Electrobiofabricated thin films for redox-linked bioelectronics

生物学利用还原-氧化（氧化还原）反应（化学反应中反应物获得一个或多个电子的反应）来执行重要的功能：能量收集（呼吸）；生物合成（由活的有机体生产化合物）；国防(炎症);和通讯（氧化还原信号）。研究人员的独特见解是，这种氧化还原模式的电学特征——通过氧化还原反应的电子“流动”——可以通过简单的基于电极的仪器获得，并且可以开发应用程序来观察（感觉）和干预（驱动）生物系统。研究小组计划发展基础理论和方法，以建立和表征一种材料界面，用于生物学分子语言和现代设备的电子语言之间的“基于氧化还原的翻译”。研究人员设想，氧化还原连接的生物电子学将使新一代生物电子学应用于医学（例如，用于即时诊断），商业（例如，可穿戴电子设备）和环境（例如，遥感）。通过这个项目，研究人员将继续培育他们的研究生态系统：(i)跨学科和跨越全球；（ii）产生新的理论/方法，并通过与关注问题的研究人员的不同合作，迭代地加速其测试；（iii）利用来自政府、学术界和私营部门的基础和应用科学家/工程师的贡献；（iv）通过个性化培训（例如，研究生、本科和高中研究人员以及教师培训暑期项目）传播这些进步，融入本科课程（在社区学院、本科学院和少数民族服务大学水平），并向公众转移（通过举办专门的技术会议和为公众制作视频）。该项目的长期愿景是通过氧化还原连接生物电子学融合生物学和电子学的正交信息处理能力。这个项目的重点是通过氧化还原信号模式进行交流的问题子集，免疫系统使用氧化还原信号模式进行炎症和伤口愈合。研究计划有三个目标。第一个目标是“构建生物设备接口的电-生物制造”。基于水凝胶的界面（即薄膜）将使用迭代方法创建，该方法“教授”电信号如何引导自组装多糖（壳聚糖）的复杂结构的出现。研究人员提出通过控制局部电场、盐浓度和静电交联来优化壳聚糖基的制备。先进的计算模拟和机器学习将被实施，以获得制造过程的机械理解。可控制地组织和重新配置生物基软物质的能力将为一系列生命科学应用创造适应性、兼容性、高性能和可持续的材料系统。第二个目标是“电化学发现和表征材料”。新的电化学方法将用于自动、自适应和最终自主地发现和表征可以控制电子和分子的传输（即流动）的材料。基于氧化还原的电化学测量的简单性、速度和数据丰富性促进了与机器学习的耦合，这些能力可以将“化学信息”的范式从化学角度（成分和浓度）转变为信息论角度。这种模式的转变既可以提高可靠性，又可以促进即时护理和可穿戴电子产品的转换。第三个目标是“氧化还原连接生物电子通信”。测试平台演示将跨目标集成活动。合成生物学结构将被生成为可观察的“信息处理器”，用于微流体肠道芯片模型的微生物组。当前的目标是证明这些多层膜允许基于分子的氧化还原信息的双向“流动”。这些试验台研究有望提供所需的技术知识，以建立设备（例如，胶囊内窥镜系统），可以调查氧化还原环境，并有助于塑造这种环境。该奖项反映了美国国家科学基金会的法定使命，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。

Biology uses reduction-oxidation (redox) reactions (reactions in which a reactant in a chemical reaction gains one or more electrons) to perform important functions: energy harvesting (respiration); biosynthesis (production of a chemical compound by a living organism); defense (inflammation); and communication (redox signaling). The investigators' unique insight is that the electrical features of this redox modality--the "flow" of electrons through redox reactions--is accessible through simple electrode-based instrumentation and that applications can be developed to both observe (sense) and intervene-in (actuate) biological systems. The research team plans to develop the fundamental theories and methods needed to build and characterize a materials-interface for the "redox-based translation" between the molecular language of biology and the electrical language of modern devices. The investigators envision that redox-linked bioelectronics will enable a new generation of bioelectronic applications for medicine (e.g., for point-of-care diagnosis), commerce (e.g., wearable electronics), and the environment (e.g., remote sensing). Through this project the investigators will continue nurturing their research ecosystem that: (i) crosses disciplines and spans the globe; (ii) generates new theories/methods and iteratively accelerates their testing through diverse collaborations with problem-focused researchers; (iii) leverages contributions from basic and applied scientists/engineers from government, academia and the private sector; and (iv) disseminates these advances through individualized training (e.g., of graduate, undergraduate and high school researchers as well as teacher-training summer programs), integration into undergraduate curricula (at the community college, undergraduate college and minority serving university levels), and transfer to the public (by hosting specialized technical conferences and generating videos for the general public).The long-term vision of this project is to fuse the orthogonal information processing capabilities of biology and electronics through redox-linked bioelectronics. The focus of this project is on a subset of problems involving communication through a redox-signaling modality that is used by the immune system for inflammation and wound healing. The Research Plan is organized under three objectives. The FIRST objective is "Electro-bio-fabrication to Build the Bio-Device Interface." Hydrogel-based interfaces (i.e., films) will be created using an iterative approach that "teaches" how electrical signals can guide the emergence of complex structure from self-assembling polysaccharides (chitosans). The investigators propose to optimize the chitosan-based fabrication by controlling the local electrical field, salt concentration and electrostatic crosslinking. Advanced computational simulation and machine-learning will be implemented to gain mechanistic understanding of the fabrication process. The ability to controllably organize and reconfigure bio-based soft matter will enable the creation of adaptive, compatible, high-performance and sustainable materials systems for a range of life science applications. The SECOND Objective is "Electrochemistry to Discover and Characterize Materials." Novel electrochemical methods will be used for the automated, adaptive and ultimately autonomous discovery and characterization of materials that can control the transport (i.e., flow) of electrons and molecules. The simplicity, speed and data-richness of redox-based electrochemical measurements facilitates coupling to machine learning, and these capabilities could shift the paradigm for "chemical information" from a chemistry perspective (composition and concentration) to an information theory perspective. Such a paradigm shift could both improve reliability and facilitate translation for point-of-care and wearable electronics. The THIRD Objective is "Redox to Link Bio-electronic Communication." Test bed demonstrations will integrate activities across objectives. Synthetic biology constructs will be generated as observable "information processors" for a microfluidic gut-on-a-chip model of the microbiome. The immediate goal is to demonstrate that these multilayer films allow a bi-directional "flow" of molecularly-based redox information. These test bed studies are expected to provide the technical knowledge needed to build devices (e.g., capsular endoscopy systems) that can survey a redox environment and contribute to sculpting this environment.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.