IDBR: CMOS cameras for high-frame-rate time-correlated single-photon counting

IDBR：用于高帧率时间相关单光子计数的 CMOS 相机

• 批准号: 1063315
• 负责人: Kenneth Shepard
• 金额: $ 75万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1063315&HistoricalAwards=false
• 关键词: IDBR; CMOS; cameras; frame; rate

IDBR: CMOS cameras for high-frame-rate time-correlated single-photon countingRecent advances in biological imaging techniques, particularly those exploring molecular dynamics, are outpacing technological innovation. Fluorescence lifetime holds great potential as a biomarker that can reveal changes in a fluorophore's local chemical and physical environment, as well as the binding dynamics of single proteins through excited state interactions and Förster resonance energy transfer (FRET). Many of the latest active dyes, molecular probes and even transgenic labeling strategies exploit FRET to enable real-time observation of cellular processes both in-vitro and in-vivo. While FRET can be detected using intensity-only measurements, quantitation can be dramatically impaired by experimental factors such as photobleaching, whereas lifetime-based FRET measurements are significantly more robust. Nevertheless, adoption and widespread use of fluorescence lifetime imaging microscopy (FLIM) for biological research has been hindered by two major factors: the speed with which FLIM images can be acquired and the cost and complexity of the instrumentation required for FLIM. In this multidisciplinary proposal, a novel two-dimensional high-frame-rate complementary metal-oxide-semiconductor (CMOS) fluorescent lifetime camera chip based on single-photon avalanche diodes (SPADs) will be developed. This chip will be applied to both wide-field and laser-scanning-based microscopy techniques to enable several important advances in FLIM imaging. In widefield imaging, this will result in acquisition of images at a incident-photon-limited frame rate as high as 1 kHz.Solid-state imagers are based primarily on two technologies, charged-coupled device (CCD) and CMOS. Both of these imaging technologies are based on converting photons to electrons and collecting many of these electrons to produce a measurable signal. These imagers are now employed in digital cameras of every type, from cell phone cameras to the high-end cameras employed in biological imaging. Since optical techniques are so pervasive in probing biological systems, cameras represent the fundamental interface between the biological world and the solid-state world. In this effort, an entirely new camera chip will be designed based on a device that, instead of collecting electrons produced by photons, counts them, one-by-one. This enables very high sensitivity for photon detection. At the same time it allows resolution of very short (and dim) optical events (on the order of 10's of ps). Such capabilities will enable new types of biological imaging applications. This project supports the multidisciplinary training of graduate and undergraduate students and a significant K-12 outreach effort.

IDBR：用于高框架速率速率时间相关的单光子计数的CMOS摄像机在生物成像技术中的进步，尤其是那些探索分子动力学的人，都超过了技术创新。荧光寿命具有巨大的潜力作为生物标志物，可以揭示荧光团局部化学和物理环境的变化，以及通过激发态相互作用和Förster共振能量转移（FRET）的单蛋白的结合动力学。许多最新的活性染料，分子问题，甚至是转基因标记策略都利用FRET来实现对体外和体内的细胞过程的实时观察。虽然可以使用仅强度测量值检测到FRET，但实验因素（例如光漂白）可以动态地损害定量，而基于终生的FRET测量值明显更强。然而，两个主要因素阻碍了荧光寿命显微镜（FLIM）对生物学研究的采用和宽度使用，这是两个主要因素：可以获取Flim图像的速度以及Flim所需的仪器的成本和复杂性。在这个多学科的建议中，将开发出一种新型的二维高率互补金属氧化物 - 氧化物 - 氧化物 - 氧化物 - 氧化物 - 氧化物 - 氧化物 - 氧化物 - 氧化物 - 荧光寿命寿命摄像机芯片，基于单光子雪崩二极管（SPADS）。将应用于宽场和激光扫描的显微镜技术，以实现FLIM成像的几个重要进步。在广场成像中，这将导致以入射 - 限制的框架速率高达1 kHz的图像获取图像。Solid-State Imagesrs主要基于两种技术，即充电耦合器件（CCD）和CMOS。这两种成像技术都是基于将照片转换为电子的，并收集了许多这些电子以产生可测量的信号。这些图像现在用于每种类型的数码相机中，从手机摄像机到生物成像中使用的高端摄像头。由于光学技术在探测生物系统方面是如此普遍，因此相机代表了生物学世界与固态世界之间的基本接口。在这项工作中，将根据设备设计一个全新的相机芯片，该设备不是收集照片生产的电子，而是一对一地计算它们。这使光子检测具有很高的灵敏度。同时，它允许解决非常短（和昏暗的）光学事件（在PS的10阶）。这样的功能将实现新型的生物成像应用。该项目支持研究生和本科生的多学科培训以及K-12的大量宣传工作。