Sample preparation for single-particle electron cryo-microscopy (cryo-EM) remains a bottleneck of this technique. The sample ice thickness cannot be accurately controlled, molecules may display strongly preferred orientations that make more elaborate data collection schemes necessary, and the sample may degrade at the air-water interface before it is finally frozen. In their pioneering work, the authors describe a prototype of a new microfluidic device that addresses some of these problems, including a refreshingly objective and critical discussion about the pros and cons of this novel approach. While some development will be required for this method to become mainstream, it has the potential to become a powerful alternative to the conventional workflow of single-particle cryo-EM, enabling full automation and making sample preparation highly reproducible.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)