ABSTRACT
For epidemic prevention and control, molecular diagnostic techniques such as field-effect transistor (FET) biosensors is developed for rapid screening of infectious agents, including Mycobacterium tuberculosis, SARS-CoV-2, rhinovirus, and others. They obtain results within a few minutes but exhibit diminished sensitivity (<75%) in unprocessed biological samples due to insufficient recognition of low-abundance analytes. Here, an electro-enhanced strategy is developed for the precise detection of trace-level infectious agents by liquid-gate graphene field-effect transistors (LG-GFETs). The applied gate bias preconcentrates analytes electrostatically at the sensing interface, contributing to a 10-fold signal enhancement and a limit of detection down to 5 × 10−16 g mL−1 MPT64 protein in serum. Of 402 participants, sensitivity in tuberculosis, COVID-19 and human rhinovirus assays reached 97.3% (181 of 186), and specificity is 98.6% (213 of 216) with a response time of <60 s. This study solves a long-standing dilemma that response speed and result accuracy of molecular diagnostics undergo trade-offs in unprocessed biological samples, holding unique promise in high-quality and population-wide screening of infectious diseases. © 2023 Wiley-VCH GmbH.