A membrane’s blueprint: In silico investigation of fluid flow and molecular transport as a function of membrane design parameters in organ-on-a-chip

Abstract

Following the rapid growth of Organ-on-a-Chip (OoaC) technology, porous membranes have become essential components for in vitro tissue barrier models. Nonetheless, literature highlights lacking knowledge on their integration and effect on microfluidic devices. Therefore, we conducted finite element modelling (FEM) to characterize the influence of membrane, channel geometry, flow and diffusion parameters, in modelling flow rate, shear stress, transient transport and steady state molecular concentration. This analysis was performed for four different conditions based on single channel (SCP) and parallel perfusion (PP). It was found that membrane and geometry parameters are crucial in determining flow and shear for SCP. However, for PP, flow and shear are predominantly governed by the inlet flow rate. Although the transient behaviour is well-controlled within SCP and PP, only PP allows modelling the steady state concentration distribution. It is highlighted that: (1) the pore radius has great influence on flow and shear; (2) a shallow cell channel and a long membrane are capable of establishing different levels of shear on opposing surfaces of the same channel; (3) the membrane thickness, membrane length, height of the cell and flow channels, and inlet flow rate provide good control over transient transport; (4) the membrane length and inlet flow rate enable changing the concentration from a uniform distribution to a complete heterogeneous state across the device. Experimental assays were performed to support the FEM and evidence its significance for OoaC applications. Ultimately, extensive, and systematic guidelines are provided on designing future OoaC devices with integrated porous membranes.