Innovation and Partnerships Office

Consistent, Reliable Preparation of Cryo-EM Specimens 2015-108


  • Preparation of biological samples for electron microscopy


  • Enables consistent and reliable production of samples
  • Thickness of cryo-EM specimens is uniform across the grid
  • Facilitates the production of extremely thin samples
  • Potentially damaging sample evaporation not required


Researchers at Berkeley Lab have proposed a cryogenic Electron Microscope (cryo-EM) specimen-preparation technology that eliminates current issues of poor reproducibility and standardizes the process of thinning EM samples. Previously used steps of blotting and (optionally) evaporation are eliminated. This technology enables the reliable and consistent production of thin, high-resolution cryo-EM samples that can be utilized to study structural and functional components of biological samples in a variety of research-based and practical settings.

The Berkeley Lab technology involves the application of an aqueous solution containing a biological sample to a hydrophilic EM grid. Excess solution is then removed from the edges of the grid, rather than being blotted off the surface as is currently practiced. This leaves a relatively thick layer of liquid that will then be thinned using a volatile surfactant. A non-volatile surfactant can be added to the surface of the film, which serves to stabilize the sample at the desired thickness.

STATUS: Patent pending. Available for licensing or collaborative research.

DEVELOPMENT STAGE: Experiments set up on an open lab bench demonstrated the proof of concept for making uniformly thin, aqueous specimens over areas as large as a few millimeters and for stabilizing these with an additional, non-volatile surfactant. In the next phase, new equipment, intended to be a fully functional prototype, will be used in the same experiments. This will be followed by electron microscopy of specimens prepared with the prototype.


High Affinity Specimen Support Film for Electron Microscopy, 2015-002

Active Cryogenic Electronic Envelope, 2014-038

Portable Cryo-plunger for Cryogenic Microscopy Sampling, IB-3145