Showing papers in "Bioprocess Engineering in 1988"
TL;DR: In this article, a liquid membrane prepared with oleyl alcohol was used in pervaporation of dilute aqueous butanol solutions, and the selectivity of this liquid membrane was found to be superior than that of silicone rubber membrane.
Abstract: The liquid membrane prepared with oleyl alcohol was used in pervaporation of dilute aqueous butanol solutions The selectivity of this liquid membrane was found to be superior than that of silicone rubber membrane, and the separation factor for butanol was 180 Energy saving effect of pervaporation in butanol purification was investigated by comparing the energies required to purify a butanol solution of 05 wt% in the following three separation systems; a conventional distillation system, a separation system combining pervaporation with distillation, and a pervaporation system using a hydrophobic membrane and a hydrohylic membrane in series When the pervaporation using oleyl alcohol liquid membrane was employed as a pretreatment process of butanol purification, the energy requirement was found to be around one-tenth of that of conventional distillation
124 citations
TL;DR: Cell growth was inhibited by 5 mM ammonia, but the cells were able to adapt to ammonia concentrations as high as 8.2 mM, and over 90% of the estimated ATP production was due to glycolysis and a large fraction of glutamines converted to lactate.
Abstract: Ammonia and lactate are the major byproducts from mammalian cells grown in medium containing glutamine and glucose. Both can be toxic to cells, and may limit the productivity of commercial bioreactors. The transient and steady-state responses of hybridoma growth and metabolism to lactate and ammonia pulse and step changes in continuous suspension culture have been examined. No inhibition was observed at 40 mM lactate. Cell growth was inhibited by 5 mM ammonia, but the cells were able to adapt to ammonia concentrations as high as 8.2 mM. Ammonia production decreased and alanine production increased in response to higher ammonia concentrations. Increased ammonia concentrations also inhibited glutamine and oxygen consumption. The specific oxygen consumption rate decreased by an order of magnitude after an ammonia pulse to 18 mM. Under these conditions, over 90% of the estimated ATP production was due to glycolysis and a large fraction of glutamine was converted to lactate.
124 citations
TL;DR: In this article, a mathematical model for the design of bubble-columns for growth of shear-sensitive insect cells is presented, based on two assumptions: first, the loss of cell viability as a result of aeration is a first-order process; and second, a hypothetical volume X, in which all viable cells are killed, is associated with each air bubble during its lifetime.
Abstract: A mathematical model for the design of bubble-columns for growth of shear-sensitive insect cells is presented. The model is based on two assumptions. First, the loss of cell viability as a result of aeration is a first-order process. Second, a hypothetical volume X, in which all viable cells are killed, is associated with each air bubble during its lifetime. The model merely consists of an equation for k
d, the first-order death-rate constant, and A
min, the minimum specific surface area of the air bubbles to supply sufficient oxygen. In addition to X, the equation for k
d contains the air flow F, the air-bubble diameter d
b, the diameter D and the height H of the bubble column. This equation has been experimentally validated. Comparison of the equations for k
d and A
min shows that especially H is the key parameter to manipulate in bubble-column design in order to meet the demands set by A
min and k
d
97 citations
TL;DR: The increase in cell concentration following the return to 10% DO was preceded by increased biosynthetic activity, as evidenced by transiently reduced yields of lactate from glucose, and alanine and ammonia from glutamine.
Abstract: Oxygen is an important nutrient that may limit the productivity of commercial cell culture reactors. The transient responses of hybridoma growth and metabolism to step changes in the oxygen supply rate have been examined for dissolved oxygen concentrations (DO) ranging from 0.1% to 10% of air saturation in continuous culture. Metabolic quotients are reported for glucose, lactate, ammonia, oxygen, glutamine, alanine and other amino acids. A majority of the estimated ATP production was due to oxidative phosphorylation under all conditions tested. Decreases in the oxygen supply rate below the value required to maintain 0.5% DO caused the viable cell concentration to decrease. Glycolysis was enhanced at the lower oxygen concentrations, and after an initial decrease, the specific glutamine consumption rate was also higher. High residual glutamine concentrations occurred below 0.5% DO. Oxidation of other amino acids and production of serine were also inhibited. The cells subsequently adapted to low oxygen concentrations. The increase in cell concentration following the return to 10% DO was preceded by increased biosynthetic activity, as evidenced by transiently reduced yields of lactate from glucose, and alanine and ammonia from glutamine.
