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

这个创新-技术转化伙伴关系项目的更广泛的影响/商业潜力是开发一种快速、可靠、简单和负担得起的新冠肺炎和其他病毒性疾病诊断测试。这项工作旨在建立一种具有许多关键好处的纳米生物传感器。这些好处包括高准确性和快速周转(不到30分钟)，以促进快速隔离和限制潜在的疾病传播。此外，该传感器将是低成本的，具有简单的检测方法，例如颜色变化，无需专门的设备即可轻松进行。这种设计的简单性将使测试能够在从诊所到学校和农村或低资源地区的各种环境中进行。此外，低成本与可扩展的制造方法相结合，可能会对大学校园或工作场所等可能需要定期测试的大型开放式社区产生影响。最后，本研究将扩展该传感器的能力，使其能够同时检测多个目标。特别是，该团队将专注于展示同时检测新冠肺炎和流感的能力，这将使人们能够通过一种简单、快速和成本效益高的测试来诊断其中一种疾病或两种疾病。该项目将利用动态DNA折纸设备设计和控制方面的先前基础研究，开发基于DNA的纳米生物传感器，为检测SARS-CoV-2RNA和其他病毒目标提供快速(30分钟内)读数。该传感器基于一种可重新配置的DNA设备，该设备将被设计为在与目标核酸结合时改变构象。这项工作可能会解决与以高精度、高灵敏度和特异度检测目标相关的几个关键技术挑战，同时用低成本设备提供健壮、快速和容易检测的读数。研究团队将在设备机械和动态特性的可调控制与目标结合机制的精确设计之间取得平衡，以优化这些特性。此外，传感器设计将得到改进，以实现多重检测建立方法，在这种方法中，可以使用两个不同的读数同时检测两个目标，例如不同的颜色荧光读数。此外，该团队将开发一种级联激活机制，在这种机制中，激活的设备可以触发其他传感器的激活，从而可以最大限度地降低检测极限。最后，这项工作将直接将开发的传感技术与当前的测试标准进行基准测试，包括实时聚合酶链式反应方法和广泛使用的快速抗原测试。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.