Microfluidic Gel Patterning Method by Use of a Temporary Membrane for Organ-On-Chip Applications

Organ-on-chip systems promise to be useful tools for disease modeling and drug testing. These systems focus on the separation of the parenchymal tissue from endothelial cells, which form the vasculature. Previous organ-on-chip models make use of artificial membranes to separate two fluidic channels representing the parenchymal and the endothelial side of native barriers. However, artificial membranes disallow close cell association. During this study, a microfluidic chip, in which a temporary chitosan-based membrane can be formed, is developed, making direct cell-cell contact between multiple cell types possible. This cell-cell contact on chip can be used to study the behavior of the blood-brain barrier. Chitosan is a polysaccharide that forms a gel-like solid upon deprotonation. By creating an interface between a basic buffer solution and an acidic chitosan solution, the chitosan gets deprotonated at the interface forming a membrane in the chip. This membrane can be used as a physical barrier for cell culture. 24 h after cell seeding, the temporary membrane of chitosan can be removed by flushing an acidic solution through one of the channels. The membrane fabrication and removal method demonstrated here can be used to create membrane-free cocultures in a microfluidic device for organs-on-chip research.