EasyGrid: a versatile platform for automated cryo-EM sample preparation and quality control.

Gemin, Olivier; Armijo, Victor; Lecomte, Léa; Hons, Michael; Deckers, Thibault; Bissardon, Caroline; Rossi, Christopher; Lauzier, Kévin et al. · Nat Methods · 2026

basic_science · Level V

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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.