Ultrasensitive, versatile sensors for molecular biomarkers are a critical component of disease diagnostics and personalized medicine as the COVID-19 pandemic has revealed in dramatic fashion. Integrated electrical nanopore sensors can fill this need via label-free, direct detection of individual biomolecules, but a fully functional device for clinical sample analysis has yet to be developed. Here, we report amplification-free detection of SARS-CoV-2 RNAs with single molecule sensitivity from clinical nasopharyngeal swab samples on an electro-optofluidic chip. The device relies on optically assisted delivery of target carrying microbeads to the nanopore for single RNA detection after release. A sensing rate enhancement of over 2,000x with favorable scaling towards lower concentrations is demonstrated. The combination of target specificity, chip-scale integration and rapid detection ensures the practicality of this approach for COVID-19 diagnosis over the entire clinically relevant concentration range from 10⁴-10⁹ copies/mL.

正如 COVID-19 大流行以引人注目的方式揭示的那样，用于分子生物标记物的超灵敏、多功能传感器是疾病诊断和个性化医疗的重要组成部分。集成电纳米孔传感器可以通过无标记、直接检测单个生物分子来满足这一需求，但尚未开发出用于临床样品分析的全功能设备。在这里，我们报告了在电光流控芯片上从临床鼻咽拭子样本中以单分子敏感性对 SARS-CoV-2 RNA 进行无扩增检测。该装置依靠光学辅助将携带微珠的目标递送至纳米孔，用于释放后的单个 RNA 检测。展示了超过 2,000 倍的感测速率增强以及向较低浓度的有利缩放。目标特异性的结合，⁴ -10 ⁹份/mL。