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Sample preparation for cryo electron microscopy (cryoEM) now represents the bottleneck in the process to high-resolution structure determination. The basic premise of cryoEM sample preparation was pioneered over 30 years ago by Dubochet and colleagues and largely has not been updated since. This process, while revolutionary in its' time, is now seen as difficult, wasteful of sample and microscope time, and requiring both skill and luck to produce a high-quality grid
Darrow et al. (Thu,) studied this question.