Abstract text (incl. figure legends and references)
For many years, life science cryo-EM has been practically synonymous with wide-field imaging in transmission. This modality has been famously successful in determination of macromolecular structure at near-atomic resolution, based on the combination of phase contrast generated by defocus with image averaging. The same wide-field TEM approach was further employed for pioneering works in 3D imaging of cells by tomography. An alternative modality is STEM, scanning transmission EM. STEM uses a focused probe and a variety of detectors to collect one or more signals pixel by pixel. Its popularity in the materials sciences has not yet been matched in cryo-EM for biological materials, due mainly to the impression that STEM is incompatible with beam-sensitive specimens. To the contrary, STEM may be more dose-efficient than TEM. A case in point is tomography of thick samples, where the energy filter required for conventional TEM can be avoided. 4D STEM and multi-segment detectors can collect every electron, but the means to combine the information they contribute are still under development. These include angle-resolved STEM, ptychography, and differential phase contrast in various configurations. The power of the scanning probe methods lies in their flexibility, and the fact that multiple image contrast modes may be generated in a single scan. The talk will describe progress and prospects for cryo-STEM in life science applications with an emphasis on cellular cryo-tomography.