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Science & Application

cryoWrite has been founded by scientists with long standing expertise in cryo-EM and sample grid preparation. They were and are driven by the conviction that a successful automated sample grid preparation is possible and will be a breakthrough in accelerating discovery in life science research.

cryoWrite continues to combine both, science & technology, and uses its expertise to listen to the needs and wishes perceived in the cryo EM community and provide innovative technological answers.

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Scientific Advances

Blot-free, nanoliter operation:

  • Only ~5–10 nL of sample required per grid — three orders of magnitude less than traditional methods.

Controlled deposition:

  • Enables tunable ice thickness via capillary-to-grid distance, writing speed, and humidity.

  • Reproducibility comparable or superior to other commercial systems.

Multiple-writing modes:

  • Double-writing boosts particle density 5–10× without higher concentration.

  • On-grid mixing (two-line writing) enables time-resolved or ligand-binding experiments directly on the grid, demonstrated with streptavidin–desthiobiotin and NrS-1 + apoF co-deposition.

Reduced orientation bias:

  • Grids of NrS-1 prepared with cryoWriter displayed more isotropic particle orientations (SCF 0.65 vs 0.45) than blotting-based methods, improving 3D reconstructions.

Integrated environmental control:

  • Operates at dew-point temperature, avoiding condensation or sample drying, critical for consistent nanoliter handling.

3D reconstruction of TMV at 1.92 Å resolution. The filaments were deposited and vitrified with the cryoWriter. Data and movie courtesy: Claudio Schmidli, Thomas Braun group, Biozentrum, University of Basel. Electron Microscopy Databank entry: EMD-4628. Protein data bank: PDB-6R7M. More information on the preparation and data processing is found in the original publication in PNAS.

Scientific Versatility

High-resolution single particle reconstruction of various types of protein samples prepared using the cryoWriter.

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  • a) Tobacco mosaic virus (TMV)

  • b) Horse spleen apoferritin (apoF)

  • c) Transient receptor potential melastatin 4 (TRPM4) channel membrane protein.

 

For each sample from top to bottom:

  • an atlas image, indicating the areas where data were collected by green boxes (scale bar = 200 μm);

  • Representative cryo-EM micrograph (scale bars from left to right = 60 nm, 80 nm, 100 nm);

  • 2D class averages of picked particles (scale bars from left to right: 19 nm, 10 nm 16 nm);

  • 3D reconstructions with local resolution shown by the color scales (in Å); Representative regions in the 3Dreconstructions, with fitted atomic protein models.

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H. Stahlberg et al., EPFL

Application notes

This page contains application notes with the cryoWriter. It gives examples of samples prepared with the cryoWriter as well as descriptions of some of our applied methods and protocols.

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