Rapid and accurate diagnosis of tuberculosis (TB) infection in resource-limited settings is critically needed to stop the spread of the disease but remains difficult to achieve. Herein, we report a fast, inexpensive nucleic acid test with distance-based readout (FINDR) for TB. Based on the unique chromatographic behavior of DNA intercalating dye on unmodified cellulose paper, our FINDR platform converted the amplicons of loop-mediated isothermal amplification (LAMP) into the migration distance on a paper-based analytical device. A suite of innovations were further introduced to enhance the accessibility of FINDR, including (1) screening optimal LAMP primers for distance-based readout; (2) developing a chip-on-cover design capable of streamlining LAMP amplification and distance-based detection in a fully sealed FINDR chip with a simple hand-based swirling for liquid transfer; and (3) integrating FINDR with an upstream portable pipetting-free DNA extractor and a downstream smartphone app to simplify sample processing and data interpretation. With these innovations, FINDR demonstrated a high clinical sensitivity (96.6%) and specificity (100%) upon validation against clinical sputum samples. Successful clinical validation was also achieved when FINDR was deployed as a point-of-care test for detecting TB under resource-limited conditions.

中文翻译：

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使用基于距离的读数的便携式核酸检测对结核病进行即时诊断


在资源有限的环境中，迫切需要快速准确地诊断结核病 （TB） 感染，以阻止疾病的传播，但仍然难以实现。在此，我们报告了一种快速、廉价的基于距离的读数 （FINDR） 的 TB 核酸检测。基于未改性纤维素纸上 DNA 嵌入染料的独特色谱行为，我们的 FINDR 平台将环介导的等温扩增 （LAMP） 的扩增子转化为纸质分析设备上的迁移距离。进一步引入了一系列创新来提高 FINDR 的可及性，包括 （1） 筛选用于基于距离的读数的最佳 LAMP 引物;（2） 开发一种盖上芯片的设计，能够在完全密封的 FINDR 芯片中简化 LAMP 扩增和基于距离的检测，并通过简单的手动旋转进行液体转移;（3） 将 FINDR 与上游便携式免移液 DNA 提取仪和下游智能手机应用程序集成，以简化样品处理和数据解析。通过这些创新，FINDR 在对临床痰液样本的验证中表现出高临床敏感性 （96.6%） 和特异性 （100%）。当 FINDR 被部署为在资源有限条件下检测结核病的即时检测时，也实现了成功的临床验证。