Flexible Multielectrode Arrays for Tonic and Phasic Serotonin Electrochemical Detection in the Brain

用于大脑中的强直性和阶段性血清素电化学检测的柔性多电极阵列

• 批准号: 10689262
• 负责人: Elisa Castagnola
• 金额: $ 18.13万
• 依托单位: LOUISIANA TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689262
• 关键词: Acids; Acute; Adenosine; Affect; Anxiety; Biological; Brain; Brain region; Carbon; Carbon Nanotubes; Cerebrospinal Fluid; Chemicals; Chronic; Cognition; Complex; Detection; Development; Devices; Diagnosis; Dopamine; Electric Stimulation; Electrodes; Electrophysiology (science); Emotions; Film; Foreign Bodies; Functional disorder; Future; Glass; Goals; Hippocampus; Histologic; Implant; Impulse Control Disorders; In Vitro; Injury; Link; Location; Measurement; Measures; Mental Depression; Mental disorders; Metals; Microdialysis; Microelectrodes; Modality; Morphology; Mus; Neurologic; Neurotransmitters; Pattern; Penetration; Performance; Periodicity; Pharmacological Treatment; Phase; Play; Polymers; Process; Property; Resistance; Resolution; Role; Running; Sampling; Scanning; Serotonin; Signal Transduction; Silicon; Site; Social Behavior; Stimulus; Surface; Techniques; Technology; Testing; Therapeutic; Thinness; Time; Tissues; Validation; Variant; Work; biomaterial compatibility; carbon fiber; design; detection sensitivity; electric impedance; experimental study; fabrication; flexibility; improved; in vivo; in vivo evaluation; lithography; meetings; miniaturize; multi-electrode arrays; nervous system disorder; neurochemistry; pharmacologic; prevent; response; sensor; temporal measurement

Project Summary Simultaneous multi-site measurements of tonic and phasic serotonin (5-hydroxytryptamine, 5-HT) dynamics across different brain regions are of utmost importance to clarify the roles that 5-HT plays in anxiety, depression, and impulse control disorders. Chronic sampling across multiple weeks is critical to investigate the 5-HT variations during neurological transitions and to understand the efficacy of specific pharmacological treatments. Despite their values, in vivo multi-site chronic measurements of 5-HT are limited by the capability of the existing technologies. For example, microdialysis measures the tonic 5-HT level with slow temporal resolution, while fast scan cyclic voltammetry (FSCV) at carbon fiber microelectrodes (CFEs) can only detect phasic 5-HT release. These experiments are currently performed one site at a time, while 5-HT dynamics are complex and differ in different brain regions or different loci of the same region, requiring high resolution multisite measurements. Additionally, to the best of our knowledge, no chronic 5-HT detection with such technique have been shown. Here, we propose to develop an implantable carbon-based multielectrode array on ultra-thin flexible substrate (C-Flex-MEA) for integrated phasic and tonic measurements of 5-HT dynamics from different brain locations. To achieve our goal: first, we will optimize a pattern transfer technique that allows for the integration of glassy carbon (GC) microelectrode arrays and interconnections on ultra-thin flexible polymeric substrate. The resulting C-Flex- MEAs will allow for multi-site FSCV detection of phasic 5-HT release. Second, we will incorporate the poly(3,4- ethylenedioxythiophene)/functionalized carbon nanotube (PEDOT/CNT) coating on selected GC microelectrodes of the same MEAs, to achieve multi-site detection of tonic 5-HT concentrations using square wave voltammetry. Combining the superior electrochemical stability of the carbon electrodes and interconnections with the excellent biocompatibility of a miniaturized thin-film flexible device, the C-Flex-MEA presents ideal properties for in vivo neurochemical sensing for both tonic and phasic 5-HT measurements, also promoting seamless tissue integration. Our Specific Aim 1 focuses on fabrication and in vitro optimization of the C-Flex-MEA with the goal of meeting the criteria in detection sensitivity, selectivity, and stability. Specific Aim 2 focuses on acute and chronic in vivo testing of multi-site sensing performance of the C-Flex-MEAs in mouse brain, and implant biocompatibility. The acute testing will guide the probe design and fabrication to minimize insertion injury and validate 5-HT sensing. The completion of the chronic experiments will allow us to determine the sensor’s lifetime and understand the abiotic and biotic factors that affect the stability of the sensor over time. Successful completion of this project will produce an unprecedented platform to study the specific implications of the different 5-HT dynamics in neurological and psychiatric disorders.

项目摘要 滋补和阶段性血清素（5-羟色胺，5-HT）动力学的多站点测量 在不同的大脑区域中，最重要的是阐明5-HT在焦虑，抑郁，， 和冲动控制障碍。多周的慢性采样对于研究5-HT至关重要 神经系统过渡过程中的变化，并了解特定药物治疗的效率。 尽管具有值，但体内多站点的慢性测量值为5-HT受到现有能力的限制 技术。例如，微透析以缓慢的临时分辨率测量补品5-HT水平，而快速 碳纤维微电极（CFE）处的扫描循环伏安法（FSCV）只能检测到相位5-HT释放。 这些实验目前一次进行一个站点，而5-HT动力学很复杂且不同 不同的大脑区域或同一区域的不同局部区域，需要高分辨率的多站点测量。 此外，据我们所知，没有显示这种技术的慢性5-HT检测。 在这里，我们建议在超薄柔性基板上开发一个可植入的碳基多电极阵列 （C-FLEX-MEA）用于从不同大脑位置进行5-HT动力学的综合阶段和补品测量。到 实现我们的目标：首先，我们将优化一种允许玻璃碳整合的模式转移技术 （GC）超柔性聚合物基板上的微电极阵列和互连。由此产生的c-flex- MEAS将允许多站点的FSCV检测阶段5-HT释放。其次，我们将合并poly（3,4-- 乙二烯二苯二磷脂/功能化的碳纳米管（PEDOT/CNT）涂层在选定的GC上 同一度量的微电极，以实现使用正方形的补品5-HT浓度的多站点检测 波伏安法。结合碳电极的优质电化学稳定性和 与小型薄膜柔性装置的极佳生物相容性，C-FLEX-MEA的互连 为体内神经化学感测的理想特性，用于滋补和阶段5-HT测量 促进无缝组织整合。我们的特定目标1专注于制造和体外优化 C-FLEX-MEA的目的是满足检测灵敏度，选择性和稳定性的标准。具体目标2 专注于小鼠C-FLEX-MEAS多站点感测性能的急性和慢性体内测试 大脑和植入物生物相容性。急性测试将指导探针设计和制造以最大程度地减少 插入损伤并验证5-HT感应。慢性实验的完成将使我们能够确定 传感器的寿命并了解会随着时间的推移影响传感器稳定性的非生物和生物因素。 该项目的成功完成将产生一个前所未有的平台来研究具体含义 神经和精神疾病中不同的5-HT动力学。