Ulrike Maier

RWTH Aachen University, Aachen, North Rhine-Westphalia, Germany

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Publications (8)24.69 Total impact

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    ABSTRACT: Screening projects in biotechnological industry performed in shake flasks risk unwanted development if not failure, when operating conditions are not suitable. Limited knowledge, however, is available for the mechanistical design of operating conditions in this type of bioreactor. The fundamental engineering variables are influenced by the geometry of the rotating bulk liquid: for momentum transfer, the contact area between the liquid and the flask inner wall is the friction area, and for mass transfer, the wetted wall exposed to the surrounding air is the mass exchange area. To assess the geometry of the rotating bulk liquid moving inside a shaken Erlenmeyer flask, with respect to the mentioned important engineering variables mentioned, a mechanistical model for the liquid distribution in shake flasks is described in this work. The model is based on a superposition of two individual movements: a circular translatoric movement and a rotation of the flask counteracting the first motion to keep the shake flasks’ spatial orientation. If the effect of viscosity is neglected, the liquid distribution results in an exactly symmetrical paraboloid. A comparison of the calculated liquid distribution with photographs shows very good qualitative agreement of the real liquid distributions by the model equations. Quantitative agreement has been demonstrated by comparison of the liquid height. Furthermore, model equations are presented for the calculation of the contact area between the liquid and the flask wall. This may eventually lead to a prediction of the volumetric power consumption. Similarly, the calculation of the mass transfer area (i.e. liquid surface area and wetted flask wall) is presented.
    No preview · Article · Jun 2007 · Biochemical Engineering Journal
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    Ulrike Maier · Mario Losen · Jochen Büchs
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    ABSTRACT: The gas–liquid mass transfer in 250 ml shake flasks has previously been sucessfully modelled on basis of Higbie’s penetration theory. The current contribution presents advances in understanding and modelling the gas–liquid mass transfer in shake flasks at waterlike liquid viscosity in flask sizes between 50 and 1000 ml. An experimental investigation of the maximum gas–liquid mass transfer capacity OTRmax using the sodium sulphite system was extended to relative filling volumes of 4–16%, shaking diameters of 1.25, 2.5, 5, 7, 10 cm and shaking frequencies of 50–500 rpm for the above flask sizes. Simultaneously, the previous model of the gas–liquid mass transfer was extended to a “two sub-reactor model” to account for different mechanisms of mass transfer in the liquid film on the flask wall and the bulk of the liquid rotating within the flask. The shake flask is for the first time considered to be a two-reactor system consisting of a stirred tank reactor (bulk liquid) and a film reactor (film on flask wall and base). The mass transfer into the film on the flask wall and base at “in-phase” operating conditions is described by Higbie’s penetration theory. Two different mass transfer theories were applied to successfully describe the mass transfer into the bulk liquid: a model by Kawase and Moo-Young and a model by Gnielinski. The agreement between the new modelling approach, which requires absolutely no fitting parameters and the experimental is within ±30%. The applicability of the models to a biological system was shown using a Pichia pastoris culture. This is particularly notable since geometrically non-similar liquid distributions in very different sizes of shaking flasks are covered. A comparable description of the gas–liquid mass transfer in bubble aerated reactors like stirred tanks is absolutely out of reach. A spatially- and time-resolved consideration of the mass transfer in the liquid film on the flask wall and base has shown that the validity of Higbie’s theory sensitively depends on the film thickness and contact time.
    Full-text · Article · Mar 2004 · Biochemical Engineering Journal
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    Cyril P. Peter · Stefan Lotter · Ulrike Maier · J Büchs
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    ABSTRACT: Screening projects dealing with filamentous microorganisms in shaking flaks may generate strains showing a less filamentous morphology with a decreased apparent viscosity of the fermentation broth. The apparent viscosity of the fermentation broths showing pseudo-plastic flow behavior can be calculated by known relations, if the average shear rate is known. A method is presented allowing the determination of the relevant average shear rate, and thus, apparent viscosity of the fermentation broth at given operating conditions of the shaking flask experiment. At elevated apparent viscosity, shaking flask fermentations are subject to the recently discovered out-of-phase conditions. Measurements of the oxygen transfer capacity (OTR max) in a highly viscous fluid have clearly shown reduced mass transfer, and therefore a reduced productivity of the investigated strains, when out-of-phase conditions are present. This leads to a selection pressure preferring a less filamentous morphology accompanied by lower apparent viscosity in screening projects in shaking flasks. In two completely different cases, the apparent broth viscosity of several consecutive strain generations was investigated. The later strain generation showed a lower apparent broth viscosity compared to the predecessor strain. In a third case, it was shown that out-of-phase conditions prevent the development of an improved culture medium.
    Preview · Article · Mar 2004 · Biochemical Engineering Journal
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    ABSTRACT: Screening cultures are usually non-monitored and non-controlled due to a lack of appropriate measuring techniques. A new device for online measurement of oxygen transfer rate (OTR) in shaking-flask cultures was used for monitoring the screening of Hansenula polymorpha. A shaking frequency of 300 rpm and a filling volume of 20 ml in 250-ml flasks ensured a sufficient oxygen transfer capacity of 0.032 mol (l h)(-1) and thus a respiration not limited by oxygen. Medium buffered with 0.01 mol phosphate l(-1) (pH 6.0) resulted in pH-inhibited respiration, whereas buffering with 0.12 mol phosphate l(-1) (pH 4.1) resulted in respiration that was not inhibited by pH. The ammonium demand was balanced by establishing fixed relations between oxygen, ammonium, and glycerol consumption with 0.245+/-0.015 mol ammonium per mol glycerol. Plate precultures with complex glucose medium reduced the specific growth rate coefficient to 0.18 h(-1) in subsequent cultures with minimal glycerol medium. The specific growth rate coefficient increased to 0.26 h(-1) when exponentially growing precultures with minimal glycerol medium were used for inoculation. Changes in biomass, glycerol, ammonium, and pH over time were simulated on the basis of oxygen consumption.
