Zwitter-repel: An anti-fouling coating promoting electrochemical biosensing in biological fluids

Most electrochemical biosensors require sample processing to reduce biofouling induced by the complex composition of biological samples that typically causes a decrease in the target-to-blank signal. Herein, we report a zwitterionic copolymer bearing sulfobetaine, carboxylic, aldehyde, and thiol groups as a thin (∼16 nm) anti-fouling coating for electrochemical biosensing platforms. The resulting polymer-coated electrodes reduced protein adsorption by ∼ 67 % compared to the bare-gold surface when incubated with radiolabeled human serum albumin (HSA) protein-spiked human plasma, while cyclic voltammetry yielded a 5 % increase in anodic current signal after incubation in 1 % HSA for 1 h compared to the 83 % decrease in anodic current observed with bare gold electrodes. The polymer-coated electrode facilitated the detection of redox-labeled DNA in buffer, as well as in unprocessed and undiluted plasma with detection limits of 23 nM and 21 nM, respectively; detection of 104 cp mL−1 lentivirus pseudotyped with the Omicron spike protein of SARS-CoV-2 in unfiltered 50 % saliva was also achieved within 5 min with improved target-to-blank ratios and reproducibility relative to the well-established PEG-based biosensing platform for detecting COVID-19. On this basis, the Zwitter-repel coating offers potential to sensitively detect other disease biomarkers/analytes while eliminating or reducing the need for sample pre-processing and/or the use of additional backfilling/blocking agents.