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

I-Corps项目更广泛的影响/商业潜力是推动单粒子冷冻电子显微镜（cryo-EM）发展成为主流结构生物学技术。核心技术是一种研究工具，为生物医学领域的科学家制备蛋白质样品提供了一种可靠、可重复、具有成本效益的方法。通过使用冷冻电镜技术研究蛋白质在自然环境中的作用，研究人员可以更好地了解它们的结构，从而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项目探索了一个独立的低温电镜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体系统的应用，以毫秒为单位在EM网格上沉积和玻璃化蛋白质溶液。此外，它为科学家提供了在蛋白质溶液到达网格之前通过调整其厚度来控制样品厚度的能力。有了这项技术，冷冻电镜网格的更大区域将具有完整的蛋白质分子和适当厚度的玻璃化水层，因此可用于结构测定，使研究人员在图像收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。这样就可以解决更多的蛋白质结构，从而可以开发出更好的治疗方法和药物。

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.