At-

lanta. Contact Biomedical Engineering Society,

+1 (301) 459-1999; info@bmes.org; www.

bmes.org.

IEEE Sensors 2012 (Oct. 28-31) Taipei, Taiwan.

Contact Chris Dyer, Conference Catalysts LLC,

+1 (785) 341-8538; cdyer@conferencecata

lysts.com; www.ieee-sensors.org.

SPIE Asia-Pacific Remote Sensing (Oct. 29-Nov. 1) Kyoto, Japan. Contact SPIE, +1 (360)

676-3290; customerservice@spie.org; spie.org.

NOVEMBERFifth International Photonics and OptoElec-tronics Meetings (POEM 2012) (Nov. 1-2)Wuhan, China. Contact Wuhan National Labo-

ratory for Optoelectronics, +86 27 877 92 227;

poem@mail.hust.edu.cn; poem.wnlo.cn.

SPIE/COS Photonics Asia (Nov. 4-7) Beijing.

Sponsored by SPIE and the Chinese Optical

Society. Contact SPIE, +1 (360) 676-3290;

customerservice@spie.org; spie.org.

MiCom 2012: Third International Conferenceon Microbial Communication (Nov. 5-8) Jena,

Germany. Contact Jena School for Microbial

Communication, Friedrich Schiller University

Jena, +49 3641 930 421; micom@uni-jena.de;

micom-conference.de.

Asia Communications and Photonics Confer-ence (ACP) (Nov. 7-10) Guangzhou, China.

Contact The Optical Society, +1 (202) 223-8130;

info@osa.org; www.acp-conf.org.

Laser Florence 2012 (Nov. 9-10) Florence,

Italy. Contact IALMS – International Academy

for Laser Medicine and Surgery, +39 055 234

2330; info@laserflorence.org; www.laser

florence. org.

2012 International Conference on ImageAnalysis and Signal Processing (IASP) (Nov. 9-11) Hangzhou, China. Contact Linda Sun,

+1 (770) 973-8732; asppress@yahoo.com;

iasp2012.zjicm.edu.cn.

Latin America Optics & Photonics Conference(LAOP) (Nov. 11-13) São Sebastião, Brazil.

Contact The Optical Society, +1 (202) 223-8130;

info@osa.org; www.osa.org.

Renewable Energy and the Environment: OSAOptics and Photonics Congress (Nov. 11-15)Eindhoven, Netherlands. Includes Optical In-

strumentation for Energy and Environmental

Applications (E2); Optical Nanostructures and

Advanced Materials for Photovoltaics (PV); Op-

tics for Solar Energy (SOLAR); and Solid State

and Organic Lighting (SOLED). Contact The

Optical Society, +1 (202) 223-8130; info@osa.

org; www.osa.org.

DECEMBERInternational Conference on Fiber Optics andPhotonics (Photonics 2012) (Dec. 9-12) Chen-

nai, India. Contact The Optical Society,

+1 (202) 223-8130; info@osa.org; www.

photonics2012.in.

Photonics Global Conference (PGC 2012) (Dec. 13-16) Singapore. Contact Director,

Optimus-Photonics Centre of Excellence,

Nanyang Technological University, +65 6790

4685; d-optimus@ntu.edu.sg; www.photonics

global.org.

2012 American Society for Cell Biology AnnualMeeting (Dec. 15-19) San Francisco. Contact

ASCB, +1 (301) 347-9300; www.ascb.org/

meetings.

CALL FOR PAPERSBiophysical Society 57th Annual Meeting • February 2-6Deadline: 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) 290-5600society@biophysics.org www.biophysics.org

33rd ASLMS Annual Conference • April 3-7Deadline: 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 year’s conference addressed topics such as

photobiomodulation, photodynamic therapy, cutaneous laser surgery,

and head and neck optical diagnostics.

Contact: ASLMS +1 (715) 845-9283information@aslms.org www.aslms.org

AACR Annual Meeting 2013 • April 6-10Deadline: 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) 440-9300aacr@aacr.org www.aacr.org

40 BioPhotonics • September 2012

For complete listings, visitwww.photonics.com/calendar

Appointments_Layout 1 8/30/12 10:11 AM Page 40

BioPhotonics • September 2012 41

ADVERTISERINDEXPhotonics Media Advertising Contacts

Please visit our websitePhotonics.com/mediakit for all our marketing opportunities.

