Time Resolved Cryo‐Correlative Light and Electron Microscopy

Abstract Complex materials exhibit fascinating features especially in situations far from equilibrium. Thus, methods for investigating structural dynamics with sub‐second time resolution are becoming a question of interest at varying spatial scales. With novel microscopy techniques steadily improving, the temporal and spatial limits of multiple imaging methods are investigated with an emphasis on the important role of correlative imaging and cryo‐fixation. A deep‐dive is taken into cryo‐correlative light and electron microscopy (CLEM) as a starting point for multimodal investigations of ultrastructural dynamics at high spatiotemporal resolution. The focus is on highlighting the different microscopy methods that capture the following key aspects: 1) samples are as close to native state as possible 2) dynamic process information is captured, 3) high structural resolution is enabled. Additionally, the size of samples that can be imaged under these conditions is looked at and approaches not only focusing on single molecules, but larger structures are highlighted.