Department of Biomedical Engineering, Tsinghua University, Beijing, 100084, China.
Changping Laboratory, Beijing, 102206, China.
Adv Sci (Weinh). 2024 Nov;11(42):e2406076. doi: 10.1002/advs.202406076. Epub 2024 Sep 13.
Emerging diagnostic scenarios, such as population surveillance by pooled testing and on-site rapid diagnosis, highlight the importance of advanced microfluidic systems for in vitro diagnostics. However, the widespread adoption of microfluidic technology faces challenges due to the lack of standardized design paradigms, posing difficulties in managing macro-micro fluidic interfaces, reagent storage, and complex macrofluidic operations. This paper introduces a novel modular-based mesoscopic design paradigm, featuring a core "needle-plug/piston" structure with versatile variants for complex fluidic operations. These structures can be easily coupled with various microfluidic platforms to achieve truly self-contained microsystems. Incorporated into a "3D extensible" design architecture, the mesoscopic design meets the demands of function integration, macrofluid manipulations, and flexible throughputs for point-of-care nucleic acid testing. Using this approach, an ultra-sensitive nucleic acid detection system is developed with a limit of detection of ten copies of SARS-CoV-2 per mL. This system efficiently conducts large-scale pooled testing from 50 pharyngeal swabs in a tube with an uncompromised sensitivity, enabling a truly "sample-in-answer-out" microsystem with exceptional performance.
新兴的诊断方案，如群体监测的混合检测和现场快速诊断，凸显了先进微流控系统在体外诊断中的重要性。然而，由于缺乏标准化的设计范式，微流控技术的广泛应用面临挑战，这给管理宏观-微观流体界面、试剂储存和复杂的宏观流体操作带来了困难。本文提出了一种新颖的基于模块的介观设计范式，其核心是具有多功能变体的“针塞/活塞”结构，可用于复杂的流体操作。这些结构可以与各种微流控平台轻松耦合，以实现真正的自给式微系统。介观设计采用“3D 可扩展”设计架构，满足功能集成、宏观流体操作以及灵活的即时核酸检测通量需求。通过这种方法，开发了一种超灵敏的核酸检测系统，其对每毫升 SARS-CoV-2 的检测限为 10 拷贝。该系统能够高效地对 50 个咽拭子进行大规模混合检测，而不影响灵敏度，实现了具有出色性能的真正“样本进结果出”微系统。
