SemiSynBio-II: Hybrid Bio-Electronic Microfluidic Memory Arrays for Large Scale Testing and Remote Deployment

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The ability to record events (“memory”) is a crucial part of many complex systems. Recording events allows these systems to modify their behavior based on previous interactions, report on their history, or communicate local information to a global community. Biological systems will benefit greatly from the creation of memory elements. Biological memories in bacterial or mammalian cells could be used to monitor a person’s microbiome, develop smart materials that respond to the environment, or create specialized sensors that react to biotoxins. Biological memories in living cells themselves require a controlled environment. This environment not only ensures their long-term survival and viability but also allows for the controlled reading and writing of the memory. Reading and writing will ultimately be how these systems are “programmed” and how the data they collect can be acted upon. This project creates novel bio-memories using devices that move small amounts of liquids (microfluidics). Microfluidics are used to test in parallel many biological-memory configurations to determine which are the best at testing specific environmental signals (e.g. toxins, metals, hormones). The best of these memories are then integrated with low-cost, embedded electronics that can read their outputs as well as control the microfluidic environments housing the memories and allowing external signals to “write” information in the memories. Biological memories, microfluidics, and electronics together form what is called “Hybrid Bio-Electronic Microfluidic Memory Arrays”. These devices will explore numerous interdisciplinary challenges and create opportunities for exploring applications at the boundaries of computer science, synthetic biology, and materials science. To maximize this project’s impact, all of the research including the microfluidic and electronics designs and software will be made open source. All genetic memory elements will be provided to the scientific community. More than 48 undergraduate students will be mentored during the project period via NSF sponsored programs and summer research programs at Boston University. This project has a three-phase structure, where in the first phase biological memories are developed with the aid of a high-throughput, electronically augmented microfluidic screening platform. Recombinase enzymatic reactions on DNA will act as the irreversible memories while epigenetic, chromatin modifications will act as the reversible mechanism. This phase will involve the creation of 1000’s of potential memory elements. In the second phase, the top candidates from the first phase are combined in a massively parallel, highly integrated microfluidics platform to develop the eventual deployed microfluidic as well as establishing the operating and control conditions needed for the memories. Finally, in phase three, a small-scale deployment environment is created to observe and tune the performance of the newly created Hybrid Bio-Electronic Microfluidic Memory Arrays in an aquatic deployment scenario meant to replicate real-world bio-sensing applications for heavy metals and other environmental signals. These phases explicitly address three bio-memory challenges (create, control, and deploy) using state-of-the-art biological reversible and irreversible memories, droplet microfluidics, and customized embedded semiconductor-based electronics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.