EasyGrid: a versatile platform for automated cryo-EM sample preparation and quality control
Olivier Gemin, Victor Armijo, Michael Hons, Caroline Bissardon, Romain Linares, Matthew W. Bowler, Georg Wolff, Kirill Kovalev, Anastasiia Babenko, Veijo T. Salo, Sarah Schneider, Christopher Rossi, Léa Lecomte, Thibault Deckers, Kévin Lauzier, Robert Janocha, Franck Felisaz, Jérémy Sinoir, Wojciech P. Galej, Julia Mahamid, Christoph W. Müller, Sebastian Eustermann, Simone Matteï, F. Cipriani, Gergely Papp
Abstract
Optimized sample preparation is essential for imaging biological macromolecules in their native state using single-particle cryo-electron microscopy (cryo-EM) or in situ cryo-electron tomography (cryo-ET). Here we present EasyGrid, a modular, automated platform designed to streamline and standardize cryo-EM/ET sample preparation. EasyGrid integrates in-line plasma treatment of the sample support, microfluidic dispensing, blot-less sample spreading, jet-based vitrification and grid quality control via light interferometry. We demonstrate its effectiveness by preparing grids for multiple purified macromolecular complexes and resolving their structures with cryo-EM. Additionally, EasyGrid achieves improved vitrification of large mammalian cells compared to conventional plunge-freezing. By enabling systematic and high-throughput optimization, EasyGrid provides a robust and time-saving solution for both structural and cellular cryo-EM applications.