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.

Close-up view of a cryo-EM grid preparation setup demonstrating the automated process.

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:

• Syntychaki A, Rima L, Schmidli C, Stohler T, Bieri A, Sütterlin R, et al. `Differential visual proteomics’: Enabling the proteome-wide comparison of protein structures of single-cells. J Proteome Res. 2019;18(9):3521–31.

• Arnold SA, Albiez S, Opara N, Chami M, Schmidli C, Bieri A, et al. Total sample conditioning and preparation of nanoliter volumes for electron microscopy. ACS Nano. 2016;10(5):4981–8.

• Kemmerling S, Arnold SA, Bircher BA, Sauter N, Escobedo C, Dernick G, et al. Single-cell lysis for visual analysis by electron microscopy. J Struct Biol. 2013;183:467–73.