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

项目总结/摘要： 动作电位是跨细胞膜的电压的时间变化，其对于 神经元和心肌细胞等易兴奋细胞的生理功能。在人的心脏中， 动作电位协调数十亿心肌细胞的同步收缩和舒张。的 细胞内动作电位的波形反映了大量离子通道的协调，其中一些离子通道 受到药物的影响，共同促成了预防性风险。的波形 细胞内动作电位也反映了诸如心房、心室或类心肌细胞的亚型， 或其成熟状态。细胞内动作电位的测量主要由贴片进行 钳位技术，准确但侵入性强，一次一个细胞，费力，需要专业知识。 由于其低通量和侵入性，膜片钳不适用于药物筛选或功能性 人多能干细胞衍生的心肌细胞的表征。 在过去的十年里，垂直排列和固态纳米电极阵列（NEAs）已经成为有前途的 有可能从单层实现并行和微创心脏AP记录的工具 干细胞衍生的心肌细胞。然而，尽管取得了重大进展和浓厚的兴趣， 技术在很大程度上局限于开发技术的研究小组，而不是广泛地 被研究界采纳。我们确定了阻碍这一努力的若干关键挑战。在 通过学术实验室和创业公司之间的合作，我们的目标是克服 这些挑战，并开发一个强大的电生理工具，使可靠的，可扩展的，长期的， 心肌细胞内记录。该提案的目标是将NEA技术从 一种可能性的证明，以一种对最终用户有用的状态。

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.