Showing papers on "Bioreactor published in 1990"
TL;DR: The results strongly suggest that cell damage can occur in the vicinity of the gas distributor and demonstrate that bubble size and gas flow rate are not the only important considerations of cell damage in sparged bioreactors.
Abstract: Pluronic F-68 is a widely used protective agent in sparged animal cell bioreactors. In this study, the attachment-independent Spodoptera frugiperda Sf9 insect cell line was used to explore the mechanism of this protective effect and the nature of cell damage in sparged bioreactors. First, bubble incorporation via cavitation or vortexing was induced by increasing the agitation rate in a surface-aerated bioreactor; insect cells were rapidly killed under these conditions of the absence of polyols. Supplementing the medium with 0.2% (w/v) Pluronic F-68, however, fully protected the cells. Next, cell growth was compared in two airlift bioreactors with similar geometry but different sparger design; one of these bioreactors consisted of a thin membrane distributor, while the other consisted of a porous stainless steel distributor. The flow rates and bubble sizes were comparable in the two bioreactors. Supplementing the medium with 0.2% (w/v) Pluronic F-68 provided full protection to cells growing in the bioreactor with the membrane distributor but provided essentially no protection in the bioreactor with the stainless steel distributor. These results strongly suggest that cell damage can occur in the vicinity of the gas distributor. In addition, these results demonstrate that bubble size and gas flow rate are not the only important considerations of cell damage in sparged bioreactors. A model of cell death in sparged bioreactors is presented.
169 citations
TL;DR: Due to the low ethanol concentration in the broth, and the immobilization of bacterial cells by the membrane, the number of viable cells, and, eventually, the ethanol productivity, increased in the membrane bioreactor.
Abstract: To attain both high productivity and efficient recovery of ethanol from broth, a membrane bioreactor consisting of a jar fermentor and a pervaporation system was applied to the direct production of ethanol from uncooked starch with a thermophilic anaerobic bacterium, Clostridium thermohydrosulfuricum. From four types of ethanol-selective membranes tested, microporous polytetrafluoroethylene (PTFE) membrane, the pores of which are impregnated with silicone rubber, was chosen for its large flux, high ethanol selectivity, and high stability. During fed-batch fermentation with pervaporation in the membrane bioreactor, ethanol was continuously extracted and concentrated in two traps with concentrations at 5.6%-6.2% (w/w) in trap 1 (20 degrees C) and 27%-32% (w/w) in trap 2 (liquid N(2)), while the ethanol concentration in the broth was maintained at 0.85-0.9% (w/w). Due to the low ethanol concentration in the broth, and the immobilization of bacterial cells by the membrane, the number of viable cells, and, eventually, the ethanol productivity, increased in the membrane bioreactor.
89 citations
TL;DR: In this article, the authors compared the performance of batch, continuous stirred tank and bubble column reactors with strict anaerobe Peptostreptococcus productus as a model organism and showed the effects of increased mass transfer and total pressure on system performance.
Abstract: Anaerobic bacteria may be utilized in the conversion of CO, CO 2 and H 2 in synthesis gas to products such as methane, acetate, ethanol and butanol. Bioreactors for these fermentations are mass transfer limited due to very low gas solubilities. Several reactor designs have been examined for these conversions including batch, continuous stirred tank and bubble column reactors. This paper presents laboratory results for these reactor systems using the strict anaerobe Peptostreptococcus productus as a model organism. Results comparing the performance of these reactors and showing the effects of increased mass transfer and total pressure on system performance are presented are discussed.
82 citations
68 citations
Book•
23 Jul 1990
TL;DR: Physico-Chemical Aspects of Cell Adsorption and Attachment of Microorganisms to Solid Support and Entrapment of Microbial Cells for Wastewater Treatment.
Abstract: Physico-Chemical Aspects of Cell Adsorption. Adsorption and Attachment of Microorganisms to Solid Support. Entrapment of Microbial Cells for Wastewater Treatment. The Morphology and Electron Microscopy of Microbial Aggregates. Application of Biomass Carrier in Activated Sludge Process. Effluent Treatment With Immobilized Microalgae and Cyanobacteria. Immobilized Cell Systems in Anaerobic Digestion Process. Biological Process in Toxic Waste Treatment. Fundamentals and Advances in Expanded Bed Reactors for Wastewater Treatment. Fluidized Bed Reactor in Wastewater Treatment.
