RT Journal Article SR Electronic T1 A simple pressure-assisted method for MicroED specimen preparation JF bioRxiv FD Cold Spring Harbor Laboratory SP 665448 DO 10.1101/665448 A1 Jingjing Zhao A1 Hongyi Xu A1 Hugo Lebrette A1 Marta Carroni A1 Helena Taberman A1 Martin Högbom A1 Xiaodong Zou YR 2021 UL http://biorxiv.org/content/early/2021/02/19/665448.abstract AB Micro-crystal electron diffraction (MicroED) has shown great potential for structure determination of macromolecular crystals too small for X-ray diffraction. However, specimen preparation remains a major bottleneck. Here, we report a simple method for preparing MicroED specimens, named Preassis, in which excess liquid is removed through an EM grid with the assistance of pressure. We show the ice thicknesses can be controlled by tuning the pressure in combination with EM grids with appropriate hole sizes. Importantly, Preassis can handle a wide range of protein crystals grown in various buffer conditions including those with high viscosity, as well as samples with low crystal contents. Preassis is a simple and universal method for MicroED specimen preparation, and will significantly broaden the applications of MicroED.Competing Interest StatementThe authors have declared no competing interest.