Vectorially-Coupled Reaction Networks in Low-Dimensional Nanofluidic Structures

反应是化学的核心事件，控制反应的行为和反应发生的地点是化学测量和制造新化学品的核心。理想情况下，科学家希望设计反应，使其快速发生，有效利用所有化学参与者，使用廉价的化学物质和环境友好的条件，并生产易于分离的化学产品。在自然界中，例如在生物细胞中，这些严格的目标是通过空间组织的反应网络来实现的。圣母大学（University of Notre Dame）的保罗·博恩（Paul Bohn）博士的研究团队通过设计和开发反应网络来模拟自然，这些反应网络的行为由电刺激控制，其位置由反应容器的大小决定。在电子转移反应的研究中，他们用纳米材料精心构建了专门设计的结构，这种材料的性质和放置导致了在特定位置发生特殊的、定义良好的、高效的反应。此外，电气控制特定位置的反应和附近液体的运动允许化学产品从一个反应地点穿梭到下游的另一个反应地点，在那里它们被用作另一个确定的反应过程的化学起始材料。所有的反应都是用酶加速的，酶是自然界的化学反应催化剂。Bohn团队正在研究如何应用电压来控制催化剂的活性。研究工作与新的教育和培训项目相结合，这些项目跨越了圣母大学的学科界限，并结合了多所大学的人才。在此过程中，这些活动解决了国家科学基金会的具体目标，包括发展多样化的，具有全球竞争力的科学-技术-工程-数学劳动力；加强学术界与工业界之间的伙伴关系；提高了经济竞争力。该项目由美国国家科学基金会的化学测量和成像项目以及分子分离、电化学系统和过程系统、反应工程和分子热力学项目共同资助，主要目标是开发空间组织的氧化还原反应网络，该网络可以通过电信号控制来管理传输、指示反应性和分离产物。总体目标是通过在零和一维电化学纳米结构中开发对反应物分子和粒子到反应位点的传递以及反应性的控制来解决。该团队还将这些纳米结构结合起来，开发了对级联反应的全三维控制，从而产生了矢量控制的反应网络（vcrn）。第一个目标是开发高精度纳米架构，通过同时控制传输和反应性，使用金属绝缘体多层堆叠纳米孔和分层组织的组件来支持vcrn。第二个目标是探索电化学电位可以用来控制与其中一个电极结合的酶的活性的方法。利用辣根过氧化物酶（HRP）作为模型氧化还原酶，利用荧光氧化还原反应跟踪电极结合酶的固有反应活性，该反应在电化学零模波导的超高灵敏度环境中将非荧光反应物转化为荧光产物。这些能力正在通过一组严格的单酶动力学实验进行组合和测试，其中HRP在可用位置之间移动，并在耦合到电化学电位控制信号时测试其固有反应性。这项工作的最终目标是利用单个反应事件的控制来创建vcrn的制备规模能力。为了测试这种能力，双酶电化学调节反应系统以空间协调的方式与单个反应耦合，并用于将反应产物输送到下游收集点。这个项目的影响超出了化学分析的主要学科，特别是在级联反应的一般领域——化学合成中使用的强大结构，例如，在酶生物燃料电池中，用于捕获燃料源的全部电化学还原能力。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。

Reactions are the central events of chemistry and controlling their behavior and the locations where they occur is at the heart of chemical measurements and making new chemicals. Ideally, scientists want to design reactions so they occur rapidly, make efficient use of all the chemical participants, employ inexpensive chemicals and environmentally friendly conditions, and produce easily-isolated chemical products. In nature, such as in biological cells, these stringent objectives are achieved by spatially-organized reaction networks. Dr. Paul Bohn's research team at the University of Notre Dame mimics nature by designing and developing networks of reactions whose behavior is controlled by electrical stimulus and whose location is defined by the size of the reaction vessel. In their work with electron-transfer reactions, they carefully build specially-designed structures from nanometer-sized materials, whose nature and placement leads to particular, well-defined, and highly efficient reactions occurring in specific locations. Furthermore, electrical control of the location-specific reactions and movement of nearby liquid allows for shuttling of chemical products from one reaction site to another one downstream, where they are used as the chemical starting materials for another defined reaction process. All the reactions are sped up using enzymes, nature's chemical reaction catalysts. The Bohn team is developing an understanding of how electrical voltages can be applied to control the activity of catalysts. The research efforts are integrated with new education and training programs that cut across disciplinary lines within the University of Notre Dame and combine talents from multiple universities. In the process, these activities address specific NSF goals including development of a diverse, globally competitive science-technology-engineering-mathematics workforce; increased partnerships between academia and industry; and improved economic competitiveness.The principal goal of this project supported by the Chemical Measurement and Imaging Program and partial co-funding from the Molecular Separations, Electrochemical Systems, and Process Systems, Reaction Engineering and Molecular Thermodynamics Programs at NSF is to develop networks of spatially-organized redox reactions which can be controlled by electrical signals to manage transport, dictate reactivity, and isolate products. The overall goal is addressed by developing control over delivery of reactant molecules and particles to a reactive site as well as control over reactivity, within zero- and one-dimensional electrochemical nanostructures. The team also combines these nanostructures to develop full three-dimensional control over cascade reactions to produce vectorially-controlled reaction networks (VCRNs). The first objective is the development of high-precision nanoscale architectures to support VCRNs by simultaneous control over transport and reactivity using both metal-insulator multilayer stack-based nanopores and hierarchically-organized assemblies. The second objective explores ways in which electrochemical potential can be used to control activity of enzymes bound to one of the electrodes. Using horseradish peroxidase, HRP, as a model oxidoreductase enzyme, the intrinsic reactivity of the electrode-bound enzyme is followed using a fluorogenic redox reaction that converts a non-fluorescent reactant into fluorescent product within the ultrahigh sensitivity environment of an electrochemical zero-mode waveguide. These capabilities are being combined and tested using a set of stringent single enzyme kinetics experiments, in which the HRP is moved among the available locations and tested for intrinsic reactivity when coupled to an electrochemical potential control signal. The ultimate goal of this work is to leverage control of single reaction events to create a preparative scale capability for VCRNs. To test this capability, two-enzyme electrochemically-modulated reaction systems are being coupled to individual reactions in a spatially coordinated manner and used to deliver the reaction products to a downstream collection point. This project has impact outside the principal discipline of chemical analysis, especially in the general area of cascade reactions - powerful constructs in chemical synthesis that are used, for example, in enzymatic biofuel cells to capture the full electrochemical reducing power of fuel sources.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.