New perspective of non-specific binding: A powerful mass cytometry barcoding strategy based on UIO-66(Hf/Zr) typed MOF utilizing its strong positive charge

Non-specific binding was a critical bottleneck in biosensing field and hindered the implementation of biosensors in bioassays. Thus, various approaches were developed to minimize the non-specific binding of biosensors. However, the rational utilization of non-specific binding will also produce generous returns. Herein, the first universal cell surface barcoding strategy for mass cytometry independent on particular cell surface molecules was developed based on nano-sized UIO-66 typed metal organic framework (MOF). Profiting from the 9 abundant stable isotopes of Zr and Hf, up to 84 mass barcode combinations can be achieved theoretically through the non-specific binding between positively charged UIO-66 and negatively charged cells. Clearly distinguished individual population sets were obtained when the cell samples were barcoded with UIO-66(Zr), UIO-66(Hf), and UIO-66(Zr/Hf) mixture. UIO-66 can also be used for flow cytometry barcoding and imaging after the modification with a fluorescent dye. Furthermore, the UIO-66 barcoding showed high compatibility with metal chelated polymer (MCP) mass tags in single-cell multiplexing and 16-fold higher sensitivity than MCP based barcoding agents. This work opens new opportunities for MOFs in mass cytometry applications and will also prompt people to evaluate the nasty non-specific binding in another perspective.