title: Optimization and control of perfusion cultures using a viable cell probe and cell specific perfusion rates.
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 approximately 5 x 10(6) 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 ( approximately 40 mg L(-1)) at 0.2 nL cell(-1) day(-1). The volumetric protein productivity ( approximately 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.
authors.affiliation: Biotechnology Laboratory, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Dowd
authors.forename: Anthea
authors.initials: A
authors.lastname: Jubb
authors.forename: K Ezra
authors.initials: KE
authors.lastname: Kwok
authors.forename: James M
authors.initials: JM
authors.lastname: Piret