An electrophysiology platform that enables robust, scalable and long-term intracellular recording of cardiomyocytes

项目摘要/摘要： 动作电位是跨过细胞膜的电压的时间变化，这对 兴奋性细胞的生理功能，如神经元和心肌细胞。在人类的心脏中，心脏 动作电位协调着数十亿个心肌细胞的同步收缩和松弛。这个 细胞内动作电位的波形反映了多种离子通道的协调，其中一些 受到药物影响的人共同增加了心律失常的风险。波形图 细胞内动作电位也反映了亚型，如房型、室型或结节型心肌细胞， 或者他们的成熟状态。细胞内动作电位的测量主要由贴片完成。 钳夹技术，准确但有创，一次一个细胞，费力，需要专门的专业知识。 由于其低吞吐量和侵入性，膜片钳不适合用于药物筛选或功能性药物筛选 人多能干细胞来源的心肌细胞的特性。 在过去的十年里，垂直排列的固态纳米电极阵列(NEA)被认为是很有前途的 具有从单层实现可并行化和微创心脏AP记录的潜力的工具 干细胞来源的心肌细胞。然而，尽管取得了重大进展和强烈的兴趣，国家能源局 技术在很大程度上局限于开发技术的研究小组，而不是广泛的 被研究界采纳。我们确定了阻碍这一努力的几个关键挑战。在……里面 这项提议，通过一个学术实验室和一家初创公司的合作，我们的目标是克服 并开发一种强大的电生理工具，以实现可靠、可扩展和长期的 心肌细胞的细胞内记录。该提案的目标是将NEA技术从 展示一种对最终用户有用的状态的可能性。

PROJECT SUMMARY/ABSTRACT: Action potentials are temporal changes of the electrical voltage across the cell membrane, which are crucial for the physiological function of excitable cells such as neurons and cardiomyocytes. In the human heart, cardiac action potentials coordinate the synchronous contraction and relaxation of billions of cardiomyocytes. The waveforms of intracellular action potentials reflect the coordination of a multitude of ion channels, some of which are affected by pharmaceutical drugs to collectively contribute toward proarrhythmic risks. The waveforms of intracellular action potentials also reflect the subtype such as atrial-, ventricular-, or nodal-like cardiomyocytes, or their maturation status. Measurements of intracellular action potentials are mostly performed by the patch clamp technique, which is accurate but invasive, one cell at a time, laborious, and requires specialized expertise. Due to its low throughput and invasive nature, patch clamp is not suitable for drug screening or functional characterization of human pluripotent stem cell derived cardiomyocytes. In the last decade, vertically-aligned and solid-state nanoelectrode arrays (NEAs) have emerged as promising tools with the potential of achieving parallelizable and minimally invasive cardiac AP recording from monolayers of stem-cell-derived cardiomyocytes. However, despite the significant progress and the strong interest, the NEA technology has largely been confined to research groups that develop the technologies, instead of being broadly adopted by the research community. We identified several critical challenges that have hindered such effort. In this proposal, through the partnership between an academic lab and a startup company, we aim to overcome these challenges and develop a robust electrophysiological tool that enables reliable, scalable, and long-term intracellular recording of cardiomyocytes. The goal of this proposal aims to transition the NEA technology from a demonstration of possibility to a status useful to end-users.