A novel multi-frequency trans-endothelial electrical resistance (MTEER) sensor array to monitor blood-brain barrier integrity

摘要

The blood-brain barrier (BBB) is a dynamic cellular barrier that regulates brain nutrient supply, waste efflux, and paracellular diffusion through specialized junctional complexes. Finding a system to mimic and monitor BBB integrity (i.e., to be able to assess the effect of certain compounds on opening or closing the barrier) is of vital importance in several pathologies. This work aims to overcome some limitations of current barrier integrity measuring techniques thanks to a multi-layer microfluidic platform with integrated electrodes and Multi-frequency Trans-Endothelial Electrical Resistance (MTEER) in synergy with machine learning algorithms. MTEER measurements are performed across the barrier in a range of frequencies up to 10 MHz highlighting the presence of information on different frequency ranges. Results show that the proposed platform can detect barrier formation, opening, and regeneration afterwards, correlating with the results obtained from immuno-staining of junctional complexes. This model presents novel techniques for a future biological barrier in-vitro studies that could potentially help on elucidating barrier opening or sealing on treatments with different drugs.