A Scenario-Adaptive Microfluidic Chip for Constructing In Vitro Models of Biological Barriers.

Abstract

Microfluidic-based in vitro physiological barrier models are capable of simulating crucial environmental factors during barrier formation, including fluid shear and geometric-level cellular cocultures, thus offering enhanced physiological fidelity relative to conventional platforms. However, the sealed structure of microfluidic barrier chips faces challenges in characterizing and monitoring the barrier performance, especially in measuring transendothelial/epithelial electrical resistance (TEER). Here, we developed a microfluidic barrier chip that can be easily adapted to commercial TEER detectors. During the barrier construction phase, continuous perfusion culture was utilized to maintain a constant fluid shear stress; for barrier characterization, commercial resistance meters were employed to measure TEER directly. Using this chip, we successfully constructed an in vitro blood-brain barrier model with a TEER of approximately 220 Ω·cm², indicating high physiological relevance. This scenario-adaptive microfluidic chip demonstrates extensive potential for developing organ-on-a-chip models across various barrier systems, with significant implications for barrier characteristic monitoring and in situ cell sampling within the chip.