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

نویسندگان

  • Lucía D Garza-García
  • Erika García-López
  • Sergio Camacho-León
  • María Del Refugio Rocha-Pizaña
  • Felipe López-Pacheco
  • Julián López-Meza
  • Diana Araiz-Hernández
  • Eduardo J Tapia-Mejía
  • Grissel Trujillo-de Santiago
  • Ciro A Rodríguez-González
  • Mario Moisés Alvarez
چکیده

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.

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عنوان ژورنال:
  • Lab on a chip

دوره 14 7  شماره 

صفحات  -

تاریخ انتشار 2014