A microfluidic platform with permeable walls for the analysis of vascular and extravascular mass transport

The interface between the blood pool and the extravascular matrix is fundamental in regulating the transport of molecules, nanoparticles and cells under physiological and pathological conditions. In this work, a microfluidic chip is presented comprising two parallel microchannels connected laterally via an array of high aspect ratio micropillars, constituting the permeable vascular membrane. A double-step lithographic process combined with a replica molding approach is employed to realize 80 different arrays of micropillars exhibiting three cross-sectional geometries (rectangular, elliptical and curved); two orientations (normal and parallel) with respect to the flow; and a variety of width and gap sizes, respectively, ranging from 10 to 20 μm and 2 to 5 μm. As compared to conventional rectangular structures, the curved pillars provide higher bending stiffness, lower adhesive interactions, and smaller intra-channel separation distances. Specifically, 10-μm-wide curved pillars, laying parallel to the flow, offered the highest mechanical stability. To assess vascular permeability, the extravascular channel was filled with a hyaluronic acid hydrogel, while fluorescent Dextran molecules and calibrated polystyrene beads were injected in the vascular channel. Membrane permeability was observed to reduce with the molecular weight of Dextran and diameter of the beads, ranging from about 6 × 10^?5 to 2 × 10^?5 cm/s for 40 and 250 kDa Dextran and up to zero for 1.5 μm beads. The presented data demonstrate the potential of the proposed microfluidic chip for analyzing the vascular and extravascular mass transport, over multiple spatial and temporal scales, in a variety of diseases involving differential permeation across vascular walls.