Review: Minibioreactors

The performance of currently available minibioreactors with volumes below about 100 ml is reviewed. Bioreactors are characterized by their area of application, by mass transfer and mixing characteristics and by their suitability for on-line monitoring and control. The review comprises shaken bioreactors such as shake-flasks, microtiter plates and test-tubes, stirred bioreactors including spinner-flasks for the cultivation of mammalian cells and various special reactors particularly involving on-line monitoring as e.g. membrane inlet mass spectrometry and NMR.

[1]  D Weuster-Botz,et al.  Parallel substrate feeding and pH-control in shaking-flasks. , 2001, Biochemical engineering journal.

[2]  E. Heinzle,et al.  Quantitative screening method for hydrolases in microplates using pH indicators: determination of kinetic parameters by dynamic pH monitoring. , 2001, Biotechnology and bioengineering.

[3]  J. Büchs,et al.  Mass transfer resistance of sterile plugs in shaking bioreactors. , 2001, Biochemical engineering journal.

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

[5]  Uwe Dingerdissen,et al.  Rapid Evaluation of Oxygen and Water Permeation through Microplate Sealing Tapes , 2003, Biotechnology progress.

[6]  P. H. Hemberger,et al.  Membrane introduction mass spectrometry: trends and applications. , 2000, Mass spectrometry reviews.

[7]  M. Gramer,et al.  Selection and isolation of cells for optimal growth in hollow fiber bioreactors. , 2000, Hybridoma.

[8]  M. Butler,et al.  Erythropoietin production from CHO cells grown by continuous culture in a fluidized-bed bioreactor. , 2002, Biotechnology and bioengineering.

[9]  H. Cha,et al.  Quantitative Monitoring for Secreted Production of Human Interleukin‐2 in Stable Insect Drosophila S2 Cells Using a Green Fluorescent Protein Fusion Partner , 2003, Biotechnology progress.

[10]  Elmar Heinzle,et al.  Measurement of oxygen uptake and carbon dioxide production rates ofmammalian cells using membrane mass spectrometry , 2004, Cytotechnology.

[11]  J Büchs,et al.  Introduction to advantages and problems of shaken cultures. , 2001, Biochemical engineering journal.

[12]  D. Weuster‐Botz,et al.  Process-engineering characterization of small-scale bubble columns for microbial process development , 2001 .

[13]  U Marx,et al.  Membrane-based cell culture systems--an alternative to in vivo production of monoclonal antibodies. , 1999, Developments in biological standardization.

[14]  Ingo Klimant,et al.  Integrated optical sensing of dissolved oxygen in microtiter plates: A novel tool for microbial cultivation , 2003, Biotechnology and bioengineering.

[15]  K. Jensen,et al.  Monitoring of Cell Growth, Oxygen and pH in Microfermentors , 2002 .

[16]  J Büchs,et al.  Power consumption in shaking flasks on rotary shaking machines: I. Power consumption measurement in unbaffled flasks at low liquid viscosity. , 2000, Biotechnology and bioengineering.

[17]  Robert Hermann,et al.  Methods for Intense Aeration, Growth, Storage, and Replication of Bacterial Strains in Microtiter Plates , 2000, Applied and Environmental Microbiology.

[18]  J. Ogbonna,et al.  Development of an apparatus for cultivation of anaerobic microorganisms , 1993 .

[19]  J Tramper,et al.  Optimization of a feed medium for fed-batch culture of insect cells using a genetic algorithm. , 2003, Biotechnology and bioengineering.

[20]  Hideo Tanaka,et al.  Influence of CO 2 ventilation on microbial cultivation in shake-flasks , 1998 .

[21]  B. Witholt,et al.  Effectiveness of orbital shaking for the aeration of suspended bacterial cultures in square-deepwell microtiter plates. , 2001, Biochemical engineering journal.

[22]  Ingo Klimant,et al.  PH-sensing 96-well microtitre plates for the characterization of acid production by dairy starter cultures. , 2003, The Journal of dairy research.

[23]  David T Stitt,et al.  Determination of growth rate of microorganisms in broth from oxygen-sensitive fluorescence plate reader measurements. , 2002, BioTechniques.

