title: Mass cytometry: a highly multiplexed single-cell technology for advancing drug development.
abstract: Advanced single-cell analysis technologies (e.g., mass cytometry) that help in multiplexing cellular measurements in limited-volume primary samples are critical in bridging discovery efforts to successful drug approval. Mass cytometry is the state-of-the-art technology in multiparametric single-cell analysis. Mass cytometers (also known as cytometry by time-of-flight or CyTOF) combine the cellular analysis principles of traditional fluorescence-based flow cytometry with the selectivity and quantitative power of inductively coupled plasma-mass spectrometry. Standard flow cytometry is limited in the number of parameters that can be measured owing to the overlap in signal when detecting fluorescently labeled antibodies. Mass cytometry uses antibodies tagged to stable isotopes of rare earth metals, which requires 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 overview we first present an overview of mass cytometry and compare it with traditional flow cytometry. We then discuss the emerging and potential applications of CyTOF technology in the pharmaceutical industry, including quantitative and qualitative deep profiling of immune cells and their applications 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 on the basis of phenotype and/or function. We end with a discussion of the anticipated impact of this technology on drug development lifecycle with special emphasis on the utility of mass cytometry in deciphering a drug's pharmacokinetics and pharmacodynamics relationship.
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism, New Biological Entities, Pfizer, Andover, Massachusetts kondala.atkuri@pfizer.com.
authors.forename: Kondala R
authors.initials: KR
authors.lastname: Atkuri
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism, New Biological Entities, Pfizer, Andover, Massachusetts.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Stevens
authors.affiliation: Pharmacokinetics, Dynamics and Metabolism, New Biological Entities, Pfizer, Andover, Massachusetts.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Neubert
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000639:trends; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008674:Metals, Rare Earth / Q000032:analysis; D010599:Pharmacokinetics; D059010:Single-Cell Analysis / Q000295:instrumentation; D013054:Spectrophotometry, Atomic
chemical_list: D015415:Biomarkers; D008674:Metals, Rare Earth