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

分子编程的前景不仅在于它能够自主地处理信息，而且还在于它能够在生化环境中这样做，以便感觉和驱动物质。由于其简单性和可编程性，一个有吸引力的化学信息处理选择是建立在DNA链置换(DSD)原语之上的，在DSD原语中，一堆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，以便进行复杂的计算。这项提议的重点是创建一种类似于分子面包板的可重新配置的DSD架构。它的目的是“扩大”这项技术的可能性，并将其应用于新的背景和新的研究领域。将开发一小部分快速、强大和广为人知的分子组件，它们可以无缝组合。还将开发促进快速电路设计和表征的必要工具。这种可重新配置的架构将被设计为满足现实世界应用中所需的挑战，范围从看护点诊断到分子系统内的传感和驱动。由于其易用性，我们预计这种分子面包板将成为教授分子编程的理想工具，并促进DSD系统的更广泛采用。基于DNA链置换系统的新泄漏减少范例，将开发、实验测试和改进强大的分子计算门的新设计。通过完善一套适合用于模块化和可重新配置电路的分子组件，这将产生一组固定的数十个高质量的门，这些门可以任意连接，以创建定制的分子电路。将开发一种编译器，该编译器将电路或逻辑功能作为输入，并提供激活所需逻辑行为所必需的优化的生化“线”集作为输出。如果成功，将有可能创建和执行快速、无泄漏和坚固的分子电路，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，这将通过开发更高效的动力学模拟软件来解决。面包板承诺足够坚固，可以立即在诊断和分子成像等应用中使用，也可以在纸基设备等新环境中使用。

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.