Rapid infrared biomedical imaging at high pixel density with a sCMOS camera

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ABSTRACT A genuine label-free imaging technology, vibrational microscopy provides maps of cells and tissues with exceptionally high chemical contrast as it directly probes the fundamental vibrationals modes of samples. Vibrational imaging approaches include IR-absorption micro-spectroscopy and confocal Raman microscopy, methods that have been successfully commercialized (a growing 500 million dollar market) and are now common tools of inquiry found in analytical and biological laboratories. Given the much stronger IR light-matter interaction, IR microscopy has a particularly high potential to make a measurable impact in the fields of biology and biomedicine. At the same time, the mid-IR (MIR) imaging technology has remained stagnant, as MIR technology still relies on cooled cameras with low pixel density, preventing practical applications in efficient mapping of cultured cells and tissue sections. This proposal aims to introduce a radically new MIR detection approach that overcomes the fundamental hurdles that have plagued a broader implementation of traditional MIR cameras. We propose that direct, on-chip MIR detection can be achieved in an sCMOS camera through the process of non-degenerate two-photon absorption (NTA) enabled by a near-infrared gate pulse. By replacing cryogenically cooled MIR arrayed detectors with a modern sCMOS camera, the proposed work overcomes a key limitation in MIR microscopy and represents an important step toward a more practical implementation of MIR imaging in the biomedical sciences. Our team includes experts in biomedical vibrational imaging and nonlinear optics, and our preliminary data underlines the feasibility of the NTA method for MIR detection. In the proposed work we push NTA for use with modern sCMOS cameras, determine its utility for MIR microscopy and compare its performance for biomedical imaging applications with established MIR microspectroscopy methods.