Monolithic 3-D Microfluidic Device for Cell Assay with an Integrated Combinatorial Mixer

We present a novel cell culture device with an integrated 3-D microfluidic mixer for screening the combinatorial effects of multiple compounds on cultured cells and demonstrated the ability to simultaneously treat arrays of cells with different combinations of compounds. The proof-of-concept chip, which has a three-input combinatorial mixer with eight micro culture chambers, was monolithically fabricated utilizing the surface micromaching of parylene C (poly-para-xylylene C). By having several microfluidic "overpasses" to allow one microfluidic channel to cross over other microfluidic channels, the combinatorial mixer was able to simultaneously generate all the combinations of the input fluidic streams for output to the micro chambers. We verified that parylene C is a biocompatible substrate for cell culturing and also showed cell culturing inside the micro culture chambers. The feasibility of using the integrated combinatorial mixer for cell assaying was demonstrated with experiments using three different cell stains, and results showed the cells in different chambers were stained with varying color patterns.