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Volume 20 Issue 6

www.photonics.com NEWS 10 BIOSCAN

BioPhotonics editors curate the most signicant headlines of the month for photonics in the life sciences and take you deeper inside the news. Featured stories include: QD method combines best of optical, electron microscopy Breakthrough enables photosensitive-drug development SERS, nanoprobes seek to detect infections early

16 RAPIDSCAN
3 Questions with Dr. Adam Wax of Oncoscope Inc. and Duke University

FEATURES

23 SMARTPHONES SET TO REVOLUTIONIZE THE MEDICAL WORLD

by Gary Boas, News Editor The many issues relevant to launching portable diagnostic devices include government regulations and developing-world cultures.

26 STED MICROSCOPY: A NEW CHAPTER IN LIGHT IMAGING

by Marie Freebody, Contributing Editor This two-decades-old nanoscale technique has broken scientific barriers and deepened our understanding of biomolecules.

30 CW LASERS BOOST RESOLUTION FOR MICROSCOPY

by Matthias Schulze and Volker Pfeufer, Coherent Inc. Optically pumped semiconductor laser technology enables optical nanoscopy and multiwavelength excitation.

26

34 BRIGHT LIGHTS IN THE BIO(PHOTONICS)SPHERE

by Laura S. Marshall, Managing Editor A constellation of photonics superstars includes teens who are developing cancer-fighting tools, and another who is introducing students to STEM.

DEPARTMENTS
THE COVER Will smartphones become the universal diagnostic tool? Design by Art Director Suzanne L. Schmidt.

8 EDITORIAL 37 BREAKTHROUGHPRODUCTS 40 APPOINTMENTS

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41 ADVERTISER INDEX 42 POST SCRIPTS

by Caren B. Les Skin scan can quantify stress levels

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BioPhotonics September 2013

THIS IS YOUR TIME T TO BE RECOGNIZED

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Laurin Publishing, 100 West Street PO Box 4949, Pittseld, MA 01202-4949 +1 (413) 499-0514; fax: +1 (413) 442-3180; email: editorial@photonics.com Subscription Policy BioPhotonics ISSN-1081-8693 (USPS 013913) is published 9 times per year by Laurin Publishing Co. Inc., 100 West Street, Pittseld, MA 01201. TITLE reg. in US Library of Congress. The issues will be as follows: January, February/March, April, May/June, July/August, September, October, November and December. Copyright 2013 by Laurin Publishing Co. Inc. All rights reserved. POSTMASTER: Periodicals postage paid at Pittseld, MA, and at additional mailing ofces. Postmaster: Send form 3579 to BioPhotonics, 100 West Street, PO Box 4949, Pittseld, MA 01202-4949, +1 (413) 499-0514. CIRCULATION POLICY: BioPhotonics is distributed without charge to qualied researchers, engineers, practitioners, technicians and management personnel working with the elds of medicine or biotechnology. Eligibility requests must be returned with your business card or organizations letterhead. Rates for others as follows: $45 domestic and $56.25 outside US per year prepaid. Overseas postage: $30 airmail per year. Publisher reserves the right to refuse nonqualied subscriptions. ARTICLES FOR PUBLICATION: Individuals wishing to submit an article for possible publication in BioPhotonics should contact Laurin Publishing Co. Inc., 100 West Street, PO Box 4949, Pittseld, 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 those of the contributors the publisher assumes no responsibility for them.

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BioPhotonics September 2013

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EDITORIAL
BioPhotonics Editorial Advisory Board Mark A. Anastasio, Ph.D. Professor of Biomedical Engineering Washington University in St. Louis

Is It Your Time to Shine?

he Prism Awards the annual international competition recognizing cutting-edge products that break conventional ideas, solve problems and improve life through photonics is accepting entries for the 2014 competition. But hurry; time is running out. Visit www.photonicsprismaward.com for details and the entry form. Because their products are the best and brightest, Prism Awards finalists get plenty of media attention. Managing Editor Laura Marshall and Senior Editor Melinda Rose previewed last years finalists in our January issue. Among the three finalists in the Life Sciences and Biophotonics category was Femtolasers Produktions GmbH of Vienna, which was recognized for its Integral core ultrafast, portable Ti:sapphire turnkey laser. Weighing less than 4 kg, it combines a femtosecond light source with <20-fs laser pulses for applications in biophotonics, such as multiphoton microscopy, OCT and terahertz imaging or spectroscopy. Another finalist, Olympus America of Massachusetts, entered its Scaleview microscope objectives, which allow biologists to see deep into the brain to better map it and understand its functions. The two microscope objectives, when used with a specific reagent, enable bright imaging up to 4 mm and 8 mm deep; both are designed to boost the capability of multiphoton and confocal microscopy. And the 2013 category winner was Raman-based disease detection from Verisante Technology of Canada. Its Aura product can quickly image biochemical changes noninvasively using a near-IR laser beam, allowing doctors to characterize the biochemical constituents of the skin based on molecular vibrations, instead of using visual characteristics to assess skin lesions. If you have recently introduced an innovative light-based technology or product that fits in the Life Sciences and Biophotonics category, or any of the 10 other categories, we hope youll enter the Prism Awards for Photonics Innovation. The awards will be presented by SPIE and Photonics Media, publisher of BioPhotonics, at a gala event held during SPIEs Photonics West. We hope to see you there. Cover Story Smartphones have opened up the world, in a sense, and opened a world of opportunity to maximize mobile technologies to benefit planet and people. Device modifications and applications that will bring oximetry to operating rooms that currently do without it, and imaging and sensing for mobile health applications also present new challenges. Among the concerns, according to our cover story, by news editor Gary Boas, are funding these new technologies and navigating regulations. Also vitally important is an understanding of how the new technologies will fit into existing infrastructure and the sociocultural impact they could have. To discover how some companies are charting a course in these new waters, read the entire article, beginning on page 23. Be sure to check out the other features in this issue, too right after you submit your Prism Awards entry.

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

David Benaron, M.D. Professor, Medicine (consulting) Founder, Stanford Biomedical Optics program Stanford University School of Medicine CEO, Spectros Corp.

Aydogan Ozcan, Ph.D. Associate Professor Electrical Engineering, Bioengineering University of California, Los Angeles

Adam Wax, Ph.D. Theodore Kennedy Associate Professor Director of Masters Studies at the Department of Biomedical Engineering, Duke University Chairman and Founder, Oncoscope Inc.

Karen A. Newman karen.newman@photonics.com

BioPhotonics September 2013

Welcome to
CONTRIBUTORS

The online companion to BioPhotonics magazine

Photonics Your Way

Now available as a FREE mobile app!

News editor Gary Boas has extensive experience as a writer and editor in the research community; he is also a contributing editor to Photonics Spectra. Page 23.

Contributing editor Marie Freebody is a freelance journalist with a masters degree in physics from the University of Surrey, England. Page 26.

To download the app, scan this QR code, or visit www.photonics.com/apps

BioPhotonics magazine print and digital subscribers can access full issues and news feeds by logging in with an email address or subscriber number. Nonsubscribers can access a preview of each issue as well as real-time news feeds from Photonics.com. Not a current BioPhotonics subscriber? Visit www.photonics.com/ subscribe to start or renew your subscription. Once your subscription is activated, you will have access to all the app features. (Allow 24 hours for activation of your account.)

Managing Editor Laura S. Marshall combines years in journalism with a lifelong love of science to cover the vast world of photonics; in addition to her magazine duties, she co-hosts the Light Matters Weekly Newscast on Photonics.com. Page 34.

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Download each issue of BioPhotonics as it is published Search archived magazine issues Access real-time news and product updates from our website Share articles via email or social media

Volker Pfeufer is a senior product line manager at Coherent Inc. of Santa Clara, Calif. Page 30.

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Matthias Schulze is director of marketing in the life sciences at Coherent Inc. of Santa Clara, Calif. Page 30.

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BioPhotonics September 2013

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

QD method combines best of optical, electron microscopy

GAITHERSBURG, Md. A fast, versatile and high-resolution technique that combines the best of optical and scanning electron microscopy could provide surface and subsurface viewing of features as small as 10 nm in size. This will be useful for a wide range of applications including materials characterization and the life sciences, its creators say. Researchers at NIST have developed the microscopy method using cathodoluminescence to image nanoscale features. In an old tube television, a beam of electrons moves over a phosphor screen to create images; the new technique works in much the same way by scanning a beam of electrons over a sample that has been coated with specially engineered quantum dots (QDs). The QDs emit low-energy visible light very close to the surface of the sample, exploiting near-field effects of light. After interacting with the sample, the scattered photons are collected using a closely placed photodetector, allowing an image to be constructed. The first demonstration of the technique was used to image the natural nanostructure of the photodetector itself. Because both the light source and detector are so close to the sample, the diffraction limit doesnt apply, and much smaller objects can be imaged. Initially, our research was driven by our desire to study how inhomogeneities in the structure of polycrystalline photovoltaics could affect the conversion of sunlight to electricity and how these devices can be improved, said Heayoung Yoon of the Energy Research Group at NIST. But we quickly realized that this technique could also be adapted to other research regimes, most notably imaging for biological and cellular samples, wet samples, samples with rough surfaces, as well as organic photovoltaics. The technique tackles two problems in nanoscale microscopy: the diffraction limit, which restricts conventional optical microscopes to resolutions no better than about half the wavelength of the light (about 250 nm for green light), and the relatively high energies and sample

A new microscopy technique developed at NIST works by scanning a beam of electrons over a sample that has been coated with specially engineered quantum dots. The dots absorb the energy and emit it as visible light that interacts with the sample at close range; the scattered photons are collected using a similarly closely placed photodetector (not depicted). Courtesy of Dill/NIST.

preparation requirements of electron microscopy, which are destructive to fragile specimens like tissue. NIST researcher Nikolai Zhitenev, a co-developer of the technique, had the idea a few years ago to use a phosphor coating to produce light for near-field optical imaging, but at the time, no phosphor available was thin enough. Thick phosphors cause the light to diverge, severely limiting the image resolution. This changed when the NIST investigators teamed with scientists from a company that engineers QDs for lighting applications. The QDs potentially could do the same job as a phosphor and be applied in a coating both homogenous and thick enough to absorb the entire electron beam while also thin enough that the light produced does not have to travel far to the sample.

The collaborators discovered that the QDs unique core-shell design efficiently produced low-energy photons in the visible spectrum when energized with a beam of electrons. The group then developed a deposition process to bind them to specimens as a film with a controlled thickness of approximately 50 nm. The investigators now would like to develop the method further, working with end users, Zhitenev said. Worcester Polytechnic Institute, QD Vision, Sandia National Laboratories and the Maryland NanoCenter at the University of Maryland also contributed to the research, which appeared online in AIP Advances (doi: 10.1063/1.4811275). Ashley N. Rice ashley.rice@photonics.com

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BioPhotonics September 2013

Breakthrough enables photosensitive-drug development

BARCELONA, Spain A chemical nanoengineering breakthrough favoring the development of light-regulated therapeutic molecules could lead to personalized medicine that limits treatment time and reduces unwanted results. Modifying biological processes with light has led to new fields of research, such as optogenetics and optopharmacology, and to the development of numerous tools for biology and medicine. Combining drugs with external devices to control light could enable the development of photosensitive drugs, but researchers must enhance the photochemical response of the compounds and be able to stimulate them at visible wavelengths for this to work. Prolonged illumination with ultraviolet light is toxic for cells and is therefore a clear limitation as well as having little tissue penetration capacity, said Dr. Ernest Giralt of the Institute for Research in Biomedicine (IRB Barcelona). Additionally, the photoconversion of the compounds needs to be improved, as does their stability in the dark, to be able to on demand, design them in such a way that they relax rapidly when irradiation with light stops, or that they remember for hours or days the light stimulation received, added Pau Gorostiza, ICREA professor and head of the Nanoprobes and Nanoswitches Lab at the Institute for Bioengineering of Catalonia (IBEC). Giralt, Gorostiza and colleagues synthesized two peptides that, upon irradia-

Researchers at IRB Barcelona and IBEC design the rst peptides regulated by light to modulate biological processes. Courtesy of Laura Nevola.

tion with light, change shape, allowing or preventing a specific protein-protein interaction. The association of these two proteins is required for endocytosis, a process in which cells allow molecules to penetrate the cell membrane. Postdoc Laura Nevola and doctoral student Andrs Martn-Quirs have spent the past four years working on the design of these photosensitive peptides. Photosensitive peptides act like traffic lights and can be made to give a green or red light for cell endocytosis, Giralt said. They are powerful tools for cell biology. These molecules allow us to use focalized light like a magic wand to control biological processes and to study them, Gorostiza said. The molecules could be used for in vitro endocytosis in cancer cells, where this process is uncontrolled, allowing selec-

tive inhibition of the proliferation of these cells. They also could enable the study of developmental biology where cells require endocytosis to change shape and function, processes that are orchestrated with great spatial and temporal precision. The investigators believe that the most immediate therapeutic applications will be for diseases affecting superficial tissue such as the skin, the retina and the most external mucosal membranes. They are now working to develop a general recipe for photoswitchable inhibitory peptides that can be used to manipulate other protein-protein interactions inside cells by applying light. The work appeared in Angewandte Chemie (doi: 10.1002/anie.201303324). ANR

SERS, nanoprobes seek to detect infections early

DURHAM, N.C. Nanoprobes can be used with surface-enhanced Raman spectroscopy (SERS) to reveal a specific molecular markers optical fingerprint and to detect infections before patients even show symptoms, according to a recent study. Biomedical engineers and genome researchers at Duke University developed the approach and have demonstrated it in human samples; they are now developing the technique for placement on a chip to provide simple patient information quickly. We have demonstrated for the first time that the use of these nanoprobes can detect specific genetic materials taken from human samples, said Tuan Vo-Dinh, the R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering in Dukes Pratt School of Engineering and director of the universitys Fitzpatrick Institute for Photonics. His team collaborated with scientists at the universitys Institute for Genome Sciences & Policy (IGSP), who

Tuan Vo-Dinh. Courtesy of Duke University.

