An Integrated and Modular Compartmentalized Microfluidic System with Tunable Electrospun Porous Membranes for Epithelialized Organs-on-a-Chip

Abstract

A modular and 3D compartmentalized microfluidic system with electrospun porous membranes (PMs) for epithelialized organ-on-a-chip systems is presented. Our novel approach involves direct deposition of polymer nanofibers onto a patterned poly(methyl methacrylate) (PMMA) substrate using electrospinning, resulting in an integrated PM within the microfluidic chip. The in situ deposition of the PM eliminates the need for additional assembly processes. To demonstrate the high throughput membrane integration capability of our approach, we successfully deposited nanofibers onto various chip designs with complex microfluidic planar structures and expanded dimensions. We characterized and tested the fully PMMA chip by growing an epithelial monolayer using the Caco-2 cell line to study drug permeability. A comprehensive analysis of the bulk and surface properties of the membrane's fibers made of PMMA and polystyrene (PS) was conducted to determine the polymer with the best performance for cell culture and drug transport applications. The PMMA-based membrane, with a PMMA/PVP ratio of 5:1, allowed for the fabrication of a uniform membrane structure along the aligned nanofibers. By modulating the fiber diameter and total thickness of the membrane, we could adjust the membrane's porosity for specific cell culture applications. The PMMA−PVP nanofibers exhibited a low polydispersity index value, indicating monodispersed nanofibers and a more homogeneous and uniform fiber network. Both types of membranes demonstrated excellent mechanical integrity under medium perfusion flow rates. However, the PMMA−PVP composition offered a tailored porous structure with modulable porosity based on the fiber diameter and thickness. Our developed platform enables dynamic in vitro modeling of the epithelial barrier and has applications in drug transport and in vitro microphysiological systems.