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Showing papers in "Bioprocess Engineering in 1991"


Journal ArticleDOI
TL;DR: In this article, the removal of dichloromethane from waste gases in a biological trickling filter was studied experimentally as well as theoretically within the concentration range of 0-10,000 ppm.
Abstract: The removal of dichloromethane from waste gases in a biological trickling filter was studied experimentally as well as theoretically within the concentration range of 0–10,000 ppm. A stable dichloromethane elimination performance was achieved during two years of operation, while the start-up of the system only amounted to several weeks at constant inlet concentrations. The trickling filter system was operated co-currently as well as counter-currently.

178 citations


Journal ArticleDOI
TL;DR: In this paper, a 66 dm3 trickle-bed bioreactor was constructed to assess the possibilities of eliminating dichloromethane from industrial waste gases, which was filled with a randomly-stacked polypropylene packing material over which a liquid phase was circulated.
Abstract: A 66 dm3 trickle-bed bioreactor was constructed to assess the possibilities of eliminating dichloromethane from industrial waste gases. The trickle-bed bioreactor was filled with a randomly-stacked polypropylene packing material over which a liquid phase was circulated. The pH of the circulating liquid was externally controlled at a value of 7 and the temperature was maintained at 25 °C. The packing material was very quickly covered by a dichloromethane-degrading biofilm which thrived on the dichloromethane supplied via the gas phase. The biological system was very stable and not sensitive to fluctuations in the dichloromethane supply. Removal of dichloromethane from synthetic waste gas was possible down to concentrations well below the maximal allowable concentration of 150mg/m3 required by West-German law for gaseous emissions. At higher dichloromethane concentrations specific dichloromethane degradation rates of 200 g h−1 m−3 were possible. At very low inlet concentrations, dichloromethane elimination was completely mass transfer limited.

132 citations


Journal ArticleDOI
H. J. Henzler1, M. Schedel1
TL;DR: In this article, the shaking flask is used in serial studies, e.g. in the screening for secondary metabolites or in the optimization of fermentation processes, and experimental investigations in these small bioreactors are often the first step in developing a large scale fermentation process.
Abstract: Due of its simplicity the shaking flask is used in serial studies, e.g. in the screening for secondary metabolites or in the optimization of fermentation processes. Experimental investigations in these small bioreactors are often the first step in developing a large-scale fermentation process.

104 citations


Journal ArticleDOI
Spp Simon Ottengraf, Jhg Konings1
TL;DR: In this paper, the discharge of microbial germs by biofilter systems used for the treatment of waste gases containing volatile organic compounds was investigated and it was concluded that the concentration of microorganisms of a highly contaminated inlet gas is considerably reduced by the filtration process.
Abstract: Experiments are reported on the discharge of microbial germs by biofilter systems used for the treatment of waste gases containing volatile organic compounds. The systems investigated concern six full-scale filter installations located in the Netherlands in several branches of industry, as well as a laboratory-scale installation used for modelling the discharge process. It is concluded that the number of microbial germs (mainly bacteria and to a much smaller extent moulds) in the outlet gas of the different full scale biofilters varies between 103 and 104 m−3, a number which is only slightly higher than the number encountered in open air and of the same order of magnitude encountered in indoor air. It is furthermore concluded that the concentration of microorganisms of a highly contaminated inlet gas is considerably reduced by the filtration process. On the basis of the experiments performed in the laboratory-scale filter bed, it is shown that the effect of the gas velocity on the discharge process results from two distinctive mechanisms: capture and emission. A theoretical model is presented describing the rate processes of both mechanisms. The model presented and the experimentally determined data agree rather well.

60 citations


Journal ArticleDOI
C. Ratledge1
TL;DR: An outline of the main features of yeast physiology is given which focusses mainly — but not exclusively — upon Saccharomyces cerevisiae and the Crabtree and Pasteur effects.
Abstract: An outline of the main features of yeast physiology is given which focusses mainly — but not exclusively — upon Saccharomyces cerevisiae. The metabolic processes of the cell related to carbon flux, energy production and the formation of reducing equivalents (NADH and NADPH) are discussed for both aerobic and anaerobic conditions. Mechanisms are described by which metabolic processes can be controlled. A brief account of the life cycle of Saccharomyces is given explaining the difference between sporulation and vegetative growth. The Crabtree and Pasteur effects are defined, discussed and explained in relation to glucose metabolism and ethanol formation.

