On-chip studies of neuron cells under magnetic field stimulation

提案标题：磁场刺激下神经细胞的芯片研究项目简介：该项目是开发一种微芯片，用于研究单个神经元细胞在磁场刺激下的相互作用。非技术摘要：每五个18岁以上的美国人中就有一个患有可诊断的神经疾病，美国每年有5万新诊断的帕金森氏症病例。在从伊拉克和阿富汗冲突中归来的看似健康的军人中，有10%到20%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(TDC)在内的非侵入性技术已经取得了一些成功，但由于对磁场与神经元相互作用的了解较少，进展受到限制。基本上，TMS下神经元的分子/细胞机制尚不清楚。为了解决这些问题，该项目的科学和技术部分侧重于研究瞬时磁场对神经元生长速度和突触活动的影响，这对于开发帕金森氏症、创伤后应激障碍和创伤性脑损伤等衰弱神经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、本科生和代表不足/少数群体的学生，向当地社区进行传播和外联。教育的总体目标是通过培训学生进行具有良好技术背景的研究并使他们能够为自己的高级职业获得动手实验室技能来帮助下一代劳动力的发展。技术摘要：拟议的项目旨在开发一种集成微芯片，首次能够研究单个神经元细胞在交流/经颅磁场刺激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细胞之间的相互作用。具体来说，本项目的重点是：(I)开发一种新的微芯片，该芯片由集成膜片钳探针的微支架阵列组成，用于存储单个神经元细胞；(Ii)研究单个神经元细胞(以n27细胞和PC12细胞为模型)在交流/经颅磁场刺激下的生长行为和动作电位监测；(Iii)模拟交流/经颅磁场刺激下三维细胞外基质内神经元细胞的生长行为；(4)在直流和交流/经颅磁场刺激下，用磁性纳米颗粒(MNPs)功能化神经元细胞来引导神经元生长的研究。这项研究可能有助于促进单个神经细胞在磁场刺激下生长和再生的基础知识，这可能从科学和工程的角度对再生医学领域产生重大影响。这个拟议的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的行为和它们之间的相互作用的能力。该平台的这些功能可能有助于触发一些基本的发现、一些重要的想法和生物医学应用的创新。

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.