BioPhotonics September 2013

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have developed a method of measuring the hosts response to infection through RNA profiling. The silver-based nanoparticle they developed targets a specific molecular marker that spills into the bloodstream at the first stages of an infection. When light is aimed at the sample, the nanoparticle attached to a molecular marker will reflect a distinct optical fingerprint. When the target molecule is coupled

with a metal nanoparticle or nanostructure, the Raman response is greatly enhanced by the SERS effect often by more than a million times, said Vo-Dinh, who has been studying the potential applications of SERS for decades. This important proof-of-concept study now paves the way for the development of devices that measure multiple genomederived markers that will assist with more accurate and rapid diagnosis of infectious

disease at the point of care, said Geoffrey Ginsburg, director of genomic medicine at the IGSP. This would guide care decisions that will lead to more effective treatment and improved outcomes of antimicrobial therapy. The research appears online in Analytica Chimica Acta (doi: 10.1016/j. aca.2013.05.017). ANR

Telescopic contact lens helps AMD patients see

SAN DIEGO, and LAUSANNE, Switzerland A slim, telescopic contact lens that switches between normal and magnified vision in combination with liquid crystal eyeglasses could provide a relatively unobtrusive way to enhance the sight of patients with age-related macular degeneration (AMD). Visual aids that magnify incoming light help AMD patients see by spreading light around to undamaged parts of the retina, but these optical aids use either bulky spectacle-mounted telescopes that interfere with social interactions, or microtelescopes that must be surgically implanted directly into the eye. For a visual aid to be accepted, it needs to be highly convenient and unobtrusive, said Eric Tremblay of cole Polytechnique Fdrale de Lausanne in Switzerland, who worked with an international team of researchers led by University of California, San Diego, professor Joseph Ford to develop the device. A contact lens is an attractive compromise between head-mounted telescopes and implanted microtelescopes, Tremblay said. The system developed by Fords team uses tightly fitting mirror surfaces to make a telescope that has been integrated into a nearly 1-mm-thick contact lens with a dual modality: The center provides unmagnified vision, while the ring-shaped telescope at the periphery of the regular contact lens magnifies the view 2.8 times. To switch between the magnified view and normal vision, users wear a modified pair of liquid crystal glasses originally made for viewing 3-D TVs. These glasses selectively block either the magnifying portion of the contact lens or its unmagnified center by electrically changing the orientation of polarized light to allow light with one orientation or the other to pass through the glasses to the lens. The design was tested both with computer modeling and lens fabrication. A life-sized model eye was created to capture images through the system. To construct the lens, the researchers used a robust material common in early contact lenses called polymethyl methacrylate (PMAA), into which they placed tiny grooves to correct for aberrant color caused by the shape of the lens, which conforms to the human eye. Tests showed that the magnified image quality through the lens was clear and provided a much larger field of view than other magnification approaches, but refinements are necessary before the proof-of-concept system could be ready for commercial use. The grooves degraded image quality and contrast, and made the lens unwearable unless it is surrounded by a smooth, soft skirt, something commonly used with rigid contact lenses today. PMAA currently is not ideal for contact lenses

Five views of the new switchable telescopic contact lens. (a) From front. (b) From back. (c) On the mechanical model eye. (d) With liquid crystal glasses. Here, the glasses block the unmagnied central portion of the lens. (e) With liquid crystal glasses. Here, the central portion is not blocked. Images courtesy of Optics Express.

Images captured through the contact lens and mechanical model eye: (a) Outdoor image taken with model eye alone. (b) This outdoor image, taken with model eye and contact lens, shows why each of the two magnication states (normal and 2.8) should be used one at a time: Here, neither section of the lens is being blocked by the glasses, and the result is an image with greatly reduced contrast. (c) Outdoor image taken with just the magnied outer portion of the contact lens (2.8). OE = optoelectronic.

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BIOSCAN

because it is gas-impermeable, limiting wear to short periods of time. The team is pursuing a similar design that will still be switchable but that will use gas-permeable materials and correct for aberrant color without grooves. In the future, it will hopefully be possible to go after the core of the problem with effective treatments or retinal prosthetics, Tremblay said. The ideal is really for magnifiers to become unnecessary. Until we get there, however, contact lenses may provide a way to make AMD a little less debilitating. The research was published in Optics Express (doi: 10.1364/OE.21.015980).

even down to the level of single molecules. The technology could allow the simultaneous detection of multiple types of RNA related to cancer, which would then raise the possibility of scientists eventually being able to screen patients in order to predict their risk of developing disease, Chen said. By allowing us to see what is happening inside cells, we also hope this research will lead to the development of

techniques to study the efficacy of drugs. The probes could also deliver cancer drugs and other molecules directly to diseased tissues, bypassing healthy cells. The researchers also believe the technique could improve food and water safety. This new approach to imaging RNA at a single-cell level may also allow scientists to develop new methods to identify various microbes which may

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Gold nanoprobes + FRET = cancer insights

GLASGOW, Scotland Gold nanoprobes paired with FRET microscopy could yield a new generation of biological imaging and sensing techniques researchers could study cancer cells in more minute detail and measure the effectiveness of medicines at subcellular levels. Gold nanoparticles have a number of advantages over the organic dye molecules currently used to study cells with fluorescence microscopy. They are less toxic to cells, more sensitive, probe over a longer distance, and are more photostable meaning they are unchanged by light exposure. University of Strathclyde scientists took these advantages into account when developing a multidisciplinary approach using gold nanoprobes paired with FRET microscopy to image message ribonucleic acids (mRNA) a kind of nucleic acid present in all living cells that carries genetic codes from DNA to make protein. By examining key mRNAs at a cellular level, the scientists could detect diseases such as cancer at an early stage and determine the effectiveness of treatments. The nanoprobes are based on a type of molecular handshake called Frster resonance energy transfer, or FRET, in which gold nanoparticles are linked with a fluorescent protein via a hairpin-structured single-stranded DNA, said Dr. Yu Chen of the universitys department of physics. Upon interacting with the target mRNA in the cell, the hairpin structure dissolves, and a fluorescent signal occurs enabling the tracking and quantification of the disease-related mRNA at a cellular level,

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have contaminated food and water, said Dr. Jun Yu of the Strathclyde Institute of Pharmacy and Biomedical Sciences. Food safety is a global challenge, and using novel nanoprobes to detect food contamination by various microbes will

open up a new way of addressing this crucial issue. The Biotechnology and Biological Sciences Research Council invested 119,000 in the project.

Laser-guided codes advance THz imaging

CHESTNUT HILL, Mass. A singlepixel imaging technique uses laser-guided codes to quickly and efficiently manipulate stubborn terahertz waves, producing clear images in a matter of seconds, which could advance areas such as realtime skin imaging to promote simple skin cancer detection. Unlike other regions of the electromagnetic spectrum, terahertz has proved extremely difficult to manipulate for capturing images of objects and materials in which these lightwaves interact. Most existing terahertz imaging devices use expensive technology or require several hours and cumbersome manual controls to generate a viable image, according to Willie J. Padilla, a physics professor at Boston College. In the terahertz gap, conventional electronic sensors and semiconductor devices are ineffective. Some systems capture only a fraction of a scene, so tuning these terahertz waves is inefficient. To tame the terahertz gap, it is crucial to overcome the obstacles of mechanics, cost and image clarity, researchers maintain. A technology that creates efficient masks capable of tuning terahertz radiation to produce clear images in just a few seconds would go a long way toward this goal. Padillas method centers on what he and graduate students David Shrekenhamer and Claire M. Watts call a coded aperture multiplex technique, where a laser beam and electronic signals are used to send a set of instructions to a semiconductor so it can guide the reproduction of the image of an object after terahertz waves have passed through it. A digital micromirror device encodes the laser beam with instructions that direct certain segments of the silicon mask to react and allow a selected sample of the terahertz waves to pass freely through, consistent with the image pattern. The combination of optical instructions and the semiconductors reaction creates a terahertz spatial light modulator, the investigators say. As with the aperture of a conventional camera, the modulator guides the digital reconstruction of the entire image based on a broad sampling of terahertz waves that have passed through the object. The method could produce masks of varying resolutions, ranging from 63 to 1023 pixels, and acquire images at speeds of up to 0.5 Hz, or about 2 s. The findings have demonstrated the viability of obtaining real-time, high-fidelity terahertz images using an optically controlled spatial light modulator with a single-pixel detector, the researchers said. Additional laboratory research is en-

A new method for single-pixel terahertz imaging uses a set of instructions delivered by a laser beam to tune terahertz waves to produce new types of terahertz images. During the process, terahertz waves pass through an object (a); then they strike a silicon semiconductor (b) given specic instructions about how to sample the image; that data is passed along to digitally reconstruct an image (c) of the original object in just a few seconds. Courtesy of Claire M. Watts, Boston College.

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hancing terahertz wave control; intricately patterned metamaterials, for example, are being used to manipulate terahertz waves for faster and more efficient image creation, Padilla said. The research was published in Optics Express (doi: 10.1364/ OE.21.012507).

Erupting nanovolcanoes for drug delivery

RALEIGH, N.C. Nanovolcanoes carved out of a synthetic polymer using UV light can store and release precise amounts of materials, which its creators say makes it suitable for drugdelivery technologies. North Carolina State University researchers created the nanovolcanoes by placing transparent, spherical nanoparticles directly on a thin film that, when irradiated with UV light, underwent a chemical change. The film was submerged in a liquid solution that washed away the parts of the film exposed to the light, yielding a small mound with a hollow core. We can control the pattern of light by changing the diameter of the nanoparticle spheres, or by changing the wavelength of the light that we shine through the spheres, said Xu Zhang, a doctoral student in mechanical and aerospace engineering. That means we can control the shape and geometry of these structures, such as how big the cavity of the nanovolcano will be. By controlling the cav- Cross section of a nanovolcano carved itys size, the researchers using UV light. The nanovolcanoes have precisely measured hollow cores and are able to control the openings at their mouth, which make size of the drug payload. them a good candidate for drug-delivery mechanisms, its developers at North And, like a volcano, the Carolina State University say. Courtesy structures have a hole at of Chih-Hao Chang, NC State. the top, the size of which controls the rate of release. A highly accurate computer model was developed to predict the shape and dimensions of the nanovolcanoes based on the diameter of the nanoscale sphere and the wavelength of light. The materials used in this process are relatively inexpensive, and the process can be easily scaled up, said assistant professor of mechanical and aerospace engineering Dr. Chih-Hao Chang. In addition, we can produce the nanovolcanoes in a uniformly patterned array, which may also be useful for controlling drug delivery. The investigators now are working to improve their understanding of the nanovolcanos release rate, including how quickly nanoparticles of different sizes will escape from different-sized volcano mouths. Thats essential information for drug-delivery applications, Chang said. Its exciting to take our understanding of how light scatters by particles and apply it to nanolithography in order to come up with something that could actually help people. The research appeared in ACS Nano (doi: 10.1021/nn402637a).

