A Low Shear Stress Modular Bioreactor for Connected Cell Culture Under High Flow Rates

A generic "system on a plate" modular multi-compartmental bioreactor array which enables microwell protocols to be transferred directly to the bioreactor modules, without redesign of cell culture experiments or protocols is described. The modular bioreactors are simple to assemble and use and can be easily compared with standard controls since cell numbers and medium volumes are quite similar. Starting from fluid dynamic and mass transport considerations, a modular bioreactor chamber was first modeled and then fabricated using "milli-molding," a technique adapted from soft lithography. After confirming that the shear stress was extremely low in the system in the range of useful flow rates, the bioreactor chambers were tested using hepatocytes. The results show that the bioreactor chambers can increase or maintain cell viability and function when the flow rates are below 500 mu L/min, corresponding to wall shear stresses of 10(-5) Pa or less at the cell culture surface. Biotechnol. Bioeng. 2010;106: 127-137. (C) 2010 Wiley Periodicals, Inc.