Automation of single-cell proteomic sample preparation.

Molecular heterogeneity exists at different spatial scales in biological samples and is an important parameter in the development of pathologies and resistances to therapies. When aiming to reach molecular heterogeneity of cells at extremely low spatial scales, single-cell analysis can be the ultimate choice. Proteomics performed in bulk population of cells (macroproteomics) is prone to mask molecular heterogeneity. Mass spectrometry-based single cell proteomics (SCP-MS) is the right solution to overcome this issue. Three main problems can be identified using SCP-MS: (i) analytical loss during sample preparation, (ii) inefficient microinjection/delivery of proteins/peptides from samples to MS and (iii) low analytical throughput. Technologies for automation of SCP have recently gained attention to improve methods accuracy, sensitivity, throughput and in-depth and low-biased proteome analysis. In this minireview, we therefore overview the state-of-the-art of automation of SCP-MS sample preparation approaches.