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 了解脑功能在正常和病理条件下的变化，提高诊断和治疗水平 神经和神经精神疾病。 高比表面积碳(HSAC)或纳米碳被认为是理想的电化学材料 神经递质的检测，由于其突出的电化学性质和化学惰性。 然而，HSAC微电极阵列(MEA)制作困难，且需要极端环境 对于纳米碳的合成，将衬底的选择限制在能够耐高温的刚性材料上。 此外，化学掺杂以改善电化学传感还需要高温后合成。 正在处理。因此，在柔性衬底上制造可植入的HSAC MEA的需求尚未得到满足 形态和化学的可调性，用于不同时间的神经递质的多点测量 分辨率(毫秒到分钟)，在大脑区域内和跨脑区域(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 可直接在柔性聚合物上按需构图可定制类型的HSAC。LINC是一种新的直写 具有前所未有的能力在充当碳的聚合物上自下而上生长纳米碳的过程 激光照射时的光源。我们的创造性方法首次实现了快速、低成本、批量制造 以高度可重复性的方式，不需要高温碳合成或多步骤 微细加工工艺。重要的是，LINC允许原位精确控制纳米碳原子结构， 纳米级的形态和表面化学。因此，我们的HSAC MEA将针对高敏感度进行量身定制 用两种不同的电化学技术快速扫描检测不同的神经递质 循环伏安法(FSCV)用于捕获快速相动力学，方波伏安法(SVW)用于 检测主音水平。经过精心的体外优化，我们将确定 HSAC MEA在急性在体电活性神经递质电化学传感中的应用 检测1)紧张性(通过SWV)和2)电诱发(通过FSCV)多巴胺和5-羟色胺的释放 分别或同时在大鼠脑内背侧纹状体和海马区(CA2区)。成功者 该项目的完成将提供1)具有变革国家的潜力的尖端技术- 用于神经化学应用的最先进的基于纳米碳的MEA的制造，以及2)将提供科学的 为研究神经递质及其相互作用提供了前所未有的平台 病理性的脑部疾病。

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.