In situ monitor l-Dopa permeability by integrating electrochemical sensor on the Blood-Brain Barrier chip

Abstract

Real-time monitoring the drugs penetration into brain is crucial for clinical therapy of neurodegenerative diseases. In this study, a Blood-Brain Barrier-electrochemical sensing (BBB-ES) platform combining BBB on chip model and electrochemical sensing system was proposed, which facilitated stable BBB growth under fluidic conditions and realized real-time detection of L-Dopa across the BBB. Based on this system, the effects of fluid force on the cell morphology, skeleton arrangement and tight junction protein ZO-1 of BBB growth were evaluated, it was verified that the fluid force promote cell rearrangement. Additionally, L-Dopa detecting performance was optimized by modifying SWNTs-AuNPs-PPy/Tyr(Single-Walled Carbon Nanotubes-Au Nanoparticles-Polypyrrole/Tyrosinase) on electrochemical electrode, which showed a wide linear response range of 10–500 μM and excellent selectivity toward L-Dopa. The integrated BBB-ES system was finally applied to real-time monitor the penetration process of L-Dopa through the BBB, it was proved that the penetration of L-Dopa increased with the increase of flow rate and time, and finding that L-Dopa was delivered by passive diffusion without disrupting the integrity of BBB. Based on these findings, the system can be used to monitor the real-time process of different drugs penetrating BBB and even different organ barriers, which also provide the possibility to solve the clinical demand for drugs screen.