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Related Concept Videos

Cryo-electron Microscopy01:28

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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Electron Microscope Tomography and Single-particle Reconstruction01:07

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Transmission electron microscopy (TEM) can be used to determine the 3D structure of biological samples with the help of techniques such as electron microscope tomography and single-particle reconstruction. While single-particle reconstruction can examine macromolecules and macromolecular complexes in vitro conditions only, tomography permits the study of cell components or small cells in vivo.
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Transmission Electron Microscopy01:15

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In 1931, physicist Ernst Ruska—building on the idea that magnetic fields can direct an electron beam just as lenses can direct a beam of light in an optical microscope—developed the first prototype of the electron microscope. This development led to the development of the field of electron microscopy. In the transmission electron microscope (TEM), electrons are produced by a hot tungsten element and accelerated by a potential difference in an electron gun, which gives them up to 400...
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Overview of Electron Microscopy01:25

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The wavelengths of visible light ultimately limit the maximum theoretical resolution of images created by light microscopes. Most light microscopes can only magnify 1000X, and a few can magnify up to 1500X. Electrons, like electromagnetic radiation, can behave like waves, but with wavelengths of 0.005 nm, they produce significantly greater resolution up to 0.05 nm as compared to 500 nm for visible light. An electron microscope (EM) can create a sharp image that is magnified up to 2,000,000X.
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Related Experiment Video

Updated: Mar 14, 2026

Manual Blot-and-Plunge Freezing of Biological Specimens for Single-Particle Cryogenic Electron Microscopy
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Single particle electron cryomicroscopy: trends, issues and future perspective.

Kutti R Vinothkumar1, Richard Henderson1

  • 1MRC Laboratory of Molecular Biology,Francis Crick Avenue,Cambridge CB2 0QH,UK.

Quarterly Reviews of Biophysics
|September 24, 2016
PubMed
Summary

Recent advancements in electron cryomicroscopy (cryoEM) enable high-resolution 3D biological structure determination. Further improvements in image processing and minimizing beam effects can unlock near-atomic resolution for smaller molecules.

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Area of Science:

  • Structural Biology
  • Biophysics
  • Microscopy

Background:

  • Single particle electron cryomicroscopy (cryoEM) has seen significant progress in determining 3D biological structures.
  • Higher resolution and reduced image requirements are now achievable.

Purpose of the Study:

  • To review recent advancements in cryoEM technology and computational methods.
  • To identify areas for future improvement to realize the full potential of cryoEM.
  • To advocate for more accessible cryoEM instrumentation.

Main Methods:

  • Improved direct electron detectors with higher detective quantum efficiency.
  • Advanced computational algorithms for image processing.
  • Optimization of biochemistry and grid preparation for macromolecule distribution.

Main Results:

  • Near-atomic resolution is increasingly attainable for biological macromolecules.
  • New detectors and algorithms have significantly enhanced cryoEM capabilities.
  • Challenges remain in minimizing image degradation from beam-induced specimen movement and charge buildup.

Conclusions:

  • Further gains in cryoEM resolution are possible by addressing image degradation issues.
  • Development of lower-cost cryoEM instruments is crucial for broader accessibility.
  • Successful high-resolution structure determination relies on image interpretation and sample preparation.