Unlocking the potential of High-speed widefield Imaging

释放高速宽场成像的潜力

• 批准号: 10669798
• 负责人: Luke Satish Kumar Theogarajan
• 金额: $ 17.75万
• 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/10669798
• 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; Performance; Phosphorylation; Photons; Physiologic pulse; Preparation; Reading; Reporter; Scanning; Signal Transduction; Silicon; Speed; System; Techniques; Technology; Testing; Time; Transistors; Tube; Validation; Visit; Work; analog; computerized data processing; data streams; density; design; detector; digital; experimental study; fluorescence lifetime imaging; imager; imaging modality; in vivo; innovation; instrumentation; manufacture; neural; neuroimaging; neurophysiology; next generation; novel; novel strategies; operation; photomultiplier; photon-counting detector; preservation; prevent; 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.

项目概要： 宽视场成像和空间多路复用对于推进成像领域至关重要。 神经科学目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。在寿命成像的情况下， CMOS成像器中完全缺乏功能。问题更微妙 因为这不仅仅是一个蛮力加速的问题， 技术.速度的提高伴随着大量的功耗， 需要更快的数据接口。一种成像技术有可能 解决这个问题的是单光子雪崩探测器（SPAD）。SPAD凭借 实际上消除了读噪声， 通常困扰着普通的成像者。然而，SPAD成像仪至今还没有 由于低像素密度而被广泛使用。的最大优点之一 SPAD成像仪的一个优点是它能够进行时间相关测量， 终身成像寿命成像仪可以产生绝对定量测量 常规成像方式无法实现。目前，SPAD 成像器需要几秒钟到几分钟的时间来计算生命周期图像， 神经成像我们建议通过以下方式克服这些基本障碍： 在器件、架构和封装层面进行创新。我们提出的 一种方法利用晶体管放大SPAD设计， 计数和寿命估计。这两项创新使阅读成为可能 像素级数据以较慢的速率传输，同时保持较快的帧速率。我们 此外，还提出了一种新的芯片级集成方法， 硅封装中的成像器管芯和处理管芯 子数组该方法使得成像器能够维持图像的帧速率。 像素子阵列作为像素密度缩放。最后，我们展示了 我们的成像仪的优势，通过成像树突状细胞的活动，无论是在强度和 终身成像模式，在前所未有的时空神经文化 鳞片