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A Fully Integrated In Vitro Diagnostic Microsystem for Pathogen Detection Developed Using a 3D Extensible Microfluidic Design Paradigm

机译:使用 3D可扩展微流体设计范例开发的用于病原体检测的全集成体外诊断微系统

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摘要

Microfluidics is facing critical challenges in the quest of miniaturizing, integrating, and automating in vitro diagnostics, including the increasing complexity of assays, the gap between the macroscale world and the microscale devices, and the diverse throughput demands in various clinical settings. Here, a “3D extensible” microfluidic design paradigm that consists of a set of basic structures and unit operations was developed for constructing any application-specific assay. Four basic structures—check valve (in), check valve (out), double-check valve (in and out), and on–off valve—were designed to mimic basic acts in biochemical assays. By combining these structures linearly, a series of unit operations can be readily formed. We then proposed a “3D extensible” architecture to fulfill the needs of the function integration, the adaptive “world-to-chip” interface, and the adjustable throughput in the X, Y, and Z directions, respectively. To verify this design paradigm, we developed a fully integrated loop-mediated isothermal amplification microsystem that can directly accept swab samples and detect automatically with a sensitivity one order higher than that of the conventional kit. This demonstration validated the feasibility of using this paradigm to develop integrated and automated microsystems in a less risky and more consistent manner.
机译:在微型化,集成化和自动化体外诊断的过程中,微流体技术面临着严峻的挑战,包括测定方法的复杂性不断提高,宏观世界与微型设备之间的差距以及各种临床环境中对通量的要求。在这里,开发了一种“ 3D可扩展”微流设计范例,该范例由一组基本结构和单元操作组成,用于构建任何特定于应用的测定。设计了四个基本结构-止回阀(进),止回阀(出),双止回阀(进和出)和开/关阀-模仿生物化学测定中的基本行为。通过线性地组合这些结构,可以容易地形成一系列单元操作。然后,我们提出了一种“ 3D可扩展”架构,以满足功能集成,自适应“世界芯片”界面以及分别在X,Y和Z方向上可调整的吞吐量的需求。为了验证这种设计范例,我们开发了一个完全集成的回路介导的等温扩增微系统,该系统可以直接接受拭子样品并以比传统试剂盒高一倍的灵敏度自动检测。该演示验证了使用这种范例以较低风险和更一致的方式开发集成和自动化微系统的可行性。

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