Synchrotron-Based Infrared Microscope for Chemical Imaging of Disease

描述(申请人提供)：傅立叶变换红外成像(FTIRI)已经成为一种在微观范围内检查生物细胞和组织的化学组成的有价值的技术，而不需要染色或标签。同步加速器红外光由于其高亮度(比常规光源亮100-1000倍)和宽光谱范围的组合，是这项技术的理想光源。因此，光谱质量和空间分辨率到衍射极限(2-10微米)的提高导致了许多生物医学应用于疾病，包括骨病、阿尔茨海默病、普里恩疾病、心脏病和癌症。 到目前为止，同步加速器红外显微镜只配备了一个探测器像素，这意味着样品必须通过红外线光束进行栅格扫描才能产生化学图像。虽然空间分辨率(2-10微米)和数据质量是无与伦比的，但数据收集速度慢得令人望而却步。最近，红外显微镜探测器已经开发出具有二维像素阵列；对于典型的64×64像素阵列，数据采集率提高了4096倍。到目前为止，这些仪器的光学限制阻止了它们适应同步加速器红外源。 这项提议要求FTIRI显微镜具有64x64阵列探测器(Bruker Hyperion 3000)，收集数据的速度比目前可用的任何同步辐射红外显微镜快4096倍。此外，同步加速器光源的亮度将实现红外图像的数学去卷积(通常用于光学显微镜和摄影)，从而提高空间分辨率(1-2微米)。 国家同步加速器光源光束线U10B的红外成像计划目前超额认购了3倍，65%-70%的用户来自生物医学成像领域。红外成像是NIH资助的项目的一个重要组成部分，该项目列出了这份提案中的10个主要用户。在过去的三年里，光束线上的生物医学用户已经出版了30份出版物。虽然他们的生产率一直很高，但收购这台仪器将极大地提高光束线的效率，增加用户数量，并使今天无法完成的实验成为可能。该仪器将在世界范围内独一无二。

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.