Unit operations for fully automated microfluidic paper-based analytical devices for diagnostic and biosensing

本研究计划的总体目标是为生物传感和诊断创造廉价，便携式即用型微流体纸基分析设备（upad）。通过这项发现资助，重点将放在开发一套用于微流控纸基设备的单元操作上，作为一个工具箱，快速构建用于环境（土壤和水）监测和生物医学应用的即用型检测试剂盒。来自不同背景（包括化学工程、材料工程、机械工程、电子工程和生物化学）的17名学生（包括2名博士、5名硕士和10名本科生）将受益于这项跨学科研究计划的培训。微流控纸基装置的操作包括：（A.1）开发外部可控阀门/流量调节器。光或热活化凝胶是很好的选择。（A.2）开发外部可控热交换器，不仅可以根据需要控制温度，更重要的是保证试验之间的一致性；在大多数分析中，反应速率和传感器产生的信号对温度敏感。（a .3）研制一套分离器，作为隔离不同组分的分离步骤。我们将创造一系列低成本的设备，作为现场传感器的分离器。（a .4）开发电子接口，监测纸张支撑的微流体装置的操作。发展/改进信号报告方法，以提供更方便用户的报告方法。目标B.用于环境监测和生物医学诊断的检测试剂盒。拟议的单元操作（来自目标A）将在纸质设备上实施，以运行复杂的分析方案，包括：（B.1）用于选择性检测饮用水中重金属的全自动微流体纸质分析试剂盒。利用所提出的单元操作的优势，将开发一种易于使用的全自动重金属传感器，同时最大限度地减少用户干预。（B.2）纸基土壤污染检测试剂盒。到目前为止，我与他人合作完成了几项仅在饮用水和流体样品中检测污染物（包括农药和微生物）的工作，但从未在固相（如土壤）样品中进行过检测。为了开发这样的检测试剂盒，一些关键的单元操作（包括上面列出的分离器，当然还有萃取器）非常需要在基于纸的微流体设备上设计和实现。（B.3）纸基凝血酶原时间（PT）检测试剂盒。该测试测量血液凝结所需的时间（凝血率）。这是检验血液稀释药物（抗凝血剂）华法林是否有效的重要试验。

The overall goal of this research program is to create inexpensive, and portable ready-to-use microfluidic paper-based analytical devices (uPADs) for biosensing and diagnostics. Through this Discovery Grant, the focus will be on the development of a set of unit operations for microfluidic paper-based devices to serve as a toolbox to rapidly build ready-to-use assay-kits for environmental (soil, and water) monitoring, and biomedical applications. A team of 17 students (including 2 Ph.D.s, 5 M.Sc.s, and 10 undergraduates students) from different backgrounds (including Chemical Engineering, Materials Engineering, Mechanical Engineering, Electrical Engineering, and Biochemistry) will benefit from training under this interdisciplinary research program. Goal A. Unit Operations on microfluidic paper-based devices include: (A.1) Development of externally controllable valves/ flow regulators. Light or heat activated gels are good candidates. (A.2) Development of externally controllable heat exchanger not only to control the temperature as needed but more importantly for consistency between tests; as in the majority of assays, the reaction rates and the generated signals from the sensors are temperature sensitive. (A.3) Development of a set of separators to serve as a separation step for the isolation of different components. We will create a family of low-cost devices to serve as a separator on the sensors in the field. (A.4) Development of an electronic interface for monitoring a paper-supported microfluidic device operation. Develop/improve the signal reporting approach to offer a more user-friendly reporting method. Goal B. Assay kits for point-of-use applications in environmental monitoring and biomedical diagnostic. The proposed unit operations (from goal A) are to be implemented on paper-based devices to run complex analytical protocols including: (B.1) Fully automated microfluidic paper-based assay kit for selective detection of the heavy metals in drinking water. Taking advantages of the proposed unit operations, an easy-to-use fully automated heavy metal sensor will be developed while minimizing the user intervention. (B.2) Paper-based assay kit for detection of soil contamination. So far, I, in collaboration with others, have done several works on detection of contaminants (including pesticide, and microorganism) in drinking water and fluid samples only, but not in a solid phase (like soil) samples ever. To develop such assay kits, a few critical unit operations (including separators as listed above, and extractor of-course), are highly needed to be designed and implemented on paper-based microfluidic devices. (B.3) Paper based assay kit for prothrombin time (PT) test. This test measures the time it takes the blood to clot (coagulation rate). This is an important assay to check whether blood-thinning medication (anticoagulant) warfarin to prevent blood clots is working.