PFI:AIR - TT: Amplified Bioelectronic Sensor for Neurotoxic Esterase Inhibitors

PFI:AIR - TT：用于神经毒性酯酶抑制剂的放大生物电子传感器

• 批准号: 1444991
• 负责人: Robert Worden
• 金额: $ 19.91万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1444991&HistoricalAwards=false
• 关键词: PFI; AIR; TT; Amplified; Bioelectronic

This PFI: AIR Technology Translation project focuses on translating research on nanoscale bioelectronics to fill the need for cost-effective biosensor systems that quickly, sensitively, and accurately measure concentrations of important compounds. The amplified bioelectronic sensor platform being developed is important because it offers an unprecedented combination of performance properties, versatility, and customizability. By varying the architecture and recognition molecules in the sensing interface, a broad range of commercially important biosensor systems could be developed for applications including screening for therapeutic agents, measurement of toxins and pathogens in food and environmental samples, point-of-care testing of biological samples, and real-time, on-site detection of chemical warfare agents for military and homeland-security applications. The project will result in prototype amplified bioelectronic sensors suitable for three types of commercial biosensor systems: portable point-of-care meters, electrochemical multiwell plates, and flow-injection analyzers. This patented bioelectronic sensor platform has the following features: (1) multiple signal-amplification mechanisms, (2) multiple types of biological recognition molecules, (3) compatibility with multiple commercial biosensor systems, and (4) disposable sensing units. These features provide the following advantages: enhanced sensitivity, versatility, user-friendliness, convenience, and cost-effectiveness when compared to the leading competing biosensor technologies in this market space. This project addresses the following technology gaps as it translates from research discovery toward commercial application. Commercial biosensors are needed to measure organophosphate (OP) compounds that target the human enzyme neuropathy target esterase (NTE) and lead to catastrophic neurological disorders. Such biosensors would need to measure NTE activity rapidly and sensitively. The patented amplified bioelectronic sensor achieves this goal by using a reaction pathway to convert NTE?s esterase activity into an electronic signal and using a redox cycle to amplify the signal. However, technology gaps must be addressed to adapt the bioelectronic sensor interface to widely used commercial biosensor systems and to extend the underlying molecular sensing mechanisms to a wide range of other important compounds. These technology gaps will be addressed by (1) exploiting an enzyme-antibody linkage that translates antibody-antigen binding events into a chemical reaction flux, (2) integrating a redox cycle that converts the chemical reaction flux into an electric current and simultaneously amplifies the current, and (3) incorporating conductive nanomaterials that massively increase the sensor?s signal. In addition, personnel involved in this project, including a Ph.D. student and undergraduates, will receive innovation and technology-translation experiences through participation in virtually all aspects of the research, including entrepreneurial/innovation discussions and activities. The PI will also provide training in entrepreneurship/innovation to students taking the Multidisciplinary Bioprocessing Laboratory (MBL) course he developed with NSF funding. The MBL course incorporates research into education and teaches students from multiple departments to work effectively in multidisciplinary research teams. The project engages Conductive Technologies, Inc., a leader in developing and manufacturing electrochemical devices for sensing commercially important analytes, to support the research effort by providing technical expertise in designing and developing electrochemical platforms as well as providing samples of printed electrodes to demonstrate biosensor performance. The project also engages MSU Technologies, the intellectual-property unit of Michigan State University, to help guide commercialization aspects in this technology translation effort from research discovery toward commercial reality.

该 PFI：AIR 技术翻译项目专注于转化纳米级生物电子学研究，以满足对快速、灵敏且准确地测量重要化合物浓度的经济高效生物传感器系统的需求。正在开发的放大生物电子传感器平台非常重要，因为它提供了前所未有的性能、多功能性和可定制性组合。通过改变传感接口中的架构和识别分子，可以开发出广泛的具有商业重要性的生物传感器系统，其应用包括治疗剂的筛选、食品和环境样品中毒素和病原体的测量、生物样品的即时检测以及用于军事和国土安全应用的化学战剂的实时现场检测。该项目将产生适用于三种类型的商业生物传感器系统的原型放大生物电子传感器：便携式护理点仪表、电化学多孔板和流动注射分析仪。该专利生物电子传感器平台具有以下特点：（1）多种信号放大机制，（2）多种类型的生物识别分子，（3）与多种商业生物传感器系统兼容，以及（4）一次性传感单元。与该市场领域领先的竞争生物传感器技术相比，这些功能具有以下优势：增强的灵敏度、多功能性、用户友好性、便利性和成本效益。 该项目在从研究发现转向商业应用的过程中解决了以下技术差距。需要商业生物传感器来测量针对人类神经病目标酯酶（NTE）并导致灾难性神经系统疾病的有机磷酸酯（OP）化合物。这种生物传感器需要快速、灵敏地测量 NTE 活性。获得专利的放大生物电子传感器通过使用反应途径将 NTE 的酯酶活性转化为电子信号并使用氧化还原循环放大信号来实现这一目标。然而，必须解决技术差距，以使生物电子传感器接口适应广泛使用的商业生物传感器系统，并将潜在的分子传感机制扩展到广泛的其他重要化合物。这些技术差距将通过以下方式解决：(1) 利用酶-抗体连接，将抗体-抗原结合事件转化为化学反应通量；(2) 集成氧化还原循环，将化学反应通量转化为电流并同时放大电流；(3) 结合导电纳米材料，大幅增加传感器信号。此外，参与该项目的人员包括一名博士。学生和本科生将通过参与研究的几乎所有方面（包括创业/创新讨论和活动）获得创新和技术转化经验。该 PI 还将为参加他在 NSF 资助下开发的多学科生物加工实验室 (MBL) 课程的学生提供创业/创新培训。 MBL 课程将研究融入教育中，教授来自多个院系的学生如何在多学科研究团队中有效地工作。该项目聘请Conductive Technologies, Inc.（一家开发和制造用于感测商业重要分析物的电化学装置的领导者）来支持研究工作，提供设计和开发电化学平台的技术专业知识以及提供印刷电极样品以展示生物传感器的性能。该项目还聘请密歇根州立大学的知识产权部门 MSU Technologies 来帮助指导这项技术转化工作中的商业化工作，从研究发现到商业现实。