47 citations


Journal ArticleDOI
C. Di Massimo1, Mark J. Willis1, Gary Montague1, M.T. Tham1, A.J. Morris1 
TL;DR: In this paper, the authors used a neural network-based process model for the estimation of a feed-batch penicillin fermentation and a continuous mycelial fermentation in a large scale industrial fermentation system.
Abstract: Artificial neural networks are made upon of highly interconnected layers of simple ‘neuron-like’ nodes. The neurons act as non-linear processing elements within the network. An attractive property of artificial neural networks is that given the appropriate network topology, they are capable of learning and characterising non-linear functional relationships. Furthermore, the structure of the resulting neural network based process model may be considered generic, in the sense that little prior process knowledge is required in its determination. The methodology therefore provides a cost efficient and reliable process modelling technique. One area where such a technique could be useful is biotechnological systems. Here, for example, the use of a process model within an estimation scheme has long been considered an effective means of overcoming inherent on-line measurement problems. However, the development of an accurate process model is extremely time consuming and often results in a model of limited applicability. Artificial neural networks could therefore prove to be a useful model building tool when striving to improve bioprocess operability. Two large scale industrial fermentation systems have been considered as test cases; a fed-batch penicillin fermentation and a continuous mycelial fermentation. Both systems serve to demonstrate the utility, flexibility and potential of the artificial neural network approach to process modelling.

43 citations


Journal ArticleDOI
TL;DR: Comparisons between batch and fed-batch cultivations showed that the former had a much lower growth yield, but energy balance calculations showed that a large part of the increase could be explained by the evaporation of ethanol during batch cultivations.
Abstract: Calorimetry has been used to control the glucose feeding in fed-batch cultures of S. cerevisiae in order to avoid ethanol formation and maintain a fully respiratory metabolism. Comparisons between batch and fed-batch cultivations showed that the former had a much lower growth yield. The growth yields for fed-batch cultivations were more than 30% higher than for batch cultures. However, energy balance calculations showed that a large part of the increase could be explained by the evaporation of ethanol during batch cultivations. When the growth yields obtained from the batch cultures were corrected for the evaporation of ethanol, the increase in growth yield for fed-batch cultures was about 10%.

37 citations


Journal ArticleDOI
TL;DR: The costs for the recycling of salt from the primary bottom phase are estimated in a protein extraction process and a mathematical description of the cost structure allows to estimate cost for various conditions.
Abstract: The costs for the recycling of salt from the primary bottom phase are estimated in a protein extraction process. The extraction of 1 kg potassium phosphate in a phase system formed in the presence of ethanol costs approximately 6 to 7 DM. This is within the same order as for the cost resulting from the purchase price of 3 DM/kgsalt and the additional costs for deposition of the primary bottom phase. A mathematical description of the cost structure is developed and allows to estimate cost for various conditions.

35 citations


Journal ArticleDOI
TL;DR: Cross-flow filtration has been investigated as a method of separating filamentously growing fungal cells and purifying the polysaccharide produced, and the effects of transmembrane pressure, module geometry, tangential feed velocity and cell as well as poly Saccharide concentration are discussed.
Abstract: Cross-flow filtration (CFF) has been investigated as a method of separating filamentously growing fungal cells and purifying the polysaccharide produced. The effects of transmembrane pressure, module geometry (e.g. channel height or tube diameter), tangential feed velocity and cell as well as polysaccharide concentration are discussed. Apart from these experiments, influences by the recirculation pump used are shown.

33 citations


Journal ArticleDOI
TL;DR: Anaerobic treatment of distillery wastewaters containing high sulfate concentrations was carried out on a two-phase process as discussed by the authors, where the acidogenic phase was operated so as to produce the more favorable intermediates for methanogenic bacteria coupled with maximum sulfate removal.
Abstract: Anaerobic treatment of distillery wastewaters containing high sulfate concentrations was carried out on a two-phase process. The acidogenic phase was operated so as to produce the more favourable intermediates for methanogenic bacteria coupled with maximum sulfate removal. Sulfate removal was directly affected by pH and dilution rate (D). The maximum sulfate removal and acetic acid production was achieved at pH 6.6 and D=0.035 h−1. A linear relationship between acetic acid produced and sulfate removal was observed, indicating that acetic acid was mainly produced by sulfate reducing bacteria with important operational advantages. Higher concentrations of butyric acid were obtained at low pH values and high dilution rates.

