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

这项研究计划的总体目标是为生物传感和诊断创造廉价、便携、即用的微流控纸基分析设备(UPADS)。通过这项发现赠款，重点将是开发一套用于微流控纸质设备的单元操作，作为工具箱，快速建立环境(土壤和水)监测和生物医学应用的现成分析试剂盒。来自不同背景(包括化学工程、材料工程、机械工程、电气工程和生物化学)的17名学生(包括2名博士、5名硕士和10名本科生)将从这一跨学科研究计划下的培训中受益。目标A。微流控纸基设备的单元操作包括：(a.1)开发外部可控阀门/流量调节器。光或热激活凝胶是很好的候选者。(a.2)开发外部可控热交换器，不仅是为了根据需要控制温度，更重要的是为了测试之间的一致性；在大多数测试中，反应速度和传感器产生的信号都是温度敏感的。(A.3)开发一套分离器，作为分离不同成分的分离步骤。我们将创建一系列低成本设备，作为现场传感器的分离器。(A.4)开发用于监测纸质微流控装置运行的电子接口。发展/改进信号报告方法，以提供更方便用户使用的报告方法。目标B.环境监测和生物医学诊断中使用点应用的分析试剂盒。拟议的单元操作(来自目标A)将在纸基设备上实施，以运行复杂的分析方案，包括：(b.1)全自动微流控纸基分析试剂盒，用于选择性检测饮用水中的重金属。利用拟议的单元操作，将开发一种易于使用的全自动重金属传感器，同时将用户干预降至最低。(b.2)用于检测土壤污染的纸质化验试剂盒。到目前为止，我和其他人合作，只在饮用水和流体样本中检测污染物(包括农药和微生物)，而不是在固相(如土壤)样本中进行检测。为了开发这样的检测试剂盒，需要在纸基微流控设备上设计和实施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)。(B.3)纸质凝血酶原时间(PT)检测试剂盒。这项测试测量血液凝结所需的时间(凝固率)。这是检查血液稀释剂(抗凝剂)华法林预防血栓有效的重要方法。

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.