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Cryo-electron Microscopy

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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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Related Experiment Video

Updated: Jan 17, 2026

Strategies for Optimization of Cryogenic Electron Tomography Data Acquisition

Strategies for Optimization of Cryogenic Electron Tomography Data Acquisition

Published on: March 19, 2021

Dose-efficient cryo-electron microscopy for thick samples using tilt- corrected scanning transmission electron

Yue Yu^1,2, Katherine A Spoth^3,4, Michael Colletta³

¹School of Applied and Engineering Physics, Cornell University, Ithaca, NY, USA. yue.yu@czii.org.

|September 23, 2025

Summary

This summary is machine-generated.

This study introduces tilt-corrected bright-field scanning transmission electron microscopy for imaging thick biological specimens. This method enhances contrast and dose efficiency, improving structural biology research.

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Last Updated: Jan 17, 2026

Strategies for Optimization of Cryogenic Electron Tomography Data Acquisition

Strategies for Optimization of Cryogenic Electron Tomography Data Acquisition

Published on: March 19, 2021

Preparation and Observation of Thick Biological Samples by Scanning Transmission Electron Tomography

Preparation and Observation of Thick Biological Samples by Scanning Transmission Electron Tomography

Published on: March 12, 2017

Single-Particle Cryo-EM Data Collection with Stage Tilt using Leginon

Single-Particle Cryo-EM Data Collection with Stage Tilt using Leginon

Published on: July 1, 2022

Area of Science:

Structural Biology
Electron Microscopy

Background:

Thick specimens in electron microscopy cause inelastic electron scattering, leading to chromatic aberrations and image defocus.
Current methods like energy-filtered transmission electron microscopy filter out inelastic scattering, reducing signal and dose efficiency.

Purpose of the Study:

To develop a dose-efficient imaging technique for thick specimens in electron microscopy.
To improve contrast and signal preservation in cryo-electron microscopy of biological samples.

Main Methods:

Utilized tilt-corrected bright-field scanning transmission electron microscopy (BF-STEM) with pixelated detectors.
Collected unfiltered image data from intact bacterial cells and large organelles.
Performed single-particle analysis on a virus-like particle.

Main Results:

Achieved enhanced contrast and 3-5x improved dose efficiency for specimens >500 nm thick.
Demonstrated successful imaging of intact bacterial cells and large organelles.
Obtained a sub-nanometer resolution single-particle analysis map for a virus-like particle.

Conclusions:

Tilt-corrected BF-STEM offers a dose-efficient and high-contrast alternative to energy-filtered TEM for thick biological specimens.
The technique is suitable for both imaging and high-resolution structural determination.