64 citations
TL;DR: The growth and metabolism of Saccharomyces cerevisiae was studied in steady‐state chemostat cultures under conditions of scarce oxygen and excess glucose, suggesting that ATP has a critical role in dictating the biomass concentration in micro‐aerobic culture.
Abstract: The growth and metabolism of Saccharomyces cerevisiae was studied in steady-state chemostat cultures under conditions of scarce oxygen and excess glucose. The specific ethanol productivity and specific glucose uptake rate were stimulated by 50% within a narrow range of air/nitrogen mixtures to the fermentor. Fermentation was inhibited at slightly higher and lower air/nitrogen ratios, confirming similar results by previous investigators. This stimulation could not be caused by obvious mechanisms, such as the Pasteur or Crabtree effects. Since this maximum in the fermentation rate occurred in a steady-state chemostat and at a constant dilution rate, the ATP yield of the culture necessarily attained a minimum. Thus, changes in the energetic efficiency of growth or the degree of wasting of ATP were surmised. The steady-state biomass concentration at various oxygenation rates exhibited hysteresis phenomena. Ignition and extinction of the biomass concentration occurred as critical oxygen feed rates were passed. The hysteresis was prevented by adding yeast extract to or reducing the antifoam concentration in the medium. These medium alterations had the simultaneous effect of stimulating the fermentation rate, suggesting that ATP has a critical role in dictating the biomass concentration in micro-aerobic culture. Silicone polymer antifoam was found to stimulate glycerol production at the expense of ethanol production, having consequences for the energy generation and the biomass concentration of the culture.
57 citations
TL;DR: In contrast to results with hybridoma or EBV-transformed cell lines, in which hollow fibre bioreactors showed comparable efficiency to perfused stirred tank reactors, the tissue-like cell density is disadvantageous as adherent cells tend to stick together leaving insufficient intercellular space for removal of product.
57 citations
TL;DR: A constant, continuous acetic acid production for over 1000 h was established using the membrane-filtration type reactor and a productivity of 149 g l−1 d−1 was established at high cell density and this value is promising for the future industrial application of this bioreactor.
55 citations
TL;DR: Eleven strains of Aspergillus oryzae were screened for production of β-galactosidase on media based on lactose and wheat bran and the best strain was considerably better than that obtained with A. niger and could not be reduced by the use of surface active agents.
53 citations
TL;DR: Chinese hamster ovary (CHO) cells were cultivated in a compact loop bioreactor using MEM-alpha medium supplemented with 10% fetal calf serum and the sophisticated cultivation and process control systems have been improved for CHO cells.
52 citations
TL;DR: Results are presented which indicate that high feed ammonium concentrations may eliminate oscillations and that under oscillatory conditions ammonium levels are generally low and oscillatory as well.
Abstract: The appearance of sustained oscillations in bioreactor variables (biomass and nutrient concentrations) in continuous cultures of Saccharomyces cerevisiae indicates the complex nature of microbial systems, the inadequacy of current growth kinetic models, and the difficulties which may arise in bioprocess control and optimization. In this study we investigate continuous bioreactor behavior over a range of operating conditions (dilution rate, feed glucose concentration, feed ammonium concentration, dissolved oxygen, and pH) to determine the process requirements which lead to oscillatory behavior. We present new results which indicate that high feed ammonium concentrations may eliminate oscillations and that under oscillatory conditions ammonium levels are generally low and oscillatory as well. The effects of pH are complex and oscillations were only observed at pH values 5.5 and 6.5; no oscillations were observed at a pH of 4.5. Under our nominal operating conditions (feed glucose concentration 10 g/L, dilution rate 0.145 h(-1), feed ammonium concentration 0.0303M, dissolved oxygen level 50%, pH 5.5, and T = 30 degrees C) we found two possible final bioreactor states depending on the transient used to reach the nominal operating conditions. One of the states was oscillatory and characteristic of oxidative metabolism and the other was nonoscillatory and fermentative.
