This project integrates digital microfluidics with thin-film photodetectors and control software to realize DNA target sensing using fluorescence. This cyberphysical vision is being realized through tight coupling between physical components, the microfluidic platform and miniaturized sensors, and cyber components, software for control, decision-making, and adaptation. Such a level of integration, decision, and controlled reconfigurability is a significant step forward in clinical diagnostics using digital microfluidic biochips. Topics being investigated include: (i) silicon-based digital microfluidics and integration of optical sensors; (ii) closed-loop operation and run-time optimization under software control; (iii) decision-tree architectures, adaptive reconfiguration, and error recovery. A complete testbed is being developed for nucleic acid identification on a fabricated chip with detection sites. Cyberphysical system integration will transform biochip use, in the same way as compilers and operating systems revolutionized computing, and design automation revolutionized chip design. Benefits to society include the potential to transform personalized medicine, home diagnostics, and portable diagnostics. Integration of digital microfluidics, optical sensing, and software control has the potential to create systems that can be used by any person, regardless of sample preparation skill. One example is the identification of bacterial DNA associated with bacterial blood infection (sepsis), which results in death if not diagnosed early (this is in the top 10 causes of death in the US). Students are being trained through a Senior Design course to understand the design