Unlocking the potential of High-speed widefield Imaging

释放高速宽场成像的潜力

• 批准号: 10517241
• 负责人: Luke Satish Kumar Theogarajan
• 金额: $ 21.18万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10517241
• 关键词: 3-Dimensional; Address; Adoption; Architecture; Area; Binding; Biochemical; Brain; Calcium; Calibration; Coupled; Custom; Data; Dendrites; Devices; Electronics; Engineering; Event; Fluorescence; Future; Goals; Image; Imaging Techniques; Imaging technology; Laser Scanning Microscopy; Lasers; Measurement; Measures; Microscopy; Mus; Neurobiology; Neurons; Neurosciences; Noise; Phosphorylation; Photons; Physiologic pulse; Preparation; Reading; Reporter; Scanning; Signal Transduction; Silicon; Speed; System; Techniques; Technology; Testing; Time; Transistors; Tube; Validation; Visit; Width; Work; analog; base; computerized data processing; data streams; density; design; detector; digital; experimental study; flu; fluorescence lifetime imaging; imager; imaging modality; in vivo; innovation; instrumentation; neuroimaging; neurophysiology; next generation; novel; novel strategies; operation; photomultiplier; preservation; prevent; relating to nervous system; spatiotemporal; voltage

Project Summary: Widefield imaging and spatial multiplexing are crucial to advancing the field of neuroscience. Current imagers do not offer the speed and versatility needed for calcium or voltage imaging experiments. In the case of lifetime imaging the functionality is completely lacking in CMOS imagers. The problem is more subtle than it seems because it is not just a matter of brute force speed-up through technology. Speed increases come with large amounts of power dissipation and the need for faster data interfaces. One imaging technique with the potential to solve this issue is the single photon avalanche detector (SPAD). SPADs by virtue of operation result in digital pulse practically eliminating read noise that commonly plagues regular imagers. However, SPAD imagers till date have not seen widespread use due to low pixel density. One of the greatest advantages of the SPAD imager is its ability to perform time correlated measurements, enabling lifetime imaging. Lifetime imagers can yield absolute quantitative measurements not possible with regular imaging modalities. However, the current SPAD imagers take seconds to minutes to compute a lifetime image, much too slow for neural imaging. We propose to overcome these fundamental barriers by innovating at the device, architecture and packaging levels. Our proposed approach utilizes a transistor amplified SPAD design coupled with in pixel analog counting and lifetime estimation. These two innovations make it possible to read the pixel level data at a slower rate, while maintaining a fast frame rate. We additionally propose a new chip level integration approach which packages the imager die and processing die in a silicon package enabling reading from subarrays. This approach enables the imager to maintain the frame rate of the pixel subarray as the pixel density scales. Finally, we demonstrate the advantages of our imager by imaging dendritic activity, both in intensity and lifetime imaging modes, in neural cultures at unprecedented spatiotemporal scales.

项目摘要： 广场成像和空间多路复用对于推进领域至关重要 神经科学。当前的成像仪不提供所需的速度和多功能性 钙或电压成像实验。在一生中成像 CMOS成像仪完全缺乏功能。问题更微妙 比看起来似乎是因为这不仅是蛮力加速的问题 技术。速度提高随大量的功率耗散而伴随着 需要更快的数据接口。一种具有潜力的成像技术 解决此问题的是单个光子雪崩检测器（SPAD）。通过美德 操作导致数字脉冲实际上消除了读取噪声 通常会困扰常规成像仪。但是，迄今为止尚未 由于像素密度低而看到广泛使用。最大的优势之一 SPAD成像仪是其执行时间相关测量的能力，使得 终身成像。终生成像仪可以产生绝对的定量测量 常规成像方式不可能。但是，当前的spad 成像器需要几秒钟到几分钟才能计算终身图像，太慢了 神经成像。我们建议通过 在设备，架构和包装级别上进行创新。我们提出的 方法利用晶体管放大的SPAD设计，并在Pixel类似物中加上 计数和寿命估计。这两个创新使阅读成为可能 像素级数据的速率较慢，同时保持快速帧速率。我们 另外提出了一种新的芯片级集成方法，该方法包装 成像仪死亡和处理以硅包装而死，从而使阅读 子阵列。这种方法使成像仪能够保持 像素子阵列作为像素密度尺度。最后，我们证明了 通过成像树突活性和强度和 终生成像模式，在前所未有的时空中的神经培养物中 秤。