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 µL 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.
Subject(s)
Antibodies, Monoclonal/biosynthesis , Bioreactors , Cell Proliferation , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Recombinant Proteins/biosynthesis , Animals , CHO Cells , Cell Adhesion , Cricetinae , CricetulusABSTRACT
We report a proof-of-principle for the use of micro-devices as continuous bioreactors for the production of monoclonal antibodies. We culture CHO cells on the surface of PMMA "zigzag" channels textured with semi-spherical cavities coated with fibronectin, observing steady-state productivities 100 times higher than those observed in full scale systems.
