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

摘要 商业上可获得的实时分子监测技术被设计成选择性地 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地工作的;相反，神经传递涉及许多化学物质。 同时调节神经回路的物种定量分析这些 神经化学信号是关键的第一步，当开发治疗策略，以治疗 神经/心理障碍，但很少有人知道如何具体的神经化学物质 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，如葡萄糖 和乳酸盐，在同一个记录点。微生物传感器具有更高的空间和时间 分辨率比目前可用的技术，最小的分析物消耗，他们可以 易于集成到现有协议中。在第一阶段，开发了7微米探针， 商业化，可以同时测量多巴胺和葡萄糖在真实的时间，在 单微米级的记录网站在体内。软件套件和FSCV教程 开发在第二阶段，我们将开发和商业化7-um多巴胺/乳酸， 多巴胺/谷氨酸和血清素/葡萄糖传感器。我们将开发更多的教程， 简化对这一重要技术的访问，我们将继续开发软件， electronics.总的来说，这个项目是创新的，因为它通过利用 酶促产生的H2 O2固有的氧化还原活性，以鉴定靶向的非电活性 甚至在电活性分子的存在下，这些电活性分子通常被排除在外， 干扰物。它是重要的，因为它结合了两个国家的最先进的和良好的特点， 神经化学监测技术，以一种聪明、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。它有望对人类社会产生变革性影响， 神经科学，使研究人员感兴趣的大脑功能的各个方面，以更好地 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。

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.