A Microelectrode-Integrated Perfusable Vessel-on-a-Chip Enabling Simultaneous Measurement of Transendothelial Electrical Resistance and Vascular Permeability

Abstract

Transendothelial electrical resistance (TEER) is a well-established method for evaluating tight junction integrity, providing real-time, non-invasive monitoring of barrier function. However, conventional TEER assays are largely restricted to 2D monolayer cultures and fail to capture the physiological complexity of 3D vascular structures. Here, we present a microfluidic platform that integrates gold-patterned electrodes on a glass substrate with a polydimethylsiloxane (PDMS)-based chip to enable simultaneous measurement of TEER and vascular permeability. Within this system, human endothelial cells undergo angiogenic self-assembly to form perfusable, lumenized microvessels that are maintained under standard culture conditions. Real-time impedance analysis using a precision LCR (Inductance, Capacitance, and Resistance) meter allows high-resolution monitoring of barrier resistance, while parallel quantification of FITC-dextran flux provides complementary permeability data. Impedance values obtained at optimized frequencies strongly correlate with paracellular tracer leakage, validating TEER as a robust functional readout in 3D vascular models. By coupling electrical and molecular assays in a physiologically relevant platform, our approach offers a scalable tool for real-time evaluation of endothelial function with broad applications in drug screening, disease modeling, and vascular biology research.