Polyethyleneimine cross-linked BSA with enhanced antifouling capability for electrochemical detection of cancer antigen 125 in complex biofluids

Biofouling is a major challenge in the practical application of electrochemical biosensors, and the exploration of antifouling materials to fabricate low-fouling sensing interfaces has attracted increasing attention. Herein, a composite material with enhanced antifouling capability was prepared through cross-linking bovine serum albumin (BSA) with polyethyleneimine (PEI). The PEI cross-linked BSA (BSA-PEI), unlike the native BSA, exhibited strong hydrophilicity and was nearly neutral in carried charge. As the excellent hydrophilicity can avoid its hydrophobic interaction with other materials, while the nearly neutral charge can significantly reduce the attraction of charged substances, the BSA-PEI possessed robust antifouling performances in complex biological media and extreme circumstances, such as high salt concentrations and varying pH conditions. Based on the unique electrical conductivity of MXene and the low-fouling BSA-PEI coating, a typical electrochemical biosensor for the sensitive assay of biomarker cancer antigen 125 (CA125) was constructed. The antifouling biosensor possessed a low detection limit of 2.6 mU/mL, and it could assay CA125 in human serum with satisfactory sensitivity comparable to the commercial ELISA method, demonstrating great potential of the BSA-PEI for the development of low-fouling biosensing devices.