CAREER: Facile molecular computation and diagnostics via fast, robust, and reconfigurable DNA circuits

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"Smart" systems pervade society. Computers appear to be on every desk, in every backpack, and in everyone’s pocket. Smart appliances, smart watches and smart autonomous cars are no longer distant research goals; they entwine with the fabric of everyday life. Yet, compared with biology, humans' ability for manipulation of structure and dynamics at the nanoscale is found wanting. Imagine a world where one can program "smart" molecules – as is done today with software – to not only store and process information, but to also manipulate matter with nanometer precision, to sense (bio-)chemical signals from their environment, to perform robust and complex computation, and to actuate a physical response in situ. Such mastery over the physical world using molecular computers will have as profound a change on society as contemporary computers have had on the ability to store and process information electronically. This research proposes new techniques, new design principles and new architectures to program the molecular world with robust, "field-programmable" DNA circuits. These circuits will be reconfigurable by non-experts and without sophisticated laboratory equipment, they will be capable of exquisite detection, and they will be embeddable within paper to enable future applications that include scientific outreach and point-of-care diagnostics that can be easily distributed in low-resource settings. Integrated with the technical goals of this project is the development of summer research experiences for upper level K-12 students, and an undergraduate class in molecular computation that will broaden participation in computing by reaching across subject boundaries.The project will develop new DNA strand displacement (DSD) architectures that maintain the robustness property of recent "leakless" systems and prioritize ease of preparation via biological production, ease of use by non-experts, and ease of reconfiguration by implementing programmable logic arrays. Robust and composable DSD modules will be developed for exponential signal amplification in vitro and in paper-based devices. These new architectures are grounded in theory and tempered by practical experimental concerns. New algorithms and software for molecular design and automation will be implemented to meet these goals.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.