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

基本信息

批准号：
10704151
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
项目类别：
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

项目摘要

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一次仅在给定记录位点测量一个分子。这是一个问题，因为化学大脑中的信号不能孤立地工作；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。这些定量分析神经化学信号是制定治疗策略以治疗治疗的关键第一步神经/心理疾病，但对特定神经化学的方式知之甚少相对波动。 Sombers Lab已确定使用快速使用的可行性扫描循环伏安法（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动活性物种，例如葡萄糖和乳酸，在同一记录网站上。微生物传感器具有较高的空间和时间。分辨率比当前可用的技术，最少的分析物消耗，它们可以是容易集成到现有协议中。在第一阶段，开发了一个7-UM探针，并商业化可以实时同时测量多巴胺和葡萄糖的商业化单个微米级记录位点在体内。软件套件和FSCV教程是发达。在第二阶段，我们将开发和商业化7-UM多巴胺/乳酸，多巴胺/谷氨酸和5-羟色胺/葡萄糖传感器。我们将开发其他教程简化对这项重要技术的访问，我们将继续开发软件和电子产品。总体而言，该项目具有创新性，因为它通过利用而偏离现状酶生成的H2O2固有的氧化还原活性以识别靶向的非电动活性物种，即使在存在的电活性分子的情况下，通常被排除为干扰物。这很重要，因为它结合了两个最先进且特征良好的聪明，直接且前所未有的神经化学监测技术方式。最终，该项目将为社区提供可以使用的传感器套件研究在复杂生理过程中的一系列关键分析物的相互作用从基本的内分泌功能到动力。它有望对神经科学通过允许对大脑功能的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裂开。