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

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.

[1]  Dirk Weuster-Botz,et al.  Methods and milliliter scale devices for high-throughput bioprocess design , 2005, Bioprocess and biosystems engineering.

[2]  Yinjie J. Tang,et al.  Evaluation of the effects of various culture conditions on Cr(VI) reduction by Shewanella oneidensis MR‐1 in a novel high‐throughput mini‐bioreactor , 2006, Biotechnology and bioengineering.

[3]  Nicolas Szita,et al.  A well‐mixed, polymer‐based microbioreactor with integrated optical measurements , 2006, Biotechnology and bioengineering.

[4]  B Allen,et al.  Design of a prototype miniature bioreactor for high throughput automated bioprocessing , 2003 .

[5]  Harry L. T. Lee,et al.  Microbioreactor arrays with integrated mixers and fluid injectors for high-throughput experimentation with pH and dissolved oxygen control. , 2006, Lab on a chip.

[6]  Nicolas Szita,et al.  Development of a multiplexed microbioreactor system for high-throughput bioprocessing. , 2005, Lab on a chip.

[7]  K. Jensen,et al.  Differential Gene Expression Profiles and Real‐Time Measurements of Growth Parameters in Saccharomyces cerevisiae Grown in Microliter‐Scale Bioreactors Equipped with Internal Stirring , 2006, Biotechnology progress.

[8]  Dirk Weuster-Botz,et al.  Scale-down and parallel operation of the riboflavin production process with Bacillus subtilis , 2007 .

[9]  Dirk Weuster-Botz,et al.  Methods and milliliter scale devices for high-throughput bioprocess design , 2005, Bioprocess and biosystems engineering.

[10]  Luke P. Lee,et al.  Nanoliter scale microbioreactor array for quantitative cell biology , 2006, Biotechnology and bioengineering.

[11]  Dirk Weuster-Botz,et al.  Miniature bioreactors for automated high‐throughput bioprocess design (HTBD): reproducibility of parallel fed‐batch cultivations with Escherichia coli , 2005, Biotechnology and applied biochemistry.

[12]  Dirk Weuster-Botz,et al.  Genetic algorithm for multi-objective experimental optimization , 2006, Bioprocess and biosystems engineering.

[13]  S. Quake,et al.  Long-Term Monitoring of Bacteria Undergoing Programmed Population Control in a Microchemostat , 2005, Science.

[14]  Amy Q. Shen,et al.  A Portable Anaerobic Microbioreactor Reveals Optimum Growth Conditions for the Methanogen Methanosaeta concilii , 2007, Applied and Environmental Microbiology.

[15]  Jonathan I. Betts,et al.  Characterization and Application of a Miniature 10 mL Stirred‐Tank Bioreactor, Showing Scale‐Down Equivalence with a Conventional 7 L Reactor , 2006, Biotechnology progress.

[16]  Gerardo Perozziello,et al.  Microchemostat-microbial continuous culture in a polymer-based, instrumented microbioreactor. , 2006, Lab on a chip.

[17]  G. Rao,et al.  Low-cost microbioreactor for high-throughput bioprocessing. , 2001, Biotechnology and bioengineering.

[18]  Yordan Kostov,et al.  Design and performance of a 24‐station high throughput microbioreactor , 2006, Biotechnology and bioengineering.

[19]  D. Weuster‐Botz,et al.  Reaction engineering studies on β-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae , 2006 .

[20]  K. Jensen,et al.  In situ measurement of bioluminescence and fluorescence in an integrated microbioreactor. , 2006, Biotechnology and bioengineering.

[21]  Mark R. Marten,et al.  Optical analysis of liquid mixing in a minibioreactor , 2006, Biotechnology and bioengineering.

[22]  D Weuster-Botz,et al.  Development, parallelization, and automation of a gas-inducing milliliter-scale bioreactor for high-throughput bioprocess design (HTBD). , 2005, Biotechnology and bioengineering.