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At least 163 records · Page 9Linked to original sources

PubMed2000

Approach to designing rotating drum bioreactors for solid-state fermentation on the basis of dimensionless design factors.

The development of large-scale solid-state fermentation (SSF) processes is hampered by the lack of simple tools for the design of SSF bioreactors. The use of semifundamental mathematical models to design and operate SSF bioreactors can be complex. In this work, dimensionless design factors are used to predict the effects of scale and of operational variables on the performance of rotating drum bioreactors. The dimensionless design factor (DDF) is a ratio of the rate of heat generation to the rate of heat removal at the time of peak heat production. It can be used to predict maximum temperatures reached within the substrate bed for given operational variables. Alternatively, given the maximum temperature that can be tolerated during the fermentation, it can be used to explore the combinations of operating variables that prevent that temperature from being exceeded. Comparison of the predictions of the DDF approach with literature data for operation of rotating drums suggests that the DDF is a useful tool. The DDF approach was used to explore the consequences of three scale-up strategies on the required air flow rates and maximum temperatures achieved in the substrate bed as the bioreactor size was increased on the basis of geometric similarity. The first of these strategies was to maintain the superficial flow rate of the process air through the drum constant. The second was to maintain the ratio of volumes of air per volume of bioreactor constant. The third strategy was to adjust the air flow rate with increase in scale in such a manner as to maintain constant the maximum temperature attained in the substrate bed during the fermentation.

Air Movements↗

PubMedDate not supplied

A bioreactor system to study survival of Salmonella Typhimurium in pig gut content.

The batch culture system included six bioreactors. Three bioreactors containing stomach slurry were maintained at pH 4.5 and 6 respectively. Bioreactors containing small intestine slurry were maintained at pH 5.6 and 7 respectively. The bioreactors were inoculated with 10 ml of viable Salmonella. The bioreactors were maintained for 6 hours. Samples of 10 ml were taken at 0 time and at 1, 2, 4 and 6 hours. The samples were analysed for the presence of Salmonella and SCFA. In the stomach samples Salmonella numbers increased at pH 6 but fell at pH 4. In the small intestine sample Salmonella numbers increased at pH 6 and 7. In terms of SCFA production, in the stomach, with samples at pH 6 there was little change in the amounts of lactate, succinate and formate to that detected at 0 time, however levels of acetate did increase slightly. In the small intestine samples levels of succinate and formate increased slightly up to 4 hours, levels of acetate increased significantly from 0 to 6 hours. In terms of the specific growth rates of the individual strains, both strains grew at pH 6 in the stomach content and to a greater extent in the small intestinal content. A bactericidal effect was observed at pH 4 in the stomach content while neither killing nor growth occurred at pH 5 either in the stomach or the small intestine content. Both strains grew well in the small intestine content at pH 7, showing generation times of up to 24 min.

Animals↗

PubMed2003

[Preparation of hollow fiber bioreactor for culturing pig hepatocytes].

OBJECTIVE: To study the method of preparing the hollow fiber bioreactor for culturing pig hepatocytes. METHODS: Hepatocytes were isolated from experimental suckling minipigs by two-step perfusion with collagenase, and seeded onto hollow fiber bioreactor, then cultured with an artificial capillary cell culture system. The albumin-excretion, lidocaine-transforming rate, lactate dehydrogenase (LDH) release and the cell viability in bioreactors were examined. RESULTS: The porcine albumin could be detected by SDS/PAGE on the 2nd, 4th, 6th day. The rates of lidocaine-transforming ranged from 89.6% to 96.1%. The release of LDH into the culture medium increased from (23.7+/-4.6) U/L to (127.8+/-17.4) U/L (F=39.582, P<0.01) during the experiments, and the viability of pig hepatocytes in hollow fiber bioreactor reduced from 95.8%+/-0.3% to 83.8%+/-4.7% (t=5.135, P<0.01). CONCLUSION: The hollow fiber bioreactor for culturing pig hepatocytes can be prepared by artificial capillary cell culture system, which provides a certain liver-specific function in 1 week.

Animals↗

PubMed2001

Anaerobic treatment of brewery wastewater with an internal membrane bioreactor.

Anaerobic treatment is growing very popular these days because of low sludge production compared to activated sludge processes. The drawback of the process is the risk of sludge washout, especially when the formation of granular sludge is not expected. By using an internal anaerobic bioreactor this problem can be overcome. A lab scale internal anaerobic membrane bioreactor was operated at SEGHERSbetter technology for Water N.V. to which brewery wastewater was fed (COD=2300 mg/l). Hollow fibres were inserted into the anaerobic bioreactor, from which the effluent was extracted by underpressure. The COD-removal was excellent and very constant at a value of 95%. No suspended solids were present in the effluent. The membrane permeability stabilised at relatively low value of 18 l/m2.h.bar due to an irreversible adhesion of constituents in the bioreactor. No growth of biomass was found during two months of operation. Inocculated granular sludge fell apart into loose flocs within several weeks of the startup, not affecting biological performance. The internal anaerobic membrane bioreactor is a promising new area within the field of wastewater treatment. It is expected that this process will have an important future.

