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Issue 7, 2014
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Continuous flow micro-bioreactors for the production of biopharmaceuticals: the effect of geometry, surface texture, and flow rate

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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.

Graphical abstract: Continuous flow micro-bioreactors for the production of biopharmaceuticals: the effect of geometry, surface texture, and flow rate

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Supplementary files

Article information


Submitted
21 Nov 2013
Accepted
06 Jan 2014
First published
06 Jan 2014

Lab Chip, 2014,14, 1320-1329
Article type
Paper
Author version available

Continuous flow micro-bioreactors for the production of biopharmaceuticals: the effect of geometry, surface texture, and flow rate

L. D. Garza-García, E. García-López, S. Camacho-León, M. del Refugio Rocha-Pizaña, F. López-Pacheco, J. López-Meza, D. Araiz-Hernández, E. J. Tapia-Mejía, G. Trujillo-de Santiago, C. A. Rodríguez-González and M. M. Alvarez, Lab Chip, 2014, 14, 1320
DOI: 10.1039/C3LC51301G

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