BioPhotonics September 2013

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RAPIDSCAN Business and Markets

3 Questions

with Dr. Adam Wax of Oncoscope Inc. and Duke University

There is currently no way for the physician to identify precancerous cells without taking a biopsy.
for detecting precancerous lesions of the esophagus. The original a/LCI system was validated in a clinical study (Terry et al, Gastroenterology 2011) that used a prototype instrument developed in my laboratory at Duke University. This system was robust enough for the 50-patient feasibility study, but in order to translate the system for clinical use, we had to redesign several aspects of the system. For example, the Duke system required installation of the fiber optic probe by our Ph.D. scientists, while the new Oncoscope probe features an easily exchanged probe that can be attached by a technician. Another important aspect is minimizing the time required for instrument preparation between patients. While the original Duke prototype required a 20-minute Cidex bath for disinfection between patients, the Oncoscope system uses a disposable sheath as a barrier. Not only does this protect the probe and maintain disinfection, but the sheath can be exchanged easily and quickly, allowing for fast turnaround between patients. In addition to these and other hardware changes designed to make the instrument more robust and durable, we have also created a new software interface which improves ease of use by the physician. With these design changes nearing completion, we are eager to begin our pivotal clinical study in the near future. Q: What are the implications of this project/work? Wax: Upon FDA approval, the a/LCI device from Oncoscope will provide a new way for monitoring patients with Barretts esophagus (BE), a metaplastic tissue transformation of the esophagus. BE patients have an increased chance for developing esophageal adenocarcinoma, an awful disease with a dismal 15 percent five-year survival rate. Because of this increased risk, BE patients undergo periodic endoscopic surveillance procedures to search for precancerous lesions. Unfortunately, there is currently no way for the physician to identify precancerous cells without taking a biopsy. However, it is not feasible to take biopsies from more than a few selected points in the tissue. The Oncoscope a/LCI device will enable a physician to examine many more points in the tissue and guide their biopsies to suspicious regions for more effective surveillance. Q: Whats the next step? Wax: Preliminary data from the BIOS lab at Duke have shown that the approach is also feasible for detecting precancerous lesions in the colon and cervix. We are preparing for an in vivo study, under support from the Coulter translational partnership, to use a/LCI for detecting precancerous tissues in patients who suffer from inflammatory bowel diseases, such as Crohns disease and colitis. This is a similar situation as BE patients where the tissue condition can cause an increased risk of cancer so that periodic surveillance is warranted. However, the colon is a larger organ than the esophagus and thus even more biopsies are required to assess tissue health. The a/LCI device could help with this clinical task by enabling more tissue sites to be evaluated in less time. Application to cervical epithelial tissues is also a compelling target, where an advanced optical technique like a/LCI can offer advantages for surveillance of at-risk patients, such as those with a positive Papanicolaou smear or human papillomavirus (HPV) DNA test, but may also impact screening of the general population. Laura S. Marshall laura.marshall@photonics.com

r. Adam Wax is changing the way we look at cancer. Literally. His research at Duke University, where he is a professor in the biomedical engineering department and on the faculty of the medical physics graduate program, has focused on improving optical spectroscopy for early cancer detection as well as microscopy and interferometry techniques for biomedical applications. He has published more than 150 papers and holds seven patents. Wax also is the chairman of Oncoscope Inc., which he and colleagues founded in 2006 to explore clinical translation of Waxs technology, known as angleresolved low coherence interferometry (a/LCI). The companys noninvasive, scattered-light platform guides physicians toward sampling cells with enlarged nuclei, the primary early marker for cancer. This allows physicians to examine more tissue and to do so more quickly, taking fewer samples for microscopic evaluation and leaving healthy tissue intact. BioPhotonics caught up with Wax this summer. Q: What is your company working on right now? Wax: Oncoscope is focused on gaining FDA approval to market our a/LCI device

For more on Waxs work at Duke, visit http://bios.bme.duke.edu.

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BioPhotonics September 2013

Global Microscopy Device Market to Hit $6.2B in 2018

couraging governments and corporate enterprises across the globe to support R&D initiatives through public funding. Nanotechnology and precision manufacturing industries such as medical device and semiconductor manufacturing boosts the adoption rate of advanced microscopes, which drives the microscopy device market significantly. North America held the largest market share in 2011: more than 35 percent. A focus on R&D in nanotechnology and life sciences industries, coupled with large federal and corporate funding in this region, serves the market as a significant driver, Transparency Market Research reported. But, the firm added, the Asian microscopy device market is expected to grow at the fastest CAGR during the forecast period to become the largest market in 2018. In 2011, Olympus Corp. held the largest market share of the optical microscopes market, while Hitachi High-Technologies Corp. topped the electron microscopes market. Some of the other companies discussed in the report are Nikon Corp., FEI Co., JEOL Ltd., Leica Microsystems and Carl Zeiss. The market report covers the following technologies: optical microscopes, inverted microscopes, stereomicroscopes, phase contrast microscopes, fluorescence microscopes, confocal scanning microscopes, near-field scanning microscopes, electron microscopes, transmission microscopes, scanning electron microscopes, scanning probe microscopes, scanning tunneling microscopes, atomic force microscopes and others.

he global market for microscopy devices was valued at $3 billion in 2011 and is expected to reach an estimated value of $6.2 billion in 2018 a compound annual growth rate (CAGR) of 11 percent between 2012 and 2018 according to Microscopy Devices Market (Optical, Electron and Scanning Probe Microscopes, Semiconductor, Life Sciences, Nanotechnology, Material Sciences) Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012-2018, a new market report published by Transparency Market Research. An increasing global focus on nanotechnology research is a major driving factor behind the market growth in microscopy devices, the firm said. Nanotechnology is finding extensive applications in the field of life sciences as well as materials sciences and semiconductors, and therefore it is en-

For more information, or to purchase the market report, visit www.transparencymarketresearch.com/microscopy-market.html.

BRIEFS
Leica Biosystems of Newcastle upon Tyne, England, has acquired privately held Kreatech Diagnostics of Amsterdam, a provider of DNA uorescence in situ hybridization probes and target labeling reagents, for an undisclosed amount. Kreatech will join Leica Biosystems Advanced Staining business unit, which is based in the UK. The combined business will develop targeted biomarker menus for Leicas instrument platforms. The acquisition will enable a renewed focus on cytogenetics and anatomic pathology as well as on personalized medicine at research and drug development companies. Leica Biosystems is a provider of ThermoBrite and Bond systems for labeling tissue specimens for diagnostic interpretation in cytogenetics and pathology laboratories. Snake Creek Lasers LLC has moved its ofce and manufacturing operations to Friendsville, Pa., 20 miles west of its previous address. The new facility offers a more energy-efcient manufacturing environment, the company said. Snake Creek Lasers manufactures diodepumped solid-state lasers and laser modules for biomedical, laser projector and aiming applications. California-based Biolase Inc.s EPIC 10 softCourtesy of Yole Dveloppement.

The microfluidic device market is expected to reach $5.7 billion by 2018, and the 28 percent compound annual growth rate will be fueled largely by point-of-care applications and pharmaceutical research, according to Microfluidic applications in the pharmaceutical, life sciences, in vitro diagnostic and medical device markets, a new report from Yole Dveloppement of Lyon, France. The health care industry is moving toward personalized medicine, which means that the line between traditional markets such as pharmaceuticals and the in vitro diagnostic markets has blurred. More than ever, rapid, accurate tests are needed to increase pharmaceutical research yield and better monitor/cure patients. Microfluidics can help to fill this need. For more information or to buy the report, visit www.yole.fr.

BioPhotonics September 2013

17

RAPIDSCAN

tissue diode laser platform was awarded the gold medal for the Dental Instruments, Equipment and Supplies category at the 15th Annual Medical Design Excellence Awards (MDEA) ceremony held this year in Philadelphia. The platform is used for a variety of surgical softtissue procedures in dentistry as an alternative to conventional devices such as the high-speed drill, scalpel and electrosurge. Its 940-nm

wavelength is better absorbed by hemoglobin and oxyhemoglobin, enabling it to cut more efciently at low power with less heat and patient discomfort. Boulder, Colo.-based REO has named Newport Corp. of Irvine, Calif., as the exclusive global sales partner for its range of HeNe lasers. Under the terms of the agreement,

Newport will inventory all of REOs HeNe products, including red, green, yellow, IR and single-frequency stabilized lasers operating at 633 nm, and will handle all sales and technical support for new customers through its global sales team. HeNe lasers are used in a wide range of applications in bioinstrumentation, spectroscopy, particle measurement, holography, general research and more.

PEOPLE

IN THE NEWS
Dr. James P. Gordon, co-inventor of the maser and a seminal contributor to optics and quantum electronics, died in Rumson, N.J., on June 21. He was 85. In 1954, as a student of Charles Hard Townes at Columbia University, Gordon analyzed, designed, built and successfully demonstrated the maser (microwave amplication by stimulated emission of radiation) with Townes and Herbert Zeiger. Their ammonia maser, based on Einsteins principle of stimulated emission, laid the groundwork for the creation of the laser. Gordon spent his entire career at AT&T Bell Labs, from 1955 until his retirement in 1996; he served as head of the Quantum Electronics Research Department from 1958 to 1980. His other contributions laid the foundation for what would become the elds of lasers and optical James P. Gordon communications, and in February 2010, his broad interests attending OSAs also included providLaserFest gala in ing the theoretical Washington. Courtesy basis for optical of OSA. tweezers. tober 2005. Before that, he was the controller for GE, General Eastern Instruments for more than 10 years. ProPhotonix also announced that Raymond Oglethorpe, lead nonexecutive director, was elected board chairman, and that Mark Weidman was appointed to ll the nonexecutive director vacancy of Dietmar Klenner. Weidman is the president of Wheelabrator Technologies Inc., a subsidiary of Waste Management Inc. Alain Couder, the chairman and CEO of laser and optical components provider Oclaro Inc. of San Jose, Calif., has retired; the board of directors has named Greg Dougherty CEO. Dougherty has been a board member since 2009 and brings substantial leadership, operations, sales, marketing and general management experience in the optical and laser industries, including previous roles as chief operating ofcer of JDSU and of SDL. The company also announced that board member Marissa Peterson had been elected chairwoman. Peterson has been a board member since 2011 and brings to her new position extensive knowledge in the areas of operations, strategy and customer relations as well as experience as a senior executive of a large, complex and well-respected technology company. She was formerly executive vice president of worldwide operations, services and customer advocacy at Sun Microsystems Inc., which was acquired by Oracle Corp. in 2010. From August 2008 to the present, Peterson has been a director of health care provider Humana Inc. James Harp has been named business development strategic account manager of optical lters manufacturer Semrock Inc. of Rochester, N.Y. He will be responsible for the Idex Optics & Photonics brands high-volume optics business, which includes hard-coated sputtered coatings and BrightLine uorescence lters for Raman spectroscopy, lasers and optical systems. His most recent experience includes senior sales leadership positions with PerkinElmer.

From left, Klaus Ulbrich, Prof. Dr.-Ing. Ludger Overmeyer and Dr. Dietmar Kracht. Courtesy of LZH. Research institute Laser Zentrum Hannover e.V. (LZH) of Hannover, Germany, has restructured its management team to include a supervisory board, a board of directors and a general assembly. Dr. Horst Schrage, chief executive of the Chamber of Commerce and Industry of Hannover, will chair the supervisory board. Under the new structure, the board of directors now includes two scientic-technical executives, Dr.-Ing. Ludger Overmeyer and Dr. Dietmar Kracht, as well as commercial executive Klaus Ulbrich. Overmeyer is head of the Institute of Transport and Automation Technology of the University of Hannover in Leibniz (LUH). German scientists and industry executives will make up the newly created Scientic Directorate and the Industrial Advisory Board. Dr. Wolfgang Ertmer of LUH will serve as chair of the Scientic Directorate; Dr. Volker Schmidt of NiedersachsenMetall has been named chair of the advisory board. William Asher has been promoted to president of Princeton Instruments (PI), a Trenton, N.J.-based maker of scientic cameras, spectrographs and optics. Asher has been vice president of product development and engineering at PI for the past eight years. He previously was general manager of Balzers Optical Corp., and executive vice president of operations and engineering at Boston Advanced Technologies and On-Site Analysis.

Charles H. Townes (left), winner of the 1964 Nobel Prize in physics, and James P. Gordon in 1955 with the rst maser. Courtesy of Photonics Spectra archives.

ProPhotonix Ltd. of Salem, N.H., has appointed Philip Feeley as acting chief nancial ofcer and announced two board appointments. Feeley has served as corporate controller of ProPhotonix since joining the company in Oc-

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BioPhotonics September 2013

RAPIDSCAN

The Biozoom scanner a portable, handheld device for noninvasive transdermal analysis of antioxidants and other biomarkers in the human body from Biozoom Inc. of Agoura Hills, Calif., and Kassel, Germany, has been used by researchers at the Charit Berlin medical school and the University of Rostock in Germany to investigate workplace stress. The scanner was used to measure antioxidants in the skin of seven midwives, who were selected because of their nighttime shift work, which reportedly raises stress. The results showed a correlation between stress intensity and a decline in the midwives antioxidative status, suggesting that antioxidative status may be adversely affected by shift work. Biozoom is currently looking for licensees or other partners for its patented mobile spectroscopy technology. The companys rst commercial product is a handheld scanner for real-time spectroscopic analysis of biomarkers in the human body, such as antioxidant levels. The intellectual property behind the technology could have applications in optics, nanoltration and database management, among others, Biozoom said. The additional revenue from its intellectual property is expected to allow the company to develop new applications for its core handheld and nanoscale spectroscopy business.

Optics and optoelectronics manufacturer Zeiss of Oberkochen, Germany, has announced that it will acquire 3-D x-ray microscope provider Xradia Inc. of Pleasanton, Calif., and will rename it Carl Zeiss X-ray Microscopy Inc.; the purchase price was not released. The acquisition will complement Zeiss microscopy business, which provides light and laser scanning microscopes, electron and ion microscopes, and spectrometer modules for research applications in the life and materials sciences. Adding 3-D imaging within objects at unprecedented resolution using x-ray microscopy will now be possible and will enable new applications and make the work ow in multimodal imaging easier, said Dr. Ulrich Simon, head of the Zeiss Microscopy business group. The transaction is subject to customary closing conditions, including ling with the US competition authorities. Light-based identication and diagnostics solutions provider Visualant Inc. of Seattle has completed a funding round in excess of $5 million led by Special Situations Technology Funds of New York. Founder and CEO Ron Erickson said that, with this funding, Visualant has strengthened its balance sheet, completed the purchase of its TransTech subsidiary and obtained working capital to support the commercialization of its ChromaID technology, which collects light patterns using a panel of LEDs to authenticate and diagnose substances. The funds also will be used to scale manufacturing of its ChromaID F12 scanner lab kits as well as to build specialized ChromaID products for the development of new devices and applications in the health, security and environment sectors. BiOptix of Boulder, Colo., has announced a partnership with the University of Colorado at Denver to offer low-cost surface plasmon resonance (SPR) services to Colorado-based

Nothing is more satisfying than helping an idea come to fruition.

