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: 10656510
• 负责人: B. JILL VENTON
• 金额: $ 53.52万
• 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/10656510
• 关键词: 3D Print; Area; Biological; Biosensing Techniques; Biosensor; Brain; Carbon; Carbon Nanotubes; Chemicals; Communities; Complex; Computer software; Deposition; Detection; Development; Diameter; Discrimination; Disease; Dopamine; Drosophila genus; Electrochemistry; Electrodes; Electron Transport; Engineering; Enzymes; Glutamates; Goals; Grant; Height; Image; Implant; Mammals; Measurement; Measures; Metals; Methods; Microelectrodes; Modeling; Monitor; Muscle Contraction; Needles; Neuromodulator; Neuromuscular Junction; Neurons; Neuropeptides; Neuropil; Neurosciences; Neurotransmitters; Octopamine; Organism; Pattern; Periodicity; Property; Reproducibility; Research; Resolution; Scanning; Signal Transduction; Surface; Synapses; System; Technology; Testing; Thinness; Time; Tryptophan; Tyrosine; Work; cantilever; carbon fiber; design; experience; fabrication; improved; in vivo; in vivo monitoring; innovation; manufacturing technology; meter; mind control; miniaturize; model organism; monoamine; nanoelectrodes; nanofiber; nanolithography; nanomaterials; neurochemistry; neuroregulation; new technology; novel; novel strategies; sensor; sensor technology; submicron; technology platform; 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.

项目摘要 脑控制中的化学信号如何功能？回答这个问题需要快速传感器 在突触时进行测量。碳纤维微电极（CFMES）的快速扫描循环伏安法（FSCV）具有 启用了神经调节剂的体内检测。但是，大多数传感器太大而无法测量突触 并且要区分神经化学物质并同时监测多个神经调节剂存在挑战。 因此，需要新的传感器技术来瞄准突触并测量实际中的多个神经调节剂 时间。在上一个时期，我们的实验室开发了新的电极开发方法，包括测试新的 碳纳米材料和3D印刷纳米光刻。但是，这些方法尚未被定制为 满足神经化学研究中新兴应用的实验要求。目标的目标 项目是开发定制的碳电极，并调整其在突触中应用的特性， 包括（1）在果蝇神经肌肉连接（NMJ）突触中进行单胺检测的纳米电极， （2）诱捕果蝇NMJ中神经肽高度敏感和选择性测量的电极， （3）多巴胺和多巴胺的多体分析物检测的微电机电系统（MEMS）平台 同时在果蝇NMJ中同时在体内和章鱼和谷氨酸同时。这 工作很重要，因为它会改变微电极设计以促进复杂的测量 神经化学将导致对突触的神经化学信号传导更好地理解。在 AIM 1，我们将通过涂层蚀刻金属来创建实用的纳米电极，以在较小的生物中进行测量 带有碳纳米传出的电线和3D打印长纳米纤维通过收缩引起的拉力。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 AIM 2，我们将设计具有捕获效果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印刷电极将用于测量 果蝇NMJ中的神经肽。在AIM 3中，我们将开发一个基于SI的生物传感器平台，并直接 电化学，启用多体分析物测量。 Si-Cantilever微针将在体内植入 在果蝇NMJ中，用于同时测量神经递质。拟议的研究是 创新，因为它使用新技术从根本上改变电极制造并启用新型电极 设计。这项工作将证明原理证明这些电极能够测量许多 模型突触果蝇NMJ和体内的神经调节剂。专注于简单的批处理制造， 这些电极将提供给神经科学社区，以促进实时研究 神经调节及其在疾病期间的故障。