PFI-TT: DNA Sensors for Rapid Detection of COVID-19 and other Viral Diseases with High Sensitivity

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is the development of a rapid, reliable, simple, and affordable diagnostic test for COVID-19 and other viral diseases. This work aims to establish a nanobiosensor with a number of key benefits. These benefits include high accuracy with rapid turnaround (less than 30 minutes) to promote fast quarantine and limit potential disease spread. In addition, the sensor will be low-cost with simple detection methods such as a color change that could easily be carried out without the need for specialized equipment. This design simplicity will enable testing in a variety of settings ranging from clinics, to schools and rural or low-resource areas. In addition, the low-cost, combined with the scalable fabrication methods, can have an impact on large open communities such as college campuses or workplaces that may require testing on a regular basis. Finally, this research will extend the capabilities of this sensor to enable simultaneous detection of multiple targets. In particular, the team will focus on demonstrating the ability to simultaneously detect COVID-19 and flu, which would allow diagnosis of either or both diseases with a simple rapid and cost-effective test. This project will leverage prior basic research in design and control of dynamic DNA origami devices to develop DNA-based nanobiosensors that provide a rapid (within 30 min) readout for detection of SARS-CoV-2 RNA and other viral targets. The sensor is based on a reconfigurable DNA device that will be designed to change conformation upon binding of a target nucleic acid. This work may solve several key technical challenges related to detecting the target with high accuracy, high sensitivity, and specificity, while providing robust, rapid, and easily detectable readouts with a low-cost device. The research team will balance tunable control of the device mechanical and dynamic properties with precise design of target binding mechanisms to optimize these characteristics. In addition, sensor designs will be enhanced to enable multiplexed detection establishing methods where two targets could be simultaneously detected with two different readouts such as different color fluorescence readouts. In addition, the team will develop a mechanism for cascaded activation where an activated device can trigger activation of other sensors, which can minimize the limits of detection. Finally, this work will directly benchmark the developed sensing technologies with current standards of testing including real-time polymerase chain reaction methods and widely used rapid antigen tests. 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.