27 citations


Journal ArticleDOI
TL;DR: A “fuzzy” expert system was developed to allow the effective use of semi-quantitative or imprecise information in the determination of the optimal operating conditions of a fermentation process and was applied to the optimization of glutamic acid production by fermentation.
Abstract: A “fuzzy” expert system was developed to allow the effective use of semi-quantitative or imprecise information in the determination of the optimal operating conditions of a fermentation process. The system incorporated fuzzy relations representing both the trends of experimental data and semi-quantitative information obtained from the literature. The inference method used consisted primarily of search and reasoning based on fuzzy set theory. The resulting expert system incorporated a generalized inference engine designed to deal with various types of fermentation processes, it only being necessary to alter the knowledge database in order to adapt the system to process modifications. The construction of the knowledge database from experimental data or semi-quantitative information was designed to be carried out semi-automatically using a graphic computer tool.

Journal ArticleDOI
TL;DR: Reactivity assays conducted on the purified antibody from both batch and perfusion cultures showed no evidence of proteolysis or altered antibody activity in the final perfusion product.
Abstract: A perfusion system for production of monoclonal antibodies was developed using an externally-mounted, hollow-fibre cartridge. The experimental apparatus was operated for 420 h and demonstrated increased steady-state viable cell concentration with increase in perfusion rate. Antibody titres were up to three times those measured for batch cultures and specific antibody productivity was doubled. The procedure was successfully scaled to a 10 dm3 system which produced antibody under conditions of Good Manufacturing Practice (GMP). A calculation of productivity between the scaled perfusion system and 260 dm3 batch cultures resulted in comparable antibody production, whereas the perfusion allowed a halving in medium utilisation. Reactivity assays conducted on the purified antibody from both batch and perfusion cultures showed no evidence of proteolysis or altered antibody activity in the final perfusion product. This study provides additional support for the use of homogeneous perfusion cultures in production of monoclonal antibodies under GMP conditions.

Journal ArticleDOI
Bernhard Sonnleitner1
TL;DR: Segregation of a population in cell classes reflecting the position of a cell in the cell cycle, its individual age, is shown to be necessary in order to account for the spontaneous synchronization of continuous S. cerevisisae cultures.
Abstract: The dynamic behavior of yeasts is discussed on the basis of transient experiments, such as pulses and shifts in continuous culture, and of oscillating synchronized cultures. The minimal elements of a structured model are evaluated and extensions by regulatory mechanisms are proposed. Segregation of a population in cell classes reflecting the position of a cell in the cell cycle, its individual age, is shown to be necessary in order to account for the spontaneous synchronization of continuous S. cerevisisae cultures.

Journal ArticleDOI
TL;DR: The energy dissipation rate concept is used for a new evaluation of the apparent viscosity in bioreactors, i.e. stirred tank and bubble column bioreACTors.
Abstract: The apparent viscosity of non-Newtonian fermentation media is examined. The present state of this subject is discussed. The energy dissipation rate concept is used for a new evaluation of the apparent viscosity in bioreactors, i.e. stirred tank and bubble column bioreactors. The proposed definition of the apparent viscosity is compared with the definitions available in the literature.

Journal ArticleDOI
TL;DR: Based on the kinetic constants determined and the mathematical model of the reactor system developed, the performance of axial flow packed bed continuous enzyme reactor system was studied experimentally and also simulated with the aid of a computer for ultimate objective of optimization of the glucose isomerase reactor system.
Abstract: Based on the kinetic constants determined and the mathematical model of the reactor system developed, the performance of axial flow packed bed continuous enzyme reactor system was studied experimentally and also simulated with the aid of a computer for ultimate objective of optimization of the glucose isomerase reactor system.

