Laser Induced NanoCarbon Multielectrode Arrays for Neurotransmitter Sensing

项目摘要 活体脑内神经递质的实时测量对于研究脑内神经递质的变化具有重要意义。 了解正常和病理条件下的脑功能，并改善诊断和治疗 神经和神经精神疾病。 高表面积碳（HSAC），或纳米碳，已经被认为是用于电化学的理想材料。 由于其出色的电化学特性和化学惰性，可用于检测神经递质。 然而，HSAC微电极阵列（MEA）很难制造，并且所需的极端环境 对于纳米碳合成，限制了对基底的选择，使其成为能够承受高温的刚性材料。 而且，化学掺杂改善电化学传感还需要高温后合成 处理.因此，对于在柔性基底上制造可植入HSAC MEA存在未满足的需求， 形态学和化学的可调性，用于在不同时间的神经递质的多位点测量 分辨率（ms到min），在大脑区域内和跨大脑区域（µm到mm）。 为了填补这一空白，该项目介绍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是一种新的直接写入 该工艺具有前所未有的能力，可在聚合物上自下而上生长纳米碳， 激光照射后的源。我们的发明方法首次实现了快速、低成本、批量制造 HSAC MEA以高度可重复的方式，而不需要高温碳合成或多步 微加工工艺。重要的是，LINC允许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多边环境协定将针对高灵敏度进行定制 使用两种不同电化学技术的不同神经递质的电化学检测：快速扫描 循环伏安法（FSCV），用于捕获快速相位动力学，方波伏安法（SVW）， 检测紧张水平经过精心的体外优化，我们将确定 提出的HSAC MEA在进行电活性神经递质的电化学传感中用于急性体内 检测大鼠中1）强直性（通过SWV）和2）电诱发（通过FSCV）多巴胺和5-羟色胺释放 背侧纹状体和海马（CA 2区），分别或同时。成功 该项目的完成将提供1）具有革命性国家潜力的尖端技术- 最先进的纳米碳基MEA制造神经化学应用，2）将提供科学的 社区与前所未有的研究平台的神经递质及其相互作用，在正常和 病理性的大脑状况

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.