PDMS Micro-Fluidic Devices as Perfusion Bioreactors for the Culture of PC3 and CHO Cells

Continuous flow microdevices have been proposed as a flexible and convenient platform for the culture of mammalian cells for diagnostic, toxicological studies, tissue engineering and biopharmaceutical and biomedical screening applications. In this contribution, we compare the mammalian cell culture performance of different PDMS micro-reactor designs (zig-zag, spiral, and a series of micro-tank bioreactors). PC3 cells (a prostate cancer cell line widely used for screening of anti-cancer therapies), and CHO cells (the battle horse for production of glycosilated bio-pharmaceutics) were selected as relevant cell models. Continuous flows in the range of 0.1 to 5 µL/min were evaluated in each microdevice geometry. Particle Image velocimetry (PIV) and Computational Fluid Dynamics (CFD) were used to characterize the velocity field within the different bioreactor configurations. Results indicate that cell adhesion of PC3 cells occurs naturally in PDMS surfaces. After an incubation period of 48 hours, attached cells are able to grow and proliferate under continuous flows in the range of 0.1 to 5 µL/min. Similarly, a CHO cell line producer of a monoclonal antibody can be cultured in PDMS surfaces treated with a commercial attachment factor. Attached CHO cells are able to proliferate and produce monoclonal antibody under continuous flows in the range 0.1 to 5 µL/min. Cell density and specific productivity at the steady state are a function of the hydrodynamic conditions imposed by different geometries and flow field.