Public health events caused by pathogens have imposed significant economic and societal burdens. However, conventional methods still face challenges including complex operations, the need for trained operators, and sophisticated instruments. Here, we proposed a fully integrated and automated centrifugal microfluidic chip, also termed IACMC, for point-of-care multiplexed molecular diagnostics by harnessing the advantages of active and passive valves. The IACMC incorporates multiple essential components including a pneumatic balance module for sequential release of multiple reagents, a pneumatic centrifugation-assisted module for on-demand solution release, an on-chip silicon membrane module for nucleic acid extraction, a Coriolis force-mediated fluid switching module, and an amplification module. Numerical simulation and visual validation were employed to iterate and optimize the chip's structure. Upon sample loading, the chip automatically executes the entire process of bacterial sample lysis, nucleic acid capture, elution quantification, and isothermal LAMP amplification. By optimizing crucial parameters including centrifugation speed, direction of rotation, and silicone membrane thickness, the chip achieves exceptional sensitivity (twenty-five Salmonella or forty Escherichia coli) and specificity in detecting Escherichia coli and Salmonella within 40 min. The development of IACMC will drive advancements in centrifugal microfluidics for point-of-care testing and holds potential for broader applications in precision medicine including high-throughput biochemical analysis immune diagnostics, and drug susceptibility testing.

中文翻译：

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用于即时多重分子诊断的完全集成和自动化离心微流控芯片

由病原体引起的公共卫生事件造成了巨大的经济和社会负担。然而，传统方法仍然面临操作复杂、需要训练有素的操作员和精密仪器等挑战。在这里，我们提出了一种完全集成和自动化的离心微流控芯片，也称为 IACMC，通过利用主动阀和被动阀的优势来进行即时多重分子诊断。 IACMC 包含多个基本组件，包括用于顺序释放多种试剂的气动平衡模块、用于按需溶液释放的气动离心辅助模块、用于核酸提取的片上硅膜模块、科里奥利力介导的流体切换模块和放大模块。采用数值模拟和视觉验证来迭代和优化芯片结构。样品加载后，芯片自动执行细菌样品裂解、核酸捕获、洗脱定量和等温LAMP扩增的整个过程。通过优化离心速度、旋转方向和硅胶膜厚度等关键参数，该芯片在 40 分钟内检测大肠杆菌和沙门氏菌时实现了卓越的灵敏度（25 个沙门氏菌或 40 个大肠杆菌）和特异性。 IACMC 的发展将推动用于即时检测的离心微流控技术的进步，并具有在精准医学领域更广泛应用的潜力，包括高通量生化分析、免疫诊断和药物敏感性测试。