Journal ArticleDOI
TL;DR: A theoretical equation for comparison of the bioreaction rates in a biofilm reactor and in a bioreactor with free suspended cells at different input substrate concentrations and substrate conversions is proposed.
Abstract: A theoretical equation for comparison of the bioreaction rates in a biofilm reactor and in a bioreactor with free suspended cells at different input substrate concentrations and substrate conversions is proposed. The main assumption is that there is no kinetic change after fixation of the cells. Some previously published experimental data are used for verification of this equation. It is shown that difference between the experimental and calculated data is within 19%.

Journal ArticleDOI
TL;DR: An optimal profile for pH, which was found to be the critical environmental parameter, was determined using a rigorous mathematical optimization procedure and a 30% increase in enzyme activity and productivity was obtained using the optimal pH strategy as compared to the pH cycling strategy.
Abstract: Cellulase enzyme production was enhanced using the mutant strain Trichoderma reesei, E-12, which was shown to be partially resistant to catabolite repression. An optimal profile for pH, which was found to be the critical environmental parameter, was determined using a rigorous mathematical optimization procedure. Semi-empirical models were used to minimize complications in the computation. A 30% increase in enzyme activity and productivity was obtained using the optimal pH strategy as compared to the pH cycling strategy.

Journal ArticleDOI
TL;DR: Extracellular lipase production by the recombinant strain Staphylococcus carnosus (pLipMut2) has been studied and lipase yield could be improved by 300% and substrate yield (lipase activity/substrate concentration) by 600% compared to former fermentation studies.
Abstract: Extracellular lipase production by the recombinant strain Staphylococcus carnosus (pLipMut2) has been studied. First substrate optimization was carried out in shaken cultures. As a result, the best substrate yield of 20 units/g (peptone + yeast extract) and maximum lipase activity in the culture supernatant of 1.7 units/cm3 could be obtained by a nutrient rich complex medium consisting of 75 kg/m3 yeast extract, 15 kg/m3 tryptone, 5 kg/m3 glucose and 0.5 kg/m3 K2HPO4. Higher initial substrate concentration caused inhibition of growth. Antifoam agent at higher levels than 1 cm3/ dm3 resulted in a negative influence on lipase yield. Comparative fermentation studies have been carried out in a bubble column reactor and in a centrifugal field bioreactor. Direct proportionality between growth, lipase production and oxygen consumption was observed. In the bubble column reactor usual superficial air velocities (4 cm/s) caused intensive foam generation, thus fermentation was only possible after installation of a broader column head to allow coalescence. In the centrifugal field bioreactor higher productivities were obtained without foam problems at superficial gas velocities which were one order of magnitude lower than in the bubble column. Fermentations have been performed batchwise and without holding pH constant. Neither pH control nor glucose feeding could improve the substrate yield further. Compared to former fermentation studies with the strain S. carnosus (pLipPS1) lipase yield (lipase activity/cell density) could be improved by 300% and substrate yield (lipase activity/substrate concentration) by 600%.

Journal ArticleDOI
TL;DR: To supervise, stabilize and optimize antibiotic fermentations in the industrial scale expert systems, various classifiers are tested using a set of 27 nourseothricin fermentation runs and optimal clustering by help of minimum variance criterion and hierarchical clusteringby help of dendrograms are applied.
Abstract: To supervise, stabilize and optimize antibiotic fermentations in the industrial scale expert systems are presently worked out. For the knowledge acquisition various classifiers are tested using a set of 27 nourseothricin fermentation runs. Two methods are applied: optimal clustering by help of minimum variance criterion and hierarchical clustering by help of dendrograms. The fermentations are classified with respect to the specific material costs as well as the product formation kinetics.

Journal ArticleDOI
TL;DR: A cell cycling model for unequal budding yeast Saccharomyces cerevisiae is proposed and verified by steady state data from experiments available in the literature, and not only the quality control, but also the whole economical profit optimization can be carried out.
Abstract: A cell cycling model for unequal budding yeast Saccharomyces cerevisiae is proposed and verified by steady state data from experiments available in the literature. This model can be used to determine the relative fraction of the cells in any cycling phase or with any genealogical age during fermentation. As the quality of yeast is strongly influenced by the cycling process, the model could therefore be used to control the quality of the harvested yeast cells. The input of the cell cycling model is the specific growth rate μ, which is obtained from a metabolic model for S. cerevisiae proposed earlier. With this extended model system not only the quality control, but also the whole economical profit optimization can be carried out. Simulations were done to optimize the profit of a commercial scale baker's yeast production process by manipulating substrate feeding rate and substrate concentration under different aeration rates, fermentation periods and other conditions applied in industry.

