SemiSynBio: Redox-enabled Bio-Electronics for Molecular Communication and Memory (RE-BIONICS)

RE-BIONICS项目（基于分子通信的氧化还原生物电子学）的目标是创建第一种生物电子设备，以介导生物学和电子学之间快速简便的信息交换。这些设备将有可能改变医疗保健，实现远程监测和远程/自主药物输送，并促进农业和网络防御中的环境监测，其中将生物现象与电子设备连接起来非常重要。这项工作的技术基础认识到，微电子设备依赖于电子进行信息处理，而生物学依赖于分子（例如，胰岛素、抗体）。这些系统本质上并不兼容，因为生物学中没有可以传输到生物导线和控制基于细胞的电子电路的自由电子。相反，设想生物混合装置可以跨越电子-分子鸿沟传输信息。我们需要新的界面，从生物学中接受分子，为设备创造电子，反之亦然。在RE-BIONICS中设计和构建的这种集成系统将能够进行这种存储和计算的双向通信。该项目将建立构建生物混合设备所需的组件和信息理论，这些设备最终可以嵌入生物系统并提供电子控制。除了建立设计和构建全新生物设备的能力外，这项工作最重要的方面是它将汇集来自许多学科的研究人员和利益相关者，包括生物学，化学，材料科学，计算机，电气，化学和生物工程。 该项目建立在项目的跨学科性质上，研究团队来自计算机科学，电气工程和生物工程。研究方向涵盖计算机科学和信息理论、微机电系统、生物制造和氧化还原生物学以及合成生物学。 此外，来自UMD和UNL的两个跨学科本科生团队将参加国际遗传工程机器（iGEM）计划和竞赛，并参加针对UNL未来问题解决计划（FPSPI）中的中学生的具体推广活动。 此外，该项目还将促进历来在电气工程专业任职人数不足的妇女的参与，她们在生物学和生物工程专业的任职人数超过了专业人数。 RE-BIONICS研究人员还将与包括NIST、FDA和陆军研究实验室在内的联邦机构进行互动，了解制造和监管问题，以及国家安全等直接应用领域。该项目利用还原-氧化（氧化还原）介质，这些介质是电子学中自由电子的生物等效物。这些反应代表了生物体内传递的信息包。 该项目分为三个具体目标。在目标1中，该团队将设计，建造和测试设备元件，以促进从生物系统的分子到微电子系统的电子的信息传递。利用合成生物学的原理，细菌细胞将被改造为识别小信号分子，一个例子是绿脓杆菌，由机会致病菌，铜绿假单胞菌分泌。基于这种认识，这些和其他工程传感细胞将产生β-半乳糖苷酶，一种可以电化学定量的酶。此外，细胞将被改造为接受来自设备的电子，并以编程的方式“打开”可以调节细胞行为的基因表达。在目标2中，该团队将设计和构建一种基于生物聚合物黑色素的生物读/写存储设备，该设备可以通过生物学和电子学方式访问。在目标3中，该团队将整合这些元素，创建生物混合电路，如生物电逻辑门，生物到电子到生物信号系统，最终形成一种电子控制的设备，可以解释分子信息，计算所需的结果，并以电子方式驱动细胞以发出信号并控制生物种群。 这项工作有三个基本的新颖之处。首先，它将展示将信息从生物系统转移到微电子系统的潜力，并形成生物电子集成计算系统的基础。其次，它将展示一种新型、可靠和稳定的生物记忆器件的电子控制合成。第三，它将为开发生物混合计算设备开发一个技术框架，这些设备可以有效地感知和处理化学信息，并在复杂的生物系统中运行和控制。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The goal of the RE-BIONICS project (Redox-enabled Bio-Electronics based on Molecular Communication) is to create first-of-kind bioelectronics devices that will mediate the rapid and facile information exchange between biology and electronics. These devices will have the potential to transform healthcare, enabling tele-monitoring and remote/autonomous drug delivery and facilitating environmental monitoring in agriculture and cyber-defense where connecting biological phenomena with electronics are important. The technical underpinnings of this work recognize that microelectronic devices depend on electrons for information processing while biology depends on molecules (e.g., insulin, antibodies). These systems are not intrinsically compatible as there are no free electrons in biology that could be transmitted to biological wires and control cell-based electronic circuits. Instead, biohybrid devices are envisioned that transmit information across this electron-molecule divide. New interfaces are needed that accept molecules from biology and create electrons for devices and the reverse. Such integrated systems designed and constructed within RE-BIONICS will be capable of this bidirectional communication for memory and computation. The project will build the components and information theory needed to construct biohybrid devices that could eventually be embedded within a biological system and provide electronic control. In addition to building capabilities for designing and constructing completely new biodevices, a most important aspect of this work is that it will bring together researchers and stakeholders from many disciplines, including biology, chemistry, materials science, and computer, electrical, chemical, and bioengineering. The project builds on the interdisciplinary nature of the project with Research Team from computer science, electrical engineering and bioengineering. The research thrusts span computer science and information theory, microelectromechanical systems, biofabrication and redox biology, and synthetic biology. Also, two interdisciplinary teams of undergraduate students from UMD and UNL will participate in the international Genetically Engineered Machine (iGEM) program and competition, and participate in specific outreach activities targeting Middle and High school students within the Future Problem Solving Program (FPSPI) at UNL. Further, this project will promote the participation of women, historically underrepresented in electrical engineering, representing more than majors in biology and bioengineering. RE-BIONICS researchers will also interact with federal agencies including NIST, FDA, and the Army Research Laboratory, gaining exposure to manufacturing and regulatory issues, as well as direct application areas such as national security. This project exploits reduction-oxidation (redox) mediators that are the biological equivalents of free electrons in electronics. The reactions represent packets of information transferred within biology. The project is organized into three specific aims. In Aim 1, the team will design, build and test device elements that facilitate information transfer from molecules of biological systems to electrons of microelectronic systems and the reverse. Using the principles of synthetic biology, bacterial cells will be engineered to recognize small signaling molecules, an example being pyocyanin that is secreted by opportunistic pathogen, Pseudomonas aeruginosa. Based on this recognition, these and other engineered sensing cells will produce -galactosidase, an enzyme that can be electrochemically quantified. In addition, cells will be engineered to accept electrons from devices and in a programmed manner, "turn on" gene expression that can modulate cell behavior. In Aim 2, the team will design and construct a biological read/write memory device, based on the biopolymer melanin, that can be accessed both biologically and electronically. In Aim 3, the team will integrate these elements creating biohybrid circuits, such as bioelectric logic gates, and biologic to electronic to biologic signaling systems, culminating in an electronically-controlled device that interprets molecular information, computes desired outcomes and electronically actuates cells to signal and control biological populations. There are three fundamentally novel aspects to this work. First, it will demonstrate the potential to transfer information from biological systems to microelectronic systems and the reverse, forming the basis for bioelectronic integrated computing systems. Second, it will demonstrate electronically-controlled synthesis of a novel, reliable and stable biological memory device. Third, it will develop a technological framework for the development of bio-hybrid computing devices that efficiently sense and process chemical information as well as operate within and control complex biological systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.