Spontaneous Recording of Cardiomyocytes’ Action Potential by Electrolyte-Gated Field Effect Transistors: A Simple, Planar, Printed In-Vitro Platform for Cardiovascular Drugs Screening

In the context of cell-based biosensors, extensive endeavours have been dedicated to find accurate, in-vitro bioelectronic platforms capable of directly recording the electrical activity of electrogenic cells, namely neurons and cardiac cells, in a non-invasive way.<br/>The amplitude, shape and duration of the Action Potentials (APs) contain significant information on the viability of cells. These attributes, in turn, facilitate the exploration of cardiac pathologies and the impact of novel pharmaceutical products.<br/>To date, the available methodologies used to assess APs predominantly involve patch clamp techniques or complex 3D nanostructured electrodes, frequently combined with electro-/opto-poration, thereby rendering them very invasive in nature.<br/>To this end, the principal objective of this study is to propose a simple and cost-effective device able to record the electrical activity of <i>in-vitro</i> cell cultures in a non-detrimental manner.<br/>Within this research, we have accomplished for the first time the spontaneous recording of intracellular action potentials of human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) by direct plating or seeding of cells on top of the channel of our printed, planar Electrolyte-Gated Field Effect Transistor (EGFET).<br/>The EGFETs were fabricated employing carbon-based semiconductors via a simple and cost-efficient printing technique, aiming to facilitate large-scale production.<br/>The cardiac cells APs were obtained by simply recording the transistor current at a fixed gate voltage V_GS corresponding to the maximum transconductance. The natural APs of cardiomyocytes are able to change the effective gate voltage applied, which is transduced in a modulation of the source-to-drain current I_SDin our device. Remarkably, this modulation occurs without the need of any external stimuli.<br/>Our planar architecture was able to record signals with shape and duration comparable with patch clamp performed on the same batch of cells, confirming the fact that we recorded a major fraction of the intracellular action potentials (estimation in the range of 40-60 mV).<br/>The exceptional sensitivity of our device made it possible to detect the APs perturbations induced by the addition of different drugs targeting specific ion channels. The Action Potential Durations (APDs) recorded in our device exhibit close congruence with those attained with patch clamp techniques, thus positioning our platform as an ideal candidate for long-term monitoring of cardiac arrhythmias, chronic disease and the screening of cardiovascular drugs.<br/>The optimal EGFET-cell coupling enabled by our planar, printed, carbon-based semiconductors, reveals high stability and quality of the signal transduced, achieving excellent reproducibility over more than a hundred tested transistors.<br/>Such an high-throughput device is opening the path to deeper comprehension of fundamental transduction mechanisms at the bio-electronic interface and possesses the potential to be further developed into a future cost-effective diagnostic tool.