Journal ArticleDOI
TL;DR: In this article, a mathematical representation based on logistic model for biomass and Luedeking-Piret model for lipid accumulation gave reasonably good agreement between the theoretical and experimental values for substrate concentration less than 60 kg/m3.
Abstract: In the microbial lipid production system using the yeast Rhodotorula gracilis, CFR-1, kinetics of lipid accumulation and substrate utilisation at initial substrate concentrations in the range of 20–100 kg/m3 were investigated using shake flask experiments. A mathematical representation based on logistic model for biomass and Luedeking-Piret model for lipid accumulation gave reasonably good agreement between the theoretical and experimental values for substrate concentration less than 60 kg/m3. The kinetic expressions and parameters obtained through shake flask studies were directly applied to experiments in the laboratory fermentors also and the models were found to hold good for the prediction of the change of biomass, product as well as substrate with time. The attainment of a saturation in the intracellular lipid accumulation with time, however, was not predicted by the model which was shown to be an inherent feature of the Luedeking-Piret model.

Journal ArticleDOI
TL;DR: In this paper, a packed bed bio-reactor consisting of entrapped yeast cells in alginate matrix for continuous production of alcohol was used for fractional conversion in terms of operating variables including initial substrate level, reactor diameter, diameter of the bead and residence time.
Abstract: Experiments were conducted in a packed bed bio-reactor consisting of entrapped yeast cells in alginate matrix for continuous production of alcohol. The variables include initial substrate level, reactor diameter, diameter of the bead and residence time. The influence of these parameters on the conversion of substrate was studied. The film and pore diffusional effects were observed by varying the column and bead diameters, respectively. The pseudo first order reaction rate constant was calculated and correlated with the bead diameter. The effectiveness factor and the Thiele modulus were estimated. A correlation was proposed for fractional conversion in terms of operating variables. It is possible to predict the residence time required and volumetric productivity achieved in a bioreactor for any given initial substrate concentration at any fractional conversion obtained.

Journal ArticleDOI
TL;DR: In this paper, a system continuously recycling the unfermentable polysaccharides and ions in the broth up to inhibiting levels has been demonstrated after about 40 d of continuous recycling.
Abstract: In order to reduce the inhibiting effect of product on ethanol fermentation and to exploit at best the sugar substrate, a system continuously recycling the unfermented sugars and recovering produced ethanol is proposed in this paper. Unacceptable increases of unfermentable polysaccharides and ions in the broth up to inhibiting levels have been evidenced after about 40 d of continuous recycling. The accumulation of these substances has been overcome by installing in the production cycle two subsequent separated stages for polysaccharide enzymatic hydrolysis and ion bioaccumulation, respectively.

Journal ArticleDOI
TL;DR: In this article, the effective interfacial area in cocurrent gas-liquid downflow through packed beds is analyzed taking into consideration the specific surface of the packing and the interdispersion of the phases.
Abstract: The effective interfacial area in cocurrent gas-liquid downflow through packed beds is analysed taking into consideration the specific surface of the packing and the inter-dispersion of the phases. Predictive equations valid for low and high interaction regimes are developed based on the experimental data of the present study, and are satisfactorily compared with the data of the earlier investigations.

Journal ArticleDOI
TL;DR: A logistic model was found to be reasonably adequate to describe the kinetics of the growth of biomass; the maximum specific growth rate of 0.105 h−1 was applicable for substrate concentrations less than 60 kg/m3, which gave reasonable agreement between predicted and actual biomass concentration values.
Abstract: As a part of the investigations on the microbial lipid production using the yeast Rhodotorula gracilis, CFR-1, kinetics of the biomass synthesis has been studied using shake flask experi- ments. Using a medium containing a carbon to nitrogen ratio of 70:1, the rates of biomass production were followed at different initial substrate concentrations in the range of 20-100 kg/m 3. A logistic model was found to be reasonably adequate to describe the kinetics of the growth of biomass; the maximum specific growth rate of 0.105 h -1 was applicable for substrate concentrations less than 60 kg/m 3, which gave reasonable agreement between predicted and actual biomass concentration values. List of symbols So, Xo kg/m 3

