Intellectual Merit: Recent developments in nanostructures manufacturing, sensing and wireless networking, will soon enable us to deploy Flow-based Cyber-Physical Systems equipped with sensing and actuation capabilities for a broad range of applications. Some of these applications will be safety critical, including water distribution monitoring (i.e., critical national infrastructure systems particularly vulnerable to a variety of attacks, including contamination with deadly agents) and interventional medicine (i.e., a medical branch that makes use of tiny devices introduced in a living body through small incisions, to detect and treat diseases). The goal of this project is to advance our fundamental understanding, through a robust mathematical framework, of emerging field of Flow-based Cyber-Physical System. The project develops new architectures, models, metrics, algorithms and protocols for optimal sensing, communication and actuation in Flow-based Cyber-Physical System deployed on-demand (i.e., reactively, when sensing and actuation is needed) or proactively. Flow-based Cyber Physical Systems consist of mobile sensor nodes and static nodes, aware of their location. For stringent requirements (e.g., form factor, cost, energy budget) nodes may or may not possess node-to-node communication capabilities. Due to the lack of localization infrastructure, mobile sensor nodes infer their location only by proximity to static nodes. Sensor nodes are moved by the flow in the network, detect events of interest and proximity to static nodes, communicate and actuate. This research will enable, for example, water distribution monitoring systems to accurately and timely detect events of interest in the infrastructure and to react to these events. It may enable doctors to detect diseases and deliver medication with microscopic precision. Broader Impacts: Ultimately, the outcomes of this research will have impact on CPS that operate in critical modes and environments and control critical infrastructures and medical applications. The results from this research may also foster new research directions in CPS applications. The PI will integrate the research results in newly approved courses on CPS at Texas A&M and disseminate course materials online through the project website and Rice University Connections Consortium. This project will also offer research opportunities to undergraduate students, underrepresented groups, and high school students participating in the Texas Science Olympiad and National Science Olympiad.