The field of single-cell omics analysis has gained substantial traction over the last couple of years with breakthroughs in various areas. One of these areas is mass spectrometry (MS)-based single-cell analysis. Once considered a distant dream, it is becoming a reality at an unexpected pace.

Bruker is one of the pioneers in the field, pushing the sensitivity of MS instruments to the range of protein abundances at the single-cell level while improving their robustness to get sustainable results over the large sample cohorts needed for clinical research, enabling researchers to investigate tissue heterogeneity one cell at a time over large numbers of cells. Advances in miniaturized sample preparation, loss-reduced sample transfer, chromatographic separation, scanning speed and sensitivity in MS, and bioinformatic tools opened the field of single-cell analysis for phenotypic characterization by different kinds of omics—proteomics (including analysis of post-translational modifications and proteoforms), lipidomics, and metabolomics.

At present, crucial groundwork is being laid by MS core laboratories around the globe. They are establishing protocols and setting benchmarks for what is possible. An especially notable result of this work is the mainstreaming of MS-based single-cell proteomics. Optimizing throughput by parallelization and reduced analysis time per sample—as proposed by research teams such as the one led by Nikolai Slavov, PhD, at Northeastern University—is what is needed to establish MS-based single-cell proteomics applications in clinical routines.

An exciting development is the emergence of deep visual proteomics, a technology for the spatially resolved analysis of tissue. Single-cell contours are cut out by laser capture microdissection and prepared for bottom-up proteomics, adding phenotypic information on cell microenvironments. This approach becomes highly relevant for cancer research or drug development studies, but also for drug delivery and drug distribution studies. It adds depth to established imaging workflows, including immunohistochemistry-based imaging workflows and MS-based imaging workflows in pathology.


Christoph Krisp, PhD, is an application development specialist in proteomics at Bruker Daltonics GmbH & Co. KG.


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