Anaerobiosis↗

PubMed1997

Production of rhEPO with a serum-free medium in the packed bed bioreactor.

Recombinant CHO (C2) cells producing human erythropoietin (rhEPO) were cultured with DMEM:F12 media containing 5% FBS for 8-10 days in a packed bed bioreactor, then rhEPO was produced with a serum-free medium (SFM-p) which was prepared in our laboratory. The SFM-p medium can support the growth of C2 cells and the production of rhEPO, and furthermore, it easily separates rhEPO from the culture supernatant. The cell culture in a packed bed bioreactor system using SFM-p was maintained in a stable condition for 20-25 days. The expression level of rhEPO was 12-28.4 mg/L. The bioreactor productivity was 71.0 mg/L.d and increased by 12-14 fold over that of the roller bottle. The glucose consumption rate was 21 g/L.d. At the end of 30 days of perfusion circulation, a final cell density of over 3.0 x 10(7)/ml of culture volume was achieved. Since the cells were entrapped in the polyester disk, the culture supernatant contained only a few detachment cells. Variations in lactate and ammonia production in the reactor were observed, and results showed that the productions of lactate and ammonia by the bioreactor were 3.5 g/L and 5 mmol/L, respectively, and did not affect the expression of interest protein. This experiment demonstrates that SFM-p is suitable for the growth and rhEPO production of recombinant C2 in the packed bed bioreactor.

Animals↗

PubMed2003

Molecular biology of stress genes in methanogens: potential for bioreactor technology.

Many agents of physical, chemical, or biological nature, have the potential for causing cell stress. These agents are called stressors and their effects on cells are due to protein denaturation. Cells, microbes, for instance, perform their physiological functions and survive stress only if they have their proteins in the necessary concentrations and shapes. To be functional a protein shape must conform to a specific three-dimensional arrangement, named the native configuration. When a stressor (e.g., temperature elevation or heat shock, decrease in pH, hypersalinity, heavy metals) hits a microbe, it causes proteins to lose their native configuration, which is to say that stressors cause protein denaturation. The cell mounts an anti-stress response: house-keeping genes are down-regulated and stress genes are activated. Among the latter are the genes that produce the Hsp70(DnaK), Hsp60, and small heat protein (sHsp) families of stress proteins. Hsp70(DnaK) is part of the molecular chaperone machine together with Hsp40(DnaJ) and GrpE, and Hsp60 is a component of the chaperonin complex. Both the chaperone machine and the chaperonins play a crucial role in assisting microbial proteins to reach their native, functional configuration and to regain it when it is partially lost due to stress. Proteins that are denatured beyond repair are degraded by proteases so they do not accumulate and become a burden to the cell. All Archaea studied to date possess chaperonins but only some methanogens have the chaperone machine. A recent genome survey indicates that Archaea do not harbor well conserved equivalents of the co-chaperones trigger factor, Hip, Hop, BAG-1, and NAC, although the data suggest that Archaea have proteins related to Hop and to the NAC alpha subunit whose functions remain to be elucidated. Other anti-stress means involve osmolytes, ion traffic, and formation of multicellular structures. All cellular anti-stress mechanisms depend on genes whose products are directly involved in counteracting the effects of stressors, or are regulators. The latter proteins monitor and modulate gene activity. Biomethanation depends on the concerted action of at least three groups of microbes, the methanogens being one of them. Their anti-stress mechanisms are briefly discussed in this Chapter from the standpoint of their role in biomethanation with emphasis on their potential for optimizing bioreactor performance. Bioreactors usually contain stressors that come with the influent, or are produced during the digestion process. If the stressors reach levels above those that can be dealt with by the anti-stress mechanisms of the microbes in the bioreactor, the microbes will die or at least cease to function. The bioreactor will malfunction and crash. Manipulation of genes involved in the anti-stress response, particularly those pertinent to the synthesis and regulation of the Hsp70(DnaK) and Hsp60 molecular machines, is a promising avenue for improving the capacity of microbes to withstand stress, and thus to continue biomethanation even when the bioreactor is loaded with harsh waste. The engineering of methanogenic consortia with stress-resistant microbes, made on demand for efficient bioprocessing of stressor-containing effluents and wastes, is a tangible possibility for the near future. This promising biotechnological development will soon become a reality due to the advances in the study of the stress response and anti-stress mechanisms at the molecular and genetic levels.

