CPS: Synergy: Collaborative Research: Cyber-physical digital microfluidics based on active matrix electrowetting technology: software-programmable high-density pixel arrays

芯片实验室(LoC)技术正准备通过开发低成本、自动化的护理点检测设备来改善全球健康。在缺乏医疗资源的国家，诊所通常有治疗疾病的药物，但缺乏诊断工具来识别需要这些药物的患者。为了在最低限度的实验室支持下实现低成本诊断，该项目将结合器件制造技术(工艺流程、传感器集成等)研究特定领域的LoC编程语言和编译器设计。该项目将最终建立一个工作的LoC，通过主机PC提供的电子信号控制流体运动；法医毒理学免疫分析将在软件中编程，并在设备上执行。本实验将展示可编程LoC技术的好处，包括小型化(减少试剂消耗)、自动化(减少成本和与人类交互相关的不确定性)和通用软件可编程性(该设备可以执行各种生化反应，所有这些都在软件中指定)。复制该设备所需的信息，以及通过这项研究开发的所有软件制品，都将被公开传播。这将促进软件可编程LoC技术在生物科学研究人员以及公共和工业部门(包括医疗保健和公共卫生、生物技术、供水管理、环境毒性监测等)中的广泛使用。本项目设计并实现了一个可执行各种生物协议的软件可编程网络物理芯片实验室(LoC)。通过在制造过程中集成传感器，LoC获得了向PC控制器实时发送反馈的能力，PC控制器然后可以就下一步执行哪些生物操作做出智能决定。为了实现这一创新和变革性的平台，该项目解决了几个艰巨的研究挑战：(1)网络物理LoC编程模型和编译器设计；(2)LoC制造，包括工艺流程和网络物理传感器集成；以及(3)依赖于网络物理感知反馈和实时决策的LoC应用。通过构建一个工作原型LoC，并编程一个典型的反馈驱动的法医毒理学免疫分析，该项目证明了所提出的系统可以自动执行需要闭合反馈环的生化反应。拟议工作的预期更广泛的影响包括降低临床诊断的成本和提高可靠性，与使用LoC技术的美国公司接触，培训研究生和本科生，增加针对女性和代表不足的少数族裔的参与和保留努力，在加州大学河滨分校由学生推动的同行指导，田纳西大学为代表不足的少数族裔高中生举办的暑期住宿计划，与橡树岭国家实验室的研究人员合作，以及创建、演示和传播教程材料，以促进更广泛的科学界采用和使用软件可编程本地程序。

Laboratory-on-a-chip (LoC) technology is poised to improve global health through development of low-cost, automated point-of-care testing devices. In countries with few healthcare resources, clinics often have drugs to treat an illness, but lack diagnostic tools to identify patients who need them. To enable low-cost diagnostics with minimal laboratory support, this project will investigate domain-specific LoC programming language and compiler design in conjunction with device fabrication technologies (process flows, sensor integration, etc.). The project will culminate by building a working LoC that controls fluid motion through electronic signals supplied by a host PC; a forensic toxicology immunoassay will be programmed in software and executed on the device. This experiment will demonstrate benefits of programmable LoC technology including miniaturization (reduced reagent consumption), automation (reduced costs and uncertainties associated with human interaction), and general-purpose software-programmability (the device can execute a wide variety of biochemical reactions, all specified in software). Information necessary to reproduce the device, along with all software artifacts developed through this research effort, will be publicly disseminated. This will promote widespread usage of software-programmable LoC technology among researchers in the biological sciences, along with public and industrial sectors including healthcare and public health, biotechnology, water supply management, environmental toxicity monitoring, and many others.This project designs and implements a software-programmable cyber-physical laboratory-on-a-chip (LoC) that can execute a wide variety of biological protocols. By integrating sensors during fabrication, the LoC obtains the capability to send feedback in real-time to the PC controller, which can then make intelligent decisions regarding which biological operations to execute next. To bring this innovative and transformative platform to fruition, the project tackles several formidable research challenges: (1) cyber-physical LoC programming models and compiler design; (2) LoC fabrication, including process flows and cyber-physical sensor integration; and (3) LoC applications that rely on cyber-physical sensory feedback and real-time decision-making. By constructing a working prototype LoC, and programming a representative feedback-driven forensic toxicology immunoassay, the project demonstrates that the proposed system can automatically execute biochemical reactions that require a closed feedback loop. Expected broader impacts of the proposed work include reduced cost and increased reliability of clinical diagnostics, engagement with U.S. companies that use LoC technology, training of graduate and undergraduate students, increased engagement and retention efforts targeting women and underrepresented minorities, student-facilitated peer-instruction at UC Riverside, a summer residential program for underrepresented minority high-school students at the University of Tennessee, collaborations with researchers at the Oak Ridge National Laboratory, and creation, presentation, and dissemination of tutorial materials to promote the adoption and use of software-programmable LoCs among the wider scientific community.