Optimizing the\nStructure of a Pt Metal-Chelating Polymer\nto Reduce Nonspecific Binding for Mass Cytometry

Mass cytometry is a bioanalytic tool\nbased on atomic\nmass spectrometry\nfor detecting biomarker expression on individual cells. Current reagents\nemploy metal-chelating polymers binding isotopes of hard metal ions.\nPolymers bearing chelators for soft metal ions offer the promise for\na large increase in multiplexing capabilities, but examples reported\nso far often have unacceptably high levels of nonspecific binding\n(NSB). We recently reported a new class of metal-chelating polymers\nwith dipicolylamine (DPA) chelators that could bind Re and Pt. They\nalso showed significant levels of NSB. Here, to reduce the NSB of\nthe Pt-DPA polymer, we grafted water-soluble oligomers to the distal\nend of the dipicolylamine pendant group. Methoxy(polyethylene glycol)\n(DP = 24) was effective as was poly(sulfobetaine methacrylate) (DP\n= 29). Reacting the Pt–Cl bond of the metalated polymer with\nglutathione was remarkably effective at suppressing NSB. These results\nopen the door to Pt-isotope-based metal-chelating polymers as new\nmass tags for mass cytometry.