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: 9889960
• 负责人: B. JILL VENTON
• 金额: $ 34.82万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9889960
• 关键词: 3D Print; Adenosine; Animal Model; Argon; Biosensor; Brain; Brain region; Caliber; Carbon; Chemicals; Chemistry; Communication; Complex; Computer software; Custom; Deposition; Detection; Development; Discrimination; Disease; Dopamine; Drosophila genus; Electrochemistry; Electrodes; Electron Transport; Fast Electron; Fiber; Frequencies; Future; Geometry; Goals; Histamine; Hydrogen Peroxide; Image; Image Analysis; Measurement; Measures; Metals; Microelectrodes; Neurotransmitters; Oxygen; Printing; Property; Research; Resolution; Rodent; Sampling; Serotonin; Shapes; Surface; Techniques; Technology; Testing; Time; Tissues; Tube; Work; base; carbon fiber; design; dopaminergic neuron; flexibility; in vivo; innovation; insight; nano; nanodiamond; nanoelectrodes; nanohorn; nanomaterials; nervous system disorder; neurochemistry; neurotransmission; new technology; novel; oxidation; real time monitoring; sensor; submicron; temporal measurement; tool; vapor

PROJECT SUMMARY Microelectrodes are popular for sensing real-time changes in neurotransmitters and understanding the dynamics of neurotransmission in the brain. However, technology has changed little in three decades and there are many unmet technological needs for in vivo electrochemical sensors. In particular, electrodes are needed with high selectivity to discriminate different molecules, small enough tips to localize in small model organisms, and geometries that enable global sensing at high temporal resolution. One new electrode is unlikely to solve all these problems; instead, the electrochemical tool-kit needs to be expanded with many types of electrode designs, materials, and fabrication strategies so that electrodes can be customized for the application. The long term goal of my lab is to develop new electrodes for the measurement of real-time changes of neurotransmitters in vivo and use them to understand real-time detection of neurotransmitter dynamics in the brain. The goal of this project is to develop carbon nanomaterial electrodes, carbon nanopipettes, and 3D printed electrodes with tunable selectivity, tip diameter, and geometry. In the first specific aim, we will use carbon nanomaterials, surface treatments, custom waveforms, and imaging-based software approaches to tune the oxidation of difficult to detect molecules and reduce biofouling. Discrimination and co-detection of histamine, adenosine, and hydrogen peroxide will be targeted, as well as reduced fouling by serotonin and its metabolites. In the second aim, carbon nanopipettes will be developed as nanoelectrodes with tunable tip diameters that can sample from submicron regions, facilitating measurements in small Drosophila brain regions without destroying the tissue. Different geometries will be compared, included closed-tip, cavity, and open tube pipettes. In the third aim, a completely new way to make an electrode will be explored: nano-3D printing. A Nanoscribe 3D printer with 500 nm printing resolution will be used and designs then oxygen/argon annealed, which causes shrinking and carbonization. This 3D printing technique will enable rational design of free-standing, high temporal resolution sensors and flexible carbon mesh electrodes that measure neurotransmitters more globally. The result of this project will be many different kinds of electrodes that enable many different neurochemical applications, from discriminating adenosine and histamine transients in vivo, to dopamine detection in discrete Drosophila regions that are less than 10 m wide, to rapid measurements of neurotransmission on a global scale. The significance of this project is that it will transform in vivo microelectrode design to facilitate complex dynamic measurements of neurochemistry that will lead to a better understanding of the how the brain functions and how if malfunctions during disease. The expected positive impact of this new electrode design is thus new platforms of electrodes with tunable electrochemistry to better understand real-time neurotransmission.

项目概要 微电极广泛用于感测神经递质的实时变化并了解神经递质的变化。 大脑中神经传递的动力学。然而，技术在三十年来几乎没有变化 体内电化学传感器还有许多未满足的技术需求。特别地，电极是 需要高选择性来区分不同的分子，足够小的尖端以在小模型中定位 能够以高时间分辨率进行全球传感的生物体和几何结构。一种新电极是 不太可能解决所有这些问题；相反，电化学工具包需要扩展许多 电极设计、材料和制造策略的类型，以便可以根据需要定制电极 应用。我实验室的长期目标是开发用于实时测量的新电极 体内神经递质的变化并利用它们来了解神经递质的实时检测 大脑中的动态。该项目的目标是开发碳纳米材料电极、碳 纳米移液器和具有可调选择性、尖端直径和几何形状的 3D 打印电极。在第一个 针对具体目标，我们将使用碳纳米材料、表面处理、定制波形和基于成像的 软件方法可以调节难以检测的分子的氧化并减少生物污垢。歧视 将针对组胺、腺苷和过氧化氢进行联合检测，并减少污垢 由血清素及其代谢物产生。第二个目标是开发碳纳米管作为纳米电极 具有可调的尖端直径，可以从亚微米区域采样，便于在小范围内进行测量 果蝇大脑区域不破坏组织。将比较不同的几何形状，包括 封闭式吸头、空腔和开管移液器。在第三个目标中，将采用一种全新的方法来制造电极 探索：纳米3D打印。将使用具有 500 nm 打印分辨率的 Nanoscribe 3D 打印机进行设计 然后进行氧气/氩气退火，导致收缩和碳化。这种 3D 打印技术将使 独立式高时间分辨率传感器和柔性碳网电极的合理设计 更全面地测量神经递质。该项目的成果将是许多不同种类的电极 使许多不同的神经化学应用成为可能，从区分腺苷和组胺瞬态 体内，在宽度小于 10 µm 的离散果蝇区域中进行多巴胺检测，以快速 全球范围内神经传递的测量。这个项目的意义在于它将改变 体内微电极设计，以促进神经化学的复杂动态测量，这将导致 更好地了解大脑如何运作以及疾病期间如何发生故障。预期的 因此，这种新电极设计的积极影响是具有可调电化学的新电极平台 更好地理解实时神经传递。