Potassium-Selective Nanoelectrode Arrays for Single-Cell Profiling of Human iPSC-Derived Cardiomyocytes

Abstract

Potassium ion (K+) dynamics are central to cardiac electrophysiology, with early disruptions in K+ flux often preceding arrhythmia and contractile dysfunction. However, current sensing technologies, such as patch-clamp, microelectrode arrays (MEAs), and fluorescent indicators, either lack chemical specificity for K+ or are unsuitable for long-term, single-cell analysis. Conventional ion-selective electrodes (ISEs), while more selective, are limited by bulk-phase design and poor spatial resolution. To address these limitations, we present KINESIS (K+-Ion Nano-Electrode Selective Interface System), a nanofabricated platform that enables direct, label-free potentiometric measurement of K+ gradients with single-cell precision. KINESIS features high-aspect-ratio nanopillars coated with a valinomycin-based K+ recognition membrane, forming a stable, noninvasive interface with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This architecture allows localized, Nernstian sensing of K+ efflux or depletion without disrupting cell membranes. Pharmacological validation shows distinct potential shifts in response to caffeine and ouabain. KINESIS thus offers a highly selective, spatially resolved approach for studying K+ handling in cardiotoxicity screening and patient-specific disease modeling.