SHF: Small: A reconfigurable architecture for digital circuit computation by fast, robust, and leakless DNA strand displacement cascades

SHF：小型：通过快速、稳健且无泄漏的 DNA 链位移级联进行数字电路计算的可重构架构

• 批准号: 1718938
• 负责人: Erik Winfree
• 金额: $ 46.5万
• 依托单位: California Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1718938&HistoricalAwards=false
• 关键词: SHF; Small; reconfigurable; architecture; digital

The promise of molecular programming lies in its ability to not only process information autonomously, but to do so in a biochemical context in order to sense and actuate matter. For its simplicity and its programmability, one attractive option for chemical information processing is built upon the DNA strand displacement (DSD) primitive, where a soup of rationally designed nucleotide sequences interact, react, and recombine over time in order to carry out sophisticated computation. The focus of this proposal is the creation of a reconfigurable DSD architecture akin to a molecular breadboard. Its purpose is to "scale-up" what is possible with this technology and to "scale-out" its adoption to new contexts and new areas of study. A small number of fast, robust and well-understood molecular components will be developed that compose seamlessly. The necessary tools to facilitate rapid circuit design and characterization will also be developed. The reconfigurable architecture will be designed to meet the challenges required in real-world applications ranging from point-of-care diagnostics to sensing and actuation within molecular systems. Due to its ease of use, we envision that this molecular breadboard will be an ideal vehicle to teach molecular programming and to facilitate wider adoption of DSD systems.Building on a new leak reduction paradigm for DNA strand displacement systems, a new design for robust molecular computing gates will be developed, experimentally tested, and refined. By perfecting a set of molecular components suitable for use in modular and reconfigurable circuits, this will result in a fixed set of dozens of high quality gates that can be arbitrarily wired-up in order to create bespoke molecular circuits. A compiler will be developed that takes as input a circuit or logic function and provides as output the optimized set of biochemical "wires" necessary to activate the desired logic behavior. If successful, it will be possible to create and execute fast, leakless and robust molecular circuits, for circuits 2×-10× larger than have been previously demonstrated and with completion times 10×-100× faster. This increase in complexity creates an even greater need for design verification that will be addressed by the development of more efficient kinetic simulation software. The breadboard promises to be robust enough for immediate use in applications, such as diagnostics and molecular imaging, and in new contexts such as paper-based devices.

分子编程的承诺不仅具有自主处理信息的能力，而且在生化环境中这样做以感知和实际物质。为了简单性及其可编程性，建立在DNA链位移（DSD）原始性的化学信息处理的一种有吸引力的选择中，其中合理设计的核卫星序列的汤随着时间的推移相互作用，反应和重新组合以进行复杂的计算。该提案的重点是创建类似于分子宽板的可重构DSD架构。其目的是“扩大”这项技术的可能性，并“扩展”其在新的环境和新的研究领域中的采用。将开发出少数快速，健壮和充分理解的分子成分，这些成分将无缝构成。还将开发促进快速电路设计和表征的必要工具。可重构体系结构将旨在应对从护理诊断到分子系统内的感应和驱动的现实应用程序所需的挑战。由于其易用性，我们设想该分子宽板将是教授分子编程并促进DSD系统的理想工具。建立在新的DNA链减少泄漏范围的范围内，用于DNA链位移系统，用于强大分子计算的新设计，将开发出强大的分子计算元素，并开发了实验性测试，并经过了细化。通过完善一组适合用于模块化和可重构电路的分子组件，这将导致固定的数十个高质量的大门，这些大门可以任意连接以创建定制的分子电路。将开发一个以输入电路或逻辑函数为输入的编译器，并提供一组优化的生化“电线”集，以激活所需的逻辑行为。成功的是，可以比以前证明的2×-10×大的电路快速，无漏和稳健的分子电路创建和执行，并且完成时间为10×-100倍。复杂性的增加创造了更大的设计验证需求，这将通过开发更有效的动力学模拟软件来解决。面包板有望足够强大，可以立即在应用中（例如诊断和分子成像）以及在诸如纸质设备之类的新环境中使用。

项目成果

Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems

• DOI: 10.1098/rsif.2018.0107
• 发表时间: 2018-12-01
• 期刊: JOURNAL OF THE ROYAL SOCIETY INTERFACE
• 影响因子: 3.9
• 作者: Berleant, Joseph;Berlind, Christopher;Winfree, Erik
• 通讯作者: Winfree, Erik

Thermodynamic Binding Networks

• DOI: 10.1007/978-3-319-66799-7_16
• 发表时间: 2017-01-01
• 期刊: DNA COMPUTING AND MOLECULAR PROGRAMMING
• 作者: Doty, David;Rogers, Trent A.;Woods, Damien
• 通讯作者: Woods, Damien

Inferring Parameters for an Elementary Step Model of DNA Structure Kinetics with Locally Context-Dependent Arrhenius Rates

推断具有局部上下文相关阿伦尼乌斯速率的 DNA 结构动力学基本步骤模型的参数

• DOI: 10.1007/978-3-319-66799-7_12
• 发表时间: 2017
• 期刊: Lecture notes in computer science
• 作者: Zolaktaf, Sedigheh;Dannenberg, Frits;Rudelis, Xander;Condon, Anne;Schaeffer, Joseph M;Thachuk, Chris;Winfree, Erik
• 通讯作者: Winfree, Erik

Towards space- and energy-efficient computations

迈向空间和能源高效的计算

• 发表时间: 2019
• 期刊: The Energetics of Computing in Life and Machines
• 作者: Condon, Anne;Thachuk, Chris
• 通讯作者: Thachuk, Chris

Verifying chemical reaction network implementations: A pathway decomposition approach

验证化学反应网络的实现：路径分解方法

• DOI: 10.1016/j.tcs.2017.10.011
• 发表时间: 2017
• 期刊: Theoretical Computer Science
• 影响因子: 1.1
• 作者: Shin, Seung Woo;Thachuk, Chris;Winfree, Erik
• 通讯作者: Winfree, Erik