Modular Integration of Impedance Sensing for Real-Time Assessment of Barrier Integrity

ABSTRACT Microphysiological systems (MPS) are essential for modeling tissue barriers, yet integrating electrical readouts often requires permanently sealed microfluidic architectures that limit access to open-well (direct-access) workflows used in bioscience laboratories. To resolve this issue, we present a modular approach in which functional components are added and removed from a standard MPS core using a magnetic interface. This design preserves compatibility with established open-well protocols for seeding and downstream analysis, while microfluidic perfusion or electrical sensing capabilities are added only when needed. We demonstrate this approach with an impedance-sensing module that enables continuous impedance measurements to assess barrier function. By fitting spectra to an equivalent circuit model, we quantify junctional and non-junctional electrical contributions to barrier integrity over time, alongside conventional single-frequency TEER, and complementary permeability and imaging readouts. We apply this platform across three representative use cases, including LPS-induced disruption, shear stress–mediated strengthening, and compatibility with barrier models formed above a 3D hydrogel matrix. Competing Interest Statement JLM is the co-founder of SiMPore, Inc. and holds an equity interest in the company. SiMPore is commercializing the ultrathin silicon-based technologies, including the membranes used in this study.