Kirsten Bjork-Jones, director of global marketing communications at Edmund Optics, as the company announced 45 finalists in its 2013 Higher Education Global Grant Program, which will award more than $85,000 in products to optics programs in science, technology, engineering and mathematics at nonprofit colleges and universities

researchers in academia and industry. The SPR services, offered through the research collaboration with the Biophysics Shared Resource Core Facility at the universitys Anschutz Medical Campus, are based on BiOptixs 404pi, a next-generation SPR platform that provides label-free analysis of protein-protein kinetics and protein-small molecule interactions. The Washington-based National Photonics Initiative (NPI) has applauded the US Preventive Services Task Force (USPSTF) for its recent recommendation strongly endorsing low-dose CT scans for patients at high risk for lung cancer. Currently, only 16 percent of lung cancer patients are diagnosed at a stage when the disease is most treatable and curable, making it the most deadly form of cancer in the US. CT scans can aid in detecting and identifying suspicious lung nodules early and can determine which nodules are growing at a rate consistent with the behavior of an aggressive lung cancer. Minimally Invasive Devices Inc. (MID) of Columbus, Ohio, has raised an additional $2.5 million from Radius Ventures, topping off its Series B nancing at $11.5 million. The Series B originally raised $9 million in a nancing led by Canaan Partners with participation by

the predicted value of the global market for microscopy devices by 2018; for more information, see the story on page 17

$6.2B

BioPhotonics September 2013

High Performance Lasers by Cobolt.

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Further investment in photonics will lead to additional technological breakthroughs that, like the CT scan, can allow for preventative screenings and treatments that will ultimately lead to better care and lower health-related costs for Americans.
National Photonics Initiative spokeswoman Emily Pappas
The new 2.3 million Europewide ABLADE (Advanced Bladder cancer LAser Diagnostics and thErapy) project coordinated by the University of Dundee, working with industrial partners will study whether advanced laser techniques can be used to both detect and treat the disease. The project will develop integrated laser diagnostic and therapeutic techniques exploiting the different ways cancerous and healthy cells respond to certain IR light. The project brings together experts from the universitys Medical School and Photonics and Nanoscience Group, with SPE Lazma Ltd. in Russia and 2M Netherlands BV. The grant comes from the EUs Marie Curie IAPP existing investor Charter Life Sciences. FloShield, MIDs agship laparoscopic vision system, maintains a clear eld of vision from beginning to end in laparoscopic surgery procedures. The technology easily attaches to modern HD vision systems, enabling surgery to occur without interruption, loss of vision, or scope removal for cleaning. Such removals are time-consuming, interfere with the OR teams focus, and frequently occur during critical points in surgery when optimal vision is critical, leading to surgeon frustration. Funds will be used for sales and marketing, clinical studies, the generation of outcomes data and additional product development.

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BioPhotonics September 2013

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PLAN TO VISIT
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(Industry-Academia Partnership & Pathways) program. The four-year project will see staff seconded between the university and the industry partners, and will create four new research posts. Quantum Wave Fund (QWave), a new Boston- and Moscow-based venture capital fund focused on physics and materials science, has made its rst round of investments in companies seeking to commercialize technology related to nanophotonics, metamaterials and quantum information processing. QWave will invest a total of $7 million in NanoMeta Technologies Inc. of Indiana, Centice Corp. of North Carolina, and Estonia-based Clifton. Nano-Meta Technologies creates technology that will enable a new generation of devices for powerful superresolution imaging, sensing and biomedical applications, among others. Zecotek Imaging Systems Pte Ltd., the wholly owned subsidiary of Zecotek Photonics Inc., based in Canada and Singapore, has signed a joint collaboration agreement with Tokyo-based Hamamatsu Photon ics KK to manufacture photodetectors, integrated detector modules, and associated electronics and data acquisition modules for imaging applications. The two companies will work to improve existing versions of photodetectors and imaging modules for immediate commercialization, as well as to develop new instruments for future markets. Both parties will retain full ownership of their respective patents and intellectual property. Bodkin Design & Engineering (BD&E) LLC of Newton, Mass., has received two US patents for enhancements to its nonscanning hyperspectral imaging product line. The patents support technology implemented for high-speed collection of 3-D hyperspectral images (two spatial dimensions plus spectral information), and provide exibility over a trade between spectral and spatial resolution. Operating in wavelengths ranging from the visible through the longwave IR, the systems can interface with any fore optics, from telescope to microscope, the company said. To expand its cell analysis offerings for both research and diagnostics applications, Life Technologies Corp. of New Delhi has acquired Ad vanced Microscopy Group (AMG), a developer of imaging systems for research microscopy incorporated as Westover Scientific Inc. AMGs portfolio of imaging instruments spans basic to advanced microscopy.

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Introducing

BioPhotonics, the worlds leading magazine about light and the life sciences, is now available as a FREE mobile app!

To download the app, scan this QR code, or visit www.photonics.com/apps.

Smartphones Set to Revolutionize the Medical World

but companies developing portable diagnostic devices for use in underserved settings must first consider a host of practical factors.
BY GARY BOAS NEWS EDITOR

he smartphone is an obvious choice for bringing diagnostic and other health care options to the developing world, rural areas and other underserved places. The technology offers the necessary computing power, storage and connectivity in a mobile technology that is already pervasive, even in regions that seem isolated. And the need is very real. For example, more than 70,000 operating rooms around the world do not have pulse oximeters. Unsurprisingly, perhaps, most of these are in the developing world: 41 percent of operating rooms in South America, 49

percent in South Asia and 70 percent in sub-Saharan Africa do not have adequate monitoring of blood oxygen levels reaching the brain. As for its impact on anesthesia-related injury, The consequences of this are staggering, said Dr. Loki Jrgenson, chief technology officer at LionsGate Technologies of Vancouver, British Columbia, Canada. Tens of thousands of lives are lost every year because doctors are not aware of oxygen levels during surgery. Anesthesia death rates in the developing world are up to 1000 times higher than in the developed world.

A ready supply of smartphones

One of the myriad challenges faced by developers of smartphone-based imaging devices is the very short life cycle of the phones themselves. Dr. Aydogan Ozcan has an idea as to how to address this challenge: encouraging development of a derivative smartphone market. With respect to smartphones, the motivation is entirely different with medical device companies than with consumers: Its not nearly as often driven by performance or novelty. So there could be an excellent business opportunity to provide device designers and diagnostics companies with a supply of reliable, inexpensive, older-generation phones. A company could invest in a large supply of a particular phone, Ozcan said, and based on sales predictions sign agreements with device developers to provide a supply of the phones for, say, the next ve years; to guarantee quality control; and so on. This wouldnt just serve health care applications in the developing world. A range of other mobile health applications could benet, including home testing and monitoring, which will be ever more important as our population continues to age.

LionsGate Technologies has developed a device called a Phone Oximeter to address global health needs. The device provides the same functionality as a conventional pulse oximeter using only a low-cost nger sensor and a smartphone. This image shows a research prototype of the device. Courtesy of LionsGate Technologies.

BioPhotonics September 2013

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Smartphones in Medicine

This digital universal reader from Dr. Aydogan Ozcans lab at UCLA consisting of only an inexpensive lens, two AAA batteries and three LED arrays clips onto a smartphone and can be used for all rapid diagnostic tests. Courtesy of Aydogan Ozcan.

On an even more catastrophic scale, acute respiratory infections in young children such as pneumonia, asthma and bronchiolitis are a leading cause of death around the developing world. In 2011, more than 1.3 million children under the age of 5 died of related infections. Annually, more than 150 million cases reach severe disease state and require hospitalization. However, more than 80 percent of the deaths occur outside of hospitals, largely due to the lack of critical tools and skills to identify key risk factors in the development of severe pneumonia. To address these significant global health issues, LionsGate has developed a device it calls the Phone Oximeter. It serves the same function as the conventional pulse oximeter but uses only a low-cost finger sensor running through the audio port of a smartphone. The device takes advantage of a proprietary analog-to-digital AC-coupled bridging framework called the Vital Signs DSP to enable mobile-based, software-defined sensing. This helps to drive down the cost of the technology, and thus to facilitate broader implementation in the developing world, where the massive penetration of smartphone technology will be integral to the success of the Phone Oximeter, Jrgenson said. But theres more to it than that. Beyond the technological considerations, companies face a host of challenges in developing portable diagnostic devices for use in resource-limited settings.

Not least of these: the question of funding. Raising money to devise a technology intended solely for the developing world can be difficult. Its not entirely clear from where the return on investment will come: There may be a demand for the technology, but is there a market? Who will actually pay for the technology? For this reason, some companies are looking for ways to leverage the technology, to develop it for other applications including point-of-care and home-testing applications that have a clearer path to commercialization. To minimize their own risks, said Dr. Aydogan Ozcan, a UCLA professor who has introduced a range of portable imaging and sensing devices for mobile health applications, theyre first targeting markets in the US, Europe or Japan and then focusing on another version of the same device for less-well-understood markets. At the same time, we are seeing considerable growth in social impact investment, where the return is measured not only in terms of profit, but also in terms

of the number of lives saved, the number of people reached, costs mitigated and so on. The types of investment can include grants and endowment capital, private equity and venture capital, and the social impact bond, a funding mechanism where investors are repaid only if particular social outcomes are achieved. Social impact investment can provide a host of funding opportunities for companies developing mobile health technologies, but the social impact description can apply more broadly as well. Increasing numbers of companies yes, even pure-profit companies are getting in on the game, focusing on social outcomes as well as the financial return. Its not a giveaway or solely an act of charity, Jrgenson said, but rather a viable business opportunity. A wellpositioned company can act critically and still be able to deliver a technology that otherwise would not be available or would simply cost too much. Also posing major challenges are the regulatory requirements that might

Holomic introduced its HRDR-200, the latest version of its smartphone-based rapid diagnostic reader, at the American Association of Clinical Chemistry (AACC) meeting in July/August of this year. The reader weighs less than 8 oz and thus could serve a range of mobile health applications. At the same time, the smartphone platform helps to make it and similar devices more affordable than conventional readers. Courtesy of Holomic LLC.

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BioPhotonics September 2013

Smartphones in Medicine

Sociocultural considerations

Its not enough to come up with a new solution to a given problem, said Dr. Loki Jrgenson of LionsGate Technologies. The company developing the solution must also understand the sociocultural context where it is to be applied. It must recognize the language, values and beliefs of the people who will be impacted as it provides training, process and support. In Pakistan, for example, Lady Healthcare Workers, or LHWs, are critical to maternal and reproductive health care programs, especially in medically underserved areas. Thus, understanding the ways in which women are viewed within their communities, the roles they are expected to play, and the challenges they face become essential to delivering effective health care. Similarly, when introducing new solutions, companies and other stakeholders must account for caste systems and class barriers. Other factors might include the persecution and oppression of ethnic minorities, tension and conict between tribal groups and, of course, politics and corruption.

or might not apply to cellphone-based devices. The regulatory burdens in this country are substantial, said Neven Karlovac, CEO of Holomic LLC, which is commercializing technologies invented by Ozcans research group at UCLA. They are costly and time-consuming, and there is no way around them in the medical field. Plus, with mobile health or digital health and especially with telemedicine, there is the additional difficulty that the FDA is not certain how to handle these [new technologies]. Questions, concerns Muchof the ambiguity stems from the question of what exactly requires regulation. With respect to mobile medical apps, for example,the FDA issued draft guidancetwo years ago but, as of the time of writing, had yet to provide the final guidelines. The uncertainty also extends to the smartphone platform and the nature of mobile apps: How should mobile apps be regulated? What roles do the FDA and other regulatory bodies play in the development of the rapidly growing mHealth (mobile health) sector? How can lay involvement in disease self-diagnosis and management be encouraged and supported without introducing new risks? Until recently, very little regulation was imposed on the rapidly growing medical-app industry. What apps should be regulated and why depend on certain key factors. It becomes a question of context and usage, Jrgenson said. How is it being

used? Is it invasive or noninvasive? Is the health care worker making decisions based on what it does? Are they using it to diagnose, predict, define? And the questions dont stop there. Questions and additional complications can arise from the very short life cycle of the phone: Will developers need to obtain clearance for each new generation of phone used with their devices or for the combination of phone and add-on in question, even if each component on its own has received FDA approval? And even beyond these questions are concerns about how mobile health will fit into the existing infrastructure of developing-world countries, and about whether sociocultural obstacles of any sort might exist (see sidebar). You cant just parachute in a technology and expect people to adopt it, or even understand what it means to adopt it, Jrgenson said. You have to make sure that what youre bringing to bear [in terms of the technology] doesnt have any roadblocks to implementation. In this sense, of course, the necessary steps for entering developing-world markets are largely the same as for entering markets in the developed world. Companies must do their research, both to determine the feasibility of commercializing a technology and to define the best path toward doing so. gary.boas@photonics.com

BioPhotonics September 2013

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STED Microscopy: A New Chapter in Light Imaging

