Beyond Transconductance: Cell-Polymer Coupling Determines Fidelity in Action Potential Recording via Electrolyte-Gated Polymer Transistors

Organic bioelectronic transistors emerged as powerful tools for probing cellular electrophysiology, offering biocompatibility, mechanical softness, and operational stability in biological environments. Despite these advantages, device benchmarking focused so far exclusively on electrical figures of merit, leaving interfacial processes that contribute to signal recording fidelity largely unexplored. Poly[2-(3,3′-bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-[2,2’-bithiophen]-5-yl)thieno[3,2-b]thiophene] (p(g2T-TT)) is a model glycolated organic mixed ionic-electronic conductor, whose high transconductance and optimal volumetric field-effect behavior in physiological environment have been widely documented in Organic Electrochemical Transistor (OECT) configurations. Thus, p(g2T-TT)-based OECT was assessed as a promising candidate for recording action potentials (APs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Surprisingly, although AP signal transduction was observed, the recorded AP waveforms failed to reproduce the expected morphology, especially when compared to signals recorded via poly(3-hexylthiophene-2,5-diyl) (P3HT)-based Electrolyte-Gated Field-Effect Transistors (EGOFETs). Immunofluorescence imaging revealed improved adhesion on P3HT with respect to p(g2T-TT), suggesting weaker cell-device coupling as the underlying limitation. Our results show that not all polymers combining biocompatibility and high electrical performance can transduce AP signals with high-fidelity. Instead, interfacial properties govern bioelectronic transduction and provide a foundation for the rational design of polymers and platforms enabling reliable in vitro cellular electrophysiology, with potential translation to in vivo applications.