SHF: Small: Continuously operable biomolecular circuits

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Biomolecular circuits can evaluate logic functions for which inputs are sensed and outputs produced directly within a physical environment. These circuits, not designed to complete with electronic computers, are meant to control physical processes such as chemical synthesis, cell behavior, or to direct how materials change their properties. Recently, it has become possible to build inexpensive, easy to design biomolecular circuits capable of a variety of nontrivial calculations using only short single strands of DNA that operate via a process called strand displacement. However, currently strand displacement circuits lack the capacity to respond dynamically to environmental changes because devices within the circuit can stop responding after a single computation. This limitation makes it impossible to design memory circuits, feedback controllers or to develop reprogrammable systems that take as input biomolecular "software." The goal of this proposal is to construct a new generation of strand displacement circuits that can operate continuously, with devices dynamically updating their outputs as their input values change. The proposed research will be integrated into the larger program at Johns Hopkins University via an interdisciplinary course in chemical and biomolecular engineering on the design of biomolecular systems from a computing perspective. Undergraduates and high school students from diverse backgrounds will participate in laboratory research. The broader notion of applying computer science principles to the design of biomolecular systems and circuits will be included as part of a set of interdisciplinary hands-on demonstrations and lessons developed by the PI for secondary school students that focus on how physical systems can compute.From a technical standpoint, the work will focus on the design of continuously operable logic devices, and multidevice logic circuits. In each case it will be demonstrated that circuits correctly recompute their outputs as input values change. The final aim of this work will be to create a flip-flop memory circuit, which requires continuous operability for function. This work has important implications for both computer science, where principles of computing machines will be tested beyond the domain of electronics, as well as for bioengineering and chemistry, where the ability to exploit logic and analog information processing within a reaction vessel or cell culture dish will open up new possibilities for diagnostics and process control.