Thiosulfate as a Novel Ligand for Metal-Chelating Polymers for Mass Cytometry

Mass cytometry (MC) is a high-throughput bioanalytical technique for single-cell biomarker detection. Metal-chelating polymer reagents for MC have been used to bind isotopes of soft metal ions, such as Pt. However, there are challenges of suppressing nonspecific binding (NSB) and achieving high signal-to-noise ratios in cell studies for these reagents. Recently, our group reported that ligand exchange of the Pt-Cl bond with glutathione (GSH), a strong sulfur nucleophile, reduced the NSB of a Pt-binding polymer. To further investigate the effects of ligand exchange, we investigated alternative sulfur-containing ligands─including thiourea, diethyldithiocarbamate, and sodium thiosulfate, for their ability to reduce NSB and increase the signal contrast in MC applications through Pt-Cl bond substitution. Here, we report a Pt-binding polymer in which thiosulfate groups were introduced by ligand exchange, achieving ultralow NSB and enhanced signal-to-noise ratios in both suspension and imaging MC compared to the GSH-modified Pt polymer. This demonstrates thiosulfate as a promising candidate for ligand exchange to develop new MCPs that bind to soft metal ions.