, Volume 42, Issue 1, pp 35-45

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

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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.

This revised version was published online in July 2006 with corrections to the Cover Date.