A universal mass tag based on polystyrene nanoparticles for single-cell multiplexing with mass cytometry

Mass cytometry (MC) is an emerging bioanalytical technique for high-dimensional biomarkers interrogation simultaneously on individual cells. However, the sensitivity and multiplexed analysis ability of MC was highly restricted by the current metal chelating polymer (MCP) mass tags. Herein, a new design strategy for MC mass tags by using a commercial available and low cost classical material, polystyrene nanoparticle (PS-NP) to carry metals was reported. Unlike inorganic materials, sub-micron-grade metal-loaded polystyrene can be easily detected by MC, thus it is not essential to pursue extremely small particle size in this mass tag design strategy. An altered cell staining buffer can significantly lower the nonspecific binding (NSB) of non-functionalized PS-NPs, revealing another method to lower NSB beside surface modification. The metal doped PS-NP_Abs mass tags showed high compatibility with MCP mass tags and 5-fold higher sensitivity. By using Hf doped PS-NP_Abs as mass tags, four new MC detection channels (¹⁷⁷Hf, ¹⁷⁸Hf, ¹⁷⁹Hf and ¹⁸⁰Hf) were developed. In general, this work provides a new strategy in designing MC mass tags and lowering NSB, opening up possibility of introducing more potential MC mass tag candidates.