Single-Cell Lipidomics Using Analytical Flow LC-MS Characterizes the Response to Chemotherapy in Cultured Pancreatic Cancer Cells

In this work, we demonstrate the development and first application of nanocapillary sampling followed by analytical flow liquid chromatography-mass spectrometry for single-cell lipidomics. Around 260 lipids were tentatively identified in a single cell, demonstrating remarkable sensitivity. Human pancreatic ductal adenocarcinoma cells (PANC-1) treated with the chemotherapeutic drug gemcitabine can be distinguished from controls solely on the basis of their single-cell lipid profiles. Notably, the relative abundance of LPC(0:0/16:0) was significantly affected in gemcitabine-treated cells, in agreement with previous work in bulk. This work serves as a proof of concept that live cells can be sampled selectively and then characterized using automated and widely available analytical workflows, providing biologically relevant outputs.

Automated summary

In this study, nanocapillary sampling combined with liquid chromatography-mass spectrometry was used for single-cell lipidomics. The method showed high sensitivity, allowing the tentative identification of around 260 lipids in a single cell. By analyzing the lipid profiles, chemotherapeutic drug-treated cancer cells were distinguished from control cells, and the relative abundance of LPC(0:0/16:0) was found to be significantly affected.