ERI:Ultrafast, Robust, Novel Four-bore Carbon-fiber Microelectrodes for Simultaneous Electrochemical Sensing of Multiple Neurotransmitters and Toxic Metals

神经系统疾病已成为一个主要的全球健康问题，尽管多个团体采取了努力，以保持大脑的功能和结构。神经保护药物的疗效有限，因此表明这些疾病背后有一系列未被发现的原因。除了一些众所周知的危险因素，如衰老，临床和流行病学研究表明，接触重金属可以启动神经细胞的死亡。此外，基于生物化学相关的计算模型，已经提出了几种机制来解释重金属暴露对各种神经退行性疾病的影响。由于缺乏适当的工具来进行实时测量，研究人员研究了死后组织样本或患者尿液和血液中的重金属。然而，这些研究或理论模型并不能准确地代表生命系统内部的测量。此外，目前的研究主要集中在一次识别一种化学信使分子或神经递质。因此，需要更好地理解神经递质和其他元素（如重金属）之间的相互作用。这项研究将专注于开发一种新型的，强大的电化学传感器，可以进行超快速，同时测量重金属和多种神经递质。该传感器将使用碳纤维微电极制作，数据采集和分析将使用快速扫描循环伏安法（FSCV）进行。这项研究的结果将解释这种新传感器的基本原理，从而在生命系统中进行测试之前提供对系统的更深入的机械理解。该项目的更广泛影响包括扩大妇女在STEM领域的参与，提高公众对重金属暴露及其对神经系统疾病的负面影响的认识。为了实现这些目标，我们将与当地一所中学合作开展多项外展活动。该项目旨在为开发电化学传感系统做出基础性贡献，以了解重金属和共同递质在大脑中的作用。该结果将提供有关神经退行性疾病多因素病因的缺失信息，以最终设计更有效的药物。作为多步骤项目的第一步，这项工作提出设计新的四孔碳纤维微电极（CFM），使用FSCV同时测量重金属和神经递质。结果将通过以下方式实现：（1）优化FSCV参数，以毫秒级时间分辨率检测砷和镉，进行实时体内测量所需的速度，（2）制造四孔CFM，以及（3）使用四孔CFM同时检测重金属和几种神经递质。这项研究背后的基本原理是，一旦确定了这种新传感平台的基本原理，它就可以应用于体内测量，以探测存在外部刺激（如重金属）时的神经元通信。这项研究将开辟新的途径，以获得关键的，准确的形态信息的重金属和潜在的共发射器的事件，特别是在高等脊椎动物与变革性的应用，在设计更有效的therapeutic.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

Neurological disorders have become a major global health problem despite efforts taken by multiple groups to preserve brain function and structure. Neuroprotective drugs have limited efficacy, thus indicating a set of undiscovered causes behind these diseases. Besides some well-known risk factors such as aging, clinical and epidemiological studies have shown that exposure to heavy metals can initiate the death of neuron cells. Moreover, based on biochemistry-related computational modeling, several mechanisms have been proposed to explain the effects of heavy metal exposure on various neurodegenerative diseases. Because of the lack of proper tools to perform real-time measurements in living systems, researchers study heavy metals in postmortem tissue samples or urine and blood obtained from patients. However, such studies or theoretical models do not accurately represent the measurements inside living systems. Additionally, current studies mainly focus on identifying one chemical messenger molecule or neurotransmitter at a time. Thus, an improved understanding of interactions among neurotransmitters and other elements, such as heavy metals, is needed. This research will focus on developing a novel, robust electrochemical sensor that can perform ultra-fast, simultaneous measurements of heavy metals and multiple neurotransmitters. The sensor will be fabricated using carbon fiber microelectrodes, and the data acquisition and analysis will be performed using fast scan cyclic voltammetry (FSCV). The outcome of this study will explain the fundamentals of this new sensor, thus, providing a greater mechanistic understanding of the system before testing in living systems. The broader impact of this project includes broadening women's participation in the STEM field and increasing public awareness of exposure to heavy metals and their negative impact on neurological disorders. These goals will be achieved through several outreach activities in collaboration with a local middle school.This project aims to make fundamental contributions to developing an electrochemical sensing system to understand the role of heavy metals and co-transmitters in the brain. The outcome will provide missing information about the multifactorial etiology of neurodegenerative diseases to ultimately design more efficient drugs. As the initial step of a multi-step project, this work proposes to engineer new four-bore carbon fiber microelectrodes (CFMs) that simultaneously measure heavy metals and neurotransmitters using FSCV. The outcome will be achieved by (1) optimizing FSCV parameters to detect arsenic and cadmium at millisecond temporal resolution, the required speed to perform real-time, in vivo measurements, (2) fabricating a four-bore CFM, and (3) detecting heavy metals and several neurotransmitters simultaneously using the four-bore CFM. The rationale behind this proposed research is that, once the fundamentals of this new sensing platform are identified, it can be applied to in vivo measurements to probe neuronal communication in the presence of external stimuli such as heavy metals. This study will open new avenues to obtain critical, accurate speciation information about heavy metals and potential co-transmitter events, particularly in higher vertebrate animals with transformative applications in designing more effective therapeutics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.