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Fully automated single-use stirred-tank bioreactors for parallel microbial cultivations

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Abstract

Single-use stirred tank bioreactors on a 10-mL scale operated in a magnetic-inductive bioreaction block for 48 bioreactors were equipped with individual stirrer-speed tracing, as well as individual DO- and pH-monitoring and control. A Hall-effect sensor system was integrated into the bioreaction block to measure individually the changes in magnetic field density caused by the rotating permanent magnets. A restart of the magnetic inductive drive was initiated automatically each time a Hall-effect sensor indicates one non-rotating gas-inducing stirrer. Individual DO and pH were monitored online by measuring the fluorescence decay time of two chemical sensors immobilized at the bottom of each single-use bioreactor. Parallel DO measurements were shown to be very reliable and independently from the fermentation media applied in this study for the cultivation of Escherichia coli and Saccharomyces cerevisiae. The standard deviation of parallel pH measurements was pH 0.1 at pH 7.0 at the minimum and increased to a standard deviation of pH 0.2 at pH 6.0 or at pH 8.5 with the complex medium applied for fermentations with S. cerevisiae. Parallel pH-control was thus shown to be meaningful with a tolerance band around the pH set-point of ± pH 0.2 if the set-point is pH 6.0 or lower.

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References

  1. Balagadde FK, You L, Hansen CL, Arnold FH, Quake SR (2005) Long-Term monitoring of bacteria undergoing programmed population control in a microchemostat. Science 309:137–140

    Article  CAS  Google Scholar 

  2. Betts J, Doig S, Baganz F (2006) Characterization and application of a miniature 10 mL stirred-tank bioreactor, showing scale-down equivalence with a conventional 7 L reactor. Biotechnol Prog 22:681–688

    Article  CAS  Google Scholar 

  3. Boccazzi P, Zhang Z, Kurosawa K, Szita N, Bhattacharya S, Jensen K, Sinskey A (2006) Differential gene expression profiles and real-time measurements of growth parameters in Saccharomyces cerevisiae grown in microliter-scale bioreactors equipped with internal stirring. Biotechnol Prog 22:710–717

    Article  CAS  Google Scholar 

  4. Engelking H, Pfaller R, Wich G, Weuster-Botz D (2006) Reaction engineering studies on ß-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae. Enz Microb Technol 38:536–544

    Article  CAS  Google Scholar 

  5. Harms P, Kostov Y, French J, Soliman M, Anjanappa M, Ram A, Rao G (2006) Design and performance of a 24-station high throughput microbioreactor. Biotechnol Bioeng 93:6–13

    Article  CAS  Google Scholar 

  6. Knorr B, Schlieker H, Hohmann H-P, Weuster-Botz D (2007) Scale-down and parallel operation of the riboflavin production process with Bacillus subtilis. Biochem Eng J 33:263–274

    Article  CAS  Google Scholar 

  7. Kostov Y, Harms P, Randers-Eichhorn L, Rao G (2001) Low-cost microbioreactor for high-throughput bioprocessing. Biotechnol Bioeng 72:346–352

    Article  CAS  Google Scholar 

  8. Lamping SR, Zhang H, Allen B, Shamlou PA (2003) Design of a prototype miniature bioreactor for high throughput automated bioprocessing. Chem Eng Sci 58:747–758

    Article  CAS  Google Scholar 

  9. Lee H, Boccazzi P, Ram R, Sinskey A (2006) Microbioreactor arays with integrated mixers and fluid injectors for high-throughput experimentation with pH and dissolved oxygen control. Lab Chip 6:1229–1235

    Article  CAS  Google Scholar 

  10. Lee P, Hung P, Rao V, Lee L (2006) Nanoliter scale microbioreactor array for quantitative cell biology. Biotechnol Bioeng 94:5–14

    Article  CAS  Google Scholar 

  11. Link H, Weuster-Botz D (2006) Genetic algorithm for multi-objective experimental optimization. Bioprocess Biosyst Eng 29:385–390

    Article  CAS  Google Scholar 

  12. Puskeiler R, Kaufmann K, Weuster-Botz D (2005) Development, parallelization and automation of a gas-inducing milliliter-scale bioreactor for high-throughput bioprocess design (HTBD). Biotechnol Bioeng 89:512–523

    Article  CAS  Google Scholar 

  13. Puskeiler R, Kusterer A, John G, Weuster-Botz D (2005) Miniature bioreactors for automated high-throughput bioprocess design (HTBD): Reproducibility of parallel fed-batch cultivations with Escherichia coli. Biotechnol Appl Biochem 42:227–235

    Article  CAS  Google Scholar 

  14. Steinhaus B, Garcia ML, Shen AQ, Angenent LT (2007) A portable anaerobic microbioreactor reveals optimum growth conditions for the methanogen Methanosaeta concilii. Appl Environ Microbiol 73:1653–1658

    Article  CAS  Google Scholar 

  15. Szita N, Boccazzi P, Zhang Z, Boyle P, Sinskey AJ, Jensen KF (2005) Development of a multiplexed microbioreactor system for high-throughput bioprocessing. Lab Chip 5:819–826

    Article  CAS  Google Scholar 

  16. Tang Y, Laidlaw D, Gani K, Keasling J (2006) Evaluation of the effects of various culture conditions on Cr(VI) reduction by Shewanella oneidensis MR-1 in a novel high-throughput mini-bioreactor. Biotechnol Bioeng 95:174–184

    Article  Google Scholar 

  17. Vallejos J, Kostov Y, Ram A, French J, Marten M, Rao G (2006) Optical analysis of liquid mixing in a minibioreactor. Biotechnol Bioeng 93:906–911

    Article  CAS  Google Scholar 

  18. Weuster-Botz D, Puskeiler R, Kusterer A, Kaufmann K, John G, Arnold M (2005) Methods and milliliter scale devices for high-throughput bioprocess design. Bioproc Biosys Eng 28:109–119

    Article  CAS  Google Scholar 

  19. Zanzotto A, Boccazzi P, Gorret N, van Dyk T, Sinskey A, Jensen K (2006) In situ measurement of bioluminescence and fluorescence in an integrated microbioreactor. Biotechnol Bioeng 93:40–47

    Article  CAS  Google Scholar 

  20. Zhang Z, Boccazzi P, Choi H-G, Perozziello G, Sinskey A, Jensen K (2006) Microchemostat - microbial continuous culture in a polymer-based, instrumented microbioreactor. Lab Chip 6:906–913

    Article  CAS  Google Scholar 

  21. Zhang Z, Szia N, Boccazzi P, Sinskey A, Jensen K (2006) A well-mixed, polymer-based microbioreactor with integrated optical measurements. Biotechnol Bioeng 93:286–296

    Article  CAS  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge the financial support by the Deutsche Bundesstiftung Umwelt (AZ 13124) and the Consortium für elektrochemische Industrie GmbH for providing the recombinant Saccharomyces cerevisiae strain.

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Correspondence to Dirk Weuster-Botz.

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Kusterer, A., Krause, C., Kaufmann, K. et al. Fully automated single-use stirred-tank bioreactors for parallel microbial cultivations. Bioprocess Biosyst Eng 31, 207–215 (2008). https://doi.org/10.1007/s00449-007-0195-z

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  • DOI: https://doi.org/10.1007/s00449-007-0195-z

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