Antifouling zwitterionic coating enhances electrochemical aptamer-based sensors for therapeutic drug monitoring

Electrochemical aptamer-based (E-AB) sensors have experienced remarkable growth across a broad range of applications, such as precision medicine, chronic disease management, food safety, and environmental monitoring, due to their exceptional capability for real-time and continuous monitoring of biomarkers. However, biofouling in complex biological environments remains a critical challenge for the E-AB sensors, compromising signal strength, operational stability, and biosensing specificity. Here, we present a zwitterionic coating strategy that integrates poly-sulfobetaine methacrylate (SBMA) and polydopamine (PDA) to enhance the antifouling properties of the E-AB sensors, thereby enabling sensitive, stable, and accurate detection of a model antibiotic drug, vancomycin. The durable and hydrophilic antifouling layer was grafted onto the electrode surface to minimize signal drift while preserving sufficient signal on the E-AB sensors. The SBMA@PDA coating was systematically optimized and demonstrated superior resistance to biofouling under various environmental conditions, including pH, temperature, and mechanical stress. Furthermore, the coating was incorporated into a wearable microneedle patch for monitoring vancomycin dynamics in artificial interstitial fluids, achieving robust stability and performance. These findings establish a reliable and effective antifouling approach, advancing the practical application of E-AB sensors for continuous therapeutic drug monitoring in clinical and wearable healthcare settings. • A zwitterionic SBMA@PDA coating with AuNPs/MXene nanocomposites enhances antifouling and signal retention of E-AB sensors. • The SBMA@PDA coating reduces signal drift , showing high robustness to pH, temperature, and mechanical stress. • The coated E-AB sensor demonstrates high sensitivity and low signal noise across diverse biological fluids. • Integrated into a wearable microneedle patch, the coating enables vancomycin detection in artificial ISF.