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.

分子编程的前景在于它不仅能够自主处理信息，而且能够在生化背景下处理信息，以感知和驱动物质。 由于其简单性和可编程性，化学信息处理的一个有吸引力的选择是建立在 DNA 链置换 (DSD) 原语的基础上，其中合理设计的核苷酸序列随着时间的推移相互作用、反应和重组，以进行复杂的计算。 该提案的重点是创建类似于分子面包板的可重新配置的 DSD 架构。其目的是“扩大”该技术的可能性，并将其采用“扩大”到新的环境和新的研究领域。 将开发少量快速、强大且易于理解的无缝组合分子组件。 还将开发促进快速电路设计和表征的必要工具。 可重构架构的设计旨在满足现实应用中所需的挑战，从现场诊断到分子系统内的传感和驱动。由于其易于使用，我们预计该分子面包板将成为教授分子编程和促进 DSD 系统更广泛采用的理想工具。基于 DNA 链置换系统的新泄漏减少范例，将开发、实验测试和完善强大的分子计算门的新设计。 通过完善一组适用于模块化和可重构电路的分子组件，这将产生一组固定的数十个高质量门，可以任意连接这些门以创建定制的分子电路。 将开发一个编译器，它将电路或逻辑函数作为输入，并提供激活所需逻辑行为所需的一组优化的生化“线路”作为输出。 如果成功，将有可能创建和执行快速、无泄漏和强大的分子电路，其电路比之前演示的电路大 2 倍-10 倍，完成时间快 10 倍-100 倍。 复杂性的增加对设计验证提出了更大的需求，这将通过开发更高效的动力学模拟软件来解决。 该面包板有望足够坚固，可以立即用于诊断和分子成像等应用以及纸质设备等新环境中。

项目成果

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

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

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

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

Computing properties of stable configurations of thermodynamic binding networks

• DOI: 10.1016/j.tcs.2018.10.027
• 发表时间: 2019-09-20
• 期刊: THEORETICAL COMPUTER SCIENCE
• 影响因子: 1.1
• 作者: Breik, Keenan;Thachuk, Chris;Soloveichik, David
• 通讯作者: Soloveichik, David