A pumpless microfluidic co-culture system to model the effects of shear flow on biological barriers.

Abstract

Biological barriers formed by the endothelium and epithelium regulate nutrient exchange, disease development, and drug delivery. Organ-on-chip (OOC) systems effectively model these barriers by incorporating key biophysical cues like microscale dimensions, co-culture, and fluid flow-induced shear stress. The majority of microfluidic OOC platforms, however, require syringe and pump systems which are hindered by several limitations, including large footprints, elaborate designs, long setup times, and a high rate of failure (contamination, leakage, <i>etc.</i>). Here we describe VitroFlo, a pump-free microfluidic device designed for <i>in vitro</i> biological barrier modeling with 12 independent co-culture modules that can be simultaneously subjected to tunable, unidirectional flow with physiological shear stresses ranging from 0.01-10 dyn/cm². We demonstrate application of the device to model vascular endothelial, blood-brain, and intestinal epithelial barriers, and confirm shear stress-dependent cell alignment, tight junction protein expression, barrier maturation, permeability, and paracrine signaling between co-cultured cells. The VitroFlo platform enables scalable and cost-effective modeling of physiological barriers to facilitate the translation of findings from <i>in vitro</i> systems to preclinical models.