When Stefan Hell invented a technique that pushed beyond the diffraction limit of light for the first time, a new field of nanoscale imaging was born. Now laboratories around the world are using STED microscopy to smash through more boundaries in fundamental science.
BY MARIE FREEBODY CONTRIBUTING EDITOR

STED imaging showing two color colocalized recordings of nuclear pore complexes in amphibian cells at resolution of 20 nm (red) and ~30 nm (green channel). The imaging is described in Biophys J 105, L01 - L03, (July 2013). Gttfert et al.

ooking back over two decades of progress, the man behind the revolutionary light imaging technique says he is very satisfied with how STED (stimulated emission depletion) microscopy has evolved our understanding of biomolecules as well as transformed the way we think about how light behaves. As a result of this development, one is now able to unravel 3-D distributions of proteins and other biomolecules in [living] cells and tissues noninvasively, and with a resolution reaching down to a few [tens of] nanometers i.e., almost to the size of the proteins themselves, said Stefan Hell, inventor of STED and a director of the Max Planck Institute for Biophysical Chemistry in Gttingen, Germany. Two decades ago, this feat was considered plainly impossible. As the patent approaches expiration Leica Microsystems GmbH of Wetzlar, Germany, is currently exclusively licensed to offer STED systems Hell believes we are about to see a new wave of advances. I anticipate the number of STED systems and STED users to grow very rapidly in the coming two years, as the basic patent on STED is expiring, he said. Although Leica has done a great job bringing STED superresolution to leading life-science laboratories around the world, competition between different companies will most naturally lead to improved performance in terms of speed, versatility and specified resolution, and make STED and STED-related microscopy methods standard in life-science laboratories around the world. Hell anticipates that STED systems will soon become available in all possible varieties: upright and inverted systems dedicated to live brain imaging, cell biology, correlation spectroscopy, the materials sciences and so on. The popularity of STED microscopy comes from its incredible potential to not only image living cells but its speed, too; it is currently the fastest nanoscopy method, delivering time-lapse images of

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60 to 80 nm in resolution at up to 80 fps. It is also remarkably flexible, having been applied to almost every area in which fluorescence plays a role, including the imaging of neurons in the brain of a living mouse. Superresolution is used more and more as a standard tool in life-science research, with the majority of users interested in subcellular details, said Jochen Sieber, product manager of superresolution technologies at Leica Microsystems. Membrane research, cell [biology] and neurobiology are the major fields of applications. In my opinion, live-cell studies are not only the most interesting, but also the most challenging discipline of superresolution microscopy, he said. STED microscopy with its ability to use common fluorescent markers like GFP [green fluorescent protein] and YFP [yellow fluorescent protein] as well as its capability to deliver superresolved images instantaneously without the need of image processing [is] by far the most suited technology for this kind of study. Christian Eggeling is a principal investigator at the MRC Human Immunology Unit and scientific director of the Wolfson Imaging Centre Oxford at the Weatherall Institute of Molecular Medicine of the University of Oxford in England. Among the advantages of STED microscopy, Eggeling highlights its targeted (scanning) readout, which delivers direct images. You see what you get without any possible bias by image analysis. In contrast, PALM [photoactivated localization microscopy]/STORM [stochastic optical reconstruction microscopy] have to use potentially biasing image reconstruction, he said. Due to its targeted readout, it can straightforward be combined with (single molecule) spectroscopy tools such as fluorescence correlation spectroscopy (STED-FCS) to highlight nanoscopic diffusion and interaction dynamics of different molecules. At the imaging center, Eggeling is introducing STED microscopy to lessexperienced biomedical researchers, and his group is using STED microscopy and other superresolution techniques to unravel nanoscopic changes at the molecular level in living cells following cellular immune responses. Infectious agents such as the influenza virus, HIV, dengue fever virus or the hepatitis C virus often cause severe symptoms and thousands of deaths each

STED and the superresolution microscopy family

The birth of superresolution microscopy began in 1994 in a laboratory at the University of Turku, Finland, when Stefan Hell came upon a new theory for feature separation. Hell realized that nanosized features can be effectively singled out from others residing within their diffraction proximity if the other features are kept dark at the time point of detection. In this case, the diffraction limit of light no longer restricts the resolving power of a microscope. This principle of keeping feature molecules transiently dark i.e., nonresponsive to the excitation light turned out to be very fundamental and hence very general. It is now at the heart of an entire arsenal of superresolution approaches, including STED, RESOLFT, SSIM (saturated structured-illumination microscopy), and PALM, STORM and GSDIM (ground-state depletion imaging). If you think about it, you realize that all current methods rely on the same basic principle for feature separation, Hell said. The uorophores of the tiny features in the near neighborhood are forced to stay off. Establishing on- and off- state uorophores for STED, RESOLFT and SSIM is created by applying a pattern of light, such as a doughnut, arrays of doughnuts or standing waves. As the pattern is scanned across the sample, uorophores of adjacent features are forced to assume the on and off states sequentially at controlled positions. In contrast, in the stochastic methods (PALM/STORM, GSDIM), the on state is assumed molecule by molecule, at random and hence unknown positions in space, Hell said. Roughly speaking, only one molecule is allowed to uoresce within the 200-nm range. The position of uorescence is then found out using the ux of photons emitted by the individual molecule, allowing a precise centroid-t, which is called localization. In short, STED microscopy locates the feature coordinate by illuminating the sample with photons, whereas in the stochastic methods, this is done with photons leaving individual molecules in the sample.

A RESOLFT image of a living mammalian cell expressing keratin plus a switchable GFP, as reported in the July 2013 issue of Nature Methods. It was recorded at low light levels using 116,000 doughnuts in parallel.

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STED Microscopy

year. Eggeling hopes that understanding the full pathway of viral infection down to the cellular and molecular level could lead to successful treatment and prevention of these infections. RESOLFT to overcome disadvantages Since a lot of laser light is needed to prepare the off states required for

STED imaging, some of this light can be accidentally absorbed, causing damage to living cells. Hells Department of NanoBiophotonics came up with a way to reduce this problem by using time-gated STED microscopy. Gated STED, which has the ability to provide sharper images at lower power, was introduced in 2011 in a paper

HeLa cells imaged by dual-color confocal (bottom) and dual-color STED image (top). Courtesy of Leica Microsystems CMS GmbH.

published in Nature Methods. The group found that by applying pulsed excitation together with time-gated detection, the fluorescence on-off contrast in CW STED microscopy is improved. This means that finer details in fixed and living cells are revealed using moderate light intensities. Leica Microsystems quickly harnessed this potential and developed a commercial implementation at high speed less than a year after publication of the first images. But the ultimate solution and the next step forward in superresolution imaging could be RESOLFT (reversible saturable or switchable optical fluorescence transitions) microscopy, which uses a different photoswitching mechanism and therefore lower levels of light for scanning and/or gated detection, necessitating less laser intensity. Although this generalized STED concept called RESOLFT has been around for more than a decade, using cis-trans isomerization for spatially targeted on-off switching has become useful only recently, due to the advent of novel reversibly

STED Microscopy

YFP-labeled keratin laments in SW-13 cells: a comparison of confocal (left), STED CW (middle) and gated STED CW imaging. Sample courtesy of Dr. Reinhard Windoffer, RWTH Aachen University, Institute of Molecular and Cellular Anatomy, Aachen, Germany. Courtesy of Leica Microsystems CMS GmbH.

switchable fluorescent proteins, such as [redshifted GFP], Hell said. A major benefit of using cis-trans isomerization and metastable on and off states is that the intensity required to turn the fluorescence off (and to create an on-off state difference in space) is lower by five to six orders of magnitude compared with STED. In fact, even light from a

compact CW laser of a few inches in size does the job. Thus, one obtains a STED-like method that is able to superresolve large fields of view (>100 3 100 m2) within a second at intensity levels that are ~100 to 1000 times lower than in PALM/STORM and ~10,000 to 100,000 times lower than in STED, Hell said. We anticipate this

concept to become extremely important in the near future, as it reconciles many of the goals of superresolution imaging. marie.freebody@photonics.com For information on lasers for STED microscopy, please see the article on page 30.

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BioPhotonics September 2013

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CW Lasers Boost Resolution for Microscopy

The growth in applications of various superresolution microscopy and nanoscopy techniques is driving a demand for small continuous-wave lasers with higher power and new wavelengths. This is the first in a two-part series on lasers for microscopy applications.
BY MATTHIAS SCHULZE AND VOLKER PFEUFER, COHERENT INC.

ince the first confocal microscope, lasers have been important illumination sources for cutting-edge microscopy techniques based on fluorescence. As these techniques have evolved, laser manufacturers have worked closely with microscope manufacturers and users to provide lasers whose output is well-matched to the specific needs. The latest trends involve optical nanoscopy and multiwavelength excitation. Thanks to optically pumped semiconductor laser (OPSL) technology, lasers ideally suited for these applications are now available. Successfully answering many impor-

tant questions about biomedicine on topics ranging from morphogenesis to drug discovery and disease pathology requires the ability to relate chemistry at the molecular level to biology at the subcellular, single-cell and completeorganism levels. To better understand the connection between single-molecule events and macroscopic structure and dynamics, researchers now are increasingly using a growing number of superresolution microscopy or nanoscopy methods that surpass the classical diffraction limit on spatial resolution.

Figure 1. Principles of STED: (a) schematic drawing of the setup of a STED nanoscope with phase plate, objective lens dichroic mirror (DC), uorescence lter (F), detector, scanning device, and excitation and STED lasers with their focal intensity distribution (right) and a representative, subdiffraction-sized observation area. (b) STED nanoscopy is based on inhibiting uorescence emission by de-exciting the excited S1 on state to the S0 off ground state via stimulated emission. Increasing the power of the STED laser drives the inhibition into saturation. (c) Combined with an intensity distribution that features at least one intensity zero, this on/off uorescence inhibition realizes subdiffraction-sized observation volumes: The volume in which uorescence emission is still allowed (green, insets) decreases with increasing STED laser power. Courtesy of Christian Eggeling of the University of Oxford, England, and Katrin Willig and Alf Honigmann of the Max-Planck Institute for Biophysical Chemistry, Gttingen, Germany.

Superresolution methods Traditionally, optical microscope resolution was limited by diffraction, resulting in a best case for spatial resolution of about half the wavelength of light (i.e., for visible light, approximately 200 to 250 nm in the X-Y plane); in the case of confocal microscopy, this is about 500 nm in the Z-direction. Unfortunately, this is larger than many of the detailed structures that biologists want to investigate, thus limiting the ability to connect the molecular and microscopic/macroscopic realms. In recent years, techniques have been developed to get past this limit; today, systems can achieve image resolution as fine as 20 nm and better. All optical superresolution or nanoscopy techniques are based on the principle of optically and reversibly preparing states of a fluorescence label that differ in their emission characteristics (e.g., a bright on and a dark off state). Based on their different mechanisms for this on/off photoswitching, optical nanoscopy methods can be loosely divided into two groups: those that directly improve microscope effective spatial resolution by deterministic photoswitching in space and time, and those that achieve the higher resolution by stochastically switching single-molecule fluorescence on and off in space. Examples of the first group include stimulated emission depletion (STED) microscopy, ground-state depletion microscopy, reversible saturable optical fluorescence transition (RESOLFT) microscopy or parallelized RESOLFT microscopy, often denoted nonlinear or saturated structured illumination microscopy. Examples of the latter include direct stochastic optical reconstruction microscopy (d-STORM) and fluorescence photoactivation localization microscopy (f-PALM). A widespread nanoscopy approach is STED, since it is flexible, fast and basi-

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cally applicable to any fluorescence label. Here, usually a TEM00 laser beam is focused to a diffraction-limited Gaussian beam waist using an objective with a high numerical aperture. Its wavelength is chosen to be near the absorption maximum of the target fluorophore. A second, longerwavelength laser beam is transformed so that it has at least one intensity zero such as a donut cross section. This second STED beam is focused into the sample co-linearly with the first. Its purpose is to deplete the population of excited fluorophores by stimulated emission, before they have time to spontaneously fluoresce. It thus darkens a specific area of the observed region of the sample. As the power of the STED beam is increased, the area that it affects expands, thus constricting the observed fluorescence to a spot much narrower than the diffraction limit (Figure 1). Pioneered by Stefan Hell and colleagues,1 gated STED using CW pulsed lasers enabled the acquisition of superresolution images with lower peak power and minimized photodamage.2 This opened a route to live-cell imaging at (to date) down to 40- to 50-nm resolution. An example of the effectiveness of gated STED can be seen in Figure 2. With stochastic-based techniques like f-PALM and d-STORM, one laser is used to stochastically drive fluorophores between the on and off states, so that only a very small, random subset of wellseparated molecules is in its on state and available to be excited by a second laser. The fluorescence spread from each of these camera-imaged point sources is then analyzed to find the centroid i.e., the point source or spatial localization, based on the point spread function of the microscope. Repetitive on/off switching brings up different random subsets in subsequent camera images for single-molecule localization. After many cycles, the microscope computer assembles all the idealized point sources into a subdiffraction image, since the localization of a single molecule can be performed with high, subdiffraction spatial precision. Higher, adjustable power These optical nanoscopy techniques are creating a need for low-noise CW lasers with higher power. In the case of the fluorescence-excitation laser, higher power can enable increased signal-to-

Figure 2. The effectiveness of STED is clear in this pair of images of uorescently tagged microtubuli in mammalian cells using a 577-nm Coherent Genesis laser to drive the STED effect: conventional confocal (left) and gated STED image (right). Courtesy of Dr. Giuseppe Vicidomini and professor Alberto Diaspro, Istituto Italiano di Tecnologia (IIT); source: G. Vicidomini et al (2013), Gated CW-STED microscopy: A versatile tool for biological nanometer scale investigation. Methods, doi: http://dx.doi.org/10.1016/ j.ymeth.2013.06.029.

noise for the resolution-sharpening techniques resulting in faster imaging. Higher power is even more of a requisite for the laser used to provide the superresolutioninducing effect. Specifically, powers in the 1- to 3-W range are needed for STED, and typically a few hundred milliwatts for PALM and STORM. These numbers are based on the typical experimental overhead and losses between the laser itself and the actual sample. And in the case of structured illumination microscopy, microscope manufacturers are looking to move up to 300-mW lasers to decrease image acquisition times, whereas early users of this method worked with as little as 100 mW.

