A low-fouling electrochemical biosensor based on multifunction branched peptides with antifouling, antibacterial and recognizing sequences for protein detection in saliva

Electrochemical sensing devices are susceptible to biofouling associated with the nonspecific adsorption of biomolecules and microorganisms in complex biological matrices. Herein, a multifunctional peptide with antifouling, antibacterial and recognizing capabilities was designed to fabricate electrochemical biosensors that can be applied to detect the receptor-binding domain (RBD) of SARS-CoV-2 spike glycoprotein. The biosensor based on the multifunctional peptide exhibited excellent antifouling and antibacterial properties, which were investigated and verified by the fluorescence imaging, electrochemical experiments and molecular dynamics simulations. The interactions between the recognizing peptide sequence and the RBD protein were probed using molecular docking, and the effective binding ability of the peptide to the RBD protein was proved. The RBD protein biosensor exhibited excellent selectivity and stability, and a wide linear range of 1.0 pg to 1.0 μg mL-1 with a low detection limit of 0.28 pg mL-1. In addition, the biosensor was capable of assaying RBD protein in human saliva samples, and the detection results have a good correlation with those measured using commercial ELISA kits. This work provides a new strategy for the design of multifunctional peptides to construct unique antifouling sensing devices for biomarker detection in complex biological media.