Cytotechnology

, Volume 42, Issue 1, pp 35–45

Optimization and control of perfusion cultures using a viable cell probe and cell specific perfusion rates

  • Jason E. Dowd
  • Anthea Jubb
  • K. Ezra Kwok
  • James M. Piret
Article

DOI: 10.1023/A:1026192228471

Cite this article as:
Dowd, J.E., Jubb, A., Kwok, K.E. et al. Cytotechnology (2003) 42: 35. doi:10.1023/A:1026192228471

Abstract

Consistent perfusion culture production requires reliable cell retention and control of feed rates. An on-line cell probe based on capacitance was used to assay viable biomass concentrations. A constant cell specific perfusion rate controlled medium feed rates with a bioreactor cell concentration of ∼5 × 106 cells mL-1. Perfusion feeding was automatically adjusted based on the cell concentration signal from the on-line biomass sensor. Cell specific perfusion rates were varied over a range of 0.05 to 0.4 nL cell-1 day-1. Pseudo-steady-state bioreactor indices (concentrations, cellular rates and yields) were correlated to cell specific perfusion rates investigated to maximize recombinant protein production from a Chinese hamster ovary cell line. The tissue-type plasminogen activator concentration was maximized (∼40 mg L-1) at 0.2 nL cell-1 day-1. The volumetric protein productivity (∼60 mg L-1 day-1 was maximized above 0.3 nL cell-1 day-1. The use of cell specific perfusion rates provided a straightforward basis for controlling, modeling and optimizing perfusion cultures.

Cell specific perfusion feed rates CHO Control Optimization t-PA Viable cell probe 

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Jason E. Dowd
    • 1
    • 2
  • Anthea Jubb
    • 3
  • K. Ezra Kwok
    • 2
  • James M. Piret
    • 1
  1. 1.Biotechnology LaboratoryUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Chemical and BiologicalEngineering, University of British ColumbiaVancouverCanada
  3. 3.Process Development & ManufacturingINEX Pharmaceuticals CorporationBurnabyCanada