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: 10527048
• 负责人: Elisa Castagnola
• 金额: $ 22.33万
• 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/10527048
• 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; Electrodes; Electrophysiology (science); Emotions; Film; Foreign Bodies; Functional disorder; Future; Goals; Hippocampus (Brain); Histologic; Impulse Control Disorders; In Vitro; Injury; Link; Location; Measurement; Measures; Mental Depression; Mental disorders; Metals; Microdialysis; Microelectrodes; Modality; Morphology; Mus; Natural graphite; Neurologic; Neurotransmitters; Pattern; Penetration; Performance; Periodicity; Pharmacological Treatment; Pharmacology; 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; base; biomaterial compatibility; carbon fiber; design; detection sensitivity; electric impedance; experimental study; flexibility; improved; in vivo; in vivo evaluation; lithography; meetings; miniaturize; multi-electrode arrays; nervous system disorder; neural implant; neurochemistry; 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.

项目概要 同时多部位测量强直性和阶段性血清素（5-羟色胺，5-HT）动态 跨不同大脑区域对于阐明 5-HT 在焦虑、抑郁、 持续数周的慢性采样对于研究 5-HT 至关重要。 神经转变期间的变化并了解特定药物治疗的功效。 尽管有其价值，但 5-HT 的体内多部位长期测量受到现有技术能力的限制。 例如，微透析以慢速时间分辨率测量强直 5-HT 水平，而快速。 碳纤维微电极 (CFE) 的扫描循环伏安法 (FSCV) 只能检测阶段性 5-HT 释放。 这些实验目前一次一个地点进行，而 5-HT 动力学很复杂，并且在 不同的大脑区域或同一区域的不同位点，需要高分辨率的多站点测量。 此外，据我们所知，尚未显示使用这种技术进行慢性 5-HT 检测。 在这里，我们建议在超薄柔性基板上开发一种可植入碳基多电极阵列 (C-Flex-MEA) 用于对不同大脑位置的 5-HT 动态进行综合相位和强直测量。 实现我们的目标：首先，我们将优化图案转移技术，以实现玻璃碳的集成 (GC) 超薄柔性聚合物基板上的微电极阵列和互连。 MEA 将允许对阶段性 5-HT 释放进行多位点 FSCV 检测 其次，我们将合并聚（3,4-）。 选定 GC 上的乙烯二氧噻吩）/功能化碳纳米管 (PEDOT/CNT) 涂层 相同MEA的微电极，利用方形实现补5-HT浓度的多位点检测 波伏安法结合了碳电极的优异电化学稳定性和 具有出色生物相容性的微型薄膜柔性器件 C-Flex-MEA 互连 为强直性和阶段性 5-HT 测量的体内神经化学传感提供了理想的特性， 我们的具体目标 1 侧重于组织的制造和体外优化。 C-Flex-MEA 的目标是满足检测灵敏度、选择性和稳定性标准 2。 专注于小鼠 C-Flex-MEA 多位点传感性能的急性和慢性体内测试 急性测试将指导探针设计和制造，以最大限度地减少大脑和植入物的生物相容性。 插入损伤并验证 5-HT 传感。慢性实验的完成将使我们能够确定。 传感器的使用寿命，并了解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为研究具体影响提供一个前所未有的平台 神经和精神疾病中不同 5-HT 动力学的研究。