Microplate-reader Compatible Perfusion Microbioreactor Array for Modular Tissue Culture and Cytotoxicity Assays

One important application of tissue engineering is to provide novel in vitro models for cell-based assays. Perfusion microbioreactor array provides a useful tool for microscale tissue culture in parallel. However, high-throughput data generation has been a challenge. In this study, a 4 x 4 array of perfusion microbioreactors was developed for plate-reader compatible, time-series quantification of cell proliferation, and cytotoxicity assays. The device was built through multilayer soft lithography. Low-cost nonwoven polyethylene terephthalate fibrous matrices were integrated as modular tissue culture scaffolds. Human colon cancer HT-29 cells with stable expression of enhanced green fluorescent protein were cultured in the device with continuous perfusion and reached a cell density over 5 x 10(7) cells/mL. The microbioreactor array was used to test a chemotherapeutic drug 5-FU for its effect on HT-29 cells in continuous perfusion 3D culture. Compared with conventional 2D cytotoxicity assay, significant drug resistance was observed in the 3D perfusion culture.