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Keywords:

  • miniature bioreactor;
  • predictive scale-up;
  • oxygen transfer;
  • power consumption;
  • high-throughput operation

Abstract

Miniature parallel bioreactors are becoming increasingly important as tools to facilitate rapid bioprocess design. Once the most promising strain and culture conditions have been identified a suitable scale-up basis needs to be established in order that the cell growth rates and product yields achieved in small scale optimization studies are maintained at larger scales. Recently we have reported on the design of a miniature stirred bioreactor system capable of parallel operation [Gill et al. (2008); Biochem Eng J 39:164–176]. In order to enable the predictive scale-up of miniature bioreactor results the current study describes a more detailed investigation of the bioreactor mixing and oxygen mass transfer characteristics and the creation of predictive engineering correlations useful for scale-up studies. A Power number of 3.5 for the miniature turbine impeller was first established based on experimental ungassed power consumption measurements. The variation of the measured gassed to ungassed power ratio, Pg/Pug, was then shown to be adequately predicted by existing correlations proposed by Cui et al. [Cui et al. (1996); Chem Eng Sci 51:2631–2636] and Mockel et al. [Mockel et al. (1990); Acta Biotechnol 10:215–224]. A correlation relating the measured oxygen mass transfer coefficient, kLa, to the gassed power per unit volume and superficial gas velocity was also established for the miniature bioreactor. Based on these correlations a series of scale-up studies at matched kLa (0.06–0.11 s−1) and Pg/V (657–2,960 W m−3) were performed for the batch growth of Escherichia coli TOP10 pQR239 using glycerol as a carbon source. Constant kLa was shown to be the most reliable basis for predictive scale-up of miniature bioreactor results to conventional laboratory scale. This gave good agreement in both cell growth and oxygen utilization kinetics over the range of kLa values investigated. The work described here thus gives further insight into the performance of the miniature bioreactor design and will aid its use as a tool for rapid fermentation process development. Biotechnol. Bioeng. 2008;100: 1144–1155. © 2008 Wiley Periodicals, Inc.