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Peer-reviewedCC BYNature Methods

EasyGrid: a versatile platform for automated cryo-EM sample preparation and quality control

  • Olivier Gemin1,2
  • Victor Armijo3,4
  • Léa Lecomte3,4
  • Michael Hons5,3,4
  • Thibault Deckers3,4
  • Caroline Bissardon3,4
  • Christopher Rossi3,2
  • Kévin Lauzier3,6,4
  • Robert Janocha3,2
  • Franck Felisaz3,2
  • Jérémy Sinoir3,4
  • Romain Linares3,4
18 more authors
  • Anastasiia Babenko7,1,4
  • Kirill Kovalev3,8,4
  • Irina Prokhorova3,4
  • Iskander Sh. Khusainov3,4
  • Claudia Schreiner9,10,4
  • Olga Kolesnikova1,4
  • Veijo T. Salo1,4
  • Sarah Schneider3,11,2
  • Matthew W. Bowler3,2
  • Georg Wolff12,1,2
  • Wojciech P. Galej3,13,2
  • Julia Mahamid14,1,4
  • Christoph W. Müller1,4
  • Kristina Djinovic Carugo9,3,10,15
  • Sebastian Eustermann1
  • Simone Mattei12,1
  • Florent Cipriani3
  • Gergely Papp16
16 affiliations
  1. 1Molecular Systems Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
  2. 2European Molecular Biology Laboratory, Structural and Computational Biology Unit, Meyerhofstraße , 697 Heidelberg, Germany
  3. 3European Molecular Biology Laboratory, EMBL Grenoble, Grenoble, France
  4. 4European Molecular Biology Laboratory, Grenoble, 71 rue des Martyrs, 38000 Grenoble, France
  5. 5Centre for Structural Systems Biology (CSSB), DESY, Hamburg, Germany
  6. 6European Molecular Biology Laboratory (EMBL), Hamburg Unit c/o DESY, Notkestrasse 85, 22607 Hamburg, Germany
  7. 7Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany
  8. 8European Molecular Biology Laboratory, EMBL Hamburg, Hamburg, Germany
  9. 9Department of Structural and Computational Biology, Center for Molecular Biology, University of Vienna, Vienna, Austria
  10. 10Max Perutz Laboratories, Vienna Biocenter Campus, Vienna, Austria
  11. 11European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany
  12. 12EMBL Imaging Centre, European Molecular Biology Laboratory, Heidelberg, Germany
  13. 13European Molecular Biology Laboratory, EMBL Imaging Centre, Meyerhofstraße 1, 69117 Heidelberg, Germany
  14. 14Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany
  15. 15The Comammox Research Platform, University of Vienna, Vienna, Austria
  16. 16European Molecular Biology Laboratory, EMBL Grenoble, Grenoble, France. [email protected]
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Abstract

Optimized sample preparation is essential for imaging biological macromolecules in their native state using single-particle cryo-electron microscopy (cryo-EM) or in situ cryo-electron tomography (cryo-ET). Here we present EasyGrid, a modular, automated platform designed to streamline and standardize cryo-EM/ET sample preparation. EasyGrid integrates in-line plasma treatment of the sample support, microfluidic dispensing, blot-less sample spreading, jet-based vitrification and grid quality control via light interferometry. We demonstrate its effectiveness by preparing grids for multiple purified macromolecular complexes and resolving their structures with cryo-EM. Additionally, EasyGrid achieves improved vitrification of large mammalian cells compared to conventional plunge-freezing. By enabling systematic and high-throughput optimization, EasyGrid provides a robust and time-saving solution for both structural and cellular cryo-EM applications.

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Cite

BibTeXRIS
BibTeX
@article{gemin2026easygrid,
  title = {{EasyGrid: a versatile platform for automated cryo-EM sample preparation and quality control}},
  author = {Olivier Gemin and Victor Armijo and Léa Lecomte and Michael Hons and Thibault Deckers and Caroline Bissardon and Christopher Rossi and Kévin Lauzier and Robert Janocha and Franck Felisaz and Jérémy Sinoir and Romain Linares and Anastasiia Babenko and Kirill Kovalev and Irina Prokhorova and Iskander Sh. Khusainov and Claudia Schreiner and Olga Kolesnikova and Veijo T. Salo and Sarah Schneider and Matthew W. Bowler and Georg Wolff and Wojciech P. Galej and Julia Mahamid and Christoph W. Müller and Kristina Djinovic Carugo and Sebastian Eustermann and Simone Mattei and Florent Cipriani and Gergely Papp},
  journal = {Nature Methods},
  year = {2026},
  month = jun,
  doi = {10.1038/s41592-026-03127-5},
  url = {https://doi.org/10.1038/s41592-026-03127-5},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - EasyGrid: a versatile platform for automated cryo-EM sample preparation and quality control
AU  - Olivier Gemin
AU  - Victor Armijo
AU  - Léa Lecomte
AU  - Michael Hons
AU  - Thibault Deckers
AU  - Caroline Bissardon
AU  - Christopher Rossi
AU  - Kévin Lauzier
AU  - Robert Janocha
AU  - Franck Felisaz
AU  - Jérémy Sinoir
AU  - Romain Linares
AU  - Anastasiia Babenko
AU  - Kirill Kovalev
AU  - Irina Prokhorova
AU  - Iskander Sh. Khusainov
AU  - Claudia Schreiner
AU  - Olga Kolesnikova
AU  - Veijo T. Salo
AU  - Sarah Schneider
AU  - Matthew W. Bowler
AU  - Georg Wolff
AU  - Wojciech P. Galej
AU  - Julia Mahamid
AU  - Christoph W. Müller
AU  - Kristina Djinovic Carugo
AU  - Sebastian Eustermann
AU  - Simone Mattei
AU  - Florent Cipriani
AU  - Gergely Papp
PY  - 2026
DA  - 2026/06/23
JO  - Nature Methods
DO  - 10.1038/s41592-026-03127-5
UR  - https://doi.org/10.1038/s41592-026-03127-5
AB  - Optimized sample preparation is essential for imaging biological macromolecules in their native state using single-particle cryo-electron microscopy (cryo-EM) or in situ cryo-electron tomography (cryo-ET). Here we present EasyGrid, a modular, automated platform designed to streamline and standardize cryo-EM/ET sample preparation. EasyGrid integrates in-line plasma treatment of the sample support, microfluidic dispensing, blot-less sample spreading, jet-based vitrification and grid quality control via light interferometry. We demonstrate its effectiveness by preparing grids for multiple purified macromolecular complexes and resolving their structures with cryo-EM. Additionally, EasyGrid achieves improved vitrification of large mammalian cells compared to conventional plunge-freezing. By enabling systematic and high-throughput optimization, EasyGrid provides a robust and time-saving solution for both structural and cellular cryo-EM applications.
SN  - 1548-7091
SN  - 1548-7105
ER  -