A Versatile and Modular Microfluidic System for Dynamic Cell Culture and Cellular Interactions.

A versatile and modular microfluidic system for cell co-culture has been developed. Microfluidic chips, each featuring dual compartments separated by a porous membrane, have been fabricated and assembled within the system to facilitate fluidic interconnection and cell-cell communication through the chip assembly. A set of fluidic valves has been successfully integrated to regulate the flow through the chip assembly. The system allows for chip assembly in various arrangements, including in parallel, in series, and complex connections. Individual chips can be interconnected or disconnected within the system at any time. Moreover, the spatial order and orientation of the chips can be adjusted as needed, enabling the study of different cell-cell arrangements and the impact of the presence or absence of specific cell types. The utility of the system has been evaluated by culturing and interconnecting multi-monolayers of intestinal epithelial cells as a model of the complex cellular system. Epithelial monolayers were grown in multiple chips and interconnected in various configurations. The transepithelial electrical resistance and permeability profiles were investigated in detail for these configurations upon treatment of the cells with dextran sulfate sodium. Immune cells were stimulated through the epithelial layers and the expression of inflammatory cytokines was detected. This miniaturized platform offers controlled conditions for co-culturing key cellular components and assessing potential therapeutic agents in a physiologically relevant setting.