Collaborative Research: A multiplexed microbiosensing platform for understanding real time neurotransmitter dynamics in the brain

合作研究：用于了解大脑中实时神经递质动态的多重微生物传感平台

基本信息

批准号：
2042544
负责人：
Emanuela Andreescu
金额：
$ 29.59万
依托单位：
Clarkson University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2042544&HistoricalAwards=false
关键词：
Collaborative Research multiplexed microbiosensing platform

项目摘要

Neurotransmitters (NTs) are responsible for biological and physiological functions controlling mood, memory, behavior and coordination in the brain. Understanding NT dynamics is essential to understanding brain function but the means by which specific neurotransmitters achieve their behavioral effects is still largely unknown and requires accurate, real-time quantification in brain structures. To meet this challenge, in this project funded by the CBET, Biosensing program of the CMMI division, a collaborative team of biosensing experts, computer engineers and neurophysiologists at Clarkson University and the White River Junction VA Medical center are developing novel electrochemical enzyme biosensors that can measure multiple NTs with increased accuracy with little or no false detection. The biosensors will be integrated with statistical and machine learning methods and will be used to study the neurochemical environment in a rat model of Parkinson’s Disease. The research will enhance education and training of life sciences and engineering students at Clarkson University who will work synergistically with the team of investigators to develop next generation biosensing technologies for monitoring neurotransmission in the brain. The project will develop biosensing devices that incorporate NT-specific materials and electrode surfaces for in vivo monitoring of neuronal activity. The research team will engineer an oxygen-rich nanoarchitecture containing an enzyme-like biomimetic catalyst and NT-specific enzymes, stabilized within a conductive network and develop automatic fabrication procedures to ensure scalable and reproducible manufacturing of these biosensors. These materials will be designed to ensure long-term bioactivity and operability for recognition of specific NTs and are expected to improve our ability to study the complex neural mechanisms involved in signaling in the brain. Research will involve the following tasks: 1) develop selective NT-specific nanostructures with high durability and sensitivity for enzyme-based microbiosensors that can measure dopamine, glutamate and acetylcholine, 2) computational work to produce predictive fingerprint models of NT dynamics using electrochemical data, and 3) in vivo work to determine the temporal profile of changes in NT concentrations during high frequency stimulation in normal and ‘hemi-parkinsonian’ animals. Educational activities will involve 1) student participation in research and dissemination through presentations and publications, 2) hands on education though implementation of a biosensing module in the new interdisciplinary Biomedical Engineering and Biomedical Science and Technology degree programs at Clarkson, 3) sites and virtual visits and demonstrations of neuromonitoring and neurostimulation experiments in live animals at Dartmouth College. The broader impacts of this work include potential societal benefit from the discovery of new NT-specific materials and the development of novel biosensing tolls that could be used broadly by the biomedical community for studying neurochemical changes in the brain, as well as the education and training of students who will be uniquely trained to tackle grand challenges in neuroscience and device engineering.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.

神经递质 (NT) 负责控制大脑中的情绪、记忆、行为和协调的生物和生理功能。了解 NT 动态对于了解大脑功能至关重要，但特定神经递质实现其行为效果的方式仍然很大程度上未知，并且需要准确的信息。为了应对这一挑战，在这个由 CBET、CMMI 部门生物传感项目资助的项目中，克拉克森大学的生物传感专家、计算机工程师和神经生理学家组成的协作团队。 White River Junction VA 医疗中心正在开发新型电化学酶生物传感器，能够以更高的精度测量多种 NT，几乎没有或没有错误检测。该生物传感器将与统计和机器学习方法相结合，用于研究神经化学环境。该研究将加强克拉克森大学生命科学和工程专业学生的教育和培训，他们将与研究人员团队协同工作，开发用于监测大脑神经传递的下一代生物传感技术。该项目将开发结合 NT 特异性材料和电极表面的生物传感设备，用于体内神经活动监测。研究小组将设计一种富氧纳米结构，其中包含酶样仿生催化剂和 NT 特异性酶，并稳定在导电材料中。网络并开发自动制造程序，以确保这些生物传感器的可扩展和可重复制造，这些材料的设计将确保识别特定 NT 的长期生物活性和可操作性，并有望改善我们的技术。研究涉及大脑信号传导的复杂神经机制的能力。研究将涉及以下任务：1）开发具有高耐用性和灵敏度的选择性 NT 特异性纳米结构，用于基于酶的微生物传感器，可测量多巴胺、谷氨酸和乙酰胆碱，2）使用电化学数据生成 NT 动态的预测指纹模型的计算工作，以及 3) 体内工作以确定正常和正常情况下高频刺激期间 NT 浓度变化的时间曲线。教育活动将包括 1) 学生通过演讲和出版物参与研究和传播，2) 通过在克拉克森新的跨学科生物医学工程和生物医学科学与技术学位课程中实施生物传感模块进行实践教育。 , 3) 达特茅斯学院活体动物神经监测和神经刺激实验的现场和虚拟参观以及演示。这项工作的更广泛影响包括发现新的 NT 特定材料和的潜在社会效益。开发新型生物传感技术，可被生物医学界广泛用于研究大脑中的神经化学变化，以及对学生进行教育和培训，让他们接受独特的培训，以应对神经科学和设备工程领域的巨大挑战。该奖项由 NSF 颁发法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。