A BBB-on-a-Chip for Ischemic Stroke Modeling: In Situ Multiparameter Monitoring with Integrated TEER and Ion Sensors

Ischemic stroke is a leading cause of death and disability worldwide, resulting in blood-brain barrier (BBB) disruption and ionic homeostasis imbalance. However, existing models lack the ability to simultaneously monitor BBB integrity and ionic homeostasis during ischemic stroke. Here, we developed a BBB-on-a-chip integrated with transendothelial electrical resistance (TEER) and ion sensors. With this chip, we constructed an in vitro BBB model and employed oxygen-glucose deprivation/reperfusion (OGD/R) to mimic ischemic stroke, with electrodes integrated into both sides enabling continuous in situ monitoring of TEER and extracellular K⁺. Experiments show that the model forms a high-integrity barrier under normal conditions, with the TEER value reaching 200.18 Ω·cm², confirming its physiological relevance. During OGD injury, TEER significantly decreased by 46.41%, while it partially recovered to about 73% of the control group after reperfusion. Simultaneous K⁺ monitoring showed that under normal conditions, the K⁺ concentration decreased; during the OGD, it increased sharply by about 23.8%, followed by a corresponding reduction after reperfusion. By integrating electrodes for multiparameter in situ detection, we revealed the dynamic relationship between BBB integrity and K⁺ concentration changes during the ischemic stroke process, providing a powerful tool for investigating the ischemic stroke pathological process and conducting drug screening.