    No preview · Article · Nov 2003 · Journal of Industrial Microbiology and Biotechnology
  • Robert Hermann · Nico Walther · Ulrike Maier · Jochen Büchs
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    ABSTRACT: The growth of microorganisms may be limited by operating conditions which provide an inadequate supply of oxygen. To determine the oxygen-transfer capacities of small-scale bioreactors such as shaking flasks, test tubes, and microtiter plates, a noninvasive easy-to-use optical method based on sulfite oxidation has been developed. The model system of sodium sulfite was first optimized in shaking-flask experiments for this special application. The reaction conditions (pH, buffer, and catalyst concentration) were adjusted to obtain a constant oxygen transfer rate for the whole period of the sulfite oxidation reaction. The sharp decrease of the pH at the end of the oxidation, which is typical for this reaction, is visualized by adding a pH dye and used to measure the length of the reaction period. The oxygen-transfer capacity can then be calculated by the oxygen consumed during the complete stoichiometric transformation of sodium sulfite and the visually determined reaction time. The suitability of this optical measuring method for the determination of oxygen-transfer capacities in small-scale bioreactors was confirmed with an independent physical method applying an oxygen electrode. The correlation factor for the maximum oxygen-transfer capacity between the chemical model system and a culture of Pseudomonas putida CA-3 was determined in shaking flasks. The newly developed optical measuring method was finally used for the determination of oxygen-transfer capacities of different types of transparent small-scale bioreactors.
    No preview · Article · Oct 2001 · Biotechnology and Bioengineering
  • Ulrike Maier · Jochen Büchs
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    ABSTRACT: The maximum gas-liquid mass transfer capacity of 250ml shaking flasks on orbital shaking machines has been experimentally investigated using the sulphite oxidation method under variation of the shaking frequency, shaking diameter, filling volume and viscosity of the medium. The distribution of the liquid within the flask has been modelled by the intersection between the rotational hyperboloid of the liquid and the inner wall of the shaking flask. This model allows for the calculation of the specific exchange area (a), the mass transfer coefficient (k(L)) and the maximum oxygen transfer capacity (OTR(max)) for given operating conditions and requires no fitting parameters. The model agrees well with the experimental results. It was furthermore shown that the liquid film on the flask wall contributes significantly to the specific mass transfer area (a) and to the oxygen transfer rate (OTR).
    No preview · Article · Apr 2001 · Biochemical Engineering Journal
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    ABSTRACT: In this first article of a series a new method is introduced that enables the accurate determination of the power consumption in a shaking flask. The method is based on torque measurements in the drive and appropriate compensation of the friction losses. The results for unbaffled shaking flasks at low viscosities are presented after varying shaking frequency, flask size, filling volume, shaking diameter, and surface quality (hydrophilic and hydrophobic) of the inner flask walls. The order of magnitude of the values of power consumption in shaking flasks is equal to, or even higher than, the values typical for agitated tank bioreactors. A physically based model equation for shaking flasks is derived that introduces a modified power number and a resulting constant as the only fitting parameter. With this equation, the measured results are correlated with sufficient accuracy. For the first time, comprehensive data for the power consumption in unbaffled shaking flasks at low viscosity is available, giving a detailed picture of the influences of the different variables.
    No preview · Article · Jul 2000 · Biotechnology and Bioengineering
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    ABSTRACT: This article is the second part of a series presenting and modeling the hydrodynamics and specific power consumption in shaking flasks on rotary (orbital) shaking machines. In part I, a new method was introduced that enables the accurate determination of the specific power consumption in shaking flasks. The method was first applied to investigate unbaffled flasks with a nominal volume of < or =1 L at low viscosity. In part II, the results for the specific power consumption of unbaffled shaking flasks at elevated viscosities are investigated after varying shaking frequency, flask size, filling volume, and shaking diameter. The theory introduced in part I is extended to liquids of elevated viscosities using nondimensional equations. With these results, the specific power consumption in unbaffled shaking flasks can now be fully described. For the first time, the phenomenon of the liquid being "out of phase" is observed and described. This occurs at certain operating conditions and is characterized by an increasing amount of liquid not following the movement of the shaking table, thus reducing the specific power consumption. This, of course, has much relevance for practical work with microbial cultures. The phenomenon of being "out-of-phase" is described in the form of a newly defined nondimensional phase number (Ph) in analogy to a partially filled, rotating horizontal drum. The Ph can be used to determine reasonable operating conditions for shaking flask experiments when using viscous media, avoiding unfavorable "out-of-phase" operation.
    No preview · Article · Jun 2000 · Biotechnology and Bioengineering

Publication Stats

573 Citations
24.69 Total Impact Points


  • 2001-2007
    • RWTH Aachen University
      • Department of Chemical Engineering, Biochemical Engineering
      Aachen, North Rhine-Westphalia, Germany