TL;DR: The scaleup of the technique of plant cell surface immobilization was performed successfully in specifically designed laboratory size bioreactors providing for a high immobilizing area‐to‐volume ratio and a best bioreactor performance characterized by low biomass frothing and highly efficient plant cell attachment and retention.
Abstract: The scaleup of the technique of plant cell surface immobilization was performed successfully in specifically designed laboratory size bioreactors. The immobilizing matrix was formed into a vertically wound spiral providing for a high immobilizing area-to-volume ratio (0.8-1.2 cm(-1)). A modified airlift and a mechanically stirred vessel delivered a best bioreactor performance characterized by low biomass frothing and highly efficient plant cell attachment and retention (>or=96%). The growth of Catharanthus roseus cells investigated in these bioreactors was found not to be mass transfer limited. It required mild mixing and aeration levels (k(L)a approximately 10-15 h(-1)). The biomass formation pattern of surface immobilized plant cells generally exhibited a linear growth phase followed by a stationary phase characterized by the presence of residual carbohydrates in the medium, contrary to suspension cultures. This behavior was found to depend on the plant cell type and/or line cultured, as well as on the inoculum age. The space restriction and unidirectional growth of the SIPC biofilm combined with the limited availability of essential intracellular nutrients rapidly accumulated from the medium by the stationary phase inoculated plant cells all likely contributed to the culture behavior.
Patent•
20 Mar 1990TL;DR: In this paper, a method of reducing soluble Cr(VI) levels in aqueous wastes from 200 ppm or more to less than 1 ppm, particularly to 0.05 ppm, was proposed.
Abstract: A method of reducing soluble Cr(VI) levels in aqueous wastes from 200 ppm or more to less than 1 ppm, particularly to less than 0.05 ppm, preferably to less than 0.01 ppm, uses fermentative sulfate-reudcing anaerobic bacteria to reduce Cr(VI) to Cr(III) and immobilize the latter as the extememly insoluble hydroxide. The process is readily adapted to operate continuously using a bioreactor containing sludge with sulfate-reducing anaerobic bacteria and operated as a chemostat.
TL;DR: Cell concentrations determined with this method agreed closely with concentrations calculated from 31P NMR nucleoside triphosphate (NTP) measurements and oxygen consumption rates, and oxygen transfer limitations were shown to be negligible for the bioreactor used.
Abstract: We have developed a technique for determining cell concentration in a hollow fiber bioreactor based on 23Na nuclear magnetic resonance (NMR) spectroscopy. Cell concentrations determined with this method agreed closely with concentrations calculated from 31P NMR nucleoside triphosphate (NTP) measurements and oxygen consumption rate measurements. Oxygen transfer limitations, which can complicate cell mass determinations based on oxygen consumption rates, were shown to be negligible for the bioreactor used. Specific antibody production rates in hollow fiber culture, calculated from these cell number estimates, were similar to those found in suspension culture for this cell line.
TL;DR: It is demonstrated that this adaptive feed‐forward strategy was capable of controlling the dissolved gas concentrations in both short‐ and long‐term studies involving the cultivation of Catharanthus roseus plant cells.
Abstract: To examine the effects of volatile components on plant cell growth, a bioreactor control system was developed to simultaneously control the dissolved concentrations of both oxygen and carbon dioxide. The first step in this work was to develop a mathematical model to account for gas-liquid mass transfer; biological utilization and production of O(2) and CO(2); and the series of chemical reactions of CO(2) in water. Using this model and dynamic measurements for dissolved O(2) and CO(2), it was observed that (1) both absorption and desorption of a volatile component could be described by a single mass transfer coefficient, K(l)a, and (2) K(l)a values for oxygen and carbon dioxide transfer were directly proportional. The second step of this work was to employ the mathematical model in an adaptive feed-forward strategy to control the dissolved O(2) and CO(2) concentrations by manipulating the inlet gas composition to the bioreactor. This strategy allowed dissolved concentrations to be controlled without the need for changing either the total gas flow rate or agitator speed. Adaptive control was required because the volumetric rates of O(2) and CO(2) consumption and production vary with time during long term operation and therefore these rates must be continually updated. As the final step, we demonstrated that this control strategy was capable of controlling the dissolved gas concentrations in both short- and long-term studies involving the cultivation of Catharanthus roseus plant cells.
