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

到目前为止，在基于DNA的分子设备的实验演示中已经取得了相当大的成功，以实现分子规模的布尔电路计算、化学反应系统和机器人技术。然而，由于反应速度相对较慢，这些实验需要几个小时才能完成。(该项目的研究人员和其他人)在加速基于DNA的计算方面取得了一些进展，但反应仍然需要数十分钟。该项目的目标是大幅提高基于DNA的计算速度。这项工作是高度跨学科的，将提供本科生和研究生水平的跨学科教育。该项目将让来自多个学科的不同学术水平的学生(重点是妇女和代表性不足的少数群体)参与指导和教学。杜克大学和北卡罗来纳州科学与数学高中将为推广项目设计DNA计算和机器人设备的动手演示。工作坊和讲座将有助于向本科生和研究生传播先进的基于DNA的纳米科学概念的知识。项目工作将包括仅利用DNA杂交和链置换聚合反应的方案的设计、模拟和实验演示。特别是，该项目不会使用慢得多的链置换杂交反应或限制性内切酶反应)。将对布尔电路计算的设计进行模拟和优化。每种设计都将进行实验演示，首先是在溶液中，然后通过实验演示连接到DNA纳米结构的组件，以便通过局部反应进一步加速。该项目的任务包括作为任务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多个大规模布尔电路计算的实验演示。该项目研究人员的初步工作已经在实验中演示了具有4个布尔输入的平方根计算的布尔电路计算(在解中)，运行大约15分钟，预计当这些反应局部化时，会有相当大的速度。任务2是使用链置换聚合酶进行局部反应的实验演示；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，工作将包括以局部方式执行布尔电路计算的实验演示。任务2还将展示在自组装DNA轨道上使用链置换聚合酶反应的高速局部连锁反应，使用一种新颖的设计，其中门形成自组装纳米轨道，反应逐渐分解轨道；这可能为感染的靶向核酸检测提供快速医学诊断系统。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。

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.