title: Identification of hypoxic cells using an organotellurium tag compatible with mass cytometry.
abstract: Mass cytometry (MC) offers unparalleled potential for the development of highly parameterized assays for characterization of single cells within heterogeneous populations. Current reagents compatible with MC analysis employ antibody-metal-chelating polymer conjugates to report on the presence of biomarkers. Here, we expand the utility of MC by developing the first activity-based probe designed specifically for use with the technology. A compact MC-detectable telluroether is linked to a bioreductively sensitive 2-nitroimidazole scaffold, thereby generating a probe sensitive to cellular hypoxia. The probe exhibits low toxicity and is able to selectively label O2-deprived cells. A proof-of-concept experiment employing metal-bound DNA intercalators demonstrates that a heterogeneous mixture of cells with differential exposure to O2 can be effectively discriminated by the quantity of tellurium-labeling. The organotellurium reagents described herein provide a general approach to the development of a large toolkit of MC-compatible probes for activity-based profiling of single cells.
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada).
authors.forename: Landon J
authors.initials: LJ
authors.lastname: Edgar
authors.forename: Ravi N
authors.initials: RN
authors.lastname: Vellanki
authors.forename: Adrienne
authors.initials: A
authors.lastname: Halupa
authors.forename: David
authors.initials: D
authors.lastname: Hedley
authors.forename: Bradly G
authors.initials: BG
authors.lastname: Wouters
authors.forename: Mark
authors.initials: M
authors.lastname: Nitz
mesh_terms: D015687:Cell Hypoxia; D002469:Cell Separation / Q000379:methods*; D015335:Molecular Probes; D009930:Organic Chemicals / Q000737:chemistry*; D013691:Tellurium / Q000737:chemistry*
chemical_list: D015335:Molecular Probes; D009930:Organic Chemicals; D013691:Tellurium
keywords: activity-based probes; mass cytometry; multiparameter analysis; organotellurium compounds; tumor hypoxia