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

Lab Chip. 2014 Apr 7;14(7):1320-9. doi: 10.1039/c3lc51301g.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis*
  • Bioreactors*
  • CHO Cells
  • Cell Adhesion
  • Cell Proliferation*
  • Cricetinae
  • Cricetulus
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidic Analytical Techniques / methods*
  • Recombinant Proteins / biosynthesis*

Substances

  • Antibodies, Monoclonal
  • Recombinant Proteins