[24]  Christoph Wittmann,et al.  Dynamic calibration and dissolved gas analysis using membrane inlet mass spectrometry for the quantification of cell respiration. , 2003, Rapid communications in mass spectrometry : RCM.

[25]  C -M. Liu,et al.  Development of a shaking bioreactor system for animal cell cultures. , 2001, Biochemical engineering journal.

[26]  Dirk Weuster-Botz,et al.  Parallel-operated stirred-columns for microbial process development , 2002 .

[27]  E. Heinzle,et al.  Mass Spectrometry for On-line Monitoring of Biotechnological Processes , 1987, Biotechnology Methods.

[28]  C. Wittmann,et al.  Free intracellular amino acid pools during autonomous oscillations in Saccharomyces cerevisiae. , 2003, Biotechnology and bioengineering.

[29]  P. Gullino,et al.  Cell Culture on Artificial Capillaries: An Approach to Tissue Growth in vitro , 1972, Science.

[30]  A. Bunch,et al.  Hollow-fibre bioreactors compared to batch and chemostat culture for the production of a recombinant toxoid by a marine Vibrio , 1997, Applied Microbiology and Biotechnology.

[31]  M. Bushell,et al.  Effect of small scale culture vessel type on hyphal fragment size and erythromycin production in Saccharopolyspora erythraea , 1997, Biotechnology Letters.

[32]  Nakayama Gr.  Microplate assays for high-throughput screening. , 1998 .

[33]  H. J. Henzler,et al.  Suitability of the shaking flask for oxygen supply to microbiological cultures , 1991 .

[34]  B. Hammer,et al.  Effect of harvesting protocol on performance of a hollow fiber bioreactor. , 1999, Biotechnology and bioengineering.

[35]  R. Gross,et al.  Oxygen transfer rate and sophorose lipid production by Candida bombicola , 2002, Biotechnology and bioengineering.

[36]  F. Cerra,et al.  Gel-entrapment bioartificial liver therapy in galactosamine hepatitis. , 1995, The Journal of surgical research.

[37]  V. Bisaria,et al.  Optimization of culture parameters for production of podophyllotoxin in suspension culture of Podophyllum hexandrum , 2002, Applied biochemistry and biotechnology.

[38]  J. Merchuk,et al.  Polysaccharide production by plant cells in suspension: experiments and mathematical modeling. , 1998, Biotechnology and bioengineering.

[39]  R. Ohashi,et al.  A mini-scale mass production and separation system for secretory heterologous proteins by perfusion culture of recombinant Pichia pastoris using a shaken ceramic membrane flask. , 1999, Journal of bioscience and bioengineering.

[40]  M. Arroyo,et al.  Activation and Stabilization of Penicillin V Acylase from Streptomyces l avendulae in the Presence of Glycerol and Glycols , 2000, Biotechnology progress.

[41]  C. Wandrey,et al.  Evaluation of parallel operated small-scale bubble columns for microbial process development using Staphylococcus carnosus. , 2001, Journal of biotechnology.

[42]  F. Wurm,et al.  Small-scale bioreactor system for process development and optimization. , 2001, Biochemical engineering journal.

[43]  J. Büchs,et al.  Characterization of gas-liquid mass transfer phenomena in microtiter plates. , 2003, Biotechnology and bioengineering.

[44]  Ronald W. Davis,et al.  Functional profiling of the Saccharomyces cerevisiae genome , 2002, Nature.

[45]  John M Woodley,et al.  The use of microscale processing technologies for quantification of biocatalytic Baeyer-Villiger oxidation kinetics. , 2002, Biotechnology and bioengineering.

[46]  J Tramper,et al.  Metabolic-flux analysis of continuously cultured hybridoma cells using (13)CO(2) mass spectrometry in combination with (13)C-lactate nuclear magnetic resonance spectroscopy and metabolite balancing. , 2001, Biotechnology and bioengineering.

[47]  B. Bochner,et al.  Phenotype microarrays for high-throughput phenotypic testing and assay of gene function. , 2001, Genome research.

