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Related Concept Videos

Preparation of Samples for Electron Microscopy01:20

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To be visualized by an electron microscope, either transmission or scanning, biological samples need to be fixed (stabilized) so the electron beam does not destroy them and dried thoroughly (desiccated/dehydrated) so the vacuum does not affect them. Fixation needs to be done as quickly as possible because the sample properties will start changing as soon as it is removed from its natural environment. For example, in a tissue sample, the oxygen levels begin decreasing, causing an altered...
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Optimizing Sample Preparation for Cryogenic Electron Microscopy
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Cool and collected: Advances in sample preparation for cryo-electron microscopy.

Shani Tcherner Elad1, Noa Ben-Asher1, Leeya Engel2

  • 1Faculty of Mechanical Engineering, Technion - Israel Institute of Technology Haifa 3200003, Israel.

Current Opinion in Structural Biology
|August 10, 2025
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Summary

Recent innovations in cryo-electron microscopy (cryo-EM) sample preparation are making high-resolution structural biology more accessible. These advances enable detailed visualization of proteins within cells and tissues.

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Area of Science:

  • Structural Biology
  • Biophysics
  • Cell Biology

Background:

  • Cryo-electron microscopy (cryo-EM) provides high-resolution visualization of macromolecules in native states.
  • Advances like cryo-focused ion beam milling (cryo-FIB) extend cryo-EM to cells and tissues.
  • High-resolution structural analysis within cellular contexts is increasingly achievable.

Purpose of the Study:

  • To review recent innovations in cryo-electron microscopy sample preparation.
  • To highlight techniques enabling study of cells and tissues.
  • To discuss how these advances expand the impact of cryo-EM.

Main Methods:

  • Review of novel support fabrication and functionalization techniques.
  • Discussion of cell micropatterning for improved sample orientation.
  • Examination of advanced methods for thinning frozen biological samples.

Main Results:

  • Innovations streamline and improve the repeatability of sample preparation.
  • New techniques enable unprecedented visualization of structures within cells and tissues.
  • Advancements facilitate structural analysis of biological processes at controlled time points.

Conclusions:

  • Cryo-EM sample preparation advancements are overcoming previous technical challenges.
  • These innovations are crucial for realizing the full potential of cryo-EM in structural biology.
  • The improved accessibility of cryo-EM will advance understanding of health and disease states.