TL;DR: A flocculating strain of Kluyveromyces marxianus was used for alcoholic fermentation in a continuous bioreactor working with zero residual concentration in effluent and specific kinetic parameters were improved by increasing dilution rate, which is similar to results obtained with ultrafiltration systems.
Abstract: A flocculating strain of Kluyveromyces marxianus was used for alcoholic fermentation in a continuous bioreactor working with zero residual concentration in effluent. Specific kinetic parameters were improved by increasing dilution rate, which is similar to results obtained with ultrafiltration systems. Specific biomass accumulation rate had always a value greater than 92.5% of specific biomass growth rate and was independent of the dilution rate. Productivity is shown to be 12.5 times greater than in conventional continuous operation and is directly proportional to dilution rate. Maximum biomass concentration also presents a linear relationship with dilution rate. The largest obtained biomass concentration is 8 times greater than in a conventional continuous fermentor.
TL;DR: A model was formulated to examine specific experimental data of growth and heterologous product formation with recombinant Saccharomyces Cerevisiae while incorporating available literature and successfully described the observed phenomena for the fermentations of S. cerevisiae strain AB103.
Abstract: A model was formulated to examine specific experimental data of growth and heterologous product formation with recombinant Saccharomyces cerevisiae while incorporating available literature. The model simulated dry cell weight, glucose, ethanol, dissolved oxygen, human Epidermal Growth Factor (hEGF) production, fraction of recombinant cells, oxygen uptake rate, and carbon dioxide production rate for batch, fed batch, and hollow fiber bioreactor configurations. Nineteen differential equations, 24 analytical equations, and 48 parameters were required. Due to the lack of detailed studies needed for the ADH-II and the TCA enzyme pool, 8 of the 48 parameters were adjustable. Simulation results are presented for verification of the model which successfully described the observed phenomena for the fermentations of S. cerevisiae strain AB103. 1 pYalphaEF-25. Also presented is a statistical analysis of the model's fit and model parameter sensitivity.
Patent•
11 Oct 1990
TL;DR: In this article, a process for improving mass transfer in a bioreactor having at least one semi-permeable membrane defining first and second chambers on opposite sides of the membrane provides for circulating a first media including nutrients and the like through the first chamber and a second media for cell culture through the second chamber.
Abstract: A process for improving mass transfer in a bioreactor having at least one semi-permeable membrane defining first and second chambers on opposite sides of the membrane provides for circulating a first media including nutrients and the like through the first chamber and for circulating a second media for cell culture through the second chamber of the bioreactor. The first and second media may be circulated through a plurality of bioreactors connected in parallel while balancing the flow in each reactor. The flow in the second circuit can be periodically reversed to provide increased cell culture.
TL;DR: A trend was observed towards a wider diversity of methanogenic subpopulations parallelling an increase in the complexity of the bioreactor's substrate.
TL;DR: The reciprocating-jet-bioreactor showed excellent properties as fermenter, especially when the biosuspension is highly viscous and non-Newtonian by nature.
Abstract: In a comprehensive study the properties of the reciprocating-jet-bioreactor have been investigated. Fermentations have been carried out with two fungi and one bacterium. The fungi were Cyathus striatus for the production of antibiotics and Aspergillus niger for the production of citric acid. The bacterium Zymomonas mobilis was used in an anaerobic fermentation for the production of ethanol. The reciprocating-jet-bioreactor showed excellent properties as fermenter, especially when the biosuspension is highly viscous and non-Newtonian by nature.
TL;DR: The new bioreactor, in both flat-bed and hollow-fiber configurations, was used to cultivate recombinant human cell, 293, for Protein C production over 60 to 90 days.
