abstract
- We used continuous flow micro-devices as bioreactors for the production of a glycosylated pharmaceutical product (a monoclonal antibody). We cultured CHO cells on the surface of PMMA/PDMS micro-channels that had been textured by micromachining and coated with fibronectin. Three different micro-channel geometries (a wavy channel, a zigzag channel, and a series of donut-shape reservoirs) were tested in a continuous flow regime in the range of 3 to 6 ¿L min-1. Both the geometry of the micro-device and the flow rate had a significant effect on cell adhesion, cell proliferation, and monoclonal antibody production. The most efficient configuration was a series of donut-shaped reservoirs, which yielded mAb concentrations of 7.2 mg L -1 at residence times lower than one minute and steady-state productivities above 9 mg mL-1 min-1. These rates are at about 3 orders of magnitude higher than those observed in suspended-cell stirred tank fed-batch bioreactors. © The Royal Society of Chemistry.