[48]  D. Hopwood.  Genetic manipulation of Streptomyces : a laboratory manual , 1985 .

[49]  Ingo Klimant,et al.  Modeling of Mixing in 96‐Well Microplates Observed with Fluorescence Indicators , 2002, Biotechnology progress.

[50]  R. Balcarcel,et al.  Metabolic Screening of Mammalian Cell Cultures Using Well‐Plates , 2003, Biotechnology progress.

[51]  J. Büchs,et al.  Characterisation of the gas-liquid mass transfer in shaking bioreactors. , 2001, Biochemical engineering journal.

[52]  G. Gilardi,et al.  High throughput assay for cytochrome P450 BM3 for screening libraries of substrates and combinatorial mutants. , 2002, Biosensors & bioelectronics.

[53]  Wouter A. Duetz,et al.  Oxygen transfer by orbital shaking of square vessels and deepwell microtiter plates of various dimensions , 2004 .

[54]  W M Miller,et al.  Stirred culture of peripheral and cord blood hematopoietic cells offers advantages over traditional static systems for clinically relevant applications. , 1998, Biotechnology and bioengineering.

[55]  D K Robinson,et al.  Industrial choices for protein production by large-scale cell culture. , 2001, Current opinion in biotechnology.

[56]  R. Larossa,et al.  A Miniature Bioreactor for Sensing Toxicity Using Recombinant Bioluminescent Escherichia coli Cells , 1996, Biotechnology progress.

[57]  Michael J Gramer,et al.  Antibody production by a hybridoma cell line at high cell density is limited by two independent mechanisms. , 2002, Biotechnology and bioengineering.

[58]  J Büchs,et al.  Out-of-phase operating conditions, a hitherto unknown phenomenon in shaking bioreactors. , 2001, Biochemical engineering journal.

[59]  Heinzle,et al.  Dynamic determination of anaerobic acetate kinetics using membrane mass spectrometry , 1998, Biotechnology and bioengineering.

[60]  James E. Bailey,et al.  Streptomycetes in micro-cultures: Growth, production of secondary metabolites, and storage and retrieval in the 96–well format , 2000, Antonie van Leeuwenhoek.

[61]  C. Wittmann,et al.  Application of MALDI-TOF MS to lysine-producing Corynebacterium glutamicum: a novel approach for metabolic flux analysis. , 2001, European journal of biochemistry.

[62]  Hideo Tanaka,et al.  Development of a novel box-shaped shake flask with efficient gas exchange capacity , 1998 .

[63]  H. Lehrach,et al.  Protein microarrays for gene expression and antibody screening. , 1999, Analytical biochemistry.

[64]  S. Giovannoni,et al.  High-Throughput Methods for Culturing Microorganisms in Very-Low-Nutrient Media Yield Diverse New Marine Isolates , 2002, Applied and Environmental Microbiology.

[65]  Christoph Wittmann,et al.  Metabolic network analysis of lysine producing Corynebacterium glutamicum at a miniaturized scale , 2004, Biotechnology and bioengineering.

[66]  Elmar Heinzle,et al.  Dynamic respiratory measurements of Corynebacterium glutamicum using membrane mass spectrometry , 2001 .

[67]  Francesco Vegliò,et al.  Empirical models for oxygen mass transfer: a comparison between shake flask and lab-scale fermentor and application to manganiferous ore bioleaching , 1998 .

[68]  Leah Tolosa,et al.  Noninvasive measurement of dissolved oxygen in shake flasks. , 2002, Biotechnology and bioengineering.

[69]  H. Fiebig,et al.  In vitro production of monoclonal antibodies in high concentration in a new and easy to handle modular minifermenter. , 1995, Journal of immunological methods.

[70]  Christoph Wittmann,et al.  Genealogy Profiling through Strain Improvement by Using Metabolic Network Analysis: Metabolic Flux Genealogy of Several Generations of Lysine-Producing Corynebacteria , 2002, Applied and Environmental Microbiology.

[71]  Christoph Wittmann,et al.  Characterization and application of an optical sensor for quantification of dissolved O2 in shake-flasks , 2003, Biotechnology Letters.