CAREER: An Integrated Platform for Measuring Neurotransmitters and Cytokines from Cells

该项目由电气、通信和网络系统(ECCS)和既定的激励竞争研究计划(EPSCoR)共同资助。了解大脑中的神经元和免疫细胞是如何通过神经递质和细胞因子的交换相互沟通的，可以揭示新的信号通路，这些信号通路对于治疗各种神经退行性疾病至关重要，如阿尔茨海默氏症和帕金森氏病。神经元通常会释放各种类型的神经递质来与邻近细胞相对应，而免疫细胞通常会释放细胞因子来调节免疫反应。最近的发现提供了强有力的证据，表明神经递质和细胞因子之间存在双向通信，目的是相互调节。因此，在一个闭环系统中交互地同时监测这两个物种的动态是至关重要的，在闭环系统中，一种或多种类型的神经递质可以影响一系列细胞因子，反之亦然。该项目研究了新的生物传感策略，并开发了一个完全集成的设备平台，可以在神经化学物质和免疫细胞释放神经化学物质和细胞因子时分别同时测量它们。这项技术的成功实施将对神经科学界产生重大影响，因为它将阐明复杂的信号通路以及大脑中神经炎症和免疫反应发生的机制。该项目的研究目标是实现一个集成的生物传感平台，能够实时测量细胞分泌的关键神经化学物质和炎性细胞因子。为了实现这一目标，将采用以下策略：(1)将使用分子模板来实现一种新型的基于聚合物的目标受体，以提高分析物识别的选择性；(2)将电化学传感技术与石墨烯场效应管集成，以增强分析物检测中的信号放大和灵敏度；以及(3)将实施集成细胞培养系统和生物传感组件的芯片实验室设备。该项目的教育目标是利用研究活动作为培训当前和下一代STEM劳动力的平台。这将通过以下战略方法实现：(1)通过K-12外展活动培训下一代科学家和工程师；(2)通过本科生和研究生教育和指导培养工程师和在岗科学家；以及(3)通过实施在线毕业生证书计划支持当前的工业劳动力。这些教育活动将使处于STEM职业生涯不同阶段的学生接触到(1)微流控器件的微制造，(2)生物传感和生物电子学的概念，以及(3)基于纳米材料和晶体管的生物分子检测。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。

This project is jointly funded by the Electrical, Communications and Cyber Systems (ECCS) and the Established Program to Stimulate Competitive Research (EPSCoR). Understanding how neurons and immune cells in the brain communicate with each other through the exchange of neurotransmitters and cytokines could reveal new signaling pathways that are crucial to treating various neurodegenerative diseases such as Alzheimer's and Parkinson's Disease. Neurons typically release various types of neurotransmitters to correspond with neighboring cells, while immune cells commonly release cytokines to modulate immune responses. Recent discoveries provide strong evidence suggesting bi-directional communication between neurotransmitters and cytokines for the purpose of modulating one another. Therefore, it is critical to monitor the dynamics of both of these species interactively and simultaneously in a closed-loop system, where one or more types of neurotransmitters can influence a series of cytokines, and vice versa. This project investigates novel biosensing strategies and the development of a fully integrated device platform that can simultaneously measure the neurochemicals and cytokines from neurons and immune cells, respectively, as they are released. Successful implementation of this technology will greatly impact the neuroscience community by elucidating the intricate signaling pathways and the mechanisms through which neuroinflammation and immune responses occur in the brain.The research objective of this project is to implement an integrated biosensing platform that enables real-time measurement of the key neurochemicals and inflammatory cytokines from cells in situ as they are secreted. To achieve this goal, the following strategies will be applied: (1) Molecular templating will be used to implement a novel polymer-based target receptor that will enhance the selectivity in analyte recognition; (2) The electrochemical sensing technique will be integrated with a graphene field-effect transistor to enhance signal amplification and sensitivity in analyte detection; and (3) A lab-on-a-chip device that integrates the cell culture system and the biosensing components will be implemented. The educational objective of this project is to utilize the research activities as a platform to train the current and the next generation of STEM workforce. This will be achieved through the following strategic approaches: (1) Training the next generation of scientists and engineers through K-12 outreach activities; (2) Preparing engineers- and scientists-in-training through undergraduate and graduate education and mentoring; and (3) Supporting the current industrial workforce by implementing an online graduate certificate program. These educational activities will expose the students in various stages in their STEM career to the areas of (1) microfabrication of microfluidic devices, (2) the concepts of biosensing and bioelectronics, and (3) nanomaterial- and transistor-based detection of biomolecules.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.