Collaborative Research: FET: Medium: Biological production and enzymatic processing for defect-free, scalable nucleic-acid circuits

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The development of “chemical central processing units” will make possible computation in bio-chemical contexts that can sense from the environment, process information, and actuate a physical response. Necessary to this goal are fast, robust and composable molecular components that can implement logic behavior with physical molecules, much like electronic components have been successfully used to process information. One attractive candidate is DNA Strand Displacement (DSD) circuits. Despite the promise of DSD circuits, there are a number of perceived barriers to their widespread adoption as a technology: (i) DSD circuits are slow & error-prone, (ii) preparation of DSD circuit components is difficult and does not easily scale, (iii) DSD circuit components, even when purified, contain defects, and (iv) measuring & controlling the concentration of DSD circuit components is problematic. Recent breakthroughs in “leakless” DSD systems have seen the first barrier fall. The project includes plans for training students at all level.The investigators are addressing the three remaining barriers to widespread adoption of DSD circuit technology. The team of researchers is combining robust nucleic-acid circuit architectures, methods of producing long, high-fidelity single-stranded DNA, additional enzymatic methods, and new experimental protocols in order to simultaneously address all four of the identified barriers. The project intends to demonstrate that biologically amplified, enzymatically prepared DSD components lead to superior nucleic-acid logic circuits leading to entirely new applications of this technology.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.