Commercialization of Enzyme Modified Carbon-Fiber Electrodes Paired with Voltammetry for Simultaneous Real-Time Monitoring of Electroactive and Non-Electroactive Species at Discrete Brain Locations

酶改性碳纤维电极与伏安法相结合的商业化，用于同时实时监测离散大脑位置的电活性和非电活性物质

• 批准号: 9903459
• 负责人: DAVID A JOHNSON
• 金额: $ 44.5万
• 依托单位: PINNACLE TECHNOLOGY, INC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903459
• 关键词: Acetylcholine; Adult; BRAIN initiative; Behavioral Research; Benchmarking; Biogenic Amines; Biosensor; Brain; Caliber; Calibration; Chemicals; Chemistry; Choline; Communities; Complex; Computer software; Couples; Custom; Data; Data Analyses; Detection; Development; Dopamine; Electrodes; Endocrine; Enzymes; Glucose; Glutamates; Goals; Hydrogen Peroxide; Intuition; Laboratories; Learning; Life; Location; Marriage; Measurement; Measures; Mediating; Mental disorders; Methods; Microelectrodes; Monitor; Motivation; Neuropeptides; Neurosciences; Neurotransmitters; North Carolina; Operative Surgical Procedures; Oxidation-Reduction; Performance; Periodicity; Peroxides; Pharmacotherapy; Phase; Physiological; Physiological Processes; Procedures; Production; Protocols documentation; Reporting; Research; Research Personnel; Resolution; Role; Scanning; Signal Transduction; Site; Small Business Innovation Research Grant; Symptoms; System; Techniques; Technology; Time; Training; Translating; United States; United States National Institutes of Health; Universities; Validation; base; brain research; carbon fiber; clinical application; commercialization; data acquisition; design; drug development; economic cost; glucose oxidase; glucose sensor; in vivo; innovation; insight; interest; nervous system disorder; neurochemistry; neurotransmission; pre-clinical; rapid detection; real time monitoring; sensor; sensor technology; software development; technology development; temporal measurement; tool; web site

ABSTRACT Commercially available biosensors are designed to measure only one molecule at a time at a given recording site. This is a problem because chemical signals in the brain do not work in isolation; rather, neurotransmission involves many chemical species simultaneously released and little is known about how specific neurochemicals fluctuate relative to one another. Understanding these relationships is critical to the development of drugs and treatments for a wide range of neurological disorders. The Sombers Lab has established the feasibility of using fast-scan cyclic voltammetry (FSCV) and carbon-fiber microelectrodes for the simultaneous detection of rapid dopamine fluctuations and those of non-electroactive species, such as glucose, at the same recording site. This is done with higher spatial and temporal resolution than currently available methods. The goal of this Lab to Marketplace: Tools for Brain and Behavioral Research SBIR is to translate and commercialize the technology developed by the Sombers team at North Carolina State University. The first goal is to transfer the core technology for the co-detection of dopamine and glucose from the Sombers laboratory to Pinnacle Technology, a company that has developed, manufactured and sold biosensors and electrochemical measurement systems worldwide. Pinnacle-produced sensors will be fully characterized and detailed specifications for the technology (sensitivity, linear range, shelf-life and benchmarks for in vivo performance) will be outlined. The second goal is to develop training tools and software to minimize the learning curve associated with the proper implementation, characterization and analysis of FSCV in research or pre-clinical applications. This will be accomplished by modifying existing Pinnacle software to create an intuitive platform for acquisition and analysis of voltammetry data using the commercial probes. Finally, high production value training videos will be created and made freely available on the Pinnacle website. These will detail experimental procedures for all aspects of in vivo voltammetry including probe calibration, surgical procedures, and data acquisition and analysis protocols. Overall, this project is innovative, because it departs from the status quo by utilizing the redox activity inherent to enzymatically generated H2O2 to identify targeted non-electroactive species, even in the presence of electroactive molecules that are typically excluded as interferents. It is significant, because it combines two state-of-the-art and well-characterized technologies for neurochemical monitoring in a clever, straightforward, and unprecedented manner to provide the community with an established tool that can be used to study the role of glucose in complex physiological processes ranging from basic endocrine function to motivation. It promises to have a transformative effect on neuroscience by allowing researchers interested in diverse aspects of brain function to better understand how these specific neurochemicals rapidly co-fluctuate in discrete brain locations.

摘要 商业上可用的生物传感器被设计成在给定的记录中一次只能测量一个分子 地点。这是一个问题，因为大脑中的化学信号并不是孤立地工作的，而是神经传递 涉及同时释放的许多化学物质，具体有多具体我们知之甚少 神经化学物质之间相互波动。理解这些关系对于 开发治疗多种神经疾病的药物和治疗方法。桑伯斯实验室有 建立了使用快速扫描循环伏安法(FSCV)和碳纤维微电极进行检测的可行性 同时检测快速多巴胺波动和非电活性物种，如 葡萄糖，在相同的记录位置。这是以比目前更高的空间和时间分辨率来完成的 可用的方法。这个实验室到市场：大脑和行为研究的工具SBIR的目标是 翻译北卡罗来纳州Sombers团队开发的技术并将其商业化 大学。第一个目标是将多巴胺和葡萄糖联合检测的核心技术从 Sombers实验室转让给Pinnail Technology，一家开发、制造和销售 世界各地的生物传感器和电化学测量系统。顶峰公司生产的传感器将完全 技术的特征和详细规格(灵敏度、线性范围、保质期和基准 对于活体性能)将被概述。第二个目标是开发培训工具和软件，以尽量减少 与FSCV的正确实施、描述和分析相关的学习曲线 研究或临床前应用。这将通过修改现有PinnacleTM软件来实现 创建一个使用商用探头获取和分析伏安数据的直观平台。 最后，将制作高制作价值的培训视频，并在Pinnacle上免费提供 网站。这些将详细说明体内伏安法的所有方面的实验程序，包括探针 校准、外科手术程序以及数据采集和分析方案。总体而言，这个项目是创新的， 因为它通过利用酶产生的过氧化氢固有的氧化还原活性来改变现状 识别目标非电活性物种，即使在存在电活性分子的情况下也是如此 被排除为干扰物。它意义重大，因为它结合了两个最先进的和很好的特点 以一种智能、直截了当和前所未有的方式提供神经化学监测技术 拥有一个成熟的工具，可以用来研究葡萄糖在复杂生理过程中的作用的社区 从基本的内分泌功能到动力的过程。它有望对…产生变革性的影响 神经科学，使对大脑功能的不同方面感兴趣的研究人员更好地了解 这些特定的神经化学物质在大脑不同的位置迅速共同波动。