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

分子编程的前景在于它不仅能够自主处理信息，而且能够在生物化学背景下这样做，以便感知和驱动物质。 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一个可重新配置的DSD架构类似于分子试验板。其目的是“扩大”这项技术的可能性，并“扩大”其采用到新的环境和新的研究领域。 将开发出少量快速、稳健和易于理解的分子组件，这些组件可以无缝组合。 还将开发必要的工具，以促进快速电路设计和表征。 可重新配置的架构将被设计为满足现实世界中的应用所需的挑战，从即时诊断到分子系统内的传感和驱动。由于它的易用性，我们设想，这个分子实验板将是一个理想的工具，教分子编程和促进更广泛地采用DSD systems.Building上的DNA链置换系统的一个新的泄漏减少范例，一个新的设计，强大的分子计算门将被开发，实验测试，并完善。 通过完善一组适用于模块化和可重构电路的分子组件，这将导致一组固定的数十个高质量门，这些门可以任意连接，以创建定制的分子电路。 一个编译器将被开发，作为输入的电路或逻辑功能，并提供作为输出的优化设置的生化“电线”必要的激活所需的逻辑行为。 如果成功，将有可能创建和执行快速，无泄漏和鲁棒的分子电路，电路比以前演示的电路大2×-10倍，完成时间快10×-100倍。 这种复杂性的增加产生了对设计验证的更大需求，这将通过开发更有效的动力学模拟软件来解决。 该试验板有望足够强大，可立即用于诊断和分子成像等应用，以及纸基设备等新环境。

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.