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1 White Paper Zecotek Visible Fiber Laser Platform Enabling the future of laser technology Zecotek Photonics Inc. (TSX- V: ZMS; Frankfurt: W1I) is a Canadian photonics technology company developing high- performance crystals, photo detectors, lasers, nuclear imaging and 3D display technologies for commercial applications in the medical diagnostics, high- energy physics, and high- tech industries. Founded in 2004, the company has three distinct operating divisions: imaging, lasers, and 3D display systems, with labs and product development facilities located in Canada, USA, Singapore, Malaysia, and Russia. Zecotek commercializes its novel, patented and patent- pending technologies both directly and through strategic alliances and joint ventures with multinational OEMs, distributors, and other industry leaders. In 2009, Zecotek was honored with the prestigious Frost & Sullivan award for North America s Best Enabling Technology for its MAPD (Multi- pixel Avalanche Photo Diode) and LFS (Lutetium Fine Silicate) scintillation materials. The Company has featured on Discovery Channel s Daily Planet, and in 2010 was cited as one of the top ten Canadian technology companies to be the next big thing for its 3D display system. Zecotek s Visible Fiber Laser Platform Zecotek s visible- spectrum fiber lasers are based on the commercially proven and efficient diode- pumped fiber laser technology that has revolutionized many instrumentation and industrial laser applications. In spite of significant difficulties that accompany the propagation of this platform into the visible wavelength range, fiber laser technology remains very attractive because many of its inherent features, including superior thermal handling and stability, which translate into advantages over conventional DPSS design, in particular for CW devices. Zecotek s fiber laser technology enables a wide range of possible output wavelengths over the entire visible spectrum, hitherto inaccessible by DPSS approach and additionally offers the possibility of broad- range continuous wavelength tuning. Zecotek s fiber lasers feature high beam quality and stability, high efficiency, adjustment- free operation, and no water cooling is required for their operation. The Competitive Advantages of Zecotek Fiber Lasers Solid- state lasers have long established themselves as the most common type of coherent light sources in the instrumentation and research fields, even though other approaches, such as optically pumped semiconductor lasers (OPSL) or directly doubled diode lasers have been introduced, and where older types of laser sources, e.g. gas lasers (He- Ne, argon- ion, He- Cd, &c) are also still widely used in bio- medical
2 applications. However, with the exception of OPSL, conventional lasers in use are limited to a fixed set of available wavelengths with a notable gap around the green- yellow range. Fibre lasers are now a promising alternative. In addition to being generally more robust and efficient, they have a broad continuous range of output wavelength that can be tailored to specific applications, with the possibility of continuously tuneable laser output within wide spectral ranges. This said, while fiber lasers have proven competitive advantages in the infrared spectral region, there are relatively high barriers to the commercial viability of visible spectrum laser sources on the basis of this platform. The most widely used approach utilizes external frequency doubling schemes based on special (and expensive) single- pass periodically poled non- linear crystal (PPLN, PPKTP) with fixed- wavelength. However, in addition to their high price and fixed wavelength, periodically poled non- linear crystals for frequency doubling are known to have long- term stability issues and a power limit of several watts which, when added to high cost, make competing with existing high- power DPSS systems highly problematic. In contrast, the Zecotek design is based on a schema, which relies on the intra- cavity doubling of inexpensive and robust unpolarized rare earth- doped fiber lasers. This unique, patent pending approach provides for both an attractive performance/cost ratio as well as significantly lower cost. Zecotek lasers also offer a range of parameters, which include higher reliability, provisions for various maximum power levels (0.25 1W) and various wavelengths in the green range ( nm) with a focus on the lines of 