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.

项目总结 大脑中的化学信号是如何控制功能的？回答这个问题需要快速的传感器来 在突触处测量。碳纤维微电极的快速扫描循环伏安法(FSCV) 能够在体内检测神经调节剂。然而，大多数传感器都太大了，无法在突触上进行测量 而且，在区分神经化学物质和同时监测多个神经调节剂方面也存在挑战。 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。 时间到了。在前一阶段，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打印纳米光刻技术。但是，这些方法尚未定制为 满足神经化学研究中新兴应用的实验要求。这样做的目的是 该项目是开发定制的碳电极，并调整它们的性能，以用于突触， 包括(1)用于检测果蝇神经肌肉接头(NMJ)突触中单胺的纳米电极， (2)高灵敏、选择性测定果蝇NMJ神经肽的捕获电极， 和(3)用于多分析物检测多巴胺和 体内谷氨酸同时存在，果蝇体内同时存在章鱼胺和谷氨酸。这 这项工作意义重大，因为它将改变微电极设计，使复杂的测量变得容易 这将有助于更好地理解突触的神经化学信号。在……里面 目标1，我们将通过涂层蚀刻的金属来创建实用的纳米电极，用于在较小的生物体中进行测量 带有碳纳米棒的导线和通过收缩诱导拉动的3D打印长纳米纤维。这些小的， 少于200-500纳米的纳米电极将被用来测量果蝇NMJ突触中的章鱼胺。在……里面 目的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 将使用纳米管(CNT)纱线电极和带有碳柱阵列的3D打印电极来测量 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平台，并直接 电化学，使多分析测量成为可能。硅悬臂式微针将在体内植入 在果蝇NMJ中进行神经递质的同步测量。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使新电极成为可能 设计。这项工作将证明这些电极能够测量许多 突触模型果蝇NMJ以及体内的神经调节剂。专注于简单、批量的制造， 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失灵。