Synchrotron-Based Infrared Microscope for Chemical Imaging of Disease

描述（由申请人提供）：傅里叶变换红外成像（FTIRI）已成为一种在显微镜下检查生物细胞和组织的化学组成而无需染色剂或标记的有价值的技术。同步辐射红外光是该技术的理想光源，因为它结合了高亮度（比传统光源亮100-1000倍）和宽光谱范围。因此，光谱质量和空间分辨率提高到衍射极限（2-10微米）已经导致许多生物医学应用于疾病，包括骨疾病、阿尔茨海默病、朊病毒疾病、心脏病和癌症。 迄今为止，同步辐射红外显微镜配备了一个单一的检测器像素，这意味着样品必须通过红外光束光栅扫描，以生成化学图像。虽然空间分辨率（2-10微米）和数据质量是无与伦比的，但数据收集速度非常慢。最近，红外显微镜探测器已经开发出二维像素阵列;对于典型的64 x64像素阵列，数据收集速率提高了4096倍。到目前为止，这些仪器上的光学限制已经禁止它们适应同步辐射红外源。 该提案要求使用带有64 x64阵列检测器（Bruker Hyperion 3000）的FTIRI显微镜，其收集数据的速度比当今可用的任何同步加速器红外显微镜快4096倍。此外，同步辐射源的亮度将使红外图像的数学解卷积（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U10 B的红外成像项目目前超额认购3倍，其中65-70%的用户来自生物医学成像领域。红外成像是NIH资助计划的重要组成部分，该计划中列出了10个主要用户。在过去的3年里，光束线上的生物医学用户已经发表了30篇论文。虽然他们的生产率一直很高，但购买这种仪器将大大提高光束线的效率，增加用户数量，并使今天无法完成的实验成为可能。这一工具将在全世界独一无二。

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.