67 citations
TL;DR: The results show that measurements of critical oxygen tensions within a process that on morphological or on physical grounds exhibits an inhomogenous structure are not likely to resemble the Monod model.
Abstract: The effect of oxygen limitation on the respiration rate of Penicillium chrysogenum was studied. The results show that measurements of critical oxygen tensions within a process that on morphological or on physical grounds exhibits an inhomogenous structure are not likely to resemble the Monod model.
66 citations
TL;DR: In this article, cells of Clostridium acetobutylicum were immobilized by adsorption onto bonechar and used for the production of solvents (ABE fermentation) from whey permeate.
Abstract: Cells of Clostridium acetobutylicum were immobilized by adsorption onto bonechar and used for the production of solvents (ABE fermentation) from whey permeate When the process was performed in packed bed reactors operated in a vertical or inclined mode, solvent productivities approximating 6 kg/(m3h) were obtained However, the systems suffered from blockage due to excess biomass production and gas hold-up These problems were less apparent when a partially-packed bed reactor was operated in the horizontal mode A fluidized bed reactor proved to be the most stable of the systems investigated, and a productivity of 48 kg/(m3h) was maintained over a period of 2000 h of operation The results demonstrate that this type of reactor may have a useful future role in the ABE fermentation
65 citations
TL;DR: In this article, an ethanol sensor has been tested for feed-rate control of baker's yeast prouction in an 8 dm3 fed-batch reactor up to a cell concentration of 60-70 kg/m3.
Abstract: An ethanol sensor has been tested for feed-rate control of baker's yeast prouction. The yeast was grown on molasses in an 8 dm3 fed-batch reactor up to a cell concentration of 60–70 kg/m3. Studies were made on three levels: reliability of the sensor system, characterisation of the control problem, and evaluation of ethanol-controlled cultivations in terms of yield and production rate. Arguments are given for the conceptual advantages of ethanol control compared to other methods of substrate control. It is also shown that ethanol control allows for a simple regulator structure. In fact, a PID regulator, with constant parameters, was used around an exponential dosage scheme. Tuning of the regulator parameters was performed by using simulation on a simplified model of the process. Several cultivations have been carried out. Results from four comparable cultivations are given in detail, and the experience from many others is summarized.
42 citations
TL;DR: Kinetic studies indicate that the enzyme is not inhibited by indole in the micellar system and that the enzymes is more stable in reverse micelles than in bulk water.
Abstract: The enzymatic production of tryptophan from indole and serine was investigated in a micellar solution of the surfactant Brij 56 in cyclohexane. An anion exchanger was employed to facilitate the transfer of tryptophan and serine between the water pool of the reverse micelle and the bulk organic phase. The influence of potassium ion, water content, pH, and co-surfactant on enzyme activity is reported. Kinetic studies indicate that the enzyme is not inhibited by indole in the micellar system and that the enzyme is more stable in reverse micelles than in bulk water. The design of a continuous reverse micelle reactor, which accommodates both product recovery and enzyme reactivation, is discussed.
22 citations
TL;DR: A description is given of the application of computer process control and on-line data aquisition for the rapid scale-up of the Efrotomycin fermentation, which involves the use of a pseudo-mycelial culture, solids and oil containing medium, and exhibits a high degree of sensitivity to small changes in sterilization conditions.
Abstract: A description is given of the application of computer process control and on-line data aquisition for the rapid scale-up of the Efrotomycin fermentation. This process involves the use of a pseudo-mycelial culture, solids and oil containing medium, and exhibits a high degree of sensitivity to small changes in sterilization conditions. The latter point presented the major scale-up challenge, especially when batch sterilization of medium was used. An example is given of how on-line computer-generated data were used to monitor overall metabolic changes and how this information was used to make process control decisions during the fermentation.
21 citations
TL;DR: In this article, the authors present a concept for the measurement and control of the substrate concentration in a continuously operated biological tank reactor (CBTR), which is successfully applied in the degradation of Naphthalenesulfonic acid by the culture Pseudomonas testosteroni.