540, 550, 560 nm (where the nm range is important in medical applications). Other options include continuous tuneability with up to 20- nm, multi- wavelength, broad- band, and narrow- band, as well as single- frequency in both in IR and visible range. A pulsed operation is also in development. Zecotek Lasers in the Life Sciences Laser sources have become essential tools in the bio- medical sciences with a wide range of applications, from basic research to widely used cosmetic procedures. In particular, lasers have become indispensible to medical research and diagnostics, most notably in the areas of flow cytometry and confocal microscopy. These technologies utilize special organic molecules called fluorophores, which are attached to different biological agents and constituents. These molecules emit light in certain spectral bands when excited by a laser light source delivering output at another, shorter wavelength. This fluorescence is then used to detect and measure various quantitative as well as qualitative parameters of organisms and cultures or to operate on them. Contemporary flow cytometers contain up to four different laser sources and sophisticated confocal microscopes have up to six laser ports. In both technologies, problems can arise through overlapping of excitation and emission wavelengths of different fluorophores. Here, the freedom of wavelength choice offered by Zecotek s fiber laser platform allows elimination of many of these problems: tuning the laser output to the maximum of the fluorophore absorption band and away from the detection wavelength both avoids contamination of detection channels by the excitation light and improves the efficiency of excitation. Tuneable versions of Zecotek s fiber lasers also offer other advantages, including the replacement of several laser sources by a single unit and for wavelength scanning during measurement. Future Developments
3 The fiber laser platform developed by Zecotek is extendable into other visible ranges with continuous tuneability possible beyond 20 nm in the green, as well as blue and red wavelength ranges. Test models have been successfully developed with a 50- mw CW output in the nm range, as well as up to 50 mw between 625 and 655 nm. The possibility of continuous wavelength tuning has also been demonstrated within nm, thus completing the proof- of- concept of a unified fiber laser platform for the entire visible range of wavelength. Zecotek is presently developing a number of laser devices to extend the available wavelength choice into these ranges. The fixed- wavelength line will be supplemented by models operating at any given selected wavelength between 460 and 480 nm in the blue spectrum, including the traditionally popular wavelength of 488 nm, as well as by those with the output options between 625 and 655 nm. Tuneable versions of these devices will be also eventually added. The specifications of these future models are approximated in the table below. Table 1. Specifications of Zecotek lasers under development Wavelength/tuneability Red fixed Red tuneable Blue fixed Blue tuneable Output wavelength nm Output power mw > 100 Beam quality M 2 < 1.2 (TEM 00 ) Linear, > 100:1 Output spectrum width GHz ~100 (FWHM) Output noise (20 Hz 2 MHz) %, rms < 1.5% < 2% < 2% < 2% Output stability (2 hours) % < ±2% < ±3% < ±2% < ±3% Operating temperature C 15 30
4 Zecotek Fibre Lasers: Experimental Performance Data A number of different laser devices have been developed at Zecotek which cover a range of wavelengths and which specifically target applications in flow cytometry and confocal microscopy. The table below summarizes the specifications of the currently available standard fixed- wavelength models. Any other wavelength within nm is also available as an option. A development effort is currently aimed at increasing the range of available wavelengths up to 570 nm. Table 2. Specifications of Zecotek fixed- wavelength lasers Fixed- wavelength laser model GFL- 515 GFL- 540 GFL- 550 GFL- 560 Output wavelength nm 515±1 540±1 550±1 560±1 Output power mw Beam quality M 2 < 1.1 (TEM 00 ) Linear, 200:1 Output spectrum width GHz ~20 (FWHM) Output noise (20 Hz 2 MHz) %, rms < 1% < 1% < 1% < 1.5% Output stability (2 hours) % < ±1.5% < ±1.5% < ±1.5% < ±2% Laser head dimensions mm Laser head weight kg 4 Control unit dimensions mm Control unit weight kg 4 Power requirements < 100 W, 110/220 50/60 Hz Operating temperature C The current tuneable laser models cover the ranges of , , and nm, and any central wavelength within the range of nm may be chosen as an option for a 10- nm continuous tuning range. The development program includes several iteration with a progressively increasing range of continuous tuneability, aiming at 30 nm and more. Table 3. Specifications of Zecotek tuneable lasers. Tuneable laser model TGFL TGFL TGFL TBD Output wavelength range nm Output power mw
