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

Area of Science:

• Biotechnology and Bioanalytical Chemistry
• Single-cell analysis technologies

Background:

• Mass cytometry (MC) is a key technique for high-throughput single-cell biomarker detection.
• Current MC reagents using platinum (Pt) binding polymers face challenges with nonspecific binding (NSB) and low signal-to-noise ratios.
• Previous work showed glutathione (GSH) ligand exchange reduced NSB in Pt-binding polymers.

Purpose of the Study:

• To investigate alternative sulfur-containing ligands for Pt-binding polymers to reduce NSB and improve signal contrast in MC.
• To evaluate the efficacy of thiosulfate as a ligand for Pt-binding polymers in MC applications.

Main Methods:

• Investigated ligand exchange of Pt-Cl bonds with various sulfur-containing ligands, including thiourea, diethyldithiocarbamate, and sodium thiosulfate.
• Developed a Pt-binding polymer incorporating thiosulfate groups via ligand exchange.
• Assessed performance in both suspension and imaging mass cytometry, comparing with GSH-modified polymers.

Main Results:

• The thiosulfate-modified Pt-binding polymer demonstrated ultralow nonspecific binding (NSB).
• Enhanced signal-to-noise ratios were achieved in both suspension and imaging MC compared to GSH-modified polymers.
• Thiosulfate proved superior to GSH in reducing NSB and increasing signal contrast.

Conclusions:

• Thiosulfate is a highly effective ligand for modifying Pt-binding polymers in MC.
• Ligand exchange with thiosulfate offers a promising strategy for developing advanced MC reagents (MCPs) for soft metal ion binding.
• This approach significantly improves the reliability and sensitivity of single-cell analysis in MC.