A DNA Triangular Prism-Based Multitargeting Transistor for Ultrasensitive Detection of Respiratory Virus

The rapid and precise quantification of viral copies in clinical samples at extremely low concentrations is crucial for controlling infections and epidemics. The widely used nucleic acid detection methods require specialized equipment, high-containment laboratories, and complex amplification processes, which render them inefficient for point-of-care testing (POCT) and population-scale screening. Herein, we propose a sensing system that integrates a triangular prism DNA nanostructure (TPDN) with a carbon nanotube-based field-effect transistor (FET) for the rapid and ultrasensitive detection of viral RNA. Three flexible single-stranded probes targeting distinct viral RNA loci were anchored to a rigid DNA framework, enabling the efficient capture of long-strand viral RNA fragments. A suitable positive gate voltage was applied to the TPDN-FET to orient the DNA probe vertically and extend the Debye screening length. Consequently, this results in a 4-fold increase in the sensitivity of the FET-based biosensor compared with those of the sensors incorporating only a single probe. The TPDN-FET sensor completed the detection process in 40 s, enabling the accurate perception of respiratory syncytial virus (RSV) at concentrations as low as 0.1 copies per microliter. The sensor identified all 10 positive cases (cycle thresholds 28.9-32.2) among 20 individual nasopharyngeal swabs and detected 6 positives in 12 pooled tests without RNA extraction or nucleic acid amplification. Thus, the rapid, ultrasensitive, user-friendly, and pooled-sample-compatible sensing device developed in this study has great potential in the POCT and in vitro diagnosis of respiratory virus and other potential epidemic-causing pathogens.