Advanced single cell analysis technologies (e.g. Mass Cytometry) that help in multiplexing cellular measurements in limited volumes of primary cells are critical in bridging the discovery efforts to successful drug approval. Mass cytometry is the state-of-the-art technology in multi-parametric single-cell analysis. Mass cytometers (also known as CyTOF or Cytometry by Time-of-Flight) combine the cellular analysis principles of traditional fluorescence-based flow cytometry with the selectivity and quantitative power of Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Standard flow cytometry is limited in the number of parameters that can be measured due to the overlap in signal when detecting the fluorescently labeled antibodies. Mass cytometry uses antibodies tagged to stable isotopes of rare earth metals, requiring minimal signal compensation between the different metal tags. This unique feature enables researchers to seamlessly multiplex up to 40 independent measurements on single cells. In this perspective we first present an overview of mass cytometry and compare it with traditional flow cytometry. We then discuss emerging and potential applications of CyTOF technology in the pharmaceutical industry that include quantitative and qualititative deep profiling of immune cells and their use application in assessing drug immunogenicity, extensive mapping of signaling networks in single cells, cell surface receptor quantification and multiplexed internalization kinetics, multiplexing sample analysis by barcoding, and establishing cell ontologies based on phenotype and/or function. We end with a discussion on the anticipated impact of this technology on drug development lifecycle with special emphasis on the utility of mass cytometry in deciphering the drug's pharmacokinetics and pharmacodynamics relationship.
- drug development/discovery
- mass spectrometry/MS
- pharmacokinetic/pharmacodynamic modeling/PKPD
- signalling pathways
- systems biology
- The American Society for Pharmacology and Experimental Therapeutics