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| Title | CryoWriter: a robotic solution for improved Cryo-EM grid preparation. |
|---|---|
| Journal, issue, pages | Nat Commun, Year 2026 |
| Publish date | May 30, 2026 |
 Authors | Chinmaya Kv / Babatunde Ekundayo / Marta Di Fabrizio / Inayathulla Mohammed / Julika Radecke / Henning Stahlberg / Massimo Kube /   |
| PubMed Abstract | Cryo-electron microscopy (cryo-EM) structure determination relies on preparing thin, vitreous films of sample solution on EM grids. Cryo-EM is a mature technology, but preparing the grids remains a ...Cryo-electron microscopy (cryo-EM) structure determination relies on preparing thin, vitreous films of sample solution on EM grids. Cryo-EM is a mature technology, but preparing the grids remains a major bottleneck. Here, we evaluate the cryoWriter, a blotting-free, microfluidic grid-preparation robot that writes nanoliter volumes onto EM grids in a controlled environment. Using capillary-writing in spiral or line patterns, we prepared high-quality grids from minimal sample volumes and obtained near-atomic reconstructions for test specimens, including TMV, apoferritin, and the membrane protein TRPM4. We further demonstrate programmable deposition modes, such as writing the sample twice to boost particle density, or two-line writing for on-grid mixing to visualize time-resolved protein-ligand binding. In a challenging case (NrS-1 DNA polymerase), the cryoWriter grids exhibited reduced orientation bias relative to conventional blotting, enabling a more isotropic reconstruction. These results show that the cryoWriter provides a versatile platform for reproducible low volume cryo-EM grid preparation and for on-grid biochemical workflows. |
 External links | Nat Commun / PubMed:42218131 |
| Methods | EM (single particle) / EM (helical sym.) |
| Resolution | 1.68 - 3.01 Å |
| Structure data |  EMDB-54957: Cryo-EM structure of horse spleen apoferritin using the cryoWriter automated grid preparation system with one-time writing with spiral pattern  EMDB-54970: Cryo-EM structure of horse spleen apoferritin using the cryoWriter automated grid preparation system with one-time writing with a line pattern  EMDB-54984: Cryo-EM structure of the transient receptor potential melastatin 4 (TRPM4) channel prepared using the cryoWriter automated grid preparation system with spiral-pattern writing  EMDB-55000: Cryo-EM structure of the desthiobiotin-bound streptavidin prepared using the cryoWriter automated grid preparation system with line pattern writing  EMDB-55006: Cryo-EM structure of Tobacco Mosaic Virus (TMV) prepared using the cryoWriter automated grid preparation system with spiral writing.  EMDB-55025: Cryo-EM Structure of Horse Spleen Apoferritin using cryoWriter with On-Grid Protein Mixing  EMDB-55027: Cryo-EM structure of horse spleen apoferritin using the cryoWriter automated grid preparation system with two-time writing with spiral pattern |
| Source |
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Equus caballus (horse)
Homo sapiens (human)
Streptomyces avidinii (bacteria)
Tobacco mosaic virus (strain vulgare) (TMV)