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Cell membranes are fundamental for cellular function as they protect the cell and control passage in and out of the cell. Despite their clear significance, cell membranes are often difficult to study, due to their complexity and the lack of available technologies to interface with them and transduce their functions. Overcoming this complexity by developing simple, reductionist models can facilitate their study. Indeed, lipid layers represent a simplified yet representative model for a cell membrane. Lipid layers are highly insulating, a property that is directly affected by changes in lipid packing or membrane fluidity. Such physical changes in the membrane models can be characterized by coupling them with an electronic transducer. Herein, a lipid monolayer that is stabilized between two immiscible solvents is integrated with an organic electrochemical transistor, which is capable of operating in a biphasic solvent mixture. The platform is used to evaluate how lidocaine, a widely used anesthetic the working mechanism of which is still a matter of debate, interacts with the cell membrane. The present study provides evidence that the anesthetic directly interacts with the lipids in the membrane, affecting their packing and therefore the monolayer permeability. The proposed platform provides an elegant solution for studying compound–membrane interactions.

Antibiotic discovery has experienced a severe slowdown in terms of discovery of new candidates. In vitro screening methods using phospholipids to model the bacterial membrane provide a route to identify molecules that specifically disrupt bacterial membranes causing cell death. Thanks to the electrically insulating properties of the major component of the cell membrane, phospholipids, electronic devices are highly suitable transducers of membrane disruption. The organic electrochemical transistor (OECT) is a highly sensitive ion‐to‐electron converter. Here, the OECT is used as a transducer of the permeability of a lipid monolayer (ML) at a liquid:liquid interface, designed to read out changes in ion flux caused by compounds that interact with, and disrupt, lipid assembly. This concept is illustrated using the well‐documented antibiotic Polymixin B and the highly sensitive quantitation of permeability of the lipid ML induced by two novel recently described antibacterial amine‐based oligothioetheramides is shown, highlighting molecular scale differences in their disruption capabilities. It is anticipated that this platform has the potential to play a role in front‐line antimicrobial compound design and characterization thanks to the compatibility of semiconductor microfabrication technology with high‐throughput readouts.