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: 10603193
• 负责人: DAVID A JOHNSON
• 金额: $ 90.72万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603193
• 关键词: Adoption; Adult; Age; American; Animals; BRAIN initiative; Biogenic Amines; Biosensor; Brain; Brain Diseases; Caliber; Calibration; Cells; Chemicals; Commercial Catalogs; Communities; Complex; Computer software; Consumption; Detection; Development; Disease; Dopamine; E-learning; Electrodes; Electronics; Endocrine; Ensure; Enzymes; Exclusion; Feedback; Glucose; Glutamates; Goals; Heart Diseases; Hospitalization; Hydrogen Peroxide; Impairment; Intuition; Laboratories; Learning; Libraries; Life; Literature; Location; Malignant Neoplasms; Marriage; Measurement; Measures; Mediating; Mental disorders; Microelectrodes; Modification; Molecular; Monitor; Motivation; Multivariate Analysis; National Institute of Mental Health; Neurologic; Neurosciences; Neurotransmitters; North Carolina; Operative Surgical Procedures; Output; Oxidases; Oxidation-Reduction; Periodicity; Phase; Physiological Processes; Procedures; Protocols documentation; Research Personnel; Resolution; Rodent; Scanning; Serotonin; Shapes; Signal Transduction; Sirenia; Site; Small Business Innovation Research Grant; Surface; Symptoms; System; Technology; Therapeutic; Time; United States; United States National Institutes of Health; Universities; Work; awake; base; carbon fiber; commercialization; design; glucose sensor; in vivo; innovation; insight; interest; neural circuit; neurochemistry; neurotransmission; real time monitoring; sensor; sensor technology; severe mental illness; software development; technology development; temporal measurement; tool; user friendly software; wireless

ABSTRACT Commercially available, real-time molecular monitoring technologies are designed to selectively 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 working to modulate neural circuits. Quantitative analysis of these neurochemical signals is a critical first step when developing therapeutic strategies to treat neurological/psychological disorders, but little is known about how specific neurochemicals fluctuate relative to one another. The Sombers Lab has established the feasibility of using fast- scan cyclic voltammetry (FSCV) and carbon-fiber microelectrodes for the real-time detection of dopamine fluctuations while simultaneously detecting non-electroactive species, such as glucose and lactate, at the same recording site. The microbiosensors have higher spatial and temporal resolution than currently available technologies, minimal analyte consumption, and they can be easily integrated into existing protocols. During Phase I, a 7-um probe was developed and commercialized that can simultaneously measure dopamine and glucose in real time, at single micron-scale recording sites in vivo. A software suite and FSCV tutorials were developed. In Phase II, we will develop and commercialize 7-um dopamine/lactate, dopamine/glutamate, and serotonin/glucose sensors. We will develop additional tutorials to simplify access to this important technology, and we will continue to develop software and electronics. 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. Ultimately, this project will provide the community with a sensor suite that can be used to study the interplay of a range of critical analytes 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 co-fluctuate in discrete brain locations.

抽象的 市售的实时分子监测技术旨在选择性地 在给定的记录位点一次仅测量一个分子。这是一个问题，因为化学 大脑中的信号并不是孤立运作的；相反，神经传递涉及许多化学物质 物种同时致力于调节神经回路。对这些的定量分析 神经化学信号是制定治疗策略时关键的第一步 神经/心理疾病，但对于具体的神经化学物质如何影响我们知之甚少 相对于彼此波动。 Sombers 实验室已经确定了使用快速 扫描循环伏安法 (FSCV) 和碳纤维微电极用于实时检测 多巴胺波动，同时检测非电活性物质，例如葡萄糖 和乳酸，在同一记录位点。微生物传感器具有更高的空间和时间 分辨率高于现有技术，分析物消耗最少，并且可以 轻松集成到现有协议中。在第一阶段，开发了 7 微米探针并 已商业化，可以同时实时测量多巴胺和葡萄糖 体内单微米级记录位点。软件套件和 FSCV 教程 发达。在第二阶段，我们将开发并商业化7微米多巴胺/乳酸， 多巴胺/谷氨酸和血清素/葡萄糖传感器。我们将开发额外的教程 简化对这一重要技术的访问，我们将继续开发软件和 电子产品。总的来说，这个项目是创新的，因为它脱离了现状，利用 酶促生成的 H2O2 固有的氧化还原活性可识别目标非电活性 物种，即使存在通常被排除在外的电活性分子 干扰物。它很重要，因为它结合了两个最先进且特征鲜明的 神经化学监测技术以巧妙、直接和前所未有的方式 方式。最终，该项目将为社区提供一个可以使用的传感器套件 研究一系列关键分析物在复杂生理过程中的相互作用 从基本的内分泌功能到动力。它有望产生变革性的影响 神经科学，让对大脑功能各个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如何在离散的大脑位置共同波动。