Archaea↗

PubMed1994

A novel membrane bioreactor for microbial growth.

A novel membrane bioreactor, previously assessed for its gas transfer characteristics, was used in various size and membrane configurations for the growth of the strictly aerobic bacterium Pseudomonas aeruginosa. The bioreactor was found to readily support growth, and the initial growth rates showed the previously demonstrated enhanced effect in gas O2 mass transfer of the dimpled membrane bioreactor over flat membrane bioreactors. The production of a secondary metabolite by a Pseudomonas sp. following growth was demonstrated, as was the biotransformation of a nitrile by Nocardia rhodochrous with the removal of the biotransformation products across a membrane. The potential of the bioreactor, in terms of other applications in the field of biotechnology, is discussed.

Acrylonitrile↗

PubMed1996

Aerobic dechlorination of low-chlorinated biphenyls by bacterial biofilms in packed-bed batch bioreactors.

Cells of an aerobic three-membered bacterial co-culture, designated as ECO3, capable of cometabolizing and aerobically dechlorinating low-chlorinated biphenyls in the presence of biphenyl, were immobilized on Manville silica beads, on frosted-glass beads and on polyurethane foam cubes in packed-bed bioreactors continuously fed with a biphenyl-saturated air stream. The ECO3 biofilm reactors were found to be capable of extensively mineralizing several pure dichlorobiphenyls (75 mg/l) and Aroclor 1221 (75 mg/l) in batch mode. Immobilized ECO3 cells could aerobically degrade and dechlorinate the dichlorobiphenyls tested more extensively than suspended ECO3 cells. Among the three biofilm reactors, the glass bead bioreactor and the polyurethane bioreactor exhibited the highest capability of mineralizing both dichlorobiphenyls and Aroclor 1221; the polychlorinated biphenyl availability in the bioreactors more than the biomass availability, both depending on the nature of the support employed, significantly governed the efficiency of the treatment. These results are of interest for the possible development of a bioreactor system for continuous treatment of polychlorinated-biphenyl-contaminated wastewaters.

Aerobiosis↗

PubMed1992

Modified CelliGen-packed bed bioreactors for hybridoma cell cultures.

This study describes two packed bed bioreactor configurations which were used to culture a mouse-mouse hybridoma cell line (ATCC HB-57) which produces an IgG1 monoclonal antibody. The first configuration consists of a packed column which is continuously perfused by recirculating oxygenated media through the column. In the second configuration, the packed bed is contained within a stationary basket which is suspended in the vessel of a CelliGen bioreactor. In this configuration, recirculation of the oxygenated media is provided by the CelliGen Cell Lift impeller. Both configurations are packed with disk carriers made from a non-woven polyester fabric. During the steady-state phase of continuous operation, a cell density of 10(8) cells per cm3 of bed volume was obtained in both bioreactor configurations. The high levels of productivity (0.5 gram MAb per 1 of packed bed per day) obtained in these systems demonstrates that the culture conditions achieved in these packed bed bioreactors are excellent for the continuous propagation of hybridomas using media which contains low levels (1%) of serum as well as serum-free media. These packed bed bioreactors allow good control of pH, dissolved oxygen and temperature. The media flows evenly over the cells and produces very low shear forces. These systems are easy to set up and operate for prolonged periods of time. The potential for scale-up using Fibra-cel carriers is enhanced due to the low pressure drop and low mass transfer resistance, which creates high void fraction approaching 90% in the packed bed.

Animals↗

PubMed1991

Membrane bioreactors: present and prospects.

Membrane bioreactors have a very handy in-situ separation capability lacking in other types of bioreactors. Combining various functions of membrane separations and biocatalyst characteristics of enzymes, microbial cells, organelles, animal and plant tissues can generate quite a number of membrane bioreactor systems. The cell retaining property of membranes and selective removal of inhibitory byproducts makes high cell density culture possible and utilizes enzyme catalytic activity better, which leads to high productivity of bioreactors. Enzyme reactions utilizing cofactors and hydrolysis of macromolecules are advantageous in membrane bioreactors. Anaerobic cell culture may be efficiently carried out in membrane cell recycle systems, while aerobic cultures work well in dual hollow fiber reactors. Animal and plant cells have much a better chance of success in membrane reactors because of the protective environment of the reactor and the small oxygen uptake rate of these cells. Industrial use of these reactors are still in its infancy and limited to enzyme and animal tissue culture, but applications will expand as existing problems are resolved.

Animals↗

PubMed1994

A comparison of monoclonal antibody productivity in different hollow fiber bioreactors.

