Accurate and accessible nucleic acid diagnostics is critical to reducing the spread of COVID-19 and resuming socioeconomic activities. Here, we present an integrated platform for the direct detection of SARS-CoV-2 RNA targets near patients. Termed electrochemical system integrating reconfigurable enzyme-DNA nanostructures (eSIREN), the technology leverages responsive molecular nanostructures and automated microfluidics to seamlessly transduce target-induced molecular activation into an enhanced electrochemical signal. Through responsive enzyme-DNA nanostructures, the technology establishes a molecular circuitry that directly recognizes specific RNA targets and catalytically enhances signaling; only upon target hybridization, the molecular nanostructures activate to liberate strong enzymatic activity and initiate cascading reactions. Through automated microfluidics, the system coordinates and interfaces the molecular circuitry with embedded electronics; its pressure actuation and liquid-guiding structures improve not only analytical performance but also automated implementation. The developed platform establishes a detection limit of 7 copies of RNA target per μl, operates against the complex biological background of native patient samples, and is completed in <20 min at room temperature. When clinically evaluated, the technology demonstrates accurate detection in extracted RNA samples and direct swab lysates to diagnose COVID-19 patients.

准确且易于使用的核酸诊断对于减少 COVID-19 的传播和恢复社会经济活动至关重要。在这里，我们提出了一个集成平台，用于直接检测患者附近的 SARS-CoV-2 RNA 靶标。该技术被称为集成可重构酶-DNA纳米结构的电化学系统（eSIREN），它利用响应性分子纳米结构和自动化微流体将目标诱导的分子激活无缝地转换为增强的电化学信号。通过响应性酶-DNA纳米结构，该技术建立了一个分子电路，可以直接识别特定的RNA靶标并催化增强信号传导；只有在目标杂交时，分子纳米结构才会激活，释放出强酶活性并引发级联反应。通过自动化微流体技术，该系统可以协调分子电路并将其与嵌入式电子设备连接起来；其压力驱动和液体引导结构不仅提高了分析性能，还提高了自动化实施。开发的平台建立了每微升 7 个 RNA 靶拷贝的检测限，针对天然患者样本的复杂生物背景进行操作，并在室温下于 20 分钟内完成。在临床评估中，该技术证明可以准确检测提取的 RNA 样本和直接拭子裂解物，以诊断 COVID-19 患者。