Advances in Mass Spectrometry-Based Single Cell Analysis

Abstract

Technological developments and improvements in single-cell isolation and analytical platforms allow for advanced molecular profiling at the single-cell level, which reveals cell-to-cell variation within the admixture cells in complex biological or clinical systems. This helps to understand the cellular heterogeneity of normal or diseased tissues and organs. However, most studies focused on the analysis of nucleic acids (e.g., DNA and RNA) and mass spectrometry (MS)-based analysis for proteins and metabolites of a single cell lagged until recently. Undoubtedly, MS-based single-cell analysis will provide a deeper insight into cellular mechanisms related to health and disease. This review summarizes recent advances in MS-based single-cell analysis methods and their applications in biology and medicine.

Keywords: mass spectrometry; mass spectrometry imaging; metabolomics; proteomics; single-cell analysis.

Figure 1

Single-cell analysis and imaging reveal cellular heterogeneity not seen by bulk analysis methods.

Figure 2

TMT-assisted single-cell proteomics. (a) The chemical structure of TMT (e.g., 18-plex), (b) Single-cell sorting and isolation onto a well plate or slide chip by FACS or a robotic system. (c) A typical workflow of single-cell proteomic analysis using TMT.

Figure 3

Schematic representation of a workflow of high-throughput single-cell proteomics analysis using CyTOF.

Figure 4

Different single-cell MSI methods. (a) Imaging mass cytometry (IMC); (b) Secondary ion mass spectrometry (SIMS); (c) Desorption electrospray ionization (DESI); (d) nanospray-DESI (nano-DESI); (e) Laser ablation electrospray ionization (LAESI); (f) Matrix-assisted laser desorption/ionization.