High-Resolution, High Speed, High-Throughput 3-Dimensional Detector for Biology

描述（由申请人提供）：本提案的目标是开发用于生物学的高性能光子计数三维成像仪（2个空间，1个时间）以及利用其新功能的新方法和新协议。该探测器将在可见光和近红外光谱范围（500-850 nm）进行超高灵敏度荧光光谱优化。它将具有：(i)基于快速GaAs光电阴极的高检测效率：~ 35%，（ii）将使用交叉带阳极设计以高空间分辨率记录单光子：35 μ m， （iii）使用微通道板的高时间分辨率：250 ps， （iv）能够同时具有高本地和全局计数率（100 kHz, 20 MHz）。这些特征被浓缩为首字母缩略词“H33D”（发音为heed），代表高空间、高时间分辨率和高吞吐量（3个“H”，因此是H3）三维探测器。H33D探测器将适用于多种生物医学应用，如活细胞和组织中的单分子、分子复合物和大分子的成像和光谱，以及动物体内成像，其中一些将在本研究计划的4年时间内进行研究。最后的应用将是将H33D探测器用于人类患者荧光分子探针的生物医学成像的第一步，具有前所未有的灵敏度。我们的跨学科研究计划的这些特点将具有生物物理/生化背景的科学家和具有物理/仪器背景的科学家重新组合在一起，这与1999年BECON组织的生物医学成像研讨会“可视化生物学和医学的未来”所表达的愿景完美匹配，并且特别符合NIGMS和NIBIB的使命，他们是BRG计划声明PA-02-011的一部分。本研究与公共卫生的相关性：H33D探测器提供的更丰富的信息将导致在分子水平上更好地理解细胞过程，这是设计旨在用药物化合物治疗异常细胞行为的智能对策的先决条件。H33D检测仪在活体动物和人体成像中的长期应用，将为在分子水平上诊断和监测疾病的演变提供一种急需的高灵敏度仪器。

DESCRIPTION (provided by applicant): The objectives of this proposal are to develop a high-performance photon-counting 3-dimensional imager (2 spatial, 1 temporal) for biology and new methodologies and protocols taking advantage of its new capabilities. This detector will be optimized for ultrahigh sensitivity fluorescence spectroscopy in the visible and near-infrared spectral range (500-850 nm). It will have: (i) a high detection efficiency based on a fast GaAs photocathode: ~35 %, (ii) will register single-photons with high spatial resolution using a cross-strip anode design: 35 um, and (iii) high temporal resolution using microchannel plates: 250 ps, and (iv) be capable of both high local and global couting rates (100 kHz, 20 MHz). These characteristics are condensed in the acronym "H33D" (pronounced heed) for High-spatial, High-temporal resolution, and High throughput (the 3 "H'"s, hence H3) 3-Dimensional detector. The H33D detector will be suitable for a variety of biomedical applications, such as imaging and spectroscopy of single molecules, molecular complexes and macromolecules in living cells and tissues, as well as in vivo animal imaging, some of which will be studied during the proposed 4 year span of this research proposal. The last application will be a first step towards using the H33D detector for biomedical imaging of fluorescent molecular probes in human patients with unprecedented sensitivity. These characteristics of our interdisciplinary research proposal regrouping scientists with a biophysical/biochemical background and scientists with a physics/instrumentation background are in perfect match with the vision expressed during the Biomedical Imaging Symposium 'Visualizing the Future of Biology and Medicine" organized by the BECON in 1999, and fits particularly well within the mission of the NIGMS and the NIBIB, who are part of BRG program announcement PA-02-011. Relevance of this research to public health: The richer information provided by the H33D detector will lead to a better understanding of cellular processes at the molecular level, a prerequisite step to design intelligent counter-measures aimed at curing abnormal cellular behavior with medical compounds. The long-term application of the H33D detector for live animal and human imaging will provide a much needed high- sensitivity instrument for diagnosing and monitoring the evolution of diseases at the molecular level.