Microscale and miniscale fermentation and screening.

Small-scale bioreactors in the microliter and milliliter range gained more importance in recent years. For the characterization of mass transfer, the volumetric mass transfer coefficient kLa and the oxygen transfer rate OTRmax are considered. kLa values up to 1440 hour(-1) are reported for small-scale bioreactors. The OTRmax is strongly influenced by the liquid film thickness and, finally, by the liquid viscosity. Optical on-line methods, such as fluorescence and scattered light measurements, are applied to monitor pH, dissolved oxygen tension (DOT), product formation and biomass. Recently, single cell microfluidics are used to obtain new insights into microbial behavior at changing operating conditions. Finally, novel fed-batch techniques are applied to assimilate the cultivation conditions between screening and production scale.

[1]  J. Büchs,et al.  The role of volumetric power input in the growth, morphology, and production of a recombinant glycoprotein by Streptomyces lividans in shake flasks , 2014 .

[2]  Michael Raven,et al.  Consistent development of bioprocesses from microliter cultures to the industrial scale , 2013 .

[3]  J Büchs,et al.  Fed‐batch mode in shake flasks by slow‐release technique , 2006, Biotechnology and bioengineering.

[4]  F. Kensy,et al.  Automated microbioreactor systems for pharmaceutical bioprocessing: profiling of seeding and induction conditions in high-throughput fermentations , 2014 .

[5]  Wilfried Mokwa,et al.  Bioprocess Control in Microscale: Scalable Fermentations in Disposable and User-Friendly Microfluidic Systems , 2010, Microbial cell factories.

[6]  J. Büchs,et al.  Metabolic studies of γ-polyglutamic acid production in Bacillus licheniformis by small-scale continuous cultivations , 2013 .

[7]  Marco Oldiges,et al.  An automated workflow for enhancing microbial bioprocess optimization on a novel microbioreactor platform , 2012, Microbial Cell Factories.

[8]  C. Santschi,et al.  Absorbance enhancement in microplate wells for improved-sensitivity biosensors. , 2014, Biosensors & bioelectronics.

[9]  Nicolas Szita,et al.  Oxygen Transfer Characteristics of Miniaturized Bioreactor Systems , 2013, Biotechnology and bioengineering.

[10]  A. deMello,et al.  A Fully Unsupervised Compartment-on-Demand Platform for Precise Nanoliter Assays of Time-Dependent Steady-State Enzyme Kinetics and Inhibition , 2013, Analytical chemistry.

[11]  Wolfgang Wiechert,et al.  Single-cell microfluidics: opportunity for bioprocess development. , 2014, Current opinion in biotechnology.

[12]  Wolfgang Wiechert,et al.  A disposable picolitre bioreactor for cultivation and investigation of industrially relevant bacteria on the single cell level. , 2012, Lab on a chip.

[13]  P. Neubauer,et al.  Small-scale slow glucose feed cultivation of Pichia pastoris without repression of AOX1 promoter: towards high throughput cultivations , 2014, Bioprocess and Biosystems Engineering.

[14]  Mário A P Nunes,et al.  Microtiter plates versus stirred mini-bioreactors in biocatalysis: a scalable approach. , 2013, Bioresource technology.

[15]  František Foret,et al.  Recent advances in the development of single cell analysis--a review. , 2013, Analytica chimica acta.

[16]  Hongkai Wu,et al.  New materials for microfluidics in biology. , 2014, Current opinion in biotechnology.

[17]  Peter Neubauer,et al.  Microbial Cell Factories BioMed Central , 2008 .

[18]  D. Weuster‐Botz,et al.  New miniature stirred-tank bioreactors for parallel study of enzymatic biomass hydrolysis. , 2012, Bioresource technology.

[19]  Elmar Heinzle,et al.  A system of miniaturized stirred bioreactors for parallel continuous cultivation of yeast with online measurement of dissolved oxygen and off‐gas , 2013, Biotechnology and bioengineering.

[20]  N. Nguyena,et al.  Design , fabrication and characterization of drug delivery systems based on lab-ona-chip technology , 2013 .

[21]  Nam-Trung Nguyen,et al.  Design, fabrication and characterization of drug delivery systems based on lab-on-a-chip technology. , 2013, Advanced drug delivery reviews.

[22]  D. Beebe,et al.  The present and future role of microfluidics in biomedical research , 2014, Nature.

