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Updated: Jan 13, 2026

Expansion Microscopy: High-Resolution Fluorescent Imaging with a Conventional Microscope
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Expansion Microscopy: High-Resolution Fluorescent Imaging with a Conventional Microscope.

Perrine Hervé1, Léo Krüttli2, Mélanie Bonhivers3

  • 1University of Bordeaux, CNRS, MFP, iMet UMR 5234.

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|January 6, 2026
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Summary
This summary is machine-generated.

Expansion microscopy (ExM) physically enlarges samples for super-resolution imaging with standard microscopes. Combining ExM with cryo-fixation preserves near-native cellular structures for detailed nanoscale observation.

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Area of Science:

  • Biophysics
  • Cell Biology
  • Microscopy

Background:

  • Expansion microscopy (ExM) offers super-resolution imaging by physically enlarging samples.
  • Conventional ExM relies on chemical fixation, which can introduce artifacts.
  • Ultrastructure Expansion Microscopy (U-ExM) enhances preservation of fine cellular details.

Purpose of the Study:

  • To detail a protocol for cryo-fixation combined with U-ExM.
  • To enable nanoscale imaging of biological samples in a near-native state.
  • To provide guidance for implementing this advanced imaging technique.

Main Methods:

  • Cryo-fixation of diverse biological samples.
  • Embedding samples in a swellable hydrogel matrix for isotropic expansion.
  • Post-expansion immunostaining and imaging using conventional confocal microscopy.

Main Results:

  • Successful nanoscale imaging of various biological samples, including cultured cells and whole organisms.
  • Preservation of near-native cellular architecture and fine structures.
  • Minimization of artifacts typically associated with chemical fixation methods.

Conclusions:

  • Cryo-fixation coupled with U-ExM provides high-resolution, artifact-minimized imaging.
  • This integrated approach offers unprecedented insights into cellular architecture.
  • The detailed protocol facilitates the adoption of this powerful technique in research laboratories.