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Updated: Jan 21, 2026

Preparation of High-Temperature Sample Grids for Cryo-EM
Published on: July 26, 2021
Challenges and opportunities in cryo-EM with phase plate
1Ministry of Education Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center of Biological Structures, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Phase plates enhance contrast in transmission electron microscopy (TEM), particularly for cryo-electron microscopy (cryo-EM) of biological samples. This review covers recent advancements, challenges, and future prospects of phase plate technology in cryo-EM.
Area of Science:
- Microscopy
- Biophysics
- Materials Science
Background:
- Transmission electron microscopy (TEM) is a powerful imaging technique.
- Phase plates were proposed early in TEM development to improve image contrast.
- Cryo-electron microscopy (cryo-EM) benefits significantly from enhanced contrast for biological specimens.
Purpose of the Study:
- To review the progress of phase plate technology in cryo-EM.
- To discuss current challenges and future opportunities for phase plates in cryo-EM applications.
Main Methods:
- Review of novel phase plate designs and fabrication for cryo-EM.
- Analysis of phase plate performance in single particle cryo-EM and cryo-electron tomography (cryo-ET).
- Discussion of established phase plate types, such as the Volta phase plate.
Main Results:
- Various novel phase plates have been developed and fabricated over the past two decades.
- Phase plates, like the Volta phase plate, have demonstrated significant utility in cryo-EM.
- These advancements are crucial for high-resolution imaging of biological samples.
Conclusions:
- Phase plate technology has matured and is integral to modern cryo-EM.
- Continued research is needed to overcome existing challenges and unlock new opportunities.
- Phase plates offer a promising avenue for further advancements in biological imaging.
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