Abstract: This paper presents a concept for the measurement and control of the substrate concentration in a continuously operated biological tank reactor (CBTR). The concept was successfully applied in the degradation of Naphthalenesulfonic acid by the culture Pseudomonas testosteroni. The measurement of the substrate concentration was carried out by means of an automated HPLC (high performance liquid chromatography) analysis of the contents of the reactor. The methods of cyclic sampling, sample filtration and evaluation of the chromatograms during the process control are explained. In addition the characteristics of the measuring system (linearity of measurement, noise disturbance data, sampling rates, transient behavior) are described in detail. The feed-back control of the substrate concentration was carried out by variations in the dilution rate with a constant substrate feed concentration. The control results were achieved with a controller which was specially developed to be used in connection with automated cyclic analysis processes. The control algorithm is explained and the conditions necessary for maintaining stability of the control loop are given.
16 citations
TL;DR: By using polyurethane foams as a carrier for the fungi Penicillium chrysogenum, the authors have studied a novel cultivation method for this microorganism and found that six times as much penicillin could be produced as is obtainable by traditional cultivation methods.
Abstract: The conventional penicillin submerged culture has several drawbacks: filamentous fungi solidify into pellets or become pulpy, which has so far had bad effects on the separation of penicillin from the broth, on the monitoring and controlling of the culture system as well as on the productivity of penicillin.
TL;DR: A selected group of high-efficiency bioreactors is described and it is shown that with increasing efficiency of the bioreactor the downstream processes will be much simplified, energy and costs will be substantially reduced.
Abstract: AbstractThe development and investigation of high-efficiency bioreactors is one of the primary problems bioprocess engineers have to solve. With increasing efficiency of the bioreactor the downstream processes will be much simplified, energy and costs will be substantially reduced.According to fundamental research on the properties of stirred tank bioreactors the following rules for the design of bioreactors should be observed:a)Prevent rotational motion of the biosuspension.b)Generate motion of the biosuspension in the radial and axial direction.c)Prevent fluid flow in big spaces.
These design rules are in general observed in the development of high-efficiency bioreactors. A selected group of such bioreactors is described.
TL;DR: The scale-down procedure seems an adequate tool in the design, optimization, and scale-up fermentation processes as discussed by the authors, and the first step in this procedure is a theoretical analysis, called process analysis, which is based on characteristic times of the mechanisms which may influence the performance of the bioreactor.
Abstract: The scale-down procedure seems an adequate tool in the design, optimization and scale-up fermentation processes. The first step in this procedure is a theoretical analysis, called process analysis, which is based on characteristic times of the mechanisms which may influence the performance of the bioreactor. This analysis must give information about the behaviour of large and small scale fermentation processes. At a small scale a verification of the results of such an analysis of the fed-batch baker's yeast production is carried out.
TL;DR: In this paper, a computer model has been developed to investigate the potential as well as to establish the limits of this process from a chemical engineering point of view, taking into account the kinetics of the reaction, the nonideality of flow and the segregation in the bioreactor.
Abstract: Fermentation in tubular recycle reactors with high biomass concentrations is a way to boost productivity in alcohol production. A computer model has been developed to investigate the potential as well as to establish the limits of this process from a chemical engineering point of view. The model takes into account the kinetics of the reaction, the nonideality of flow and the segregation in the bioreactor. In accordance with literature, it is shown that tubular reactors with biomass recycle can improve productivity of alcohol fermentation substantially.
TL;DR: This new technique using hollow fiber modules offers completely new possibilities for long-term high-capacity, highly specific glucuronidation of phenolic compounds, not only the economical production of special glucuronides, but also the specific elimination of phenols from waste fluids or from serum and blood of patients.
