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Rapid, Untargeted Chemical Profiling of Single Cells in Their Native Environment

by John F Cahill, Julian Riba, Vilmos Kertesz
Publication Type
Journal Name
Analytical Chemistry
Publication Date
Page Numbers
6118 to 6126

We report a method that enables untargeted, high throughput and quantitative mass spectrometric analysis of single cells in their native media without needing additional sample preparation procedures (e.g., molecular tagging) through the combination of single-cell printing and liquid vortex capture-mass spectrometry (SCP-LVC-MS). The SCP-LVC-MS approach was validated by analyzing the chemical composition of microalgae, Chlamydomonas reinhardtii (ChRe) and Euglena gracilis (EuGr), and HeLa cells in their native growth media. ChRe and EuGr microalgae mixed together in the same solution were differentiated cell-by-cell in real-time based on measured lipid profiles. Several DGTS lipids present in ChRe were quantified with single-cell resolution by normalizing to a DGTS(32:0) internal standard added to the LVC probe solvent during analysis. Single-cell quantitation of lipids was validated by comparing to bulk lipid extracts. Lastly, single-cell chemical distributions measured from hundreds of ChRe cells were compared after 5 days of nitrogen-limited and normal growth conditions.