A Micromachined, Multielectrode Microprobe for Monitoring Glutamate and Dopamine

描述（由申请人提供）：该项目的目标是开发一种微机械多电极微探针，能够同时在活体啮齿动物的大脑中近乎实时地检测多种分析物，例如谷氨酸和多巴胺。谷氨酸和多巴胺是神经递质，其失衡与亨廷顿氏病和帕金森病等神经系统疾病有关。设想中的微探针将成为阐明此类神经系统疾病背后机制的有力新工具。该项目是工程师和神经科学家的合作成果，旨在设计和制造带有探针参考微电极的微探针，以及用于同时选择性检测谷氨酸和多巴胺的微电极。该微探针还将在体外和体内进行充分的表征和测试。使用微机电系统（MEMS）制造技术，100多个器件将同时在4英寸的硅片上制造，每个探针有2到5微米大小的电极。每个探针的一个或多个微电极位点将用过选择性聚合物薄膜和固定化谷氨酸氧化酶进行化学修饰，用于谷氨酸的电酶检测。一种将谷氨酸氧化酶包封在多孔聚合物纳米颗粒中的新技术将被用于提高谷氨酸氧化酶的稳定性，并使其能够在微电极上选择性电沉积。多巴胺将在一个或多个微电极位点被检测到，这些微电极位点被修改为快速、直接的电氧化分析物。这些微探针将作为一个平台，用于创建额外的多分析物传感装置，用于体内测量。公共卫生相关性：该项目的目标是生产一种微传感器，神经科学家可以使用它来测量实验室啮齿动物大脑中多种化学物质同时水平的变化。这个新工具将导致发现包括帕金森氏病在内的重要神经系统疾病的新基础知识。

DESCRIPTION (provided by applicant): The goal of this project is to develop a micromachined, multielectrode microprobe capable of detecting multiple analytes, e.g., glutamate and dopamine, simultaneously in near real-time in the brains of live rodents. Glutamate and dopamine are neurotransmitters whose imbalance has been linked to neurological disorders such as Huntington's disease and Parkinson's disease. The envisioned microprobe would be a powerful new tool for the elucidation of the mechanisms behind such neurological disorders. This project is a collaborative effort among engineers and a neuroscientist that aims to design and fabricate the microprobes with an on- probe reference microelectrode as well as microelectrodes engineered for the selective electrochemical detection of both glutamate and dopamine simultaneously. The microprobe also will be characterized fully and tested both in vitro and in vivo. Over 100 devices will be constructed simultaneously on four-inch silicon wafers with two to five micron-sized electrodes per probe using micro-electro-mechanical-systems (MEMS) fabrication technologies. One or more microelectrode sites per probe will be chemically modified with permselective polymer films and immobilized glutamate oxidase for the electroenzymatic detection of glutamate. A novel technology to encapsulate glutamate oxidase in porous polymer nanoparticles will be used to improve enzyme stability and to enable its selective electrodeposition on microelectrodes. Dopamine will be detected at one or more microelectrode sites modified for the rapid, direct electrooxidation of this analyte. These microprobes will serve as a platform for the creation of additional multi-analyte sensing devices useful for measurements in vivo. PUBLIC HEALTH RELEVANCE: The goal of this project is to produce a microsensor that can be used by neuroscientists to measure changes in the levels of multiple chemical species simultaneously in the brains of laboratory rodents. This new tool will lead to the discovery of new fundamental knowledge on important neurological disorders including Parkinson's disease.