A Novel Soft Lithography Technique for Porous Membrane Fabrication as a Permeable Barrier in Gut- and Lung-on-Chip Devices

To mimic the epithelium-endothelium barrier in microfluidic devices, the fabrication of porous membranes through soft-lithography is a common option. Thus far, SU8 photoresist micropillars are the prevailing master molds. However, they suffer from the fragile behavior of pillars and need sophisticated clean room facility. To overcome these limitations, we developed a novel spin-coatable epoxy-based mold of micropillars. PDMS was spincoated on the epoxy mold of micropillars and peeled off after baking, thus obtaining stretchable porous membranes.
Both intestinal and lung epithelium cell lines were cultured in microchannels to validate the functionality of the porous membrane. Three different culture methods were tested: pump perfusion, tilting rocker perfusion, and steady. Confocal microscopy of the cellular epithelium represented faster monolayer formation, improved tight junction development and lower cell mortality in both perfusion conditions as compared to steady cultures. The medium perfusion led also to 3D morphogenesis of gut epithelium. The results could be explained by the shear stress and the continuous medium replenish provided by perfusion. In conclusion, the proposed technique represents a cost-effective alternative to traditional photolithography to achieve epithelial in vitro models.