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Optimization of Cryo-EM Data Collection Using Advanced Direct Detectors

The development of direct detection cameras for transmission electron microscopy has enabled recording of images with unprecedented quality. These large-format ( > 4 million pixels) cameras can deliver a continuous stream of images with near-optimal detective quantum efficiency (DQE). Notably, this development led to the “resolution revolution” [1] in biological electron cryo-microscopy (cryo-EM), culminating in the 2017 Nobel Prize in Physics for the development of this technique. The latest generation of direct detectors have numerous improvements in speed, sensitivity, and array size that offer increased flexibility and throughput as microscope time has become more competitive with large facilities requiring preliminary data. Typically slow techniques such as cryo-electron tomography (cryo-ET) [2] and microcrystalline electron diffraction (microED) [3] have seen significant speed increases by coupling a continuously tilting stage with synchronized readout from the detector.