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Novel and Optimized Cryo-EM Sample Preparation with Cryo EleMent™

Technology Benefits
Low sampleoptimization, short screening time, and high reproducibilityBlot-freeapproach reduces quantity of protein needed for 3D structure determinationEliminatesair-water interface to improve protein orientation distributionsStandardization of sample preparation reducescost and enables quick cryo-cell production scaling
Technology Application
Cyro-cell can serve as a standardized sample preparation for all cryo-EM microscope on the market.
Detailed Technology Description
Rapid, efficient, blot-free,and low-cost sample optimization for cryo-EM
Countries
United States
Application No.
PCT/US2017/064831
*Abstract

Cryo-electronmicroscopy (cryo-EM) is emerging as the preferred method to determine 3Dprotein structures in biomedical research and drug discovery. The method’simportance was acknowledged with the 2017 Nobel Prize in Chemistry. Cryo-EM isperformed by taking pictures of frozen proteins using an electron microscope,then processing the images with a computer to create a 3D structure of theprotein. This method thereby enables atomic-resolution molecular structuresunder native conditions and without the need for crystallization. We have anovel nanofabricated invention, Cryo EleMent™, to address the problems withcryo-EM sample preparation, enhance automation in cryo-EM workflows, and pushcryo-EM to the next frontier.

Our device targetsa central problem in existing cryo-EM workflows – the process of freezingproteins in a thin film of water before imaging. Current technology forpreparing these thin ice samples is associated with an array of problems rootedin lack of control over sample geometry, uniformity, and environment (LEFT). The new technology we present usesa nanofabricated chamber that gives full control over sample preparation,thereby ensuring consistency and reproducibility for every sample (RIGHT). Additionally, slits in the topof Cryo EleMent™ nanochamber allow for passive protein loading by capillaryaction, thereby eliminating traditional blotting and reducing the proteinmaterial requirements over 1,000-fold. Our innovation thus delivers a low-cost,blot-free approach that accelerates automation while smoothly incorporatinginto existing cryo-EM workflows. We also envision that these features will makecryo-EM easier to use, and thereby broaden the cryo-EM market.

Prototype testinghas shown the viability of the core technology. The design was conceived forscalable manufacturing by leveraging existing semiconductor manufacturingprocesses. We anticipate the mature incarnation of Cryo EleMent™ will helpbreach current problems in cryo-EM and open new scientific and commercialopportunities.

BrandeisOTL is seeking statements of interest from parties interested in licensingand/or sponsoring collaborative research to further develop, evaluate, orcommercialize this technology and its applications.


*IP Issue Date
None
*IP Type
Utility
Country/Region
USA

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