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.

项目摘要：PI提议开发一个超快生物成像项目，该项目可以开辟一个新领域空间和时间这两个关键的物理现象。维度构成了现代计量学的基础，并获得了 2014 年诺贝尔奖的认可。化学，在提高显微成像的空间分辨率方面取得了惊人的进步，产生了令人印象深刻的纳米显微镜工具库，可以突破光的衍射极限。重要的是，由于出现了以下问题，对高时间分辨率的追求最近才引起人们的关注开发这些超快成像仪的动机源于多种支持技术。当代生物学从形态学探索和表型探索的景观转变有机体寻求分子水平上潜在机制的定量见解。分子事件发生的时间尺度从配体结合所需的数十到数百微秒不等，因此，分子振动需要数十飞秒，超快成像对于观察至关重要。以及此类动态事件的表征。迄今为止，大多数微观尺度的超快现象都是使用非成像技术来探测的然而，由于大多数瞬态分子事件是分子级联的结果。另一方面，缺乏图像限制了分析的范围。另一方面，尽管能够捕捉二维图像，但基于电子的传统相机图像传感器（例如 CCD 和 CMOS）无法在所需成像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）而导致的条件。为了解决这个基本问题，我们的策略是将压缩感知范式引入到我们将不再测量事件数据立方体的每个时空体素。利用生物场景的可压缩性并更有效地利用相机的带宽，从而图像数据在数字化并传输到主机之前会被压缩。使我们的方法特别有利于记录高速图像数据，否则会如果基于奈奎斯特采样进行测量，则需要巨大的相机带宽和硬件资源。根据这一策略，我们将探索帧速率从几 MHz 到 10 THz 的超快生物成像，该范围是对于理解生物分子行为至关重要，但目前传统高速无法实现由此产生的研究项目将最终产生新一代超快生物成像仪和相机。对最先进的方法做出变革性的进步。