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I-Corps: Time-Resolved Sample Preparation for Single-Particle Cryo-Electron Microscopy

I-Corps：单粒子冷冻电子显微镜的时间分辨样品制备

基本信息

批准号：
1807881
负责人：
Rhonda Shrader
金额：
$ 5万
依托单位：
University of California-Berkeley
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-01 至 2018-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807881&HistoricalAwards=false
关键词：
Corps Time Resolved Sample Preparation

项目摘要

The broader impact/commercial potential of this I-Corps project is to propel the development of single-particle cryo-electron microscopy (cryo-EM) into a mainstream structural biology technique. The core technology is a research tool that provides a reliable, reproducible, cost-effective method for scientists to prepare their protein samples in the biomedical field. By studying proteins in their natural environment using cryo-EM, researchers get a better understanding of their structures and thus their functions within the cells. This new knowledge will potentially facilitate as well as accelerate the development of therapeutic treatments.This I-Corps project explores the commercial potential of a stand-alone cryo-EM sample preparation stage. The core technology in discussion is based on the application of state-of-the-art microfluidic systems to deposit and vitrify protein solution on EM grids in milliseconds. Furthermore, it offers scientists the ability to control their sample thickness by adjusting the thickness of the protein solution before it hits the grid. With this technology, a larger region of the cryo-EM grids will have intact protein molecules and the right thickness of vitrified aqueous layer and is thus usable for structural determination, allowing researchers to save significant time and money in terms of image collection as well as tedious protein extraction and purification. This way more protein structures can be solved, and thus better therapeutics and drugs can be developed.

这个i-Corps项目的更广泛的影响/商业潜力是推动单粒子低温电子显微镜(Cryo-EM)的发展成为一项主流的结构生物学技术。核心技术是一种研究工具，为科学家在生物医学领域准备他们的蛋白质样本提供了一种可靠、可重复、成本效益高的方法。通过使用低温EM研究自然环境中的蛋白质，研究人员可以更好地了解它们的结构，从而更好地了解它们在细胞内的功能。这一新知识将潜在地促进和加速治疗方法的发展。这个i-Corps项目探索了独立的低温EM样品制备阶段的商业潜力。讨论的核心技术是基于最先进的微流控系统的应用，在几毫秒内将蛋白质溶液沉积并玻璃化在EM网格上。此外，它为科学家提供了通过在蛋白质溶液到达网格之前调整其厚度来控制样品厚度的能力。有了这项技术，更大范围的冷冻-EM网格将拥有完整的蛋白质分子和合适的玻璃化水层厚度，从而可用于结构测定，使研究人员在图像采集以及繁琐的蛋白质提取和纯化方面节省大量时间和金钱。这种方法可以解决更多的蛋白质结构，从而可以开发出更好的疗法和药物。