Zwitterionic Thiophene-Functionalized Sensing Interface Enables Robust Antifouling Electrochemical Analysis

The ideal electrochemical sensing interface must have good electron transfer performance and could resist nonspecific adsorption in complex actual sample analysis. Herein, we creatively synthesized a zwitterionic thiophene (Th-Zw) monomer with dual functions of conduction and antifouling. The Th-Zw, graphene oxide, and antigen molecules are further in situ meridized on the surface of commercial screen-printed electrodes by electrodeposition to complete the manufacture of electrochemical sensors. The improved design of this commercial screen-printed electrode has three significant merits: (1) protein-resistant hydrophobicity via zwitterionic groups, (2) enhanced conductivity through π-conjugated thiophene-graphene networks, and (3) stable antigen immobilization via covalent deposition. The Th-Zw-modified electrode was further applied to the detection of the anti-p53 antibody (anti-p53) and anti-COVID-19 IgG in spiked human plasma samples and obtained a low detection limit of 5.95 and 6.58 ng/mL, respectively. Finally, in the detection of anti-p53 in blood samples of cancer patients and healthy volunteers, there was a significant difference in the results, proving that this strategy has good application potential in actual clinical samples. This study developed a conductive and antifouling electrochemical sensor that enables the rapid and sensitive detection of antibodies in actual samples without requiring sample purification or molecular labeling, offering a new strategy for one-step electrochemical detection.