On-chip studies of neuron cells under magnetic field stimulation

磁场刺激下神经元细胞的芯片研究

• 批准号: 1610967
• 负责人: Long Que
• 金额: $ 36.31万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1610967&HistoricalAwards=false
• 关键词: chip; studies; neuron; cells; under

Proposal Title: On-chip studies of neuron cells under magnetic field stimulation Brief description of project Goals:This project is to develop a microchip for studying the single neuron cells and their interaction under magnetic field stimulation.Nontechnical Abstract:One in five Americans above the age of 18 suffer from diagnosable neurological disorders and there are 50,000 new cases of Parkinson's disease diagnosed every year in the United States. 10 to 20% of apparently healthy service members returning from conflicts in Iraq and Afghanistan suffer from post-traumatic stress disorder (PTSD). Therefore there is a critical need to develop new, safe, non-invasive methods for the treatment of deep brain disorders. Non-invasive techniques including repetitive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have had some success, but progress has been limited because of poor understanding of interaction of magnetic fields with neurons. Basically the molecular/cellular mechanisms of neurons under TMS are still lacking. To address these issues, the scientific and technical component of this project focuses on the investigation of the effect of transient magnetic fields on the neuronal growth rate and synaptic activity, which is essential in developing new treatment procedures for debilitating neurological disorders such as Parkinson's disease, PTSD and traumatic brain injury. The education, dissemination and outreach component of this project includes mentoring graduate, undergraduate and underrepresented/minority students, dissemination and outreach to the local community. The overall educational goal is to help next-generation workforce development by training students to carry out research with sound technical background and allowing them to gain hands-on laboratory skills for their advanced careers.Technical Abstract:The proposed project seeks to develop an integrated microchip that allows, for the first time, studying the growth, synaptic activity and regeneration of single neuron cells and interaction among the separated neuron cells under both AC/transcranial magnetic and DC magnetic field stimulation. Specifically, this project focuses on: (i) the development of a new microchip, which consists of microholder arrays with integrated patch-clamp probes to store single neuron cells; (ii) the study of the growth behavior and monitoring of the action potential of single neuron cells (N27 cells and PC12 cells as the models) under AC/transcranial magnetic field stimulation; (iii) the study of the growth behavior of the neuron cells inside a 3D extracellular matrix, mimicking the in vivo environment, under AC/transcranial magnetic field stimulation; and (iv) the study of the guided neuron growth by functionalizing the neuron cells with magnetic nanoparticles (mNPs) under DC and AC/transcranial magnetic field stimulation. This proposed research may help advance fundamental knowledge of growth and regeneration of single neuron cells under the magnetic field stimulation, which might have significant impact on the field of regenerative medicine from both scientific and engineering points of view. This proposed integrated technical platform offers some unique features otherwise unavailable by any other existing platforms, providing the capability for monitoring the behaviors of single neuron cells and the interactions among them. These functions in this platform might help trigger some basic discoveries, some important ideas and innovations for biomedical applications.

提案标题：在磁场刺激下的神经元细胞的芯片研究项目简介目标：本项目是开发一种用于研究单个神经元细胞及其在磁场刺激下的相互作用的微芯片。非技术摘要：在18岁以上的美国人中，有五分之一的人患有可诊断的神经系统疾病，在美国每年有50，000例新的帕金森氏病诊断病例。从伊拉克和阿富汗冲突中返回的10%至20%的看似健康的服务人员患有创伤后应激障碍（PTSD）。因此，迫切需要开发新的、安全的、非侵入性的方法来治疗深部脑疾病。包括重复经颅磁刺激（TMS）和经颅直流电刺激（tDCS）在内的非侵入性技术取得了一些成功，但由于对磁场与神经元的相互作用了解甚少，进展有限。基本上，TMS下神经元的分子/细胞机制仍然缺乏。为了解决这些问题，该项目的科学和技术部分侧重于调查瞬变磁场对神经元生长速度和突触活动的影响，这对于开发帕金森病、创伤后应激障碍和创伤性脑损伤等衰弱性神经系统疾病的新治疗程序至关重要。 该项目的教育、传播和外联部分包括指导研究生、本科生和代表性不足/少数民族学生，向当地社区进行传播和外联。本项目的总体教育目标是培养学生具备扎实的技术背景进行研究，并为他们的高级职业生涯提供实际操作的实验室技能，从而帮助下一代劳动力的发展。技术摘要：本项目旨在开发一种集成微芯片，该芯片首次允许研究单个神经元细胞在交流/经颅磁场和直流磁场刺激下的生长，突触活动和再生以及分离的神经元细胞之间的相互作用。具体而言，本项目的重点是：（i）开发一种新的微芯片，由集成膜片钳探针的微夹阵列组成，用于存储单个神经元细胞;（ii）研究单个神经元细胞的生长行为和监测动作电位（N27细胞和PC 12细胞为模型）在AC/经颅磁场刺激下;（iii）在AC/经颅磁场刺激下，模拟体内环境的3D细胞外基质内的神经元细胞的生长行为的研究;以及（iv）通过在DC和AC/经颅磁场刺激下用磁性纳米颗粒（mNPs）功能化神经元细胞来研究引导的神经元生长。这项拟议的研究可能有助于推进磁场刺激下单个神经元细胞生长和再生的基础知识，从科学和工程的角度来看，这可能对再生医学领域产生重大影响。该集成技术平台提供了一些其他现有平台无法提供的独特功能，提供了监控单个神经元细胞行为及其相互作用的能力。该平台中的这些功能可能有助于引发生物医学应用的一些基础发现，一些重要的想法和创新。