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

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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.