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，而且能够在生化环境中这样做，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链位移（DSD）原语之上，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类似于分子面包板的可重构DSD架构。它的目的是“扩大”这项技术的可能性，并“扩大”它在新环境和新研究领域的应用。少量快速、健壮且易于理解的分子成分将被开发出来，它们可以无缝地组合在一起。必要的工具，以促进快速电路设计和表征也将开发。可重构架构的设计将满足现实世界应用中的挑战，从护理点诊断到分子系统内的传感和驱动。由于它易于使用，我们设想这个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。在DNA链置换系统的新泄漏减少范例的基础上，稳健的分子计算门的新设计将被开发、实验测试和改进。通过完善一组适合用于模块化和可重构电路的分子元件，这将产生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。将开发一种编译器，它将电路或逻辑功能作为输入，并提供激活所需逻辑行为所需的生化“线”的优化集作为输出。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，电路2×-10×比以前演示的更大，完成时间10×-100×更快。复杂性的增加对设计验证产生了更大的需求，这将通过开发更高效的动力学仿真软件来解决。面包板保证足够坚固，可以在诊断和分子成像等应用中立即使用，也可以在纸质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.