Raman spectroscopy is a potentially important clinical tool for real-time diagnosis of diseases and in situ evaluation of living tissues. However, the application of Raman spectroscopy for tissue evaluation has been limited by the strong tissue fluorescence that often overwhelms the extremely weak Raman signal. The goal of this proposal is to develop an infrared Raman spectroscopy system with its excitation laser wavelength extending beyond 1000 nm, where the tissue fluorescence is completely suppressed and narrow line width diode lasers, such as those DFB lasers developed for optical communication applications, are readily available. A low-light-level infrared camera is proposed as the core component of the Raman spectroscopy system. It utilizes the miniaturized and monolithically integrated version of a proven solid-state detector technology, and is expected to be able to detect femto-Watts (namely, 10^(-15) Watt) of optical signal on each pixel. This sensitivity is several orders of magnitude better than standard silicon based CCD detectors and is comparable to the current image intensifying tubes, thanks to modern semiconductor integration techniques and recent breakthroughs in nano-materials. The proposed low-light-level camera covers 900 nm - 1650 nm spectral range. It is designed for high sensitivity with gain of 1,000. Its readout noise is as small as 1 electron/pixel/frame, lower than the current non-intensified systems. The high resolution of 15,000 linear pixels leads to 1 A spectral resolution. Its high speed of operation at 1 MHz allows 1 micro-second gating time. At volume production, the manufacturing cost of the proposed camera is $500. Based not on incremental improvements over existing solutions, but on a disruptive technology platform developed at B&W TEK, the proposed low-noise camera separates the low-noise high- speed detection and low-noise parallel amplification in the photo-detector array from the high- speed serialization and readout in the CCD/CMOS readout electronics, with high-gain low-noise parallel amplification as the noise isolation buffer between the two processes. All is made possible by the recent boom in nanotechnology - the core amplifier utilizes 60 nano-meters of amplification layer and 30 nano-meters of surface oxide layer to achieve low-noise high- sensitivity detection and amplification. As a result, the proposed low-light-level camera is expected to enable infrared Raman spectrometers of higher sensitivity and faster response time, thus more efficiently analyze biological samples and more accurately help diagnose diseases.
Public Health Relevance: The proposed low-light-level infrared camera is an enabling technology for infrared Raman spectroscopy at beyond 1000 nm, which is a potentially important clinical tool for real-time diagnosis of diseases and in situ evaluation of living tissues.
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