Abstract: A new bioreactor for animal cell cultivation employs two compartments for cells and medium respectively. The two chambers are separated by an ultrafiltration membrane. Cells and solution of collagen or collagen/chitosan mixture were loaded to the cell chamber and were allowed to form gel inside. Contraction of the cell-laden gel occurred subsequently to create a new zone in the cell chamber. In such a bioreactor cells are retained in the reactor, the high molecular product(s) accumulate in the cell chamber, while the small molecular weight nutrients and metabolites are replenished and removed from the medium chamber. By adjusting the flow rates for cell and medium chambers, the resident time for cells, high and low molecular weight components of the system can be manipulated separately. The new bioreactor, in both flat-bed and hollow-fiber configurations, was used to cultivate recombinant human cell, 293, for Protein C production over 60 to 90 days.
TL;DR: Itaconic acid production from xylose by immobilized Aspergillus terreus TKK 200-5-2 mycelia was optimized both in repeated shake-flask fermentations and in continuous column bioreactors using statistical experimental design and empirical modelling.
Abstract: Itaconic acid production from xylose by immobilized Aspergillus terreus TKK 200-5-2 mycelia was optimized both in repeated shake-flask fermentations and in continuous column bioreactors using statistical experimental design and empirical modelling. Using continuous 9-1 scale air-lift bioreactors, a pH of 2.5, aeration rate of 0.6 v/v per minute and residence time of 160 h gave the highest itaconic acid concentration. In air-lift bioreactors a cubic carrier size of 0.5 cm gave a 3.3-fold higher product concentration than 1-cm cubes. Packed-bed column reactors had a higher production rate than air-lift reactors.
TL;DR: It was found that low dissolved oxygen levels and low temperatures decreased the rate of DEP degradation and the growth rate, and that the facultative strain was much less affected by the lower DO concentrations than the aerobic strain.
Abstract: The effects of temperature, dissolved oxygen, and other environmental parameters under both aerobic and anaerobic conditions were investigated using one aerobic and one facultative strain isolated from wastewater treatment plant sludge. Among other results, we found that low dissolved oxygen levels and low temperatures decreased the rate of DEP degradation and the growth rate, and that the facultative strain was much less affected by the lower DO concentrations than the aerobic strain.
TL;DR: Glucoamylase production by Aureobasidium pollulans A-124 was compared in free-living cells, cells immobilized in calcium alginate gel beads aerated on a rotary shaker, and immobilized cells aerated in an air bubble column reactor.
Abstract: Glucoamylase production by Aureobasidium pullulans A-124 was compared in free-living cells, cells immobilized in calcium alginate gel beads aerated on a rotary shaker (agitation rate 150 rpm), and immobilized cells aerated in an air bubble column reactor. Fermentation conditions in the bioreactor were established for bead concentration, substrate (starch) concentration, calcium chloride addition to the fermentation medium, and rate of aeration. Production of glucoamylase was optimized at approximately 1.5 units of enzyme activity/ml medium in the bioreactor under the following conditions: aeration rate, 2.0 vol air per working volume of the bioreactor (280 ml) per minute; gel bead concentration, 30% of the working volume; substrate (starch) concentration, at 0.3% (w/v); addition of calcium chloride to the medium at a final concentration of 0.01 M. Productivity levels were stabilized through the equivalent of ten batches of medium with the original inoculum of immobilized beads.
TL;DR: A novel bioreactor using magnetically stabilized fluidized bed technology has been developed that allows for the production of cells while maintaining a controlled cell residence time and is compared to the results obtained in shake flask culture.
Abstract: A novel bioreactor using magnetically stabilized fluidized bed (MSFB) technology has been developed that has certain advantages for cultivating cells continuously. In this system, the cells are protected from shear and are constrained to move through the fermenter in lock-step fashion by being immobilized in calcium alginate beads. The MSFB permits good mass transfer, minimizes particle collisions, and allows for the production of cells while maintaining a controlled cell residence time. Details of the experimental system are described. In addition, the experimental performance of an MSFB used to grow plant cells in batch mode is compared to the results obtained in shake flask culture.
