用于心肌细胞并行和稳健的细胞内记录的纳米冠电极。

Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes.

机构信息

Department of Chemistry and Stanford Wu-Tsai Neuroscience Institute, Stanford University, Stanford, CA, 94305, USA.

Department of Nanoengineering, Jacobs school of Engineering, University of California, San Diego, CA, 92039, USA.

出版信息

Nat Commun. 2022 Apr 26;13(1):2253. doi: 10.1038/s41467-022-29726-2.

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.

药物性心脏毒性主要是由于化合物改变了心肌细胞的电生理特性。细胞内动作电位（iAP）的特征是预测致心律失常风险的有力生物标志物。在过去的十年中，已经有许多垂直纳米电极被证明可以实现平行和微创的 iAP 记录。然而，成功率和信号强度的巨大差异阻碍了纳米电极在心律失常药物评估中的广泛应用。在这项工作中，我们开发了垂直排列的纳米冠电极，该电极具有机械强度，通过电穿孔获得细胞内通道的成功率超过 99%。我们通过对同一细胞进行同时的膜片钳记录来验证纳米冠电极记录的准确性。最后，我们证明纳米冠电极能够实现 iAP 的长时间记录，从而可以在连续添加四种递增药物剂量时对同一细胞进行连续监测。我们的技术发展为建立用于临床前评估药物致心律失常性的 iAP 筛选检测方法提供了进展。