Power adjustment is also necessary because the resolution enhancement is usually power dependent. For example, in the case of STED, increasing the power of the STED laser constrains the fluorescence excitation to an ever-smaller volume i.e., higher resolution. In the case of STORM, it is essential to balance the density of fluorophore doping and the power of the activation laser to get an optimal density of single-point emitters in each frame. These requirements are being met by lasers based on OPSL technology, such as the Sapphire and Genesis series from Coherent. For example, products having up to 3 W of output power were recently

Figure 3. Synapses at neuromuscular junctions from Drosophila melanogaster stained for bruchpilot of the presynaptic active zone (false-colored in green), glutamate receptor of the postsynaptic membrane (false-colored in red) and presynaptic membrane (false-colored in blue). Shown are the structured illumination microscopy image, left, and the wide-eld image, right. The insets are magnied views of the boxed regions. Courtesy of Jan Pielage, Friedrich Miescher Institute, Basel, Switzerland; imaged on a Zeiss Elyra S.1.

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CW Lasers

introduced specifically to meet the growing needs of superresolution microscopy. Moreover, output power for these lasers can be smoothly adjusted between 10 and 100 percent of maximum with no effect on output beam characteristics. OPSL technology is easy to powerscale because of the absence of thermal lensing in the thin semiconductor gain chip. Diode-pumped solid-state lasers

are also used for microscopy, but their power-dependent thermal lensing makes it difficult to adjust power without compromising the beam quality, shifting the beam direction and changing its divergence. These lasers would therefore require the cost and complexity of some type of variable attenuator to be used with most nanoscopy techniques.

New wavelengths Another key trend is the growing demand for new laser wavelengths, and particularly longer wavelengths, to optimally excite many of the new fluorophores. These include the mFruit series of fluorescent proteins and a host of new green, yellow and orange excited dyes originally developed for multichannel flow cytometry applications. These fluorophores are valuable alternatives to older fluorophores such as GFP (green fluorescent protein). And, as with wide-field microscopy, new nanoscopy methods often use combinations of multiple fluorophores to permit simultaneous mapping or probing for more than one type of structure or biochemical (Figure 3). Fortunately, wavelength scalability is another key advantage of OPSL technology; lasers can be fabricated for any arbitrary output wavelength across much of the visible and near-UV spectrum, merely by tweaking the design of the gain semiconductor chip. For example, new lasers at 588 nm and 594 nm were recently introduced for exciting orange fluorophores. Other models at 550 nm have also been developed, as this wavelength can be used to simultaneously excite green dyes and several new yellow fluorophores with a single laser. Yet another new OPSL wavelength is 568 nm, designed to provide the first solid-state replacement of krypton ion lasers formerly used at this wavelength. In contrast, diode-pumped solid-state lasers can reach only a few fixed wavelengths and often rely on complex frequency-mixing schemes that can add cost and potentially reduce reliability. And, although a growing number of visible wavelengths can be obtained directly from laser diodes, these do not have the power or beam quality to support demanding optical nanoscopy methods. Long-lived ber Fiber delivery of laser light is another trend common to all types of laser microscopy, not just optical nanoscopy methods. Fiber delivery allows the laser(s) to be placed away from the microscope, which simplifies mechanical design and thermally decouples the microscope from the laser. In addition, single-mode, polarization-preserving fiber acts as an extended spatial filter, yielding a perfectly round Gaussian beam from its output facet. In contrast, using macroscopic optics for

BioPhotonics September 2013

CW Lasers

multiangle mounts and their potential for long-term loss of optimum alignment. Combining ber-coupled lasers With both conventional and optical nanoscopy techniques now often using multiple excitation lasers, instrument builders and end users are increasingly faced with the major challenge of combining multiple fiber-coupled lasers. The stringent optomechanical requirements for single-mode fiber beam coupling have traditionally made combining multiple fiber-coupled lasers a complex task. Typically, this necessitated the cost and complexity of aligning collimating lenses, dichroic beamsplitters, polarizers and wave plates at each successive laser wavelength. A new plug-and-play combiner, the Obis Galaxy from Coherent, simplifies this problem. This passive device can integrate up to eight different laser wavelengths using a patent-pending combination of a minimum number of refractive optical components, together with a novel fiber having constant numerical aperture

over the entire 405- to 640-nm range. This reduces the task to simple plug and play with snap-in (FC/UFC) fiber connectors. Meet the authors
Matthias Schulze is director of marketing in the life sciences at Coherent Inc. of Santa Clara, Calif.; email: matthias.schulze@ coherent.com. Volker Pfeufer is a senior product line manager at Coherent; email: volker. pfeufer@coherent.com. The authors wish to acknowledge the assistance of Dr. Christian Eggeling (principal investigator at the Human Immunology Unit and scientific director at Wolfson Imaging Centre at Weatherall Institute of Molecular Medicine at the University of Oxford) in the form of personal communications about optical nanoscopy techniques and specifically the STED technology.

Figure 4. The Obis Galaxy ber combiner from Coherent uses eight wavelength-dedicated plugand-play input sockets to combine multiple lasers in a single output ber. Courtesy of Coherent.

beam delivery can lead to beam distortion, astigmatism and other compromises in original beam quality. The traditional approach for OEMs and end users was to couple the laser into the single-mode fiber using mounts with up to 6 of freedom that had to be individually optimized and then locked. Because the fiber core diameter was only 3.5 m, the process required an experienced user and could take tens of minutes, often resulting in a non-optimum alignment. Moreover, the final alignment was vulnerable to creep and misalignment due to vibrations or changes in ambient temperature. In response, some laser manufacturers began to offer laser heads that were fiberpigtailed at the factory. However, these products had lifetimes as short as hundreds of hours, because as lasers were pushed to higher power, the small dimensions of the input and output facets led to deterioration and early failure, meaning the entire laser/fiber component would have to be replaced. Also, the coupling efficiency could often change with operating temperature in these earlier laser/fiber assemblies, meaning loss of output power and a reduced polarization extinction ratio. And temperature changes during transport or operation could even result in a permanent misalignment/detuning of the laser. A special fiber now solves the longevity problem; its input and output facets are significantly larger than conventional single-mode fiber, yet it still functions as single-mode and polarization-preserving. As a result, fiber-coupled lasers using this fiber exhibit typical lifetimes of 10,000 hours or more, even at the multiwatt power level. Just as important, in the latest fiber-coupled CW lasers for microscopy, this fiber is brought directly into the heart of the laser, where it is permanently fixed, eliminating the cost of multiaxis,

References
1. S.W. Hell (2007). Far-field optical nanoscopy. Science, Vol. 316, pp. 1153-1158. 2. G. Vicidomini et al (2011). Sharper lowpower STED nanoscopy by time gating. Nat Methods, Vol. 8, pp. 571-573.

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Bright Lights in the Bio(photonics)sphere

As students around the world head back to school, lets take a moment to acknowledge some of the work being carried out by the under-20 crowd. Last month, in a news story, we highlighted the work of Arjun Nair, the 16-year-old high school student from Calgary, Alberta, Canada, who won top national honors in the 2013 Sanofi BioGENEius Challenge Canada (SBCC) for an experimental therapy that deploys gold nanoparticles in the fight against cancer. But Nair isnt the only teen working toward biophotonics advances. The following three young people are among those who will likely help to shape the future of biophotonics and, in so doing, help shape all our futures.
Laura S. Marshall laura.marshall@photonics.com STEM Outreach: Ritankar Das At 18, Das is the youngest University Medalist in the University of California, Berkeleys history; the annual award includes a $2500 scholarship and is given to the years top graduating senior. In his mere three years at Berkeley, Das doublemajored in bioengineering and chemical biology with a minor in creative writing. Next, hes off to Oxford University to pursue a masters degree in biomedical engineering, and after that he will take up study at MIT, where he has already been admitted to the Ph.D. program in chemistry. Das is also the founder and chairman of See Your Future, a student-run nonprofit that uses digital learning techniques such as visual demonstrations on YouTube and tutoring via Skype to attract disadvantaged students to careers in STEM (science, technology, engineering and mathematics) fields. The program operates in the Berkeley community currently, but Das would like it to expand nationwide. He also has formed a campus chapter of the American Chemical Society, according to the school, and founded the Berkeley Chemical Review. He and Marcin Majda, professor and undergraduate dean in the College of Chemistry, are developing a book on education reform with contributions from Fortune 50 CEOs, Nobel laureates, US cabinet secretaries and university presidents. The University Medal is not his first award. Das has won more than 40 awards, totaling more than $300,000, including a graduate research fellowship from the National Science Foundation, and he has conducted research projects at the likes of the Energy Biosciences Institute and the US Department of Energy. Courtesy of Michael Barnes/UC Berkeley.

Finding Cancer Cells: Kelly Zhang For her method to help surgeons visualize tumor margins by staining cancer cells selectively with fluorescent dyes, the 17-year-old Zhang was named a finalist in Intel Science Talent Search (Intel STS) 2013. She is a student at The College Preparatory School in Oakland, Calif. The Intel STS is a precollege science competition; alumni have made extraordinary contributions to science and hold more than 100 of the worlds most coveted science and math honors, including the Nobel Prize and the National Medal of

Science. The Intel STS recognizes and rewards 300 students, as well as their schools, as semifinalists each year. From that pool, 40 finalists are invited to Washington every March for final judging as well as to display their work to the public, meet with notable scientists and compete for $630,000 in awards, including the top award of $100,000. For her entry, Zhang adapted drugdelivery nanotechnology concepts to derive a nanoscale imaging agent from a combination of the protein albumin and fluorescent dye, according to Intel. She

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then incubated a variety of cell lines with the new stain and found that tumor cells became more luminous than healthy cells. She believes her study will contribute to the improvement of cancer imaging techniques for surgeons resecting tumors. Zhang also has created BioLabScope, a website that seeks to spread the world of science to high school students. The site (www.biolabscope.com) features videos on basic lab science and biology applications that arent always taught in high school classrooms. The photonics world is full of achievers of all ages. The following list includes award winners from all corners of the eld. These awards were announced within the past year. Dr. Mark Foster, an assistant professor in the department of electrical and computer engineering at Johns Hopkins Whiting School of Engineering, received a five-year, $400,000 National Science Foundation Faculty Early Career Development (CAREER) Award for his high-speed IR imaging system, which is designed to continuously record images at a rate of more than 100 million fps 100 times more rapidly than current technology allows. It could eventually be used for cell screening for disease prediction or to observe a scientific phenomenon that occurs at a very fast rate. Dr. Bjrn Lillemeier and Dr. Axel Nimmerjahn of the Waitt Advanced Biophotonics Center each received $1.5 million from the National Institutes of Health (NIH) as two of only 51 recipients of the 2012 NIH Directors New Innovator Award. Lillemeier develops optical microscopy techniques that visualize the molecular organization of plasma membrane signaling in live cells and will use the award to boost his understanding of how cellular communication is controlled in space and time. Nimmerjahn creates and develops research tools for dissecting glial cell function in both the intact healthy and the diseased brain. He will use the prize to support his research into microglia, resident immune cells in the brain involved in all brain pathologies. Dr. James J. Wynne, Dr. Rangaswamy Srinivasan and Dr. Samuel Blum, all IBM scientists, received the US Na-

Liaising for Light: Jana Huisman As a young girl in the Netherlands, Jana Huisman had a curiosity about the world around her that led her to study physics. That same curiosity now drives the 18-year-olds interest in photonics, and shes putting it to good use in her new appointment as Young Ambassador for Photonics Education. Huisman, now in her third year of undergraduate studies at the University of Bonn in Germany, was officially given the role this spring by European Commissioner Neelie Kroes at the annual meeting of Photonics21, the European technology platform for photonics. The position was created by Photonics21 and the European Commission. In her undergraduate work, Huisman is studying the interaction between light and matter. Theres a connection to life, she said. There are photonics applications in environmental and health sciences, and with photovoltaics, we can imitate nature by getting energy from sunlight. The ambassadorship was created to help stimulate interest in studying photonics, one of Europes key enabling technologies. The European photonics industry makes up 20 percent of the global market, and the European Union is home to more than 5000 SMEs (small- and medium-sized enterprises) in the sector, Kroes pointed out at the meeting. At the award ceremony, Kroes asked Huisman to join, as an observer, her group of Young Advisors on the Digital Agenda, which provides insight into digital communication technologies and applications. In her role, Huisman will visit three European research institutes this year to observe photonics research in action. Im looking forward to learning about what they are doing, bringing my enthusiasm, and then writing and blogging about it hopefully, I can transmit some of that enthusiasm to other students, Huisman said.

