Laser Induced NanoCarbon Multielectrode Arrays for Neurotransmitter Sensing

用于神经递质传感的激光诱导纳米碳多电极阵列

• 批准号: 10288138
• 负责人: Mostafa Bedewy
• 金额: $ 42.33万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10288138
• 关键词: 3-Dimensional; 5-Hydroxytryptophan; Acids; Acute; Adenosine; Affect; Area; Behavior; Brain; Brain region; Calibration; Carbidopa; Carbon; Carbon Nanotubes; Chemicals; Chemistry; Chronic; Communities; Controlled Environment; Corpus striatum structure; Coupled; Deposition; Detection; Devices; Diagnosis; Dopamine; Dorsal; Drug abuse; Electrodes; Electron Transport; Environment; Fast Electron; Film; Future; Growth; High temperature of physical object; Hippocampus (Brain); Implant; In Situ; In Vitro; Inflammatory Response; Injury; Kinetics; Lasers; Learning; Light; Manuals; Measurement; Measures; Mechanics; Mediator of activation protein; Memory; Mental Depression; Methods; Microelectrodes; Microfabrication; Modality; Modulus; Morphology; Motivation; Movement; Nanostructures; Nervous System Physiology; Neurotransmitters; Newspapers; Parkinson Disease; Pathologic; Pattern; Performance; Periodicity; Pharmacology; Phase; Polymers; Porosity; Positioning Attribute; Printing; Process; Production; Property; Rattus; Reproducibility; Scanning; Serotonin; Site; Source; Structure; Surface; Techniques; Technology; Thick; Time; Tissues; Validation; Work; Writing; base; biomaterial compatibility; carbon fiber; chemical property; cost; density; detection sensitivity; effectiveness evaluation; effectiveness validation; electric impedance; flexibility; graphene; improved; in vivo; internal control; invention; irradiation; multi-electrode arrays; nanoscale; nervous system disorder; neurochemistry; neuropsychiatric disorder; neurotransmission; optogenetics; scale up; sensor; temporal measurement

Project Summary The real-time measurement of neurotransmitters in vivo in living brain is of utmost importance for understanding brain functions in normal and pathological conditions and to improve diagnosis and treatments of neurological and neuropsychiatric diseases. High surface area carbon (HSAC), or nanocarbon, has been considered the ideal material for electrochemical detection of neurotransmitters, due to its outstanding electrochemical properties and chemical inertness. However, HSAC microelectrode arrays (MEAs) are difficult to fabricate, and the extreme environments needed for the nanocarbon synthesis limit the choice of substrate to rigid materials that can withstand high temperatures. Moreover, chemical doping to improve electrochemical sensing also requires high-temperature post-synthesis processing. Thus, there is an unmet need for fabricating implantable HSAC MEAs on flexible substrates with tunability of morphology and chemistry, for multisite measurements of neurotransmitters at different temporal resolutions (ms to min), within and across brain regions (µm to mm). To fill this gap, this project introduces a new laser-induced nanocarbon (LINC) fabrication technique, capable of patterning customizable types of HSAC on-demand directly on flexible polymers. LINC is a new direct-write process with the unprecedented ability for bottom-up growth of nanocarbons on polymers that act as the carbon source upon laser irradiation. Our inventive approach enables for the first time, a fast, low-cost, batch-fabrication of HSAC MEAs in a highly reproducible way, without the need of high-temperature carbon synthesis, or multistep microfabrication processes. Importantly, LINC allows in situ precise control of the nanocarbon atomic structure, nanoscale morphology, and surface chemistry. Thus, our HSAC MEAs will be tailored for high-sensitivity electrochemical detection of different neurotransmitters using two different electrochemical technique: fast scan cyclic voltammetry (FSCV), for capturing of fast phasic dynamics, and square wave voltammetry (SVW) for detecting tonic levels. Following a meticulous in vitro optimization, we will determine the effectiveness of the proposed HSAC MEA in performing electrochemical sensing of electroactive neurotransmitters for acute in vivo detection of 1) tonic (via SWV) and 2) electrically evoked (via FSCV) dopamine and serotonin release in the rat dorsal striatum and in the hippocampus (CA2 region) of rat brain, respectively or simultaneously. The successful completion of this project will provide 1) a cutting-edge technology with the potential to revolutionize the state- of-the-art of nanocarbon-based MEA fabrication for neurochemical applications, and 2) will provide the scientific community with a platform for unprecedented studies of neurotransmitters and their interactions in normal and pathological brain conditions.

