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

到目前为止，已经有相当大的成功，在实验演示的DNA为基础的分子器件，实现分子规模的布尔电路计算，化学反应系统，和机器人。然而，由于反应速率相对较慢，这些实验需要数小时才能完成。在加速基于DNA的计算方面已经取得了一些进展（由该项目的研究人员和其他人），但反应仍然需要几十分钟。该项目的目标是大大加快基于DNA的计算。这项工作是高度跨学科的，将提供本科和研究生水平的跨学科教育。该项目将使来自多个学科不同学术水平的学生（重点是妇女和代表性不足的少数民族）参与辅导和教学。DNA计算和机器人设备的实际演示将为杜克和北卡罗来纳州科学数学高中的外展项目而设计。工作坊和讲座将有助于向本科生和研究生传播基于DNA的先进纳米科学概念的知识。项目工作将包括设计、模拟和实验演示仅使用DNA杂交和链置换聚合反应的协议。特别是，该项目将不使用慢得多的链置换杂交反应或限制性酶反应。布尔电路计算的设计将被模拟和优化。将对每种设计进行实验演示，首先在溶液中进行，然后用附着在DNA纳米结构上的组件进行实验演示，以便通过局部反应进一步加速。项目任务包括任务1，使用链置换聚合酶反应设计，模拟和演示快速DNA逻辑电路;这将包括在解决方案中执行的多个大规模布尔电路计算的实验演示。该项目的研究人员的初步工作已经通过实验证明了具有4个布尔输入的平方根计算的布尔电路计算（在解决方案中），该计算在大约15分钟内运行，并且预计当这些反应被本地化时会有相当大的加速。任务2是使用链置换聚合酶的局部化反应的实验演示;在这里，DNA逻辑电路将连接到自组装的DNA纳米轨道和DNA折纸，工作将包括以局部化方式执行的布尔电路计算的实验演示。任务2还将展示使用链置换聚合酶反应在自组装DNA轨道上进行的高速局部链式反应，该反应使用新的设计，其中门形成自组装纳米轨道，并且反应逐渐分解轨道;这可能为感染的靶向核酸检测提供一种快速的医学诊断系统。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

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.