Jana Huisman (center) accepts the Young Ambassador for Photonics Education award from Photonics21 President Dr. Michael Mertin and European Commissioner Neelie Kroes at the Photonics21 annual meeting. Courtesy of Photonics21.

tional Medal of Technology and Innovation from President Barack Obama for the development of excimer lasers for medical use. The award recognizes the impact that excimer lasers have made in medical procedures such as lasik eye surgery. Dr. Tomasz Tkaczyk, a bioengineering assistant professor at Rice University, won Edmund Optics 2012 Norman Edmund Inspiration Award for his low-cost,

portable optical systems for global health applications. Tkaczyk received $5000 in Edmund Optics products, in addition to the $10,000 in goods he received from the company as a first-place winner in its 2012 Higher Education Grant Program. His work involves advancing microscopy for in vivo detection of cancer and infectious diseases.

BioPhotonics September 2013

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Ocelot LWIR Lenses

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Two new microscope cameras from Leica Microsystems are equipped with sensors for live imaging up to 30 fps and a USB 3.0 interface for fast data transfer. The Leica Application Suite (LAS) and the LAS Advanced Fluorescence software provide image acquisition, analysis and documentation for routine bright-eld or uorescence applications. The DFC3000 G, suited for routine uorescence applications, features a passive cooling architecture and correlated pixel double sampling for clear uorescence signals and low background noise. With its CCD sensor, it is suitable for low-light situations. The DMC2900 features a 3.1-megapixel CMOS sensor for bright-eld applications in research, industry and life sciences. news@leica-microsystems.com

Universal Diode Lasers c

BrixX ps series compact universal diode lasers from Omicron-Laserage Laserprodukte GmbH can be pulsed in the picosecond range as well as operated in CW and modulated mode. With completely integrated driver electronics, high-precision temperature regulation and beam-shaping optics, the lasers can emit ultrashort pulses down to 50 ps, pulses in the nanosecond range, and fast analog and digital-modulated CW emission. Diodes with up to 1500-mW optical output power and wavelengths between 375 and 2300 nm can be used in the systems. CW operation is possible with up to 100 MHz digital and up to 1 MHz analog modulation. Applications include microscopy, spectroscopy and uorescence analysis. r.dietzl@omicron-laser.de

Ti:Sapphire-Pumped OPO m

Z-Axis Elevator Stage

Made for adapting onto the top of standard X-Y microscopy stages, the PZ 300 AP Z-axis elevator stage from piezosystem jena has two parallel working piezo drives that allow the centrically located microscopy probe adapter to be lifted symmetrically. The device is suitable for laser scanning microscopy and other techniques such as uorescence, superresolution and image processing. The stages at design can be used for standard microscopes or for inverted stands. The monolithic stage design is free of mechanical play and offers a travel range of up to 300 m, a step resolution of 2.5 nm and a settling time under a load of a few milliseconds. sales@piezojena.com

Available from Radiantis, the Oria IR Ti:sapphire-pumped optical parametric oscillator (OPO) is suited for nonlinear microscopy and spectroscopy. Fully automated, it provides wavelength coverage with high average power in the near- and mid-IR and is suitable for applications where short pulse durations, high beam pointing and high power stability are required in the IR. Pumped by a mode-locked femtosecond MHz Ti:sapphire oscillator, it offers broad tunability. Two separate pump and signal output ports provide independent tuning of the pump wavelength from 720 to 810 nm and of the signal wavelength from 1000 to 1580 nm. The system is sealed and operation is hands-free. info@radiantis.com

Spectra-Physics, a Newport Corp. brand, has extended the Excelsior One CW laser series with the release of three new wavelengths: 515, 553 and 594 nm. The expanded series of 14 diode-pumped solid-state and direct-diode lasers is suitable for a variety of uorescence-based bioinstrumentation applications, including ow cytometry, confocal microscopy and DNA sequencing. The 515and 553-nm models deliver output power of 50 mW, and the 594-nm instrument has an output power of 100 mW. The laser cavity and control electronics are integrated into a single, compact package. The instruments deliver TEM 00 mode quality and low optical noise for a high signal-to-noise ratio. elizabeth.peartree@spectra-physics.com

CW Laser Series c

Imaging Software m

The HCS Studio suite of high-content imaging and analysis software from Thermo Fisher Scientic Inc. allows researchers to interact with and analyze cell images and corresponding data. The software features built-in intelligence and enhanced usability to analyze multiple parameters simultaneously and to generate data reliably and repeatedly. Tools include icon-driven interfaces, step-bystep work ows and a desktop navigator. An automated plate-handling capability allows the proprietary Orbitor RS plate mover to be used in conjunction with either the companys ArrayScan XTI high-content analysis reader or its CellInsight NXT high-content screening platform. analyze@thermosher.com

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BREAKTHROUGHPRODUCTS

Label Printer

equipment. Text, graphics and linear or 2-D bar codes can be laser-ablated onto a range of adhesive-backed label materials. Finished labels do not require lamination to withstand extended exposure to UV light, chemicals, liquids or temperatures of up to 300 C. sales@primera.com

power from 0.9 to 75 mW. They provide a suitable beam source for OEM applications including medical alignment. sales@oe-company.com

UV Fiber Assemblies
Assembled patch cords based on UV bers

Laser Diode Collimators

Instead of ink, Primera Technology Inc.s DL500 label printer uses a specially designed laser diode along with high-precision, matched optics. The combination has never before been used in a roll-fed, desktop laser label imager, the company said. The process allows fast in-house production of highly durable labels for rough-service applications, including UDI (unique device identication) labels for medical devices and health care

New laser diode collimators from The Optoelectronics Co. have high alignment accuracy and are aimed at OEMs and system integrators who use laser-based technology in their products. The devices measure 6 3 8 mm and offer an elliptical output beam with a collimated diameter of 2.5 3 2 mm, which is bore-sighted for greater precision. By adjusting the distance between the laser diode and the collimating lens, the factory-xed beam can be set for a collimated or focused output. The collimators are available in lasing wavelengths from 635 to 852 nm, with output

are available from Laser Components GmbH for applications including uorescence spectroscopy, medical technology and UV illumination. At very short wavelengths, solarization-resistant bers with low UV damage are recommended. From 190 to 240 nm, damage to conventional optical bers leads to losses in transmission and even blinding of the ber (solarization). The companys FBPI ber features a high solarization resistance and has suitable transmission properties across a wavelength range from 200 to 2100 nm. The buffer material for the UV bers is mostly

Piezo Stages Positioning Technology

Lambda XL
Extended Life Light Source
The Lambda XL is a broad spectrum, highly stable light source (1% peak-to-peak uctuations) with an expected lamp life of 10,000 hours. The light intensity can be adjusted to different levels of attenuation and the liquid light guide connection assures output uniformity in the eld of view.

www.piezosystem.com

Z-Elevator Stage for Probe Alignment

Nanopositioning Microscopy Z-Stage

Standard microscopy copy copy probe adapters High scanning accuracy ccuracy Low prole design n

FEATURES
10,000 hour expected life Highly stable No high-voltage pulse No alignment necessary Built-in driver for lter wheel and shutter Adaptable to most microscopes

DE (+49) 36 41 66 88 0 US (+1) 508 634 - 6688 info@piezojena.com

PHONE: 415. 8 8 3.0128 | FA X : 415. 8 8 3.0 572 EM A IL : INFO @SU T T ER .COM | W W W. SU T T ER .COM

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BioPhotonics September 2013

BREAKTHROUGHPRODUCTS

polyimide, which can withstand temperatures of up to 300 C. info@lasercomponents.com

Cooled Scientic Cameras

incident laser power and the potential for pumping of adjacent uorophores within a sample, resolving population data that previously may not have been obtainable. customer.service@jdsu.com

Multimode Detection Platform

The SpectraMax i3 multimode detection platform from Molecular Devices is a stand-alone reader that can be combined with various proprietary modules for added capabilities, including time-resolved uorescence, uorescence polarization and assay screening. The platforms base system features an integrated optical system enabling top and bottom reads for 6- to 384-well microplates and three broad detection modes: luminescence, absorbance and uorescence. The patented user-exchangeable cartridge design expands the systems detection capability, enabling uorescence and bright-eld cellular imaging. Data from the SpectraMax i3 system is captured and analyzed using the proprietary SoftMax Pro Software. info@moldev.com

The VS line of thermoelectrically cooled scientic cameras from Artemis CCD Ltd. is aimed at OEMs of integrated imaging, spectroscopy and other low-light-detection systems. The line now includes a version with an integrated lter wheel controlled by the inclusive software package. The cameras feature CCD sensors from 1.4- to 9.2-megapixel resolution in both monochrome and color and offer low-noise mode and a liveview option for real-time focusing. They provide an I/O port for external triggering and sequencing, extended cooling with a 35 C delta, up to 8 3 8 binning and 16-bit digitization at 12 MP/s. chris.andrews@artemisccd.com

actuator is optimized for OEM instrumentation applications in elds including precision optics, the life sciences, medical design, bio-/ nanotechnology, and microuidics/nanodispensing. Customer-specic adaptations can be provided. info@pi-usa.us

Color Line-Scan Camera

Luminescence Imaging

Lasers for Industry and Science

JDSU s two new series of lasers, ST and FCD561, are geared toward the manufacturing and life sciences markets, respectively. The ST series ber laser pump, powered by a proprietary diode laser chip, offers 140 W of output power within a 106.5-m core to speed metal cutting and shaping processes. Optical and mechanical design innovations enable thermal management and ultralow optical loss. The FCD561 frequency-converted-diode CW lasers enable targeted uorescence pumping of specic uorophores at their ideal absorption band, minimizing the

Aspect Imaging s LumiQuant is a software and hardware solution for co-registering and measuring 3-D luminescence imaging with the Bruker Icon compact MRI system. It uses a multimodality cassette that allows a mouse to be imaged in an optical instrument and then moved and imaged in the MRI system without perturbation. LumiQuant is called as a routine from inviCROs VivoQuant software. The package uses a proprietary set of algorithms to create a 3-D distribution of luminescence signal. LumiQuant seeks to resolve this obstacle through quantitation of 3-D luminescence/MRI and disease phenotyping. info@aspectimaging.com

e2v has launched two color versions of its ELiiXA+ line-scan cameras. The new 16k/8k and 8k/4k cameras offer a true-color mode for inspection of food, pharmaceuticals and more. The cameras incorporate a CMOS pixel architecture combining an advanced signal-to-noise ratio (even when integration times are short or illumination is limited) with multiline architecture to boost sensitivity by sequentially integrating the same object line with full exposure control. The cameras provide up to 95,000 line rates per second, high response and an extremely low noise level. The 5-m-pixel size is arranged in four active lines; the dual-line lter conguration allows operation in several modes. sylvie.mattei@e2v.com

BREAKTHROUGHPRODUCTS

Piezo Linear Actuator

Physik Instrumente (PI) has added the P-604 model to its PiezoMove family of motionamplied, exure-guided piezo linear actuators. Providing a displacement of 300 m and measuring only 20 3 13 3 4 mm, the

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.

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APPOINTMENTS
CALL FOR PAPERS
Biophysical Society 58th Annual Meeting February 15-19 Deadline: Abstracts, October 1 San Francisco. Authors are encouraged to contribute to the Biophysical Society 58th annual meeting, which will address a variety of areas, including optogenetics, diffraction and scattering technologies, single-molecule spectroscopy, optical microscopy and superresolution, scanning probe microscopy, and advances in UV-VIS-IR spectroscopy. Presentation format options are platform, poster or member-organized session. Contact: Biophysical Society +1 (240) 290-5600 society@biophysics.org www.biophysics.org ISBI 2014 April 28-May 2 Deadline: Submissions, October 1 Beijing. Papers are sought for the IEEE International Symposium on Biomedical Imaging. Organizers encourage high-quality results on all aspects of biomedical imaging, including image formation, processing and analysis; performance assessment; hybrid imaging; and imaging informatics. Submissions on anatomical, functional, cellular and molecular imaging, either basic or translational, are encouraged. Four-page papers for oral or poster presentation will be published on IEEE Xplore. There is a deadline of Dec. 1 for one-page late-breaking items. Contact: d.bernstein@ieee.org http://biomedicalimaging.org/2014 Laser 2014 April 2-6 Deadline: Abstracts, October 14 Phoenix. Researchers are invited to submit abstracts for presentation at Laser 2014, the 34th ASLMS Annual Conference, an event of the American Society for Laser Medicine and Surgery Inc. Last years conference addressed areas including cutaneous laser surgery, photobiomodulation, photodynamic therapy, lasers in dermatology, interstitial laser therapy, and experimental and translational research. Contact: ASLMS +1 (715) 845-9283 information@aslms.org www.aslms.org

OCTOBER

DoKDoK 2013 (Oct. 6-10) Suhl, Germany (doctoral students conference for the discussion of optical concepts). Contact Matthias Falkner, Friedrich Schiller University Jena, dokdok@uni-jena.de; www.asp.uni-jena.de/ dokdok.

