SHF: Small: Continuously operable biomolecular circuits

生物分子电路可以评估在物理环境中直接产生输入和输出的逻辑函数。这些电路并不是为完成电子计算机而设计的，它们的目的是控制物理过程，如化学合成、细胞行为，或指导材料如何改变其性质。最近，只使用短小的单链DNA就可以构建廉价、易于设计的生物分子电路，这些电路能够进行各种重要的计算，这些DNA链通过一种名为链置换的过程进行操作。然而，目前的链式位移电路缺乏动态响应环境变化的能力，因为电路中的器件可能会在一次计算后停止响应。这种限制使得设计存储电路、反馈控制器或开发可再编程系统作为输入生物分子“软件”变得不可能。该方案的目标是构建新一代可以连续工作的链式位移电路，设备可以随着其输入值的变化动态更新其输出。这项拟议的研究将通过化学和生物分子工程的跨学科课程整合到约翰·霍普金斯大学的更大项目中，该课程将从计算角度设计生物分子系统。来自不同背景的本科生和高中生将参与实验室研究。将计算机科学原理应用于生物分子系统和电路设计的更广泛的概念将作为PI为中学生开发的一套跨学科动手演示和课程的一部分，重点是物理系统如何计算。从技术角度来看，这项工作将集中在连续可操作的逻辑器件和多器件逻辑电路的设计上。在每种情况下，都将证明当输入值改变时，电路正确地重新计算它们的输出。这项工作的最终目标将是创建一个触发器存储电路，这需要功能的连续可操作性。这项工作对计算机科学以及生物工程和化学都有重要影响，计算机科学的原理将在电子学领域之外进行测试，生物工程和化学利用反应容器或细胞培养皿内的逻辑和模拟信息处理的能力将为诊断和过程控制开辟新的可能性。

Biomolecular circuits can evaluate logic functions for which inputs are sensed and outputs produced directly within a physical environment. These circuits, not designed to complete with electronic computers, are meant to control physical processes such as chemical synthesis, cell behavior, or to direct how materials change their properties. Recently, it has become possible to build inexpensive, easy to design biomolecular circuits capable of a variety of nontrivial calculations using only short single strands of DNA that operate via a process called strand displacement. However, currently strand displacement circuits lack the capacity to respond dynamically to environmental changes because devices within the circuit can stop responding after a single computation. This limitation makes it impossible to design memory circuits, feedback controllers or to develop reprogrammable systems that take as input biomolecular "software." The goal of this proposal is to construct a new generation of strand displacement circuits that can operate continuously, with devices dynamically updating their outputs as their input values change. The proposed research will be integrated into the larger program at Johns Hopkins University via an interdisciplinary course in chemical and biomolecular engineering on the design of biomolecular systems from a computing perspective. Undergraduates and high school students from diverse backgrounds will participate in laboratory research. The broader notion of applying computer science principles to the design of biomolecular systems and circuits will be included as part of a set of interdisciplinary hands-on demonstrations and lessons developed by the PI for secondary school students that focus on how physical systems can compute.From a technical standpoint, the work will focus on the design of continuously operable logic devices, and multidevice logic circuits. In each case it will be demonstrated that circuits correctly recompute their outputs as input values change. The final aim of this work will be to create a flip-flop memory circuit, which requires continuous operability for function. This work has important implications for both computer science, where principles of computing machines will be tested beyond the domain of electronics, as well as for bioengineering and chemistry, where the ability to exploit logic and analog information processing within a reaction vessel or cell culture dish will open up new possibilities for diagnostics and process control.