Expanding the boundaries of cryo-EM with phase plates

•Phase plates are an emerging technology in cryo-electron microscopy (cryo-EM).•In cryo-electron tomography (cryo-ET) phase plates allow the visualization of cellular structures in high detail.•For single particle analysis (SPA) phase plates enable the study of small molecules and complexes.•Future improvements to phase plate technology are possible and some new designs are already under development.

Phase plates have long been considered as a means for improving the performance of cryo-electron microscopy (cryo-EM). But practical limitations, such as a short lifespan or cumbersome usage have prevented their widespread adoption. The recently developed Volta phase plate overcomes most of the practical issues and it is now commercially available. Results from both, electron cryo-tomography (cryo-ET) and single particle analysis (SPA), have demonstrated the benefits of using a phase plate. In CET phase plates have helped to visualize cellular ultrastructure in unprecedented detail. In SPA phase plates allowed to determine the structures of small proteins at near-atomic resolutions. Further improvements in phase plate technology are possible and new designs are already under development.