The integrity of CaCo‐2 cell barriers is investigated by organic electrochemical transistors (OECTs) in a current‐driven configuration. Ion transport through cellular barriers via the paracellular pathway is modulated by tight junctions between adjacent cells. Rupturing its integrity by H2O2 is monitored by the change of the output voltage in the transfer characteristics. It is demonstrated that by operating the OECT in a current‐driven configuration, the sensitive and temporal resolution for monitoring the cell barrier integrity is strongly enhanced as compared to the OECT transient response measurement. As a result, current‐driven OECTs are useful tools to assess dynamic and critical changes in tight junctions, relevant for clinical applications as drug targeting and screening.

The barrier functionality of a cell layer regulates the passage of nutrients into the blood. Modulating the barrier functionality by external chemical agents like poly‐l‐lysine (PLL) is crucial for drug delivery. The ability of a cell layer to impede the passage of ions through it and therefore to act as a barrier, can be assessed electrically by measuring the resistance across the cell layer. Here, an organic electrochemical transistor (OECT) is used in a current‐driven configuration for the evaluation of reversible modulation of tight junctions in Caco‐2 cells over time. Exposure to low and medium concentrations of PLL initiates reversible modulation, whereas a too high concentration induces an irreversible barrier disruption due to nonfunctional tight junction proteins. The results demonstrate the suitability of OECTs to in situ monitor temporal barrier modulation and recovery, which can offer valuable information for drug delivery applications.

In this progress report an overview is given on the use of the organic electrochemical transistor (OECT) as a biosensor for impedance sensing of cell layers. The transient OECT current can be used to detect changes in the impedance of the cell layer, as shown by Jimison et al. To circumvent the application of a high gate bias and preventing electrolysis of the electrolyte, in case of small impedance variations, an alternative measuring technique based on an OECT in a current-driven configuration is developed. The ion-sensitivity is larger than 1200 mV V -1 dec -1 at low operating voltage. It can be even further enhanced using an OECT based complementary amplifier, which consists of a p-type and an n-type OECT connected in series, as known from digital electronics. The monitoring of cell layer integrity and irreversible disruption of barrier function with the current-driven OECT is demonstrated for an epithelial Caco-2 cell layer, showing the enhanced ion-sensitivity as compared to the standard OECT configuration. As a state-of-the-art application of the current-driven OECT, the in situ monitoring of reversible tight junction modulation under the effect of drug additives, like poly-l-lysine, is discussed. This shows its potential for in vitro and even in vivo toxicological and drug delivery studies.