Development of Pico-ESI-MS for Single-Cell Metabolomics Analysis.

In this chapter, we introduced a Pico-ESI strategy for metabolomics analysis with picoliter-level samples. This Pico-ESI strategy was technically achieved by pulsed direct current electrospray ionization source (Pulsed-DC-ESI). This source could collect MS signals for a few minutes from a cell, enabling us to obtain large-scale MS2 data of metabolite IDs in single-cell analysis. Further identification of the single-cell metabolome such as the database match and chemical modification to metabolome was thereby achieved. Technically, this source could ionize sample with no need of sample and electrode contact, which can be potentially applied for high-throughput analysis. We also introduced several strategies related to Pico-ESI to reduce the matrix interference especially for extremely small samples developed in our group, including step-voltage nanoelectrospray, picoliter sample desalting method, droplet-based microextraction method, and probe-ESI, etc. All these strategies have been successfully applied to single-cell analysis.