Abstract
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 H2 O2 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.
Highlights
The integrity of CaCo-2 cell barriers is investigated by organic electrochemical drug delivery for instance.[1,2] In the body, transistors (OECTs) in a current-driven configuration
As the epithelium consists of a packed monolayer cent cells as shown in Figure 1.[1,3] Loss or dysfunction of tight of cells, it provides a physical barrier to separate the organism junctions would lead to an uncontrolled passage of ions, macrofrom the external environment,[1] and several transport routes molecules, and other cells through the barrier, which might diswithin this barrier exist.[1,2]
The paracellular pathway is limited by specialized complexes the state of the cell barrier integrity acts as a precursor between adjacent cells, including the tight junctions.[1,2]
Summary
Recordings of organs in terms of electrically active tissues, to biosensing applications, as in the detection of electrolytes and metabolites or integration with cells.[9,11,12,13] In particular, using the OECT for assessing cell barrier integrity has been proven to be an attractive method in comparison to traditional techniques.[3,6,14,15] By integrating the OECT with epithelial cells, minute variations in paracellular ion flow, caused by toxic compounds, has been detected.[4,5,14] A further enhancement of the sensitivity level of the OECTs would enable real-time detection of the integrity of tight junctions during disease and treatment. It should be noted that one requirement for using the reference OECT method as a sensor for cell barrier integrity is the need to increase the effective cell layer resistance of the Transwell filter.[3,20] Expressed in an equivalent circuit, the integration of a cell layer is represented in an additional resistor Rcell (=TEER) and capacitor Ccell in parallel, which are connected in series with the capacitor of the channel CCP and the resistor of the electrolyte medium Rmed.[3,20] By decreasing the cell filter area with polydimethylsiloxane (PDMS), the effective cell layer resistance can be increased In this way, the change in resistance caused by the cell layer disruption is amplified and after all detectable. The current-driven OECT is a useful method to assess dynamic and critical changes in tight junctions, achieving a depth of information, useful for clinical applications as drug targeting and screening
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