14th International Young Scientists Conference, Optics and High Technology Material Science SPO 2013 (Oct. 24-27) Kiev, Ukraine. Contact SPO Organizing Committee, Taras Shevchenko National University of Kiev, +380 44 526 2296; spo_tsknu@ukr.net; http://spo.univ.kiev.ua. MIPPR2013: Eighth International Symposium on Multispectral Image Processing & Pattern Recognition (Oct. 26-27) Wuhan, China. Contact Fa-xiong Zhang, +86 27 875 40131; mippr@126.com; http://iprai.hust. edu.cn/mippr. MOC 13: 18th Micro-Optics Conference (Oct. 27-30) Tokyo. MOC 13 Registration Desk, Event & Convention House Inc., +81 3 3831 2601; regdesk@moc2013.com; www.moc2013.com. Advanced Solid-State Lasers; Application of Lasers for Sensing & Free Space Communication (LS&C); and Mid-Infrared Coherent Sources (MICS) (Oct. 27-Nov. 1) Paris. Contact The Optical Society, +1 (202) 223-8130; info@osa.org; www.osa.org.

l Neuroscience 2013 (Nov. 9-13) San Diego. Contact Society for Neuroscience, +1 (202) 962-4000; www.sfn.org.
Laser World of Photonics India (Nov. 12-14) Mumbai, India. Contact Bhupinder Singh, MMI India Pvt. Ltd., +91 981 1090046; bhupinder.singh@mmi-india.in; http:// world-of-photonics.net/en/laser-india/start. Asia Communications and Photonics Conference (ACP) and IPOC 2013: International Conference on Information Photonics and Optical Communications (Nov. 12-15) Beijing. Contact acp2013@bupt.edu.cn; www.acpconf.org. Compact X-ray and EUV Light Sources Incubator Meeting (Nov. 13-15) Washington. Contact The Optical Society, +1 (202) 2238130; info@osa.org. www.osa.org. 2013 International Conference on Optical Instrument and Technology (OIT 2013) (Nov. 17-19) Beijing. Contact Liquan Dong, +86 10 68912559; kylind@bit.edu.cn; www.oe-oem. org/oit. Visual Communications and Image Processing (VCIP) Conference (Nov. 17-20) Kuching, Malaysia. Contact Chee Seng Chan, University of Malaysia, cs.chan@um.edu.my; www.vcip2013.org. APDSC 13: Asia-Pacic Data Storage Conference (Nov. 20-22) Hualien, Taiwan. Contact APDSC 13 Secretariat, Taiwan Information Storage Association, +886 3 5918350; www.tl.ntu.edu.tw/2013/apdsc13. 2013 International Conference on Adaptive Science and Technology (ICAST) (Nov. 25-27) Pretoria, South Africa. Contact Olalekan Samuel Ogunleye, Meraka Institute CSIR, +27 12 84 2783; oogunleye@csir.co.za; www.icast-conference.org.

l Frontiers in Optics 2013/Laser Science XXIX (Oct. 6-10) Orlando, Fla. Contact The Optical Society, +1 (202) 416-1907; custserv@ osa.org; www.osa.org.
International Congress on Applil ICALEO cations of Lasers & Electro-Optics (Oct. 6-10) Miami. Contact Laser Institute of America, +1 (800) 345-2737 (US); +1 (407) 380-1553 (international); icaleo@lia.org; www.lia.org. 3DTV-CON: Vision Beyond Depth (Oct. 7-9) Aberdeen, Scotland. Contact Jacqueline Bergstrom, AECC, +44 1224 330 407; jberg strom@aecc.co.uk; www.3dtv-con.org.

Thierry Guermonprez, +33 1 44 31 83 21; thierry.guermonprez@gl-events.com; www. enova-event.com. Fourth Asia-Pacic Optical Sensors Conference 2013 (APOS) (Oct. 15-18) Wuhan, China. Contact Conference Secretariat, Wuhan University of Technology, +86 27 87651850; info@apos2013.org; www.apos2013.org.

l Opto 2013 (Oct. 8-10) Paris. Contact

l LEDs & the SSL Ecosystem 2013: Phase 2, the Path to Prot (Oct. 28-29) Boston. Contact Brian Santos, Smithers Apex, +1 (207) 781-9618; bsantos@smithers.com; www.ledsconference.com.
2013 IEEE International Topical Meeting on Microwave Photonics (MWP) (Oct. 28-31) Alexandria, Va. Contact info@mwp2013.org; www.mwp2013.org.

l Photonex (Oct. 16-17) Coventry, England. Contact Clare Roberts, Xmark Media Ltd., info@xmarkmedia.com; +44 1372 750 555; www.photonex.org.
ARCFO-2013: All-Russian Conference on Fiber Optics (Oct. 16-18) Perm, Russia. Contact Galina Shakirova, technical secretary, shakirova@ppk.perm.ru; +7 342 240 05 26; www.bopt.ru/rfo2013/index_e.html. Establishing and Providing Light Microscopy Core Facility Services Course (Oct. 23-24) London. Contact Alice Pyper, Royal Microscopical Society, +44 1865 254760; alice@ rms.org.uk; www.rms.org.uk.

l Renewable Energy and the Environment (Nov. 3-7) Tucson, Ariz. Includes Optical Instrumentation for Energy and the Environment (E2); Optical Nanostructures and Advanced Materials for Photovoltaics (PV); Optics for Solar Energy (SOLAR); SolidState and Organic Lighting (SOLED); and Freeform Optics. Contact The Optical Society, +1 (202) 223-8130; info@osa.org; www.osa.org.

NOVEMBER

l Indicates shows Photonics Media will be attending.

Complete listings at www.photonics.com/calendar.

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BioPhotonics September 2013

ADVERTISERINDEX
Photonics Media Advertising Contacts Please visit our website Photonics.com/mediakit for all our marketing opportunities. Ken Tyburski Director of Sales Voice: +1 (413) 499-0514, Ext. 101 Fax: +1 (413) 443-0472 ken.tyburski@photonics.com New England, FL, Rocky Mountains, AZ & NM Rebecca L. Pontier Associate Director of Sales Voice: +1 (413) 499-0514, Ext. 112 Fax: +1 (413) 443-0472 becky.pontier@photonics.com NY, NJ & PA Timothy A. Dupree Regional Manager Voice: +1 (413) 499-0514, Ext. 111 Fax: +1 (413) 443-0472 tim.dupree@photonics.com Northern CA, Pacic Northwest, AK, NV, Yukon & British Columbia Joanne C. Mirke Regional Manager Voice: +1 (413) 499-0514, Ext. 226 Fax: +1 (413) 443-0472 joanne.mirke@photonics.com Central CA, Eastern Canada & South Central US Maureen Riley Moriarty Regional Manager Voice: +1 (413) 499-0514, Ext. 229 Fax: +1 (413) 443-0472 riley.moriarty@photonics.com Europe, Israel, Southeastern US, Midwest, Southern CA & HI Matt Beebe Regional Manager Voice: +1 (413) 499-0514, Ext. 103 Fax: +1 (413) 443-0472 matt.beebe@photonics.com Austria, Germany & Liechtenstein Olaf Kortenhoff Voice: +49 2241 1684777 Fax: +49 2241 1684776 olaf.kortenhoff@photonics.com Asia (except Japan) Hans Zhong Voice: +86 755 2872 6973 Fax: +86 755 8474 4362 photonicsasia@gmail.com Japan Scott Shibasaki Voice: +81 3 5225 6614 Fax: +81 3 5229 7253 s_shiba@optronics.co.jp Reprint Services Voice: +1 (413) 499-0514 Fax: +1 (413) 442-3180 editorial@photonics.com Mailing addresses: Send all contracts, insertion orders and advertising copy to: Laurin Publishing PO Box 4949 Pittseld, MA 01202-4949 Street address: Laurin Publishing 100 West Street Pittseld, MA 01201 Voice: +1 (413) 499-0514 Fax: +1 (413) 442-3180 advertising@photonics.com

Andor Technology plc ..................................................................................................................................................... 36 www.andor.com Applied Scientic Instrumentation Inc. ......................................................................................................................... 6 www.asiimaging.com

Cobolt AB .......................................................................................................................................................................... 20 www.cobolt.se Coherent Inc. ...................................................................................................................................................................... 3 www.coherent.com

Edmund Optics ................................................................................................................................................................. 32 www.edmundoptics.com Esco Optics ....................................................................................................................................................................... 29 www.escooptics.com

i l

Iridian Spectral Technologies Ltd. ................................................................................................................................. 14 www.iridian.ca Lumencor Inc. .................................................................................................................................................................. 19 www.lumencor.com Mad City Labs Inc. ........................................................................................................................................................... 29 www.madcitylabs.com MPB Communications Inc. ............................................................................................................................................. 28 www.mpbcommunications.com

NKT Photonics A/S ....................................................................................................................................................... CV2 www.nktphotonics.com Novotech Inc. ................................................................................................................................................................... 36 www.novotech.net

o p

Optical Building Blocks Corp. ........................................................................................................................................ 33 www.obbcorp.com

Photonics Consortium ...................................................................................................................................................... 7 Photonics Media ........................................................................................................................................................ 22, 36 www.photonics.com PI (Physik Instrumente) L.P. ............................................................................................................................................ 39 www.pi-usa.us PicoQuant GmbH ............................................................................................................................................................. 13 www.picoquant.com piezosystem jena GmbH ................................................................................................................................................. 38 www.piezosystem.com Prior Scientic Inc. .......................................................................................................................................................... 20 www.prior.com Prism Awards ..................................................................................................................................................................... 5 www.prismawards.org

Raptor Photonics Ltd. ...................................................................................................................................................... 15 www.raptorphotonics.com Reynard Corporation ....................................................................................................................................................... 25 www.reynardcorp.com

Spectra-Physics, A Newport Corporation Brand ..................................................................................................... CV4 www.newport.com SUTTER INSTRUMENT ................................................................................................................................................... 38 www.sutter.com

The American Society for Cell Biology ...................................................................................................................... CV3 www.ascb.org Toshiba Imaging Systems Division ............................................................................................................................... 36 www.toshibacameras.com

Xmark Media Ltd. ............................................................................................................................................................ 21 www.photonex.org

BioPhotonics September 2013

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POSTSCRIPTS

Based on reectance spectroscopy, the Biozoom skin scanner system could help people measure and manage workplace stress. Courtesy of Biozoom Inc.

Skin scan can quantify stress levels

xactly how stressed out are you? Can you put a number on it? Evaluating stress levels could be easier, more objective and, well, less stressful, thanks to a handheld optical system tested recently in the workplace. The system, called Biozoom, aims to help users manage their antioxidant levels, nutritional uptake and general fitness, according to Biozoom Inc. of Agoura Hills, Calif. The reflectance spectroscopy-based skin scanner provides noninvasive analysis of antioxidants and other biomarkers in the human body. The concentration of antioxidants in human skin has been linked to an individuals stressors, the company said. So, a quick scan of your palm would collect spectroscopic data to send to Biozooms servers, which would then return both results and wellness tips. The technique could replace other invasive and time-consuming methods for measuring antioxidants. The device was developed by Opsolution GmbH of Kassel, Germany, which is now associated with Biozoom. Six years ago, Prof. Dr. Jrgen Lademann, director of Charit Medicine Berlins Center of Experimental and Applied Cutaneous Physiology, and his colleagues at Charit developed a Raman microscopic measuring system with German industrial partners for in vivo and online determination of dermal carotenoids marker substances indicating antioxidant levels. They used the system for studies on anti-aging processes. To test the device on workers, researchers from Charit and the University of Rostock, also in Germany, conducted a study on seven midwives. They chose midwives because of the unpredictable nature of the work and the nighttime shifts involved, a common cause of work stress. Such a schedule is associated with insomnia, gastrointestinal disorders and a 40 percent higher risk of developing coronary heart diseases, according to Charit. The study found a correlation between stress intensity and a decline in the midwives antioxidant status, Biozoom said. The Biozoom scanner is now moving from prototype to commercial scale. Caren B. Les caren.les@photonics.com

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BioPhotonics September 2013

Illuminate Your Pathways to Discovery

It All Starts with In-Depth Experience
Advancements and possibilities in multiphoton imaging are evolving fast; the one constant the continued ultrafast innovation by Spectra-Physics. When it comes to multiphoton, our Mai Tai and InSight DeepSee are the preferred laser solutions, with the largest installed base and the highest performance backed by Spectra-Physics in-depth experience and global support. Our family of ultrafast lasers goes even further taking your research to new depths. Achieve deep in vivo imaging with InSight DeepSees straightforward access to long infrared excitation wavelengths. Generate bright, crisp images enabled by our lasers short pulse widths and built-in dispersion compensation to achieve the highest multiphoton imaging contrast. And whats more, our robust and automated lasers are built for turn-key and hands-off operation another way we support your research and scientic breakthroughs. Explore how Spectra-Physics lasers illuminate your pathways to discovery. For more information, visit www.newport.com/discovery or call 1-800-775-5273.
Multicolor 3D Image of Mouse Brain Cortex Yusuke Oshima, Translational Research Center, Ehime University Hospital (Japan) Takeshi Imamura, Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine (Japan)