Patent•
10 Jul 1990
TL;DR: In this article, a physical-biochemical process system and apparatus for removal of toxic volatile organic compounds (VOCs) and other organics from contaminated groundwater or wastewater is described.
Abstract: A physical-biochemical process system and apparatus for removal of toxic volatile organic compounds (VOCs) and other organics from contaminated groundwater or wastewater is described. This process system involves influent pumping groundwater or wastewater treatment by air stripping, biological oxidation and powdered activated carbon (PAC) adsorption in an enclosed gas stripping bioreactor, air purification by granular activated carbon contactor, and recycling of GAC-purified air for further groundwater or wastewater treatment. The bioreactor effluent is processed processed by a clarifier, a filter and a disinfection unit. The clarifier sludge is partially recycled to the bioreactor and partially wasted. The process system is cost-effective and eliminates the problem of secondary air contamination caused by conventional gas stripping tower and coventional biological treatment processes.
Patent•
27 Mar 1990TL;DR: In this article, a foam inhibitor is added to the fermentation broth in the bioreactor vessel in order to prevent the accumulation and buildup of foam caused by oxygen sparging of fermentation broth contained therein.
Abstract: A method for processing aqueous fermentation broths in a bioreactor vessel, in which a foam inhibitor is added to the fermentation broth in the bioreactor vessel in order to prevent the accumulation and buildup of foam in the bioreactor vessel caused by oxygen sparging of the fermentation broth contained therein. The aqueous fermentation broth processed in the bioreactor vessel is conveyed as a feed solution to an ultrafiltration system including a membrane for concentrating the aqueous fermentation broth. The ultrafiltration system is typically located downstream of the bioreactor vessel. The improvement involves reducing the amount of fouling of the membrane in the ultrafiltration system by adding to the aqueous fermentation broth in the bioreactor vessel as the foam inhibitor, an antifoam which is an oil based liquid in the form of droplets, the droplets of the oil based liquid antifoam being dispersed, encased, entrapped and imbedded, within solid particles of a water soluble encapsulating material.
TL;DR: Anaerobic treatment of terephthalic acid plant wastewater with a lab-scale downflow tubular fixed film reactor achieved 75% of COD removal with a HRT of 3.4 days at 33°C as discussed by the authors.
Abstract: Anaerobic treatment of terephthalic acid plant wastewater with a lab‐scale downflow tubular fixed film reactor achieved 75% of COD removal with a HRT of 3.4 days at 33°C. The raw wastewater from a petrochemical plant was settled and neutralized prior to reactor feeding. The responses to shock loads and to periods without feeding were satisfactary, and no inhibitory effects were noticed. A primary settling ‐ anaerobic ‐ aerobic process configuration is proposed as a highly efficient, energy saving alternative to the conventional aerobic process.
Patent•
03 Jul 1990TL;DR: A hollow fiber membrane bioreactor process for continuous selective removal of organic toxicants or other oleophilic solutes present in an aqueous process stream is described in this paper.
Abstract: A hollow fiber membrane bioreactor process for continuous selective removal of organic toxicants or other oleophilic solutes present in an aqueous process stream wherein low concentration levels of said toxicant are removed from the aqueous process stream by being extracted and concentrated by the permeably selective hollow fiber membrane and then provided to a microorganism for metabolization into a water soluble metabolite. The water soluble metabolite is prevented from reentering the aqueous process stream and removed from the bioreactor in the aqueous nutrient effluent stream.
TL;DR: The authors examines the effect of particle size on reactor type (heap versus slurry), problems of gas transfer into heaps and concentrated slurries, and the desirability of longitudinal mixing.
Abstract: The bioremediation of contaminated soils, bacterial leaching of metals from ores, biode-sulfurization of coal, and the direct fermentation of biomass to ethanol are all relatively new processes in which the microbial substrate is a solid They involve high volume low-value products, so if they are to be economically viable, the bioreactor must be as small and cheap as possible Bioreactor design for all these processes has much in common, but it has not been addressed in a systematic way This paper examines the effect of particle size on reactor type (heap versus slurry), problems of gas transfer into heaps and concentrated slurries, and the desirability of longitudinal mixing