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Related Concept Videos

Cryo-electron Microscopy01:28

Cryo-electron Microscopy

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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Optimizing Sample Preparation for Cryogenic Electron Microscopy
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EasyGrid: a versatile platform for automated cryo-EM sample preparation and quality control.

Olivier Gemin1, Victor Armijo2, Léa Lecomte2

  • 1Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.

Nature Methods
|June 23, 2026
PubMed
Summary

EasyGrid is a new automated platform that streamlines and standardizes sample preparation for cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET). This technology improves vitrification for both macromolecules and cells, accelerating structural and cellular cryo-EM applications.

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Area of Science:

  • Structural Biology
  • Cell Biology
  • Microscopy

Background:

  • Optimized sample preparation is critical for high-resolution imaging of biological samples using cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET).
  • Current methods can be time-consuming and difficult to standardize, hindering throughput and reproducibility.

Purpose of the Study:

  • To develop and validate EasyGrid, a modular, automated platform for streamlined and standardized cryo-EM/ET sample preparation.
  • To demonstrate the platform's effectiveness for both purified macromolecules and intact cells.

Main Methods:

  • EasyGrid integrates automated plasma treatment, microfluidic dispensing, blot-less spreading, jet vitrification, and interferometry-based grid quality control.
  • The platform was tested with purified macromolecular complexes and large mammalian cells.

Main Results:

  • Successful preparation of grids for multiple purified macromolecular complexes, enabling structure determination via cryo-EM.
  • Demonstrated improved vitrification of large mammalian cells compared to conventional plunge-freezing.
  • EasyGrid facilitates systematic, high-throughput optimization of sample preparation.

Conclusions:

  • EasyGrid offers a robust, automated, and time-saving solution for cryo-EM/ET sample preparation.
  • The platform enhances efficiency and standardization for both structural and cellular cryo-EM applications.
  • This technology accelerates the advancement of cryo-EM and cryo-ET studies.