Single-Probe Mass Spectrometry Analysis of Metabolites in Single Cells

Mass spectrometry (MS) is an indispensable analytical technique for bioanalysis. Based on the measurement of mass/charge ratios (m/z) of ions, MS can be used for sensitive detection and accurate identification of species of interest. In traditional studies, MS is utilized to measure analytes in prepared solutions or gas-phase samples. Benefited from recent development of sampling and ionization approaches, MS has been extensively applied to the analysis of broad ranges of biological samples. We have developed a new device, the Single-probe, that can be used for in situ, real-time MS analysis of metabolites inside individual living cells. The Single-probe is a miniaturized multifunctional sampling and ionization device that is directly coupled to the mass spectrometer. With a sampling tip size smaller than 10 μm, we can insert the Single-probe tip into single cells to extract intracellular compounds, which are analyzed using MS in real-time. We have successfully used the Single-probe MS technique to detect a variety of endogenous and exogenous cellular metabolites in individual eukaryotic cells. Single cell mass spectrometry (SCMS) is a new scientific technology that has the potential to reshape approaches in biological and pharmaceutical bioanalytical research.