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CAREER: Facile molecular computation and diagnostics via fast, robust, and reconfigurable DNA circuits

职业：通过快速、稳健且可重新配置的 DNA 电路进行简便的分子计算和诊断

基本信息

批准号：
2143227
负责人：
Christopher Thachuk
金额：
$ 72.95万
依托单位：
University of Washington
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-15 至 2027-02-28
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2143227&HistoricalAwards=false
关键词：
CAREER Facile molecular computation diagnostics

项目摘要

"Smart" systems pervade society. Computers appear to be on every desk, in every backpack, and in everyone’s pocket. Smart appliances, smart watches and smart autonomous cars are no longer distant research goals; they entwine with the fabric of everyday life. Yet, compared with biology, humans' ability for manipulation of structure and dynamics at the nanoscale is found wanting. Imagine a world where one can program "smart" molecules – as is done today with software – to not only store and process information, but to also manipulate matter with nanometer precision, to sense (bio-)chemical signals from their environment, to perform robust and complex computation, and to actuate a physical response in situ. Such mastery over the physical world using molecular computers will have as profound a change on society as contemporary computers have had on the ability to store and process information electronically. This research proposes new techniques, new design principles and new architectures to program the molecular world with robust, "field-programmable" DNA circuits. These circuits will be reconfigurable by non-experts and without sophisticated laboratory equipment, they will be capable of exquisite detection, and they will be embeddable within paper to enable future applications that include scientific outreach and point-of-care diagnostics that can be easily distributed in low-resource settings. Integrated with the technical goals of this project is the development of summer research experiences for upper level K-12 students, and an undergraduate class in molecular computation that will broaden participation in computing by reaching across subject boundaries.The project will develop new DNA strand displacement (DSD) architectures that maintain the robustness property of recent "leakless" systems and prioritize ease of preparation via biological production, ease of use by non-experts, and ease of reconfiguration by implementing programmable logic arrays. Robust and composable DSD modules will be developed for exponential signal amplification in vitro and in paper-based devices. These new architectures are grounded in theory and tempered by practical experimental concerns. New algorithms and software for molecular design and automation will be implemented to meet these goals.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.

“智能”系统遍布整个社会。电脑似乎在每一张桌子上，在每一个背包里，在每个人的口袋里。智能家电、智能手表和智能自动汽车不再是遥远的研究目标;它们与日常生活的结构融为一体。然而，与生物学相比，人类在纳米尺度上操纵结构和动力学的能力是不够的。想象一下，在这样一个世界里，人们可以对“智能”分子进行编程--就像今天的软件一样--不仅可以存储和处理信息，还可以以纳米精度操纵物质，感知来自环境的（生物）化学信号，执行强大而复杂的计算，并在原地启动物理反应。使用分子计算机对物理世界的这种控制将对社会产生深远的影响，就像当代计算机对电子存储和处理信息的能力一样。这项研究提出了新的技术，新的设计原则和新的架构，以强大的，“现场可编程”的DNA电路编程的分子世界。这些电路将由非专家重新配置，无需复杂的实验室设备，它们将能够进行精密检测，并且它们将嵌入纸张中，以实现未来的应用，包括科学推广和即时诊断，这些应用可以在低资源环境中轻松分布。与该项目的技术目标相结合的是为高水平的K-12学生开发夏季研究经验，以及一个分子计算的本科课程，通过跨越学科界限来扩大对计算的参与。该项目将开发新的DNA链置换（DSD）架构，保持最近“无泄漏”的鲁棒性。系统，并优先考虑通过生物生产的制备容易性，非专家的使用容易性，以及通过实施可编程逻辑阵列的重新配置容易性。将开发强大且可组合的DSD模块，用于体外和纸质设备中的指数信号放大。这些新的体系结构是建立在理论基础上的，并通过实际的实验问题进行了调整。该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。