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Updated: Aug 15, 2026

Cryo-electron Microscopy Specimen Preparation By Means Of a Focused Ion Beam
10:54

Cryo-electron Microscopy Specimen Preparation By Means Of a Focused Ion Beam

Published on: July 26, 2014

Application of cryofixation and cryoultramicrotomy for biological electron microscopy

Kenji Saga1

  • 1Department of Dermatology, Sapporo Medical University School of Medicine, Minami 1 Nishi 16, Chuo-ku, Sapporo, 060-8543, Japan. ksaga@sapmed.ac.jp

Medical Molecular Morphology
|September 20, 2005
PubMed

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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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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...