项目概要 实时测量活体大脑中的神经递质对于 了解正常和病理条件下的大脑功能，并改善疾病的诊断和治疗 神经系统和神经精神疾病。 高表面积碳（HSAC）或纳米碳被认为是电化学的理想材料 由于其出色的电化学特性和化学惰性，可用于神经递质的检测。 然而，HSAC微电极阵列（MEA）制造困难，并且需要极端的环境 纳米碳合成限制了基底的选择，只能是能够承受高温的刚性材料。 此外，化学掺杂以改善电化学传感还需要高温后合成 加工。因此，在柔性基底上制造可植入 HSAC MEA 的需求尚未得到满足。 形态和化学的可调性，用于不同时间神经递质的多位点测量 大脑区域内和大脑区域之间的分辨率（毫秒到分钟）（微米到毫米）。 为了填补这一空白，该项目引入了一种新的激光诱导纳米碳（LINC）制造技术，能够 直接在柔性聚合物上按需图案化可定制类型的 HSAC。 LINC 是一种新的直写 具有前所未有的能力，可以在充当碳的聚合物上自下而上生长纳米碳 激光照射下的光源。我们的创新方法首次实现了快速、低成本的批量制造 以高度可重复的方式制备 HSAC MEA，无需高温碳合成或多步 微加工工艺。重要的是，LINC 可以原位精确控制纳米碳原子结构， 纳米级形态和表面化学。因此，我们的 HSAC MEA 将为高灵敏度量身定制 使用两种不同的电化学技术对不同神经递质进行电化学检测：快速扫描 循环伏安法 (FSCV) 用于捕获快速相动力学，方波伏安法 (SVW) 用于捕获 检测补品水平。经过细致的体外优化后，我们将确定该方法的有效性 提议 HSAC MEA 在体内急性电活性神经递质的电化学传感中 检测大鼠体内 1) 强直（通过 SWV）和 2）电诱发（通过 FSCV）多巴胺和血清素释放 分别或同时在大鼠大脑的背侧纹状体和海马（CA2区）中。成功者 该项目的完成将提供：1）一项有可能彻底改变国家的尖端技术 用于神经化学应用的最先进的基于纳米碳的 MEA 制造，2) 将提供科学的 社区拥有一个前所未有的研究神经递质及其在正常和正常情况下相互作用的平台 病理性脑部状况。

项目成果

Effects of central nervous system electrical stimulation on non-neuronal cells.

• DOI: 10.3389/fnins.2022.967491
• 发表时间: 2022
• 期刊: FRONTIERS IN NEUROSCIENCE
• 影响因子: 4.3
• 作者: Williams, Nathaniel P.;Kushwah, Neetu;Dhawan, Vaishnavi;Zheng, Xin Sally;Cui, Xinyan Tracy
• 通讯作者: Cui, Xinyan Tracy

Stable in-vivo electrochemical sensing of tonic serotonin levels using PEDOT/CNT-coated glassy carbon flexible microelectrode arrays.

• DOI: 10.1016/j.bios.2023.115242
• 发表时间: 2023-03-27
• 期刊: BIOSENSORS & BIOELECTRONICS
• 影响因子: 12.6
• 作者: Castagnola，Elisa;Robbins，Elaine M.;Cui，Xinyan Tracy
• 通讯作者: Cui，Xinyan Tracy