Synchrotron-Based Infrared Microscope for Chemical Imaging of Disease

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DESCRIPTION (provided by applicant): Fourier transform infrared imaging (FTIRI) has become a valuable technique for examining the chemical makeup of biological cells and tissues on a microscopic scale without the need for stains or labels. Synchrotron infrared light is an ideal source for the technique due to the combination of its high brightness (100-1000 times brighter than a conventional source) and broad spectral range. Accordingly, the improvement in spectral quality and in spatial resolution to the diffraction limit (2-10 microns) has led numerous biomedical applications to disease including bone disease, Alzheimer's disease, prion diseases, heart disease, and cancer. To date, synchrotron infrared microscopes are equipped with a single detector pixel, meaning that the sample must be raster-scanned through the infrared beam to generate a chemical image. While the spatial resolution (2-10 microns) and data quality are unsurpassed, the data collection rates are prohibitively slow. Recently, infrared microscope detectors have been developed with 2-dimensional arrays of pixels; for a typical 64x64 pixel array, data collection rates are improved by a factor of 4096. Until now, optics constraints on these instruments have prohibited them from adaptation to a synchrotron infrared source. This proposal requests a FTIRI microscope with a 64x64 array detector (a Bruker Hyperion 3000) that can collect data up to 4096 times faster than any synchrotron infrared microscope available today. Moreover, the brightness of the synchrotron source will enable mathematical deconvolution of the infrared images (typically done for light microscopy and photography), resulting in improved spatial resolution (1-2 microns). The infrared imaging program at the National Synchrotron Light Source Beamline U10B is currently 3-fold oversubscribed with 65-70% of its users coming from the biomedical imaging field. Infrared imaging is an important component of the NIH-funded programs of each of the 10 major users listed in this proposal. Biomedical users on the beamline have produced 30 publications over the past 3 years. While their productivity has been high, acquisition of this instrument will dramatically improve the efficiency of the beamline, increase the number of users, and enable experiments that cannot be done today. This instrument will be unique worldwide.