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Publication

The CryoWriter Goes MS: Expanding Beyond EM

Our collaborators at the Biozentrum integrated single-cell lysis with mass spectrometry and reverse-phase protein arrays, enabling correlative single- and few-cell analyses that combine light microscopy with metabolomics and targeted proteomics.

Originally, CryoWriter technology was developed for single-cell analysis via electron microscopy (single-cell visual proteomics), with its writing system directly coupled to a single-cell lysis method for adherent eukaryotic cells. Now, the system integrates light microscopy, cell targeting, and lysis with liquid chromatography-mass spectrometry for single-cell metabolite detection and protein microarrays for protein analysis.

These technologies paves the way for correlative multiomics analysis on the single cell level!

Rima L, Berchtold C, Arnold S, Fränkl A, Sütterlin R, Dernick G, et al. Single and few cell analysis for correlative light microscopy, metabolomics, and targeted proteomics. Lab Chip. 2024.

Relevant publications for single-cell visual proteomics:

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Publication

Faraday Discussion: Coverslip injector

Together with cryoWrite and Roche, a research group in the Biozentrum of the University Basel presented a Faraday Discussion paper improving the grid quality and reducing background noise using cryoWriter technology. They use a “coverslip” injector to modulate the air-water interface with amphiphilic molecules:

  • Rima, L.; Zimmermann, M.; Fränkl, A.; Clairfeuille, T.; Lauer, M.; Engel, A.; Engel, H.-A.; Braun, T. CryoWriter: A Blotting Free Cryo-EM Preparation System with a Climate Jet and Cover-Slip Injector. Faraday Discussions2022. https://doi.org/10.1039/D2FD00066K.
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Publication

cryoWriter Technology in action

Here you will find an early video explaining the cryoWriter technology for negative stain, cryo-EM, and single-cell visual proteomics.

References

Reference for the video:

  • Schmidli, C.; Rima, L.; Arnold, S. A.; Stohler, T.; Syntychaki, A.; Bieri, A.; Albiez, S.; Goldie, K. N.; Chami, M.; Stahlberg, H.; Braun, T. Miniaturized Sample Preparation for Transmission Electron Microscopy. JoVE2018, No. 137, e57310. https://doi.org/10.3791/57310.

The video summarizes technologies and methods published before:

  1. Kemmerling, S.; Ziegler, J.; Schweighauser, G.; Arnold, S. A.; Giss, D.; Müller, S. A.; Ringler, P.; Goldie, K. N.; Goedecke, N.; Hierlemann, A.; Stahlberg, H.; Engel, A.; Braun, T. Connecting 𝜇-Fluidics to Electron Microscopy. J. Struct. Biol.2012, 177 (1), 128–134. https://doi.org/10.1016/j.jsb.2011.11.001.
  2. Arnold, S. A.; Albiez, S.; Opara, N.; Chami, M.; Schmidli, C.; Bieri, A.; Padeste, C.; Stahlberg, H.; Braun, T. Total Sample Conditioning and Preparation of Nanoliter Volumes for Electron Microscopy. ACS Nano2016, 10 (5), 4981–4988. https://doi.org/10.1021/acsnano.6b01328.
  3. Kemmerling, S.; Arnold, S. A.; Bircher, B. A.; Sauter, N.; Escobedo, C.; Dernick, G.; Hierlemann, A.; Stahlberg, H.; Braun, T. Single-Cell Lysis for Visual Analysis by Electron Microscopy. J. Struct. Biol.2013, 183, 467–473. https://doi.org/10.1016/j.jsb.2013.06.012.
  4. Arnold, S. A.; Albiez, S.; Bieri, A.; Syntychaki, A.; Adaixo, R.; McLeod, R. A.; Goldie, K. N.; Stahlberg, H.; Braun, T. Blotting-Free and Lossless Cryo-Electron Microscopy Grid Preparation from Nanoliter-Sized Protein Samples and Single-Cell Extracts. J. Struct. Biol.2017, 197 (3), 220–226. https://doi.org/10.1016/j.jsb.2016.11.002.
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