Abstract: A lipophilic hollow fiber membrane preparation was used for the enzymatic glucuronidation of lipophilic aromatic compounds. A crude solubilized microsomal enzyme preparation was circulated on the external side of the lipophilic membrane while the phenol containing buffer solution was circulated through the internal side of the hollow fiber membrane. Phenols, which accumulate in and penetrate the lipophilic membrane, were converted by UDP-glucuronyltransferase to the corresponding glucuronides. During this process the lipophilic compounds are converted to hydrophilic substances, which are not able to rediffuse through the lipophilic membrane into the donor side of the hollow fiber module. The produced glucuronide is separated by means of a coupled dialysis with a module of hydrophilic surface (cellulose acetate), while the enzyme protein is retained. On the stripping side of the dialysing module the glucuronide can be separated by solid phase extraction (Lichroprep RP-18) while a continuous substitution of cofactor into this compartment is possible. UDPGA follows its own concentration gradient and migrates into the enzymatic mixture, where it is utilized. This new technique using hollow fiber modules offers completely new possibilities for long-term high-capacity, highly specific glucuronidation of phenolic compounds. Fields of application are not only the economical production of special glucuronides, but also the specific elimination of phenols from waste fluids or from serum and blood of patients. For the production of glucuronides by this technique the use of highly purified enzymes is not essential. Cheap crude enzyme preparations are quite adequate for an optimal reaction. Using a crude enzyme preparation with a specific batch activity of 13 nMol/min per mg of protein, the activity in the reactor system was observed to be 4.6 nMol/min of 2-naphtol glucuronide formed per mg of protein. This corresponds to 3.6 nMol/h of product formed per mg of protein per cm2 of hollow fiber surface. Using a membrane surface of 0.5 m2 the production of 18 mMol of glucuronide per h and mg protein can be achieved.
TL;DR: It was found in this cultivation system that the optimum region concerning inoculum size was enlarged, and the production amount of penicillin produced by this new method was about twelve times as high as that produced by the traditional method.
Abstract: Urethane foam was applied to immobilize the fungus Penicillium chrysogenum in order to accelerate penicillin fermentation. Various operational conditions, such as cultivation temperature, initial pH value, composition of substrate and inoculum size of spores, which might influence penicillin fermentation significantly, were studied in a shaking flask culture system.
TL;DR: In this paper, an emulsion of polydimethylsiloxane and polypropylene glycol-based anti-foam agents adversely influence the ultrafiltration rate of a protease solution with polysulfon membranes.
Abstract: Polydimethylsiloxane and polypropylene glycol-based anti-foam agents adversely influence the ultrafiltration rate of a protease solution with polysulfon membranes. Four propietary agents have been compared, of which Rhodosil 426 R (ex Rhone Poulenc, France), an emulsion of polydimethylsiloxane, proved to have the least influence. With this agent, the relative filtration flux of a protease solution decreased by a factor of two for concentrations of anti-foam agent higher than 0.25 cm3/dm3. A simple, quasisteady-state model developed on the basis of data obtained from total recycle experiments with this anti-foam agent, well predicted the temporal variation of protease concentration during batch ultrafiltration experiments with and without Rhodosil 426 R.
TL;DR: The biological transformation from rifamycin B to rIFamycin S was carried out with the live whole cells of Humicola sp.
Abstract: The biological transformation from rifamycin B to rifamycin S was carried out with the live whole cells of Humicola sp., ATCC 20620, immobilized in a dual hollow fiber bioreactor (DHFBR). Humicola sp., inoculated in the DHFBR, proliferated successfully to a high density cell mass within the space between an outer silicone tubing and three inner polypropylene hollow fiber membranes. In order to control the cell growth a nitrogen deficient medium was fed. Conversion of rifamycin B continued for more than 30 d, whereas that of immobilized rifamycin B oxidase lasted only for 3 d in comparable conditions. In the DHFBR the volumetric productivity of rifamycin S was 0.65–1.03 mmol/(dm3 · h) with 60% conversion, while that in the rotating packed disk reactor was 0.27 mmol/(dm3 · h) with 40% conversion at a residence time of 0.5–1.5 h.
TL;DR: The comparison of the results obtained with plasmids RK2 and pTJS26 was used to analyze the effect of mutations in the replication region on growth dynamics and plasmid stability.
Abstract: Host-plasmid interactions were studied for the broad-host range plasmid RK2 and its derivative pTJS26. To isolate host and plasmid contributions to the host-plasmid interaction, experiments were performed with the same plasmid in three different gram-negative hosts. The three hosts were: Pseudomonas putida, Pseudomonas aeruginosa and Escherichia coli. Separate experiments were performed for both host and recombinant cells to identify their growth characteristics. Cells were grown in different media to investigate the effect of growth rate on plasmid stability, and at two different temperatures (30°C and 37°C) to investigate the effect of plasmid content on growth dynamics. The comparison of the results obtained with plasmids RK2 and pTJS26 was used to analyze the effect of mutations in the replication region on growth dynamics and plasmid stability.
TL;DR: In a two-stage pilot plant substantial degradation of dissolved organic carbon compounds and ammonium has been achieved by an aerobic biological process at an extremely short residence time of the waste water in the bioreactors, due to the application of a new type ofBioreactor, called the reciprocating jet bioreactor.