Ken TyburskiDirector of SalesVoice: +1 (413) 499-0514, Ext. 101Fax: +1 (413) 443-0472ken.tyburski@photonics.com

New England, Southeastern US, FL,Rocky Mountains, AZ, NM & MidwestRebecca L. PontierAssociate DirectorVoice: +1 (413) 499-0514, Ext. 112Fax: +1 (413) 443-0472becky.pontier@photonics.com

NY, NJ & PATimothy A. DupreeRegional ManagerVoice: +1 (413) 499-0514, Ext. 111Fax: +1 (413) 443-0472tim.dupree@photonics.com

Northern CA, Pacific Northwest, AK, NV, Yukon & British ColumbiaJoanne C. GagnonRegional ManagerVoice: +1 (413) 499-0514, Ext. 226Fax: +1 (413) 443-0472joanne.gagnon@photonics.com

Southern CA, Central CA & HI Tracy L. ReynoldsRegional ManagerVoice: +1 (413) 499-0514, Ext. 104Fax: +1 (413) 443-0472tracy.reynolds@photonics.com

Eastern CanadaMaureen Riley MoriartyRegional ManagerVoice: +1 (413) 499-0514, Ext. 229Fax: +1 (413) 443-0472riley.moriarty@photonics.com

Europe, Israel & South Central USOwen BrochRegional ManagerVoice: +1 (413) 499-0514, Ext. 108Fax: +1 (413) 443-0472owen.broch@photonics.com

Austria, Germany & LiechtensteinOlaf KortenhoffVoice: +49 2241 1684777Fax: +49 2241 1684776olaf.kortenhoff@photonics.com

Asia (except Japan)Hans ZhongVoice: +86 755 2872 6973Fax: +86 755 8474 4362hans.zhong@yahoo.com.cn

JapanScott ShibasakiVoice: +81 3 5225 6614Fax: +81 3 5229 7253s_shiba@optronics.co.jp

Reprint ServicesVoice: +1 (413) 499-0514Fax: +1 (413) 442-3180editorial@photonics.com

Mailing addresses:Send all contracts, insertion orders and advertising copy to:Laurin PublishingPO Box 4949Pittsfield, MA 01202-4949

Street address:Laurin PublishingBerkshire Common, 2 South St.Pittsfield, MA 01201Voice: +1 (413) 499-0514Fax: +1 (413) 442-3180advertising@photonics.com

aAndor Technology plc. .................................................................................................CV2, 34www.andor.com

Applied Scientific Instrumentation Inc. .................................................................................5www.asiimaging.com

cCoherent Inc. .......................................................................................................................CV4www.coherent.com

CVI Melles Griot ......................................................................................................................11www.cvimellesgriot.com

eEdmund Optics........................................................................................................................19www.edmundoptics.com

Esco Products Inc. ..................................................................................................................37www.escoproducts.com

iIridian Spectral Technologies Ltd. ..........................................................................................7www.iridian.ca

lLumencor Inc. ........................................................................................................................23www.lumencor.com

mMad City Labs Inc. .................................................................................................................15www.madcitylabs.com

nNKT Photonics A/S ...................................................................................................................3www.nktphotonics.com

oOptical Building Blocks Corp. .........................................................................................27, 30www.obbcorp.com

pPhotonics Media ......................................................................................................34, 39, CV3www.photonics.com

PI (Physik Instrumente) L.P. ...................................................................................................16www.pi.ws

Prior Scientific Inc. .................................................................................................................13www.prior.com

rRaptor Photonics Ltd. ............................................................................................................15www.raptorphotonics.com

sSutter Instrument....................................................................................................................37www.sutter.com

uUVP LLC ...................................................................................................................................34www.uvp.com

xXmark Media Ltd. ..................................................................................................................33www.photonex.org

Ad Index_Layout 1 8/31/12 8:31 AM Page 41

POSTSCRIPTS

Stem 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 optionemerging 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.

Ahn’s 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 cangrow 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 cellsimplanted in mice to track the cells’ viability andtheir development into hair follicles. They per-formed the imaging technique on the implantedcells five times over the course of 21 days.

The key finding was that molecular imagingtechniques 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 themunder the microscope.“This study is the first study of hair follicle regenera-

tion using an in vivo molecular imaging technique,” Ahnsaid – which means that more studies must be conducted be-

fore clinical trials can be put in place to determine whether thetherapy could work to regenerate human hair.

The research was presented at the Society of Nuclear Medicine’s2012 annual meeting and published in the Journal of Nuclear Medicine.

42 BioPhotonics • September 2012

Caren B. Lescaren.les@photonics.com

Bioluminescence imaging lights up hair renewal

Postscripts_Layout 1 8/30/12 10:11 AM Page 42

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