A universal, multimodal cell-based biosensing platform for optimal intracellular action potential recording

Abstract

Intracellular recording of action potentials is an essential mean for studying disease mechanisms, and for electrophysiological studies, particularly in excitable cells as cardiomyocytes or neurons. Current strategies to obtain intracellular recordings include three-dimensional (3D) nanoelectrodes that can effectively penetrate the cell membrane and achieve high-quality intracellular recordings in a minimally invasive manner, or transient electroporation of the membrane that can yield temporary intracellular access. However, the former strategy requires a complicated and costly fabrication process, and the latter strategy suffers from high dependency on the method of application of electroporation, yielding inconsistent, suboptimal recordings. These factors hinder the high throughput use of these strategies in electrophysiological studies. In this work, we propose an advanced cell-based biosensing platform that relies on electroporation to produce consistent, high-quality intracellular recordings. The suggested universal system can be integrated with any electrode array, and it enables tunable electroporation with controllable pulse parameters, while the recorded potentials can be analyzed in real time to provide instantaneous feedback on the electroporation effectiveness. This integrated system enables the user to perform electroporation, record and assess the obtained signals in a facile manner, to ultimately achieve stable, reliable, intracellular recording. Moreover, the proposed platform relies on microelectrode arrays which are suited for large-scale production, and additional modules that are low-cost. Using this platform, we demonstrate the tuning of electroporation pulse width, pulse number, and amplitude, to achieve effective electroporation and high-quality intracellular recordings. This integrated platform has the potential to enable larger scale, repeatable, convenient, and low-cost electrophysiological studies.

Keywords: Cardiomyocytes; Integrated multimodal electroporation and evaluation; Intracellular electrophysiological recording; Microelectrode arrays.