Physical and Life Science Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Engineering Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
Lab Chip. 2017 May 16;17(10):1732-1739. doi: 10.1039/c7lc00210f.
Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. Here we report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions and under drug stimuli. Human induced pluripotent stem cell-derived cardiomyocytes were cultured as a model system, and used to validate the platform with an excitation-contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. This platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.
目前用于体外药物开发的商业化心脏平台主要利用平面微电极阵列来绘制动作电位，或利用阻抗感应实时记录收缩，但不能在同一芯片上以高空间分辨率同时记录这两种功能。在这里，我们报告了一种新型的心脏平台，它可以在同一芯片上记录心脏组织黏附、电生理学和收缩性。该平台集成了两个独立但相互渗透的传感器阵列：用于场电位读出的微电极阵列和用于阻抗读出的叉指电极阵列。这些阵列共同提供了在生理条件下和药物刺激下实时、非侵入性的心电生理和收缩性数据采集。人诱导多能干细胞衍生的心肌细胞被培养为模型系统，并使用兴奋-收缩分离化学物质来验证该平台。将该平台用于研究药物去甲肾上腺素的作用的初步数据与计算工作相结合。该平台提供了一种定量和预测分析系统，有可能在药物发现过程的早期更全面地评估心脏毒性。
