Comprehensive SummaryWith the advantages of high sensitivity, rapid response, label‐free, and simple operation, field effect transistor biosensors have shown promising application prospects in large‐scale pathogen screening. However, in practical biological fluids with relatively high ionic strength, such as saliva and serum, the Debye screening effect will weaken the interaction between FET biosensors and target bio‐molecules, thereby affecting the sensing sensitivity and accuracy. Herein, an interfacial polymer‐engineered field effect transistor (IPE FET) biosensor was developed for the efficient identification of SARS‐CoV‐2 N antigens in saliva samples. The inclusion of a polymer layer shortens the distance between target molecules and the electrode interface, which effectively overcomes the limitation of Debye screening. The constructed IPE FET biosensors exhibit high sensitivity and anti‐fouling capability, achieving efficient detection of SARS‐CoV‐2 N antigen in saliva within 5 min with a detection limit of 4.6 fg·mL−1. In a cohort of 35 simulated throat swab samples of SARS‐CoV‐2 N antigen, IPE FET exhibits an identification accuracy of up to 97.1%, with predictive sensitivity and specificity of 96.0% and 100.0%, respectively. The excellent performance of IPE FET not only provides a strategy to design efficient detection platforms but also suggests a pathway to realize rapid and scalable epidemic screening.
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