CAREER: Engineering Light Addressable Electrochemical Sensors for Imaging Chemical Neurotransmission

细胞间的化学信号是生命的基本组成部分。几十年的工作已经在理解大脑中称为神经递质的小分子的运动如何影响行为和疾病方面取得了巨大的进展。然而，我们对神经传递过程的理解仍然存在差距，因为用于研究这些过程的分析工具没有足够的分辨率。该项目将开发工具，以高分辨率产生活神经元周围神经递质的化学图像，以便更好地在亚细胞水平上了解神经传递。半导体/金属结将作为传感器，以高空间和时间分辨率测量神经递质。这项研究的教育计划旨在解决社区大学转学学生在高级化学课程中的留存问题。除了科学发展，该项目还寻求为代表性不足的群体提供研究机会，通过示范和外联活动提供社区参与，并在技术相关领域为本科生和研究生提供培训。当一个神经元释放信号分子，称为神经递质，进入它与邻近神经元之间的小间隙，称为突触时，就会发生化学神经传递。一旦离开突触，神经递质要么被突触后神经元吸收，要么扩散出去。测量活神经元周围神经递质的流量对于增加我们对化学神经传递的理解至关重要。不幸的是，缺乏同时具有高空间和时间分辨率的测量这些通量的分析工具。这项职业计划的目标是开发光寻址电化学传感器，用于高空间和时间分辨率检测个体活细胞体外排泄的神经递质通量。本研究的两个具体目的是：(1)通过最大限度地提高灵敏度和降低背景信号来提高光寻址电化学传感器的检测极限；(2)开发利用光寻址电化学传感器的定量成像平台，用于化学神经传递的体外成像。研究目标将通过使用物理和电化学方法对半导体金属结进行仔细的研究、对半导体/金属/溶液界面进行有限元建模以及对半导体/金属界面进行局部电化学测量来实现。这项研究在生物传感、半导体光电化学和光寻址电化学传感方面做出了重大贡献。该教育计划将通过提供一条增加社区学院转学学生在高级课程工作中留住的途径，将研究和教学结合在一起。这一方法将使社区学院转学学生有机会获得研究经验。接受该项目培训的学生将学习最先进的制造、分析、测量和表征技能，这些技能将有助于他们进入劳动力大军或研究生院。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Chemical signaling between cells is a fundamental component of life. Decades of work have made tremendous gains in understanding how the movement of small molecules called neurotransmitters in the brain influence behavior and disease. However, there are still gaps in our understanding of neurotransmission processes because the analytical tools for studying these processes do not have sufficient resolution. This project will develop tools that will produce chemical images of neurotransmitters around living neurons with high resolution in order to better understand neurotransmission at the sub-cellular level. Semiconductor/metal junctions will serve as sensors for measuring neurotransmitters with high spatial and temporal resolution. The educational plan of this research seeks to address retention of community college transfer students in upper-level chemistry courses. In addition to the scientific developments, this project seeks to provide research opportunities to underrepresented groups, provide community engagement through demonstrations and outreach activities, and provide training to undergraduate and graduate students in technologically relevant areas. Chemical neurotransmission occurs when one neuron releases signaling molecules, called neurotransmitters, into the small gap between itself and an adjacent neuron, called a synapse. Once outside the synapse, neurotransmitters are either taken up by the post-synaptic neuron or diffuse away. Measuring the flux of neurotransmitters around living neurons is critical to increasing our understanding of chemical neurotransmission. Unfortunately, analytical tools to measure these fluxes with both high spatial and temporal resolution are lacking. The objective of this CAREER proposal is to develop light-addressable electrochemical sensors for high spatial and temporal resolution detection of neurotransmitter fluxes excreted from individual living cells in vitro. The two specific aims of this research are to: (1) Improve the detection limits of light-addressable electrochemical sensors by maximizing sensitivity and decreasing background signal, (2) Develop a quantitative imaging platform using light-addressable electrochemical sensors for in vitro imaging of chemical neurotransmission. The research aims will be accomplished by performing careful studies of semiconductor metal junctions using physical and electrochemical methods, finite element modeling of the semiconductor/metal/solution interface, and performing localized electrochemical measurements on semiconductor/metal interfaces. This research makes significant contributions to biosensing, semiconductor photoelectrochemistry, and light-addressable electrochemical sensing. The educational plan will integrate research and teaching by providing a pathway to increase retention of community college transfer students in upper-level coursework. This approach will enable community college transfer students to have access to research experience. Students trained on this project will learn state-of-the-art fabrication, analysis, measurement, and characterization skills that will assist them when they enter the workforce or graduate school.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.