[23]  J. Büchs,et al.  Pitfalls in optical on-line monitoring for high-throughput screening of microbial systems , 2014, Microbial Cell Factories.

[24]  L. Poughon,et al.  A new stoichiometric miniaturization strategy for screening of industrial microbial strains: application to cellulase hyper-producing Trichoderma reesei strains , 2012, Microbial Cell Factories.

[25]  J. Büchs,et al.  Fed-batch operation in special microtiter plates: a new method for screening under production conditions , 2014, Journal of Industrial Microbiology & Biotechnology.

[26]  Jochen Büchs,et al.  Development of a modified Respiration Activity Monitoring System for accurate and highly resolved measurement of respiration activity in shake flask fermentations , 2012, Journal of biological engineering.

[27]  Uwe Marx,et al.  Monitoring and control of microbioreactors: an expert opinion on development needs. , 2012, Biotechnology journal.

[28]  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.

[29]  Beum Jun Kim,et al.  Batch, fed‐batch, and microcarrier cultures with CHO cell lines in a pressure‐cycle driven miniaturized bioreactor , 2012, Biotechnology and bioengineering.

[30]  Sven Hansen,et al.  Cross-section perimeter is a suitable parameter to describe the effects of different baffle geometries in shaken microtiter plates , 2014, Journal of biological engineering.

[32]  Francisco Valero,et al.  Comprehensive clone screening and evaluation of fed-batch strategies in a microbioreactor and lab scale stirred tank bioreactor system: application on Pichia pastoris producing Rhizopus oryzae lipase , 2014, Microbial Cell Factories.

[33]  J. Büchs,et al.  Improvement and scale-down of a Trichoderma reesei shake flask protocol to microtiter plates enables high-throughput screening. , 2014, Journal of bioscience and bioengineering.

[34]  A. Pacheco,et al.  Microplates as a microreactor platform for microalgae research , 2009, Biotechnology progress.

[35]  Gary J. Lye,et al.  Impact of aeration strategies on fed-batch cell culture kinetics in a single-use 24-well miniature bioreactor , 2014 .

[36]  G. Rao,et al.  Real‐time monitoring of shake flask fermentation and off gas using triple disposable noninvasive optical sensors , 2012, Biotechnology progress.

[37]  J. Büchs,et al.  Dialysis shake flask for effective screening in fed-batch mode , 2012 .

[38]  Anja Kuenz,et al.  Filamentous fungi in microtiter plates—an easy way to optimize itaconic acid production with Aspergillus terreus , 2014, Applied Microbiology and Biotechnology.

[39]  S. Tay,et al.  Microfluidic cell culture. , 2014, Current opinion in biotechnology.

[40]  H. Hailes,et al.  An automated microscale platform for evaluation and optimization of oxidative bioconversion processes , 2012, Biotechnology progress.

[41]  J. Büchs,et al.  Advances in shaking technologies. , 2012, Trends in biotechnology.

[42]  Wolfgang Kroutil,et al.  Minireactor-based high-throughput temperature profiling for the optimization of microbial and enzymatic processes , 2014, Journal of biological engineering.

[43]  Cyril P. Peter,et al.  Effective shear rates in shake flasks , 2014 .

[44]  N. Nguyen,et al.  Fabrication and Experimental Characterization of Nanochannels , 2012 .

[45]  J. Büchs,et al.  Scale-down of vinegar production into microtiter plates using a custom-made lid. , 2014, Journal of bioscience and bioengineering.

[46]  Karl-Erich Jaeger,et al.  Real-time determination of intracellular oxygen in bacteria using a genetically encoded FRET-based biosensor , 2012, BMC Biology.

[47]  Cyril P. Peter,et al.  Liquid films on shake flask walls explain increasing maximum oxygen transfer capacities with elevating viscosity , 2014, Biotechnology and bioengineering.

[48]  Michael L Shuler,et al.  Mini‐scale bioprocessing systems for highly parallel animal cell cultures , 2012, Biotechnology progress.

[49]  Robert Huber,et al.  Microbial Cell Factories Robo-lector – a Novel Platform for Automated High-throughput Cultivations in Microtiter Plates with High Information Content , 2022 .

[50]  J. Büchs,et al.  Time efficient way to calculate oxygen transfer areas and power input in cylindrical disposable shaken bioreactors , 2014, Biotechnology progress.