Subcellular Mass Spectrometry Imaging and Absolute Quantitative Analysis across Organelles

Aurélien Thomen, Neda Najafinobar, Florent Penen, Emma Kay, Pratik P. Upadhyay, Xianchan Li, Nhu T.N. Phan, Per Malmberg, Magnus Klarqvist, Shalini Andersson, Michael E. Kurczy, Andrew G. Ewing

Research output: Contribution to journalArticlepeer-review

Abstract

Mass spectrometry imaging is a field that promises to become a mainstream bioanalysis technology by allowing the combination of single-cell imaging and subcellular quantitative analysis. The frontier of single-cell imaging has advanced to the point where it is now possible to compare the chemical contents of individual organelles in terms of raw or normalized ion signal. However, to realize the full potential of this technology, it is necessary to move beyond this concept of relative quantification. Here we present a nanoSIMS imaging method that directly measures the absolute concentration of an organelle-associated, isotopically labeled, pro-drug directly from a mass spectrometry image. This is validated with a recently developed nanoelectrochemistry method for single organelles. We establish a limit of detection based on the number of isotopic labels used and the volume of the organelle of interest, also offering this calculation as a web application. This approach allows subcellular quantification of drugs and metabolites, an overarching and previously unmet goal in cell science and pharmaceutical development.

Original languageEnglish (US)
Pages (from-to)4316-4325
Number of pages10
JournalACS nano
Volume14
Issue number4
DOIs
StatePublished - Apr 28 2020

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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