Collaborative Research: Multi-Input Biosensors with Built-in Logic

合作研究：具有内置逻辑的多输入生物传感器

• 批准号: 1066531
• 负责人: Joseph Wang
• 金额: $ 12万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1066531&HistoricalAwards=false
• 关键词: Collaborative; Research; Multi; Input; Biosensors

1066531WangIntellectual Merits: Recent advances in signal processing with cascades of enzymatic reactions realizing logic gates, such as AND, OR, etc., as well as progress in networking these gates and coupling of the resulting systems to signal-responsive electrodes for output readout, have opened new biosensing opportunities. The goal of the proposed collaborative research program is to develop a new paradigm of digitally operating biosensors logically processing multiple biochemical signals through Boolean logic networks composed of biomolecular systems, yielding the final output signal as YES/NO responses. This activity will thus lead to high-fidelity biosensing compared to common single or parallel sensing devices. We will develop biochemical signal processing systems for novel biosensor concepts, with multiple input signals being processed via enzymatic or immune-recognition processes, in combination with electrochemical transduction of the output signal. To demonstrate the new concept of digital multi-signal processing biosensors, we will, for instance, design a model multi-enzyme sensing system aimed at rapid identification of the complex biomarker changes from a healthy person to the conditions of various pathophysiological dysfunctions. These experimental developments will be facilitated by theoretical modeling and design of new low-noise, scalable, multi-stage signal processing networks with digital logic gates, as well as non-Boolean network elements carried out by biochemical reactions. We will develop a comprehensive approach for optimization of networks for biosensing, incorporating components for analog/digital error suppression for larger networks. Specifically, for multiinput systems we will advance a novel strategy including modular network analysis, detailed network representation and adjustment of relative component activities, gate function optimization for the key gates in the network, and exploration of the role of non-Boolean network elements, e.g., filters. An important component of our research will be in interfacing of the biosensing logic systems with electrochemical transducers and chemical actuators, towards the development of practical logic gate biosensors and feedback-loop systems. Fundamental studies aimed at addressing the distinct challenges associated with the new biosensing paradigm will be carried out. Particular attention will be given to the surface confinement of the biomolecular "machinery" components, to the role of the system scalability, and to the efficient transduction of the output signals. We will also interface directly the new biochemical signal-processing assemblies with signal-responsive chemical actuators to yield "smart" feedback-loop systems, responding reversibly to inputs from the biochemical environment. This research is transformative since the improved understanding of the novel biomolecular logic systems will lead to powerful multi-analyte sensing devices and intelligent "Sense/Act" systems. Our collaborative, interdisciplinary program will require a coordinated effort at two institutions, and will utilize the state-ofthe-art bioelectronics and bionanotechnology advances recently developed by the participating teams. We offer the necessary complementary expertise and an established track record, as well as successful ongoing collaboration evidenced by joint high-quality publications and patent applications.Broader Impacts and Outreach: Novel biosensor systems with built-in logic hold great promise to benefit a wide range of applications ranging from environmental and health monitoring to national defense and food safety. Logic biosensor systems of even moderate complexity will allow realizations of closed-loop ("Sense/Act/Treat") assemblies for security or biomedical applications, e.g., patient-tailored therapy. Our program will contribute to education and to ensuring national leadership in advanced science and technology. These impacts will be realized through training of the next generation of scientists, graduate students, and postdocs, and the introduction of new Nanobioelectronics and Nanobiotechnology classes. Inspiring high school and undergraduate students for scientific careers is a key element of our outreach. Outreach K-12 activities in both universities will thus include extensive pre-college mentorships and community activities.

1066531 Wangintellectual的优点：信号处理的最新进展与酶促反应的层叠实现了逻辑大门，例如和或等等，以及在这些门上进行网络和耦合在产生的系统中的进展以及信号响应电极的输出读数，已有开放了新的生物传感机会。拟议的协作研究计划的目的是开发一个新的范式，该范式通过逻辑上的生物传感器通过布尔逻辑网络来处理多个生化信号，该信号由生物分子系统组成，从而产生最终输出信号为是/否响应。因此，与常见的单个或平行感应装置相比，该活性将导致高保真生物传感。我们将开发用于新型生物传感器概念的生化信号处理系统，并通过酶促或免疫识别过程处理多个输入信号，并结合输出信号的电化学转导。为了展示数字多信号处理生物传感器的新概念，例如，我们将设计一种模型的多酶传感系统，旨在快速识别复杂的生物标志物从健康的人变为各种病理生理功能障碍的状况。这些实验发展将通过具有数字逻辑门以及生化反应执行的非树立网络元素以及生化反应进行的新的低噪声，可扩展的多阶段信号处理网络的理论建模和设计来促进这些实验发展。我们将开发一种用于优化网络进行生物传感的综合方法，并结合用于较大网络的模拟/数字错误抑制组件。具体而言，对于多发射系统，我们将推进一种新颖的策略，包括模块化网络分析，详细的网络表示和相对组件活动的调整，网络中的关键门的门功能优化以及探索非树状网络元素的作用，例如。 ，过滤器。我们研究的一个重要组成部分是将生物传感逻辑系统与电化学传感器和化学执行器的接口，以开发实用的逻辑栅极生物传感器和反馈环系统。旨在解决与新的生物传感范式相关的不同挑战的基本研究将进行。将特别注意生物分子“机械”组件的表面限制，系统可伸缩性的作用以及输出信号的有效转导。我们还将与信号响应化学执行器直接连接新的生化信号处理组件，以产生“智能”反馈 - 环境系统，从而可逆地响应生化环境的输入。这项研究具有变革性，因为对新型生物分子逻辑系统的理解有了深刻的了解，将导致强大的多分析物传感设备和智能的“ Sense/Act”系统。我们的合作，跨学科计划将需要在两个机构进行协调的努力，并将利用参与团队最近开发的最先进的生物电子学和Bionanotechnology Advances。我们提供必要的互补专业知识和已建立的往绩，并通过联合高质量出版物和专利申请证明了成功的持续合作。Broader的影响和外展：具有内置逻辑的新型生物传感器系统具有巨大的希望，可以使广泛的范围受益。从环境和健康监测到国防和食品安全的申请。甚至适度复杂性的逻辑生物传感器系统将允许实现用于安全性或生物医学应用的闭环（“ sission/act/act/treats”）组件，例如患者守则治疗。我们的计划将有助于教育并确保在高级科学技术领域的国家领导力。这些影响将通过培训下一代科学家，研究生和博士后的培训，以及引入新的纳米单位电子学和纳米元素技术课程。启发高中和本科生从事科学职业是我们宣传的关键要素。因此，两所大学的宣传K-12活动将包括广泛的大学前指导和社区活动。