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Updated: Jun 1, 2026
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Cryo-Electron Microscopic Grid Preparation for Time-Resolved Studies using a Novel Robotic System, Spotiton
Published on: February 25, 2021
CryoWriter: a robotic solution for improved Cryo-EM grid preparation
Chinmaya Kv1,2, Babatunde Ekundayo1,2, Marta Di Fabrizio1,2,3,4
1Laboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
Nature Communications
|May 30, 2026
Summary
The cryoWriter robot automates cryo-electron microscopy (cryo-EM) grid preparation using microfluidics, overcoming a key bottleneck. This blotting-free method yields high-quality grids for near-atomic resolution structures and novel on-grid experiments.
Area of Science:
- Structural Biology
- Biophysics
- Microscopy Techniques
Background:
- Cryo-electron microscopy (cryo-EM) is crucial for determining molecular structures.
- Sample grid preparation is a significant bottleneck in cryo-EM workflows.
- Conventional blotting methods can be inconsistent and require larger sample volumes.
Purpose of the Study:
- To evaluate the cryoWriter, a novel microfluidic robot for automated cryo-EM grid preparation.
- To assess the performance of blotting-free, capillary-writing techniques for cryo-EM sample deposition.
- To explore advanced deposition modes for enhanced particle density and on-grid biochemical assays.
Main Methods:
- Utilized the cryoWriter robot for microfluidic, capillary-writing of nanoliter sample volumes onto EM grids.
- Employed spiral and line deposition patterns in a controlled environment.
- Tested with various biological specimens including TMV, apoferritin, TRPM4, and NrS-1 DNA polymerase.
Main Results:
- Achieved high-quality cryo-EM grids with minimal sample volumes.
- Obtained near-atomic resolution reconstructions for multiple test specimens.
- Demonstrated programmable deposition for increased particle density and on-grid mixing for time-resolved studies.
- Observed reduced orientation bias in reconstructions from cryoWriter grids compared to conventional blotting.
Conclusions:
- The cryoWriter offers a versatile and reproducible platform for low-volume cryo-EM grid preparation.
- Blotting-free microfluidic approach overcomes key limitations of traditional methods.
- Enables advanced on-grid biochemical workflows and improved structural determination.
