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Cryo-electron Microscopy

Cryo-electron Microscopy

Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...

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Cryogenic Liquid Jets for High Repetition Rate Discovery Science

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Ultracold cryogenic TEM with liquid helium and high stability.

Emily Rennich^1,2, Suk Hyun Sung^1,3, Nishkarsh Agarwal³

¹The Rowland Institute at Harvard, Harvard University, Cambridge, MA 02138.

Proceedings of the National Academy of Sciences of the United States of America

|September 5, 2025

Summary

Researchers developed a new ultracold liquid helium specimen holder for transmission electron microscopes. This stable, continuous cryogen flow instrument enables atomic resolution imaging at sub-25 K temperatures.

Keywords:

cryo-EM cryo-TEM electron microscopy liquid helium

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Last Updated: Sep 8, 2025

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A Simple Dewar/Cryostat for Thermally Equilibrating Samples at Known Temperatures for Accurate Cryogenic Luminescence Measurements

A Simple Dewar/Cryostat for Thermally Equilibrating Samples at Known Temperatures for Accurate Cryogenic Luminescence Measurements

Published on: July 19, 2016

Area of Science:

Structural biology
Materials science
Electron microscopy

Background:

Cryogenic transmission electron microscopy (cryo-TEM) is vital for advanced research.
Existing liquid helium stages for cryo-TEM are complex and unstable, hindering high-resolution imaging.
Challenges are amplified in side-entry specimen holders used in modern transmission electron microscopes.

Purpose of the Study:

To introduce a novel ultracold liquid helium transmission electron microscope side-entry specimen holder.
To overcome the limitations of existing cryogenic stages for high-resolution imaging.
To enable stable imaging at temperatures below 25 K.

Main Methods:

Development of a side-entry specimen holder with continuous cryogen flow.
Integration of vibration decoupling mechanisms.
Compatibility testing with modern aberration-corrected transmission electron microscopes.

Main Results:

Achieved a base temperature below 25 K.
Demonstrated exceptional thermal stability of ±2 mK over extended periods.
Attained atomic resolution imaging capabilities.

Conclusions:

The new specimen holder significantly enhances the stability and performance of cryogenic transmission electron microscopy.
Enables unprecedented high-resolution imaging at ultralow temperatures.
Paves the way for new discoveries in structural biology and materials science.