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）和促进竞争研究的既定计划（EPSCoR）共同资助。了解大脑中的神经元和免疫细胞如何通过神经递质和细胞因子的交换相互沟通，可以揭示对治疗各种神经退行性疾病（如阿尔茨海默病和帕金森病）至关重要的新信号传导途径。神经元通常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的双向交流是为了相互调节。因此，在一个闭环系统中，一种或多种类型的神经递质可以影响一系列细胞因子，同时监测这两种物种的动态是至关重要的，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，可以同时测量神经元和免疫细胞释放的神经化学物质和细胞因子。这项技术的成功实施将通过阐明大脑中神经炎症和免疫反应发生的复杂信号通路和机制，极大地影响神经科学界。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时的关键神经化学物质和炎症细胞因子。为了实现这一目标，将采用以下策略：(1)分子模板将用于实现一种新的基于聚合物的靶受体，这将提高分析物识别的选择性；(2)电化学传感技术将与石墨烯场效应晶体管集成，以增强信号放大和分析物检测的灵敏度；(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)通过本科和研究生教育和指导，培养工程师和科学家的培训；(3)通过实施在线研究生证书课程来支持当前的产业劳动力。这些教育活动将使学生在STEM职业生涯的各个阶段接触到以下领域：(1)微流控器件的微加工，(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。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.