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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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Updated: Jun 8, 2026

Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction

Do's and Don'ts of Cryo-electron Microscopy: A Primer on Sample Preparation and High Quality Data Collection for Macromolecular 3D Reconstruction

Published on: January 9, 2015

How to operate a cryo-electron microscope.

Jingchuan Sun¹, Huilin Li

¹Biology Department, Brookhaven National Laboratory, Upton, New York, USA.

Methods in Enzymology

|October 5, 2010

Summary

This summary is machine-generated.

This guide details transmission electron microscopy (TEM) for frozen-hydrated specimens. It offers a step-by-step protocol for new users to achieve high-quality cryo-electron micrographs.

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Area of Science:

Structural Biology
Microscopy Techniques

Background:

Transmission electron microscopy (TEM) is crucial for visualizing biological specimens at high resolution.
Imaging frozen-hydrated samples (cryo-TEM) preserves native structures but requires specialized techniques.

Purpose of the Study:

To provide a comprehensive, step-by-step guide for new users on imaging frozen-hydrated specimens using TEM.
To detail microscope operation, specimen handling, and image acquisition parameters for cryo-EM.

Main Methods:

Detailed protocol for starting up, aligning, and shutting down a JEOL transmission electron microscope.
Instructions for loading cryo-grids, inserting specimen holders, and setting up low-dose imaging modes.
Techniques for minimizing specimen drift, charging, and radiation damage during imaging.

Main Results:

A practical procedure applicable to various TEM systems with minor modifications.
Methods for estimating vitreous ice thickness and electron exposure dose.
Tips to enhance image quality and reduce artifacts in cryo-electron micrographs.

Conclusions:

Successful cryo-electron microscopy relies on meticulous technique and attention to detail.
This guide empowers new researchers to confidently perform cryo-TEM imaging.
Optimized procedures are essential for obtaining high-resolution structural information from biological samples.