5 Beam quality M 2 < 1.2 (TEM 00 ) Linear, 200:1 Output spectrum width GHz ~20 (FWHM) Output noise (20 Hz 2 MHz) %, rms < 1% < 1% < 1.5% < 2% Output stability (2 hours) % < ±1.5% < ±1.5% < ±2% < ±3% Laser head dimensions mm TBD Control unit dimensions mm TBD Laser head dimensions mm 3 ~ Operating temperature C Both fixed- wavelength and tuneable devices have been tested by the life science research community who have conclusively demonstrated that, for many fluorescent dyes, Zecotek lasers offer a superior fit to other, more conventional light sources. For example, Zecotek s 550- nm lasers have shown much better performance in flow cytometry J_ID: Z3W Customer A_ID: Cadmus Art: CYTO20790 Date: 31-AUGUST-09 Stage: I Page: 5 measurements when compared to standard 532- nm sources. Similarly, while Zecotek s lasers deliver sensitivity comparable to that obtained with 561- nm lasers, due to the enhanced isolation between excitation and detection channels, the overall performance exceeds that of these TECHNICAL traditional NOTE laser sources. Figure 3. PE and red fluorescent proteins. Three left columns, EL4 mouse thymoma cells were labeled with biotin-anti-cd3, CD44, or CD95 antibody followed by streptavidin conjugated to PE and analyzed on the LSR II Fig. 1. Sensitivity indices of cytometry measurements of populations TM using 532-, 550-, or 561-nm lasers at matched power levels and the same optical detection path. Two right columns, SP2/0 cells were stably expressing transfected with different DsRed and dtomato fluorescent and similarly agents and the analyzed. All cells were analyzed through a 590/20-nm bandpass filter (to accommodate the 561-nm laser). Filled peaks indicate labeled degree of isolation cells, unfilled between peaks indicated the control unlabeled (untagged) controls. The sensitivity and labeled indices (described cells in (source: the Materials W and Telford Methods) et are al, indicated Cytometry on each Part A, 75A: histogram. PMT voltages were fixed for all samples , 2009). Tuneable versions of Zecotek fiber lasers allow even better optimization of various parameters such as the width filter, elevating the fluorescence background and preventing it easier discrimination to use of all standard but the brightest filters microspheres and other optics excitation efficiency and channel isolation. They also make with different fluorophores when used simultaneously. Alignment and detector sensitivity for this laser on the LSR II was then assessed using premixed Spherotech Rainbow 8-peak microspheres. The 550-nm unit was tested at three power levels (50, 100, and 150 mw) and compared with a previously evaluated 561-nm unit at 50 mw. The 550-nm unit was able to resolve all eight microsphere populations, including the Paper dimmest population from the unstained control Zecotek Fiber Laser White Copyright 2011 Zecotek (data now Photonics shown). Inc. Both the dim bead resolution and peak C.V.s were comparable to a previously standardized 561-nm unit, indicating that the laser was properly aligned and could resolve a low-sensitivity microsphere standard. Green 532-nm and yellow 561-nm lasers are prone to laser light impingement on standard fluorescein and PE bandpass filters, respectively, forcing modification of detection (Fig. 1, second column, indicated with a black arrow). Modification of the standard fluorescein filter to a 510/20 nm was required to exclude 532-nm laser light, slightly reducing fluorescein sensitivity (Fig. 1, left-most column). Similarly, the 561-nm laser could not be used with a standard 585/42-nm PE filter; the two dimmest populations of MESF PE low microspheres could not be resolved, requiring instead a 590/20-nm filter (Fig. 3, right-most two columns, black F3 arrow). This 585/42-nm filter is typical of those supplied with commercial systems and did not exclude 561-nm laser light. However, the 550-nm laser fell neatly within these ranges, causing no loss of sensitivity or resolution of either MESF
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