Nanocapillary sampling coupled to liquid chromatography mass spectrometry delivers single cell drug measurement and lipid fingerprints

Holly-May Lewis, Priyanka Gupta, Kyle D G Saunders, Shazneil Briones, Johanna von Gerichten, Paul A Townsend, Eirini Velliou, Dany J V Beste, Olivier Cexus, Roger Webb, Melanie J Bailey

Research output: Contribution to journalArticlepeer-review

Abstract

This work describes the development of a new approach to measure drug levels and lipid fingerprints in single living mammalian cells. Nanocapillary sampling is an approach that enables the selection and isolation of single living cells under microscope observation. Here, live single cell nanocapillary sampling is coupled to liquid chromatography for the first time. This allows molecular species to be separated prior to ionisation and improves measurement precision of drug analytes. The efficiency of transferring analytes from the sampling capillary into a vial was optimised in this work. The analysis was carried out using standard flow liquid chromatography coupled to widely available mass spectrometry instrumentation, highlighting opportunities for widespread adoption. The method was applied to 30 living cells, revealing cell-to-cell heterogeneity in the uptake of different drug molecules. Using this system, we detected 14-158 lipid features per single cell, revealing the association between bedaquiline uptake and lipid fingerprints.

Original languageEnglish
Pages (from-to)1041-1049
Number of pages9
JournalThe Analyst
Volume148
Issue number5
Early online date31 Jan 2023
DOIs
Publication statusPublished - 7 Mar 2023

Keywords

  • Animals
  • Chromatography, Liquid/methods
  • Lipids
  • Mammals
  • Mass Spectrometry/methods

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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