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Ultrafast Bioimaging

超快生物成像

基本信息

批准号：
10477387
负责人：
Liang Gao
金额：
$ 37.97万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-07-31
项目状态：
已结题

项目摘要

Project Summary: The PI proposes to develop an ultrafast bioimaging program which could open a new area of investigation and lead to a series of fundamental scientific discoveries. Space and time, two key physical dimensions, constitute the basis of modern metrology. In bio-imaging, as recognized by the 2014 Nobel Prize in chemistry, there have been breathtaking advances in improving the spatial resolution of microscopic imaging, resulting in an impressive arsenal of nanoscopy tools that can break the diffraction limit of light. Despite equally important, the pursuit of a high-temporal resolution has only recently caught attention thanks to the emergence of several enabling technologies. The motivation to develop these ultrafast imagers originates from the landscape shift of the contemporary biology from morphological explorations and phenotypic probing of organisms to seeking quantitative insights into underlying mechanisms at molecular levels. The transient molecular events occur at a timescale varying from tens and hundreds of microseconds that ligands take to bind, to tens of femtoseconds that molecules take to vibrate. Ultrafast imaging, therefore, is essential for observation and characterization of such dynamic events. Heretofore, most ultrafast phenomena at microscopic scales were probed using non-imaging-based methods. However, since most transient molecular events are a consequence of a cascade of molecular interactions, rather than occurring in isolation, the lack of images limits the scope of the analysis. On the other hand, despite the capability of capturing two-dimensional images, conventional cameras based on electronic image sensors, such as CCD and CMOS, fall short in providing a high frame rate under desirable imaging conditions due to electronic bandwidth limitations (data transfer, digitalization, and writing). To solve this fundamental problem, our strategy is to introduce the paradigm of compressed sensing into high-speed optical imaging. Rather than measuring each spatiotemporal voxel of an event datacube, we will leverage the compressibility of biological scenes and thereby utilizes the camera’s bandwidth more efficiently— the image data is compressed before being digitalized and transferred to the host computer. This feature will make our approaches especially advantageous for recording high-speed image data, which otherwise would require tremendous camera bandwidth and hardware resources if measured under Nyquist sampling. Based on this strategy, we will explore ultrafast bioimaging at a frame rate from a few MHz to ten THz, a range which is essential for understanding the biomolecular behaviors but currently inaccessible by conventional high-speed cameras. The resultant research program will ultimately lead to a new generation of ultrafast bioimagers and make transformative advancements to the state-of-the-art methods.

项目概述：PI提议开发一种超快生物成像计划，这可能开辟一个新领域并导致了一系列基础性的科学发现。空间和时间，两个关键的物理尺寸，构成现代计量学的基础。在生物成像方面，正如2014年诺贝尔奖所承认的那样在化学方面，在提高显微成像的空间分辨率方面取得了惊人的进展，从而产生了令人印象深刻的纳米工具武器库，可以打破光的衍射极限。尽管同样重要的是，对高时间分辨率的追求直到最近才引起人们的注意，这要归功于几种使能技术。开发这些超高速成像器的动机源于当代生物学的景观转移--从形态探索和表型探索在分子水平上寻求对潜在机制的量化洞察。《过客》分子事件发生的时间尺度从配体结合所需的数十微秒到数百微秒不等，分子振动所需的几十飞秒。因此，超快成像对于观察是必不可少的。以及对这种动态事件的描述。到目前为止，大多数微观尺度上的超快现象都是使用非基于成像的方法来探测的方法：研究方法。然而，由于大多数瞬时分子事件是分子级联反应的结果相互作用，而不是孤立地发生，缺乏图像限制了分析的范围。另一方面另一方面，尽管有捕捉二维图像的能力，但基于电子设备的传统相机图像传感器，如ccd和cmos，不能在理想的成像条件下提供高帧速率。由于电子带宽限制(数据传输、数字化和写入)的条件。为了解决这个根本问题，我们的策略是将压缩感知的范例引入到高速光学成像。我们不是测量Event DataCube的每个时空体素，而是利用生物场景的可压缩性，从而更有效地利用摄像机的带宽- 图像数据在被数字化并传输到主计算机之前被压缩。此功能将使我们的方法特别有利于记录高速图像数据，否则将如果在奈奎斯特采样下进行测量，则需要巨大的摄像头带宽和硬件资源。基于这一策略，我们将探索超高速生物成像，帧速率从几兆赫到十太赫兹，这个范围是对于理解生物分子行为是必不可少的，但目前无法通过传统的高速摄像机。由此产生的研究计划最终将导致新一代超高速生物成像仪和对最先进的方法进行变革性的进步。