Ready-to-Use OECT Biosensor toward Rapid and Real-Time Protein Detection in Complex Biological Environments

Organic electrochemical transistor (OECT) sensors are a promising approach for point-of-care testing (POCT) thanks to their high sensitivity and ability to operate in an aqueous environment. However, OECTs suffer from biological fouling at the gate and channel interfaces when exposed to complex biological samples. These nonspecific interactions can often obscure the weak signal from the trace biomarker, compromising the accuracy and sensitivity of measurements and even leading to false detection outcomes. In this study, we developed an intrinsically antifouling OECT by modifying both the gate and channel with phosphorylcholine-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT-PC). This modification notably enhances the OECT performance by leveraging the material's inherent mixed electron-ion conductivity, which increases transconductance and decreases gate voltage. Additionally, the zwitterionic nature of the device enables its ultrasensitive detection of C-reactive protein (CRP) with a limit of detection of 0.11 pg/mL, mediated by calcium ions. This exceptional sensitivity arises from the device's enhanced transconductance and ability to sense through the gate and channel interfaces simultaneously. Furthermore, the zwitterionic OECT sensor has demonstrated the fastest sample-to-result time for protein detection (<= 60 s), making it highly suitable for real-time CRP monitoring. Importantly, it provides precise real-time detection of CRP without interference from nonspecific proteins such as bovine serum albumin, fibrinogen, lysozyme, and fetal bovine serum. We envision this intrinsically antifouling OECT device offering a robust biosensing platform for the rapid and convenient detection of biomarkers in complex biological environments, providing a reliable and efficient solution for POCT diagnostics.