Mirroring Action Potentials: Label‐Free, Accurate, and Noninvasive Electrophysiological Recordings of Human‐Derived Cardiomyocytes

Abstract

The electrophysiological recording of action potentials in human cells is a long‐sought objective due to its pivotal importance in many disciplines. Among the developed techniques, invasiveness remains a common issue, causing cytotoxicity or altering unpredictably cell physiological response. In this work, a new approach for recording intracellular signals of outstanding quality and with noninvasiveness is introduced. By taking profit of the concept of mirror charge in classical electrodynamics, the new proposed device transduces cell ionic currents into mirror charges in a microfluidic chamber, thus realizing a virtual mirror cell. By monitoring mirror charge dynamics, it is possible to effectively record the action potentials fired by the cells. Since there is no need for accessing or interacting with the cells, the method is intrinsically noninvasive. In addition, being based on optical recording, it shows high spatial resolution and high parallelization. As shown through a set of experiments, the presented methodology is an ideal candidate for the next generation devices for the reliable assessment of cardiotoxicity on human‐derived cardiomyocytes. More generally, it paves the way toward a new family of in vitro biodevices that will lay a new milestone in the field of electrophysiology.

Biology-guided engineering of bioelectrical interfaces

“…Barbaglia et al demonstrate optical-based recording of cardiomyocytes using a device that mirrors ionic currents in a microfluidic chamber. 119 This advancement enables future in vivo devices and reliable determination of cardiac cell activities.…”

Advances in Cell-Conductive Polymer Biointerfaces and Role of the Plasma Membrane

“… 17 , 168 , 201 , 207 , 208 Furthermore, the biomimetic potential of mushroom-shaped electrodes has also been employed to guide and simultaneously record from HL-1 cells 209 and for optical detection of action potentials. 210 …”

“…The potential of pseudo-3D inorganic electrodes to induce PM local reshaping has found several applications in the electrophysiology field and inspired CP-based pseudo-3D platforms. In fact, the top rearrangement at the cell–material interface and the consequent reduction of the cleft guaranteed by biomimetic mushroom-shaped electrodes, allowed Hai et al to record “intracellular-like” signals from Aplysia buccal neurons, enabling the acquisition of attenuated action potentials and subthreshold synaptic potentials like those achieved with the patch clamp technique. ,,,, Furthermore, the biomimetic potential of mushroom-shaped electrodes has also been employed to guide and simultaneously record from HL-1 cells and for optical detection of action potentials …”

In-Cell Nanoelectronics: Opening the Door to Intracellular Electrophysiology

“…Electrical stimulation is an effective strategy to regulate cell activity and expression, its combination with nanoelectronics is exciting for applications in biomedical environments, such as pacemakers for precise stimulation and synchronous monitoring. Microfluidic is a promising technology that can be combined with nanoelectronics to achieve multifunctional delivery and signal monitoring [170][171][172]. Finally, integrating nanodevices into implantable devices for intracellular recording in vivo is an exciting challenge.…”