Enrichment and analysis of circulating tumor cells by integrating multivalent membrane nano-interface and endogenous enzyme-signal amplification

For circulating tumor cells(CTCs)-based cancer diagnosis and monitoring,effective enrichment and specific analysis of CTCs present significant challenges.The biomembrane interfaces can enhance the highaffinity interactions between various receptors and ligands in life activities by mediating the rearrangement and positioning of membrane-bound components through its fluidity.Inspired by this,we have constructed a multivalent membrane nano-interface using aptamer-linked liposomes for the efficient capture of CTCs.Furthermore,the subsequent introduction of rolling circle amplification(RCA)reaction has increased the number of aptamers and extended them to the surrounding space to improve the affinity of the membrane nano-interface for CTCs.After CTCs are enriched,alkaline phosphatase overexpressed on the surface of tumor cells is used as endogenous enzyme-mediated signal amplification by catalyzing 4-nitrophenyl phosphate(p NPP)with color change,achieving the analysis of CTCs.Finally,the enrichment and visual analysis of human hepatocellular carcinoma(HepG2)with a detection limit of 10 cells/m L can be obtained by integrating the multivalent membrane nano-interface and endogenous enzyme signal amplification.The detection of the target in the serum proved this method has the potential for further clinical application and provides a potential method for studying the correlation between alkaline phosphatase dimer and cancer progression.