Journal ArticleDOI
TL;DR: A circulation unit made of four inorganic membranes in stainless steel tubes in parallel configuration, the so-called Tubular Bioreactor (TBR) was introduced, thereby creating a strong jet flow into the reactor and thus improving the mixing and the oxygen transfer rate.
Abstract: In order to improve the cultivation properties of a traditional continuous stirred tank reactor (CSTR), we introduced a circulation unit made of four inorganic membranes in stainless steel tubes in parallel configuration, the so-called Tubular Bioreactor (TBR). Furthermore, the TBR outlet tube, which has a restriction nozzle at the end, was installed on top of the fermentor vessel, thereby creating a strong jet flow into the reactor and thus improving the mixing and the oxygen transfer rate. The k La could be increased by approximately 50%. This setup was used for cultivations of recombinant Escherichia coli in a minimal medium and high cell density. More than 50 g dry cell mass/dm3 was obtained. Simultaneously, we have produced an elongated form of human insulin-like growth factor II, which was a secreted fusion protein utilizing the E. coli secretion system based on staphylococcus protein A. The product could be recovered continuously through the TBR-membrane.

Journal ArticleDOI
TL;DR: A recombinant CHO cell line producing human prorenin was cultivated on microcarriers in serum-free medium and the specific prorenIn productivity was not significantly affected by the cell growth rate, and the secretion ofProrenin continued even after the cells had ceased to grow.
Abstract: A recombinant CHO cell line producing human prorenin was cultivated on microcarriers in serum-free medium. Best growth was obtained when the cells were cultivated on a collagen coated microcarrier (Cytodex 3) using a serum-free medium (SF-02) supplemented with fibronectin. It was possible to reduce the necessary concentration of fibronectin in the feed medium from 10 μg/cm3 to 2 μg/cm3 during perfusion cultures in a spinner reactor equipped with an UF-membrane. Also in this system, the prorenin concentration increased up to 8 times higher compared to that in a conventional repeated-batch culture. The cells grew in multilayers on the microcarriers during the perfusion culture. The specific prorenin productivity was not significantly affected by the cell growth rate, and the secretion of prorenin continued even after the cells had ceased to grow.

Journal ArticleDOI
TL;DR: In this article, the use of Pd-MOS sensors for the quantification of H2 in studies of biogas production is discussed and a model is presented which includes the other major gas components in the studied process.
Abstract: The present study gives support for the use of Pd-MOS sensors for the quantification of H2 in studies of biogas production. Furthermore, the study indicates a possibility of simultaneous H2S quantification by use of the Pd-MOS device. A model is also presented which includes the other major gas components in the studied process. Given suitable parameter adjustments, all the major gas components are accounted for, yielding a sum within ±3% from the ideal.

Journal ArticleDOI
TL;DR: In this paper, a tissue culture of Bupleurum falcatum L. was used to produce saikosaponins with several kinds of media and plant hormones, including B-5 medium containing 0.5 ppm kinetin (k) and 1.0 ppm 3-indolebutyric acid (IBA).
Abstract: The studies for production of saikosaponins by tissue culture of Bupleurum falcatum L. were carried out to produce saikosaponins with several kinds of media and plant hormones. Among the media and plant hormones studied, Gamborg's B-5 [23] medium containing 0.5 ppm kinetin (k) and 1.0 ppm 3-indolebutyric acid (IBA) was the most effective medium and hormone for production of saikosaponins. The highest content of saikosaponin-d in the dried cells was 0.26%, which was similar to a concentration of Bupleuri Radix.

Journal ArticleDOI
TL;DR: In this paper, the authors presented an application of the control law based on the ratio of measured and optimal values for a real fermentation pilot plant operated in continuous mode, which can be designed by using classical linear methods.
Abstract: This paper is the first one presenting an application of the control law based on the ratio of measured and optimal values for a real fermentation pilot plant operated in continuous mode. A controller of this type takes into account the process variables and may be designed by using classical linear methods. A simple algorithm is applied for a real CSTR to control the substrate concentration. The results obtained confirm that this approach offers the possibility to combine simplicity and effectiveness in bioprocess control.