PDMS microfluidic chip for rapid time-resolved cryo-EM

Unmet Need: Method for assessing molecule structures in rapid reactions

Cryogenic electron microscopy (cryo-EM) is a method to determine the structure of biological molecules with high resolution. In time-resolved cryo-EM, the structures of molecules are determined at various stages of a reaction. However, methods to perform cryo-EM are manual, and some reactions proceed too quickly, preventing the intermediate structures from being determined. Sample preparation and loading in particular slow down the process of cryo-EM.

The Technology: Microfluidic chip with automated sample prep and rapid loading for cryo-EM

This technology is a PDMS-based microfluidic chip that can be used to determine intermediate molecular structures in rapid reactions. The chip integrates a mixer, a reaction channel, and a microsprayer to mix reactants quickly and effectively and to generate a consistent thickness on a cryo-EM grid. The chip design can be modified to accommodate reactions of various lengths.

This technology has been validated with various reactions, including the association reaction of the 70S ribosome by mixing 30S ribosomal and 50S ribosomal subunit.

Applications:

Time-resolved cryo-EM
Research tool for understanding drug metabolism
Microfluidic chip for other reactions involving mixing (ex: PCR)
Protein synthesis
Research tool for studying embryogenesis

Advantages:

Low cost
High-throughput platform for cryo-EM
Automated sample preparation and loading
Compatible with fast reactions

Lead Inventor:

Joachim Frank, Ph.D.

Patent Information:

Patent Pending

Related Publications:

Feng X, Fu Z, Kaledhonkar S, Jia Y, Shah B, Jin A, Liu Z, Sun M, Chen B, Grassucci RA, Ren Y, Jiang H, Frank J, Lin Q. “A fast and effective microfluidic spraying-plunging method for high-resolution single-particle cryo-EM” Structure. 2017 Apr; 25(4): 663-670.

Tech Ventures Reference:

IR CU19167
Licensing Contact: Kristin Neuman