Simultaneous detection of multiple neuroendocrine tumor markers in patient serum with an ultrasensitive and antifouling electrochemical immunosensor

Neuroendocrine tumors (NETs) are rare heterogeneous tumors that are often misdiagnosed and mistreated. Most NETs patients are diagnosed as advanced. Early on-time detection of NETs is significant for precision therapy. Here, an ultrasensitive and antifouling label-free electrochemical immunosensor was constructed for simultaneous analysis of NETs biomarkers chromogranin A (CgA) and chromogranin B (CgB). The metal ion functionalized porous magnesium silicate/gold nanoparticles/polyethylene glycol/chitosan (PMS-M2+/AuNPs/PEG/CS) composites were employed as the sensing platforms. By combining PEG and CS with good hydrophilicity, the sensing interface exhibited outstanding antifouling ability in complex biological systems. PMS with high surface area and the porous structure can efficiently load Cu2+ and Pb2+, which could directly generate independent electrochemical peak currents that reflected the concentrations of CgA and CgB. Under optimal conditions, this immunosensor can detect CgA and CgB with good linearity from 0.1 pg mL-1 to 100 ng mL-1 as low as 5.3 and 2.1 fg mL-1, respectively. Moreover, this immunosensor can accurately detect CgA and CgB levels in clinical serum, which were well consistent with the enzyme-linked immunosorbent assay (ELISA). This strategy provided a sensitive, simple and low-cost platform for clinical screening and point-of-care diagnosis of NETs.