title: Continuous flow micro-bioreactors for the production of biopharmaceuticals: the effect of geometry, surface texture, and flow rate.
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.
authors: Centro de Biotecnología-FEMSA, Tecnológico de Monterrey at Monterrey, Ave. Eugenio Garza-Sada 2501, Monterrey, N. L., México. Mario.alvarez@itesm.mx.
authors: Lucía D
authors: LD
authors: Garza-García
authors: Erika
authors: E
authors: García-López
authors: Sergio
authors: S
authors: Camacho-León
authors: María
authors: M
authors: Del Refugio Rocha-Pizaña
authors: Felipe
authors: F
authors: López-Pacheco
authors: Julián
authors: J
authors: López-Meza
authors: Diana
authors: D
authors: Araiz-Hernández
authors: Eduardo J
authors: EJ
authors: Tapia-Mejía
authors: Grissel
authors: G
authors: Trujillo-de Santiago
authors: Ciro A
authors: CA
authors: Rodríguez-González
authors: Mario Moisés
authors: MM
authors: Alvarez
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D019149:Bioreactors; D016466:CHO Cells; D002448:Cell Adhesion; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D011994:Recombinant Proteins / Q000096:biosynthesis*
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins