IDBR: Collaborative Research: Development of a Time-Resolved Photon-Counting Imager for Biology

这是支持一个合作项目的两个奖项之一，该项目旨在开发一种新的时间分辨单光子成像仪，优化用于超高灵敏度荧光光谱和显微镜。该探测器将能够以高量子效率和时间分辨率记录单个（单）光子，并以高计数率在二维（2D）中具有高空间分辨率。该仪器将适用于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学，具有更高的灵敏度、信噪比和信本比，同时从每个检测到的光子（二维位置、相对于一系列短激光脉冲激发的微观和宏观到达时间，或波长和极化各向异性）提供多参数、高信息含量。该设备被称为“H33D探测器”，即高空间分辨率、高时间分辨率和高计数率的三维探测器。目标探测器性能是：(i)量子效率（QE） 35% @ 600nm。（ii） 50 um x 50 um的空间分辨率，允许至少256 x 256分辨率元素（像素），（iii） 150皮秒的时间分辨率，以及（iv）每单个像素100 kHz的最大计数率和整个探测器的5 MHz。H33D探测器的发展包括两个互补的方面：1)基于初始原型的新探测器设计，2)新的生物成像和光谱应用。新的探测器设计由安装在微通道板堆栈前的快速砷化镓光电阴极和交叉带阳极组成。读出电子设备将由其中一个合作小组设计、制造和测试。另一个合作小组将建造光学仪器和所需的软件。将建造两台仪器；第一个是一个未经优化的原型，最初将安装在加州大学洛杉矶分校的校园共享设施中，最终转移到加州纳米系统研究所高级光学显微镜/光谱学共享设施。通过这些安置，该仪器将可供一些独立调查人员和学生使用。从这种使用中获得的经验将有助于开发第二种更优化的仪器。该项目的广泛影响源于学生参与仪器的建造和测试，以及大量研究人员在共享设施中使用仪器。

This is one of two awards supporting a collaborative project aimed at development of a new time-resolved single-photon imager optimized for ultrahigh sensitivity fluorescence spectroscopy and microscopy. The detector will be capable of registering individual (single) photons with high quantum efficiency and time resolution, and with high spatial resolution in two-dimensions (2D) at high-count rates. The instrument will be suitable for imaging and spectroscopy of single molecules, molecular complexes and macromolecules in living cells and tissues with increased sensitivity, signal-to-noise ratio and signal-to-background ratio, while providing multi-parametric, high information content from each detected photon (2D position, microscopic and macroscopic time of arrival with respect to an excitation by a train of short laser pulses, or wavelength and polarization anisotropy). The device has been dubbed the "H33D detector" for High-spatial resolution, High-temporal resolution and High count-rate 3-Dimensional detector. Targeted detector performance is: (i) quantum efficiency (QE) of 35 % @ 600nm. (ii) spatial resolution of 50 um x 50 um, allowing at least 256 x 256 resolution elements (pixels), (iii) temporal resolution of 150 picoseconds, and (iv) maximum count rate of 100 kHz per single pixel and 5 MHz over the whole detector. The development of the H33D detector comprises two complementary aspects: 1) a new detector design based on an initial prototype, and 2) new biological imaging and spectroscopy applications. The new detector design consists of a fast GaAs photocathode mounted in front of a stack of microchannel plates and a cross-strip anode. The readout electronics will be designed, built and tested by one of the collaborating groups. The other collaborating group will build the optical instrumentation and software needed for it. Two instruments will be built; the first, a non-optimized prototype, will be installed initially in a campus shared-use facility at UCLA, and eventually transferred to the California NanoSystems Institute Advanced Light Microscopy/Spectroscopy Shared Facility. Through these placements, the instrument will be available for use by a number of independent investigators and students. The experience gained from such use will be helpful in development of a second, more optimized instrument. Broader impacts of the project derive from the involvement of students in instrument construction and testing, and the availability of the instrument by a large number of investigators in a shared facility.