Tunable Carbon Electrodes for in vivo Neurotransmitter Detection

用于体内神经递质检测的可调谐碳电极

• 批准号: 10522260
• 负责人: B. JILL VENTON
• 金额: $ 53.2万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10522260
• 关键词: 3D Print; Address; Animal Model; Area; Biological; Biosensing Techniques; Biosensor; Brain; Caliber; Carbon; Carbon Nanotubes; Chemicals; Communities; Complex; Computer software; Custom; Deposition; Detection; Development; Discrimination; Disease; Dopamine; Drosophila genus; Electrochemistry; Electrodes; Electron Transport; Engineering; Enzymes; Glutamates; Goals; Grant; Height; Image; Mammals; Measurement; Measures; Metals; Methods; Microelectrodes; Modeling; Monitor; Muscle Contraction; Neuromodulator; Neuromuscular Junction; Neurons; Neuropeptides; Neuropil; Neurosciences; Neurotransmitters; Octopamine; Organism; Pattern; Periodicity; Property; Research; Resolution; Scanning; Signal Transduction; Surface; Synapses; System; Technology; Testing; Thinness; Time; Tryptophan; Tyrosine; Work; base; cantilever; carbon fiber; design; experience; improved; in vivo; in vivo monitoring; innovation; mind control; miniaturize; monoamine; nanoelectrodes; nanofiber; nanolithography; nanomaterials; neurochemistry; neuroregulation; new technology; novel; novel strategies; sensor; sensor technology; submicron; temporal measurement

PROJECT SUMMARY How does chemical signaling in the brain control function? Answering this question requires fast sensors to measure at the synapse. Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFMEs) has enabled in vivo detection of neuromodulators. However, most sensors are too big to measure at the synapse and there are challenges to distinguish neurochemicals and monitor multiple neuromodulators simultaneously. Thus, new sensor technology is needed to target the synapse and measure multiple neuromodulators in real- time. In the previous period, our lab developed new approaches to electrode development, including testing new carbon nanomaterials and 3D printing nanolithography. However, these methods have not been customized to meet the experimental requirements for emerging applications in neurochemical research. The goal of this project is to develop customized carbon electrodes and tune their properties for applications at the synapse, including (1) nanoelectrodes for monoamine detection in the Drosophila neuromuscular junction (NMJ) synapse, (2) trapping electrodes for highly sensitive and selective measurements of neuropeptides in Drosophila NMJ, and (3) a microelectromechanical systems (MEMS) platform for multianalyte detection of dopamine and glutamate simultaneously in vivo and octopamine and glutamate simultaneously in the Drosophila NMJ. This work is significant because it will transform microelectrode design to facilitate complex measurements of neurochemistry that will lead to a better understanding of neurochemical signaling at the synapse. In Aim 1, we will create practical nanoelectrodes for measurements in smaller organisms by coating etched metal wires with carbon nanospikes and 3D printing long nanofibers through shrinkage-induced pulling. These small, less than 200-500 nm nanoelectrodes will be used to measure octopamine in the Drosophila NMJ synapse. In Aim 2, we will design electrodes with trapping effects to improve sensitivity and selectivity. These carbon nanotube (CNT) yarn electrodes and 3D printed electrodes with arrays of carbon pillars will be used to measure neuropeptides in the Drosophila NMJ. In Aim 3, we will develop a Si-based platform for biosensors and direct electrochemistry, enabling multianalyte measurements. The Si-cantilever microneedle will be implantable in vivo and in Drosophila NMJ for simultaneous measurements of neurotransmitters. The proposed research is innovative because it uses new technology to radically change electrode fabrication and enable novel electrode designs. This work will demonstrate proof of principle that these electrodes are capable of measuring many neuromodulators in a model synapse Drosophila NMJ as well as in vivo. With a focus on easy, batch fabrication, these electrodes will be made available to the neuroscience community, to facilitate studies of real-time neuromodulation and how it malfunctions during disease.

项目概要 大脑中的化学信号如何控制功能？回答这个问题需要快速传感器 在突触处测量。碳纤维微电极 (CFME) 的快速扫描循环伏安法 (FSCV) 实现神经调节剂的体内检测。然而，大多数传感器太大而无法在突触处进行测量 区分神经化学物质和同时监测多种神经调节剂也存在挑战。 因此，需要新的传感器技术来瞄准突触并实时测量多种神经调节剂。 时间。在上一时期，我们的实验室开发了电极开发的新方法，包括测试新的电极 碳纳米材料和3D打印纳米光刻。然而，这些方法还没有经过定制 满足神经化学研究中新兴应用的实验要求。此举的目标 项目是开发定制的碳电极并调整其特性以适应突触的应用， 包括（1）用于果蝇神经肌肉接头（NMJ）突触中单胺检测的纳米电极， (2) 用于高灵敏度和选择性测量果蝇 NMJ 神经肽的捕获电极， (3) 用于多巴胺和多分析物检测的微机电系统 (MEMS) 平台 谷氨酸在体内同时存在，章鱼胺和谷氨酸在果蝇 NMJ 中同时存在。这 这项工作意义重大，因为它将改变微电极设计以促进复杂的测量 神经化学的研究将有助于更好地理解突触的神经化学信号传导。在 目标 1，我们将通过涂覆蚀刻金属来创建实用的纳米电极，用于较小生物体的测量 带有碳纳米尖峰的电线，并通过收缩诱导拉力 3D 打印长纳米纤维。这些小， 小于 200-500 nm 的纳米电极将用于测量果蝇 NMJ 突触中的章鱼胺。在 目标2，我们将设计具有捕获效应的电极，以提高灵敏度和选择性。这些碳 纳米管 (CNT) 纱线电极和带有碳柱阵列的 3D 打印电极将用于测量 果蝇 NMJ 中的神经肽。在目标 3 中，我们将开发一个基于硅的生物传感器和直接平台 电化学，实现多分析物测量。硅悬臂微针将可植入体内 以及在果蝇 NMJ 中同时测量神经递质。拟议的研究是 创新是因为它使用新技术从根本上改变电极制造并实现新型电极 设计。这项工作将证明这些电极能够测量许多 果蝇 NMJ 模型突触以及体内的神经调节剂。专注于简单的批量制造， 这些电极将提供给神经科学界，以促进实时研究 神经调节及其在疾病期间如何发生故障。