PT - JOURNAL ARTICLE AU - Jingjing Zhao AU - Hongyi Xu AU - Hugo Lebrette AU - Marta Carroni AU - Helena Taberman AU - Martin Högbom AU - Xiaodong Zou TI - A simple pressure-assisted method for MicroED specimen preparation AID - 10.1101/665448 DP - 2021 Jan 01 TA - bioRxiv PG - 665448 4099 - http://biorxiv.org/content/early/2021/02/19/665448.short 4100 - http://biorxiv.org/content/early/2021/02/19/665448.full 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.