Journal
LAB ON A CHIP
Volume 14, Issue 7, Pages 1320-1329Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3lc51301g
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Funding
- Tecnologico de Monterrey [CAT-122]
- Laboratorios Landsteiner Scientific, Mexico
- CONACyT (Consejo Nacional de Ciencia y Tecnologia)
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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 mu 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.
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