A simple pressure-assisted method for MicroED specimen preparation

Abstract Micro-crystal electron diffraction (MicroED) has shown great potential for structure determination of macromolecular crystals too small X-ray diffraction. However, specimen preparation remains a major bottleneck. Here, we report simple method preparing MicroED specimens, named Preassis, in which excess liquid is removed through an EM grid with the assistance pressure. We show ice thicknesses can be controlled by tuning pressure combination grids appropriate carbon hole sizes. Importantly, Preassis handle wide range protein grown various buffer conditions including those high viscosity, as well samples low crystal concentrations. and universal preparation, will significantly broaden applications MicroED.