Tunable Carbon Electrodes for in vivo Neurotransmitter Detection

项目摘要 大脑中的化学信号是如何控制功能的？解决这个问题需要快速的传感器， 在突触处测量。碳纤维微电极上的快速扫描循环伏安法（FSCV） 能够在体内检测神经调质。然而，大多数传感器太大，无法在突触处测量 并且存在区分神经化学物质和同时监测多种神经调质的挑战。 因此，需要新的传感器技术来靶向突触并在真实的环境中测量多种神经调质。 时间在前一时期，我们的实验室开发了电极开发的新方法，包括测试新的 碳纳米材料和3D打印纳米光刻。然而，这些方法还没有被定制为 满足神经化学研究中新兴应用的实验要求。这个目标 该项目是开发定制的碳电极，并调整它们的特性，以应用于突触， 包括（1）用于果蝇神经肌肉接头（NMJ）突触中的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中神经肽的捕获电极， 以及（3）用于多巴胺的多分析物检测的微机电系统（MEMS）平台， 在果蝇NMJ中，章鱼胺和谷氨酸盐同时存在。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 这将有助于更好地理解突触处的神经化学信号。在 目标1，我们将通过涂覆蚀刻金属来创建用于较小生物体测量的实用纳米电极 通过收缩诱导拉伸，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 目标二，设计具有捕集效应的电极，以提高灵敏度和选择性。这些碳 纳米管（CNT）纱线电极和具有碳柱阵列的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Si的生物传感器平台， 电化学，使多分析物测量。硅悬臂微针将植入体内 和在果蝇NMJ中用于神经递质的同时测量。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 的设计.这项工作将证明这些电极能够测量许多 神经调质在模型突触果蝇NMJ以及在体内。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。 神经调节以及它在疾病期间如何发生故障。

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.