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Related Concept Videos

Cryo-electron Microscopy01:28

Cryo-electron Microscopy

3.8K
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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Phase Contrast and Differential Interference Contrast Microscopy01:26

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Phase-Contrast Microscopes
In-phase-contrast microscopes, interference between light directly passing through a cell and light refracted by cellular components is used to create high-contrast, high-resolution images without staining. It is the oldest and simplest type of microscope that creates an image by altering the wavelengths of light rays passing through the specimen. Altered wavelength paths are created using an annular stop in the condenser. The annular stop produces a hollow cone of...
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Related Experiment Video

Updated: Oct 21, 2025

Cryo-EM and Single-Particle Analysis with Scipion
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Cryo-EM and Single-Particle Analysis with Scipion

Published on: May 29, 2021

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Toward Compositional Contrast by Cryo-STEM.

Michael Elbaum, Shahar Seifer, Lothar Houben

  • 1Department of Physics, Arizona State University, 550 E Tyler Drive, Tempe, Arizona 85287, United States.

Accounts of Chemical Research
|September 7, 2021
PubMed
Summary
This summary is machine-generated.

Cryo-electron microscopy (cryo-EM) can now quantitatively measure sample composition. This new approach uses scanning transmission electron microscopy (STEM) to reveal elemental contrast in biological specimens without staining.

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Area of Science:

  • Materials Science
  • Biophysics
  • Microscopy

Background:

  • Electron microscopy (EM) is crucial for nanoscale studies, but biological samples require careful preservation due to their sensitivity to vacuum and irradiation.
  • Cryogenic fixation (cryo-EM) revolutionized biological imaging by preserving samples in a native, vitrified state, enabling high-resolution structural determination.
  • Conventional cryo-transmission electron microscopy (TEM) has limitations in quantitative compositional analysis due to contrast dependence on defocus and low-frequency signal loss.

Purpose of the Study:

  • To explore the potential of quantitative contrast imaging in cryo-electron microscopy by adapting principles from soft X-ray cryo-tomography.
  • To investigate the application of scanning transmission electron microscopy (STEM) for compositional contrast in cryo-EM of biological specimens.

Main Methods:

  • Utilized scanning transmission electron microscopy (STEM), which employs incoherent elastic scattering sensitive to atomic number (Z).
  • Treated STEM as a pixel-by-pixel, low-angle diffraction measurement in amorphous materials, where dark-field signals quantitatively measure scattered flux.
  • Applied STEM to cryo-EM and cryo-tomography of biological specimens, focusing on interpreting scattering signals for compositional information.

Main Results:

  • Demonstrated that STEM provides compositional contrast in cryo-EM by leveraging Z-dependent scattering, offering a new dimension for analysis.
  • Showcased the potential for quantitative measurement of elemental composition in biological materials without the need for staining or heavy metal salts.
  • Highlighted the ability to interpret pixel intensities quantitatively, moving beyond traditional contrast limitations in cryo-TEM.

Conclusions:

  • Quantitative compositional contrast is achievable in cryo-EM using STEM, enabling direct measurement of sample makeup.
  • This approach overcomes limitations of conventional cryo-TEM by providing Z-sensitive contrast, opening avenues for unstained biological imaging.
  • Further development in interpreting STEM signals promises enhanced quantitative analysis and a deeper understanding of biological macromolecules at the atomic level.