SHF: Small: Hot DNA Computation: Speeding up DNA-based Computation, CRNs, and Robotics using Strand-Displacing Polymerase

To date, there has been considerable success in experimental demonstrations of DNA-based molecular devices to implement molecular-scale Boolean circuit computations, chemical reaction systems, and robotics. However, these experiments take hours to perform due to relatively slow reaction rates. Some progress has been made (by the project's investigators and others) in speeding up DNA-based computations, but the reactions still take tens of minutes. The objective of this project is to substantially speed-up DNA-based computations. The work is highly interdisciplinary and will provide interdisciplinary education at undergraduate and graduate levels. The project will engage students (with stress on women and under-represented minorities) from different academic levels across multiple disciplines in mentoring and teaching. Hands-on demonstrations of DNA computing and robotic devices will be designed for outreach programs at Duke and North Carolina Science & Math High School. Workshops and lectures will help disseminate knowledge of advanced DNA-based nanoscience concepts to undergraduate and graduate student audiences.

The project work will include design, simulation, and experimental demonstration of protocols which make use of only DNA hybridization and strand-displacing polymerization reactions. In particular, the project will not make use of the much slower either strand-displacement hybridization reactions or restriction enzyme reactions). The designs for Boolean circuit computations will be simulated and optimized. Experimental demonstrations will be made for each design, first in solution, and then experimentally demonstrated with the components attached to DNA nanostructures to allow for further speed-up via localized reactions. The project tasks include as Task 1, the design, simulation and demonstration of fast DNA logic circuits using strand-displacing polymerase reactions; this will include experimental demonstrations of multiple large-scale Boolean circuit computations executed in solution. Initial work by the project's investigators has already experimentally demonstrated a Boolean circuit computation (in solution) of a square root computation with 4 Boolean inputs that ran in approximately 15 minutes, and it is expected that considerable speed-ups when these reactions are localized. Task 2 is the experimental demonstration of localized reactions using strand-displacing polymerase; here DNA logical circuits will be attached to self-assembled DNA nanotracks and DNA origami, and the work will include experimental demonstrations of Boolean circuit computations executed in a localized fashion. Task 2 will also demonstrate a high-speed localized chain reaction on a self-assembled DNA track using strand-displacing polymerase reactions using a novel design where the gates form a self-assembled nanotrack and the reaction gradually de-assembles the track; this may provide a swift medical diagnostic system for targeted nucleic acid detection of infections.

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.