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

神经递质(NTS)负责控制情绪、记忆、行为和大脑协调的生物和生理功能。了解NT动力学对于了解大脑功能是必不可少的，但特定的神经递质实现其行为效果的方法在很大程度上仍不清楚，需要准确、实时地量化大脑结构。为了应对这一挑战，在这个由CBET资助的项目中，CMMI部门的生物传感计划，由Clarkson大学和White River Junction VA医学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的电化学酶生物传感器，该传感器可以提高测量多个NT的准确性，几乎没有错误检测。这些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氏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。该项目将开发结合NT特定材料和电极表面的生物传感设备，用于活体监测神经元活动。研究小组将设计一种富氧纳米结构，其中包含一种类似酶的仿生催化剂和NT特有的酶，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，并有望提高我们研究大脑中涉及信号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高灵敏度的选择性NT特定纳米结构，用于基于酶的微生物传感器，可以测量多巴胺、谷氨酸和乙酰胆碱；2)计算工作，利用电化学数据产生NT动力学的预测指纹模型；3)体内工作，确定正常动物和‘半帕金森病’动物在高频刺激期间NT浓度变化的时间分布。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Clarkson新的跨学科生物医学工程和生物医学科学和技术学位课程中实施生物传感模块进行动手教育，3)在达特茅斯学院对活体动物进行神经监测和神经刺激实验的现场和虚拟参观和演示。这项工作的更广泛影响包括发现新的NT专用材料和开发可被生物医学界广泛用于研究大脑中神经化学变化的新型生物传感收费，以及对将接受独特培训以应对神经科学和设备工程中的重大挑战的学生的教育和培训。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。

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.