Optimizing the Structure of a Pt Metal-Chelating Polymer to Reduce Nonspecific Binding for Mass Cytometry

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