Modern approaches to improving phase contrast electron microscopy

TL;DR

This paper reviews recent advances in phase contrast enhancement techniques for cryo-electron microscopy, including phase plates, laser light methods, and STEM with segmented detectors, aiming to improve high-resolution imaging.

Contribution

It provides a comprehensive overview of recent technological developments and experimental successes in phase contrast methods for cryo-EM.

Findings

Successful application of phase plates in high-resolution cryo-EM

Emerging laser light techniques as alternatives for phase contrast

Use of segmented detectors in STEM for improved contrast

Abstract

Although defocus can be used to generate partial phase contrast in transmission electron microscope images, cryo-electron microscopy (cryo-EM) can be further improved by the development of phase plates which increase contrast by applying a phase shift to the unscattered part of the electron beam. Many approaches have been investigated, including the ponderomotive interaction between light and electrons. We review the recent successes achieved with this method in high-resolution, single-particle cryo-EM. We also review the status of using pulsed or near-field enhanced laser light as alternatives, along with approaches that use scanning transmission electron microscopy (STEM) with a segmented detector rather than a phase plate.