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

• 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

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.

该I-Corps项目的更广泛的影响/商业潜力是推动单粒子冷冻电子显微镜（Cryo-EM）的开发到主流结构生物学技术中。 核心技术是一种研究工具，它为科学家提供了一种可靠，可重复的，具有成本效益的方法，可以在生物医学领域准备其蛋白质样品。 通过使用冷冻EM在自然环境中研究蛋白质，研究人员可以更好地了解其结构，从而可以在细胞中的功能。 这种新知识将有可能促进并加速治疗治疗的发展。该I-Corps项目探讨了独立的冷冻EM样品制备阶段的商业潜力。 讨论中的核心技术是基于最先进的微流体系统在毫秒内将蛋白质溶液沉积和剥落蛋白质溶液的应用。 此外，它为科学家提供了通过调整蛋白质溶液的厚度来控制其样品厚度的能力。 借助这项技术，较大的冷冻EM网格区域将具有完整的蛋白质分子和正确的玻璃化水层厚度，因此可用于结构测定，从而使研究人员能够在图像收集以及乏味的蛋白质提取和纯化中节省大量的时间和金钱。 这样可以解决更多蛋白质结构，因此可以开发出更好的治疗剂和药物。