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Modern approaches to improving phase contrast electron microscopy.

Jeremy J Axelrod1,2, Jessie T Zhang1, Petar N Petrov1,2

  • 1Department of Physics, University of California Berkeley, Berkeley, CA 94720, USA.

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Summary

Phase plates enhance contrast in cryo-electron microscopy (cryo-EM) by shifting electron beam phases. This review covers laser-based methods and scanning transmission electron microscopy (STEM) alternatives for high-resolution imaging.

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Area of Science:

  • Microscopy
  • Biophysics
  • Materials Science

Background:

  • Transmission electron microscopy (TEM) traditionally uses defocus for partial phase contrast.
  • Cryo-electron microscopy (cryo-EM) requires enhanced contrast for high-resolution imaging of biological samples.
  • Phase plates offer a method to increase contrast by altering the phase of the unscattered electron beam.

Approach:

  • Investigating phase plates that utilize the ponderomotive interaction between light and electrons.
  • Reviewing alternative approaches using pulsed or near-field enhanced laser light.
  • Exploring scanning transmission electron microscopy (STEM) with segmented detectors as a phase plate alternative.

Key Points:

  • Recent successes in high-resolution single-particle cryo-EM using ponderomotive phase plates are highlighted.
  • The efficacy of laser-based phase shifting techniques is evaluated.
  • STEM with segmented detectors presents a viable alternative to traditional phase plates.

Conclusions:

  • Phase plates significantly improve contrast in cryo-EM, enabling higher resolution.
  • Laser-driven and STEM-based methods offer promising avenues for advancing cryo-EM technology.
  • Continued development in phase contrast techniques is crucial for future breakthroughs in electron microscopy.