Time-Resolved Cryo-EM Specimen Preparation with Single Millisecond Precision

Molecular structures can be determined in vitro and in situ with cryo-electron microscopy (cryo-EM). Specimen preparation is a major obstacle in cryo-EM. Typical sample preparation is orders of magnitude slower than biological processes. Time-resolved cryo-EM (TR-cryo-EM) can capture short-lived states. Here, we present Cryo-EM Sample Preparation with light-Activated Molecules (C-SPAM), an open-source, photochemistry-coupled device for TR-cryo-EM with single millisecond resolution, tunable timescales, and broad biological applications.