SHF: Small: Continuously operable biomolecular circuits

生物分子电路可以评估在物理环境中直接感知输入和输出的逻辑功能。这些电路不是设计用来完成电子计算机的，而是用来控制物理过程，如化学合成、细胞行为或指导材料如何改变其性质。最近，已经有可能建立廉价的，易于设计的生物分子电路，能够使用通过称为链位移的过程操作的短单链DNA进行各种重要计算。然而，目前的链位移电路缺乏动态响应环境变化的能力，因为电路中的设备在一次计算后就会停止响应。这一限制使得设计记忆电路、反馈控制器或开发以生物分子“软件”为输入的可编程系统成为不可能。本提案的目标是构建可连续运行的新一代链位移电路，随着输入值的变化，设备动态更新其输出。拟议的研究将通过从计算角度设计生物分子系统的化学和生物分子工程跨学科课程整合到约翰霍普金斯大学的更大项目中。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的设计这一更广泛的概念，将作为PI为中学生开发的一系列跨学科实践演示和课程的一部分，重点是物理系统如何进行计算。从技术角度来看，这项工作将侧重于设计连续可操作的逻辑器件和多器件逻辑电路。在每种情况下，它将证明电路正确地重新计算其输出作为输入值的变化。这项工作的最终目标将是创建一个触发器存储电路，它需要功能的连续可操作性。这项工作对计算机科学、生物工程和化学都有重要意义，在计算机科学中，计算机器的原理将在电子领域之外进行测试，在生物工程和化学中，在反应容器或细胞培养皿中利用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.