An Automated Platform for High-throughput Network Electrophysiology

描述（由申请人提供）：为响应IIb期复杂体外大脑和行为工具提案的计划公告（PA-11-135），本拟议研究自动化了体外微电极阵列（MEA）技术的所有方面，以提供首个基于MEA的高通量筛选系统。这一发展不仅将使基础网络水平电生理学研究取得快速进展，而且还将为CNS疾病建模和表型筛选创造新的机会。该IIb期提案涉及神经学研究的两项重大进展，均建立在II期开发的商业化768通道多孔MEA系统上。具体而言，Aim 1使化合物给药和实验管理自动化，以产生用于给药神经培养物以及捕获、压缩和存储网络电生理数据集的交钥匙平台。在其众多优势中，该平台将恢复传统上被刺激伪影掩盖的信号。这种能力，再加上同时管理768个微电极和自动化实验方案的能力，将以无与伦比的速度捕获单细胞和网络级神经活动。此外，Aim 2将自动分析Aim 1开发所生成的大量连续数据跟踪，将大量原始数据集转化为有意义的指标，准确反映细胞网络之间的相互作用。最终，最终的MEA筛选平台将提供自动化液体处理，用户友好的实验工具和复杂的神经分析软件。对于科学家来说，这种整合将显著提高他们从神经培养物中提取功能信息的能力，为药物发现、安全性评估和基础科学的新进展铺平道路。

DESCRIPTION (provided by applicant): In response to the program announcement for Phase IIb proposals for complex, in-vitro brain and behavior tools (PA-11-135), this proposed study automates all aspects of in-vitro Microelectrode Array (MEA) technology to deliver the first ever high throughput MEA-based screening system. This development will not only enable rapid advancements in the study of basic network-level electrophysiology, but it will also create new opportunities for CNS disease modeling and phenotypic screening. This Phase IIb proposal involves two significant developments for neurological research, both building on the commercialized 768-channel multiwell MEA system developed in Phase II. Specifically, Aim 1 automates compound administration and experiment management to produce a turnkey platform for dosing neural culture as well as capturing, com- pressing, and storing network electrophysiological datasets. Among its many advantages, this platform will recover signals traditionally obscured by stimulation artifacts. This capability, combined with the ability to simultaneously manage 768 microelectrodes and automate experimental protocols, will capture single-cell and network-level neural activity at unparalleled rates. In addition, Aim 2 will automate the analysis of the immense volumes of continuous, data traces generated by the Aim 1 developments, translating massive raw datasets into meaningful metrics that accurately reflect the interactions between networks of cells. Ultimately, the final MEA screening platform will provide automated liquid handling, user-friendly experiment tools, and sophisticated neural analysis software. For scientists, this integration will significantly improve their ability to extact functional information from neural cultures; paving the way for new progress in drug discovery, safety assessment, and basic science.