Electron counting with direct electron detectors in MicroED

The combination of high sensitivity and rapid readout makes it possible for electron-counting detectors to record cryogenic electron microscopy data faster and more accurately without increasing the number of electrons used for data collection. This is especially useful for MicroED of macromolecular crystals where the strength of the diffracted signal at high resolution is comparable to the surrounding background. The ability to decrease fluence also alleviates concerns about radiation damage which limits the information that can be recovered from a diffraction measurement. The major concern with electron-counting direct detectors lies at the low end of the resolution spectrum: their limited linear range makes strong low-resolution reflections susceptible to coincidence loss and careful data collection is required to avoid compromising data quality. Nevertheless, these cameras are increasingly deployed in cryo-EM facilities, and several have been successfully used for MicroED. Provided coincidence loss can be minimized, electron-counting detectors bring high potential rewards.