Time‐Multiplexed Organic Electrochemical Transistor for Saliva‐Based Rapid Detection of Viral Proteins

Timely and accurate diagnosis of respiratory infections is complicated by the symptomatic overlap between highly transmissible pathogens such as respiratory syncytial virus (RSV), influenza A (IAV), and influenza B (IBV), highlighting the need for rapid and reliable diagnostics. Here, we report a time-multiplexed nanobody-functionalized organic electrochemical transistor (OECT) biosensor for the sensitive detection of RSV, IAV, and IBV directly from unprocessed saliva samples. The platform integrates arrays of nanobody-functionalized gate electrodes that are exposed in parallel to a single sample and sequentially addressed through a shared transistor channel. We characterize nine previously reported nanobodies and immobilize the best-performing ones using an oriented SpyDirect self-assembly strategy. The nanobody-functionalized gate electrodes are paired with a high-performance p-type organic mixed ionic-electronic conductor channel, enabling efficient signal transduction. The sensor achieves a limit of detection of ca. 1 fm and identifies viral targets within 15 min, without sample preprocessing. In a clinical validation using 17 samples, the platform demonstrated 100% specificity, 86.7% sensitivity, and 88.2% overall accuracy. By combining highly specific nanobodies, a high-gain transducer, customized surface pre-treatment, and a time-multiplexed multi-gate architecture, this approach provides a scalable and user-friendly platform for point-of-care virus detection.