Abstract: In a two-stage pilot plant substantial degradation of dissolved organic carbon compounds and ammonium has been achieved by an aerobic biological process at an extremely short residence time of the waste water in the bioreactors. This success is due to the application of a new type of bioreactor, called the reciprocating jet bioreactor.
TL;DR: In this paper, a two-phase system employing an organic liquid membrane was investigated, and a diffusion cell was constructed to study the transport of the various components of the reaction through an organic layer of cyclohexane.
Abstract: Tryptophan synthesis was investigated in a two-phase system employing an organic liquid membrane. A diffusion cell was constructed to study the transport of the various components of the reaction through an organic layer of cyclohexane. The organic phase was supported by two polymeric membranes, and Aliquat-336 was used as the anion exchanger. A differential in pH was maintained between the aqueous phases to facilitate extraction of the product from the reaction phase. A mathematical model was developed to estimate effective diffusivities and predict the sensitivity of the system to changes in the partition coefficients and liquid membrane thickness. The use of liquid membrane emulsion-type reactors is discussed.
TL;DR: In this paper, a conical rotating surface for mass transfer between gases and liquids is described, where a thin rising film is generated by centrifugal force, thus exposing a large area of flowing liquid to the gaseous phase.
Abstract: A device based on a conical rotating surface for promoting mass transfer between gases and liquids is described. A thin rising film is generated by centrifugal force, thus exposing a large area of flowing liquid to the gaseous phase.
TL;DR: The kinetics of reextraction of penicillin from the LA-2-penicillin complex-n-butylacetate solution by phosphate buffer was investigated experimentally and theoretically and can be described by a mathematical model in a wide range of pH-values and complex concentrations.
Abstract: The kinetics of reextraction of penicillin from the LA-2-penicillin complex-n-butylacetate solution by phosphate buffer was investigated experimentally and theoretically. The concentration time functions can be described by a mathematical model in a wide range of pH-values and complex concentrations.
TL;DR: The interaction between Schizosaccharomyces pombe and S. cerevisiae was investigated by growing the yeasts in sterile, partially fermented glucose asparagine medium in flasks, and also in the Ecologen containing either synthetic medium or grape must be separating the adjacent chambers with membranes which allow free movement of medium but not of cells as mentioned in this paper.
Abstract: The interactions between Schizosaccharomyces pombe and Saccharomyces spp. (S. cerevisiae, S. cerevisiae sake, S. bayanus, S. uvarum) were investigated by growing the yeasts in sterile, partially fermented glucose asparagine medium in flasks, and also in the Ecologen containing either synthetic medium or grape must be separating the adjacent chambers with membranes which allow free movement of medium but not of cells. The growth of Sch. pombe was inhibited by Saccharomyces spp. to a varied extent, but the reverse was not observed. Saccharomyces uvarum, and S. cerevisiae more strongly inhibited Sch. pombe than the other species tested. All three strains of Sch. pombe (ICV-M, BG, ATCC-16979) were inhibited by S. cerevisiae although ICV-M and ATCC strains were more sensitive than BG. The higher growth rate of S. cerevisiae resulted in the exhaustion of nutrients, and its metabolic products could possibly be responsible for the growth inhibition of Sch. pombe. In the light of the present experimental results, the suitability of a two-step fermentation process for making better quality wines from acidic grape musts is discussed.
TL;DR: In this paper, the concentrations of glucose, phosphate, ammonium, ethanol and dissolved O2 and CO2 in the medium and O 2 and CO 2 in the outlet gas as well as the cell mass by culture fluorescence were measured on-line.
Abstract: Ethanol was produced with Zymomonas mobilis Z6 (ATCC 29191), in batch culture with synthetic medium on glucose as substrate and in the presence of aspartate. The concentrations of glucose, phosphate, ammonium, ethanol and dissolved O2 and CO2 in the medium and O2 and CO2 in the outlet gas as well as the cell mass by culture fluorescence were measured on-line. Cell mass, glucose and aspartate concentrations were measured off-line. In the presence of a sufficient amount of aspartate, the ethanol inhibition effect can be reduced considerably. However, the improvement with yeast extract is more incisive. The relationship between the intensity of culture fluorescence and cell mass concentration is linear, if sufficient aspartate is present.