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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动力学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应的方式在很大程度上仍然是未知的，需要在大脑结构中进行准确，实时的量化。为了应对这一挑战，在CBET资助的这个项目中，CMMI部门的生物传感项目，一个由克拉克森大学和白河交汇处VA医疗中心的生物传感专家，计算机工程师和神经生理学家组成的合作团队正在开发新型电化学酶生物传感器，该传感器可以测量多个NT，并且具有更高的准确性，很少或没有错误检测。生物传感器将与统计和机器学习方法相结合，并将用于研究帕金森病大鼠模型的神经化学环境。这项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，开发下一代生物传感技术，用于监测大脑中的神经传递。该项目将开发生物传感设备，包括NT特定材料和电极表面，用于体内监测神经元活动。该研究小组将设计一种富含氧气的纳米结构，含有酶样仿生催化剂和NT特异性酶，稳定在导电网络中，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再现制造。这些材料将被设计为确保识别特定NT的长期生物活性和可操作性，并有望提高我们研究大脑中信号传导所涉及的复杂神经机制的能力。研究将涉及以下任务：1）开发具有高耐久性和灵敏度的选择性NT特异性纳米结构，用于可以测量多巴胺、谷氨酸和乙酰胆碱的基于酶的微生物传感器，2）使用电化学数据产生NT动力学的预测指纹模型的计算工作，和3）在正常和“偏侧帕金森病”动物中测定高频刺激期间NT浓度变化的时间分布的体内工作。教育活动将涉及1）学生参与研究和传播通过演示文稿和出版物，2）动手教育，通过在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在克拉克森，3）网站和虚拟访问和演示神经监测和神经刺激实验在达特茅斯学院活动物的实施模块。这项工作的更广泛影响包括发现新的NT特异性材料和开发新的生物传感器的潜在社会效益，这些生物传感器可被生物医学界广泛用于研究大脑中的神经化学变化，以及对学生的教育和培训，这些学生将接受独特的培训，以应对神经科学和设备工程方面的重大挑战。该奖项反映了NSF的法定使命，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。