Cell culture in hollow fiber bioreactors has been used as a method for large-scale production of monoclonal antibodies, viruses, cell-associated proteins and cancer antigens. We have examined an important variable in culturing cells in hollow fiber bioreactors: bioreactor composition. Eight different bioreactor designs which varied in nominal molecular weight cutoff, surface area, fiber material and ultra filtration rate were compared in large-scale hollow fiber cultures. A standard protocol utilizing the hybridoma 3C11 (ATCC HB 8511) or African green monkey kidney cells (Vero cells, ATCC CRL 1587) was designed so that the only variable examined was the hollow fiber bioreactor in use. The results suggest that surface area has little effect on antibody productivity, while fiber composition and ultrafiltration rate may play an important role. Vero cell growth was affected by both fiber composition and ultrafiltration rate.

Animals↗

PubMedDate not supplied

Expansion and differentiation of human hematopoietic cells from static cultures through small-scale bioreactors.

Maintenance of the progenitor cells responsible for hematopoiesis has generally been accomplished using a feeder layer of stromal cells in stationary culture. Here, we compared the expansion of the total cell and progenitor cell populations using low-density mononuclear cells (LDMCs) obtained from human bone marrow in static culture (T-flasks) and in different cell culture bioreactors designed for the scale-up of mammalian cells. Static cultures were performed without the presence of a previously established stromal cell layer. Expansion of marrow in all cases was accomplished through the use of added cytokines such as IL-3, GM-CSF, and c-kit ligand. The results for the total cell expansion in static culture ranged from 4.4- to 32-fold. The cell number increase was affected by such factors as patient to patient variability, freeze-thawing, and the combination of cytokines used. Due to widespread use and the small amount of marrow needed, static cultures were used as a basis for comparison with other expansion systems. The cell culture systems used to evaluate the scale-up of marrow cultures included suspension, microcarrier, airlift, and hollow fiber bioreactors. Using identical media, cytokines, and feed schedules, LDMCs in the suspension bioreactor expanded to a value of 1.6 compared to a normalized value of 1.0 for static cultures for the two runs investigated. Expansion results for microcarrier cultures averaged 0.75 when compared to static cultures. A cell number increase in the airlift bioreactor resulted in an expansion which was 0.70 of the control static culture. Granulocyte-macrophage and erythroid progenitor assay data were also evaluated for the suspension, microcarrier, and airlift bioreactors.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotechnology↗

PubMedDate not supplied

Development of scale-down techniques for investigation of recombinant Escherichia coli fermentations: acid metabolites in shake flasks and stirred bioreactors.

We have developed shake-flask screening conditions that are predictive of specific expression of the chimeric toxin, TGF alpha-PE40, by recombinant Escherichia coli JM109 in stirred bioreactors. When a nutrient-rich stirred bioreactor medium was used in shake flasks, neither the extent of growth nor the specific level of recombinant protein expression duplicated the performance in stirred bioreactor fermentations. Incomplete oxidation of glucose and concomitant accumulation of organic acid metabolites, as well as oxygen limitation and lack of pH control, were examined as contributors to the poorer performance in the flask. The medium buffering capacity, initial glucose level, and flask aeration were evaluated to establish the limits of "scale-down" conditions for expression both in a complex nutrient medium (M101) similar to that used in stirred bioreactors and in a defined (FM) medium. Acid metabolites and ethanol were measured as indicators of carbon flow from glucose as well as indirect indicators of oxygen limitation. For the complex M101 medium, optimal shake-flask performance in 250-mL, nonbaffled flasks at 37 degrees C occurred with 0.3 x medium strength, supplementation with 0.3 m HEPES buffer (pH 7.5), and 10 mL of medium per flask. Cultures grown under these conditions produced a maximum density of 3.6 g of dry cell weight/L (as estimated by absorbance measurements at 600 nm) and maintained a pH near neutrality. Additionally, metabolite markers of anaerobic or microaerobic conditions, such as ethanol, lactate, and pyruvate, were not detected, and specific expression of TGF alpha-PE40 was comparable to stirred bioreactors induced for expression at various biomass levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotechnology↗

PubMed1998

Acetic acid production from fructose by clostridium formicoaceticum immobilized in a fibrous-Bed bioreactor

The fermentation kinetics of acetic acid production from fructose by Clostridium formicoaceticum was studied at pH 7.6 and 37 degreesC. Recycle batch, fed-batch, and continuous fermentations using immobilized cells in a fibrous-bed bioreactor were studied for their potential application in producing acetic acid from fructose, a fermentable sugar commonly found in corn steep liquor and many other food processing wastes. For the immobilized cell fermentation, acetic acid yield from fructose was approximately 1.0 g/g, with a final acetate concentration of approximately 78 g/L and the overall reactor productivity (based on the fibrous bed bioreactor volume) of approximately 0.95 g/(L.h) in the fed-batch fermentation. For a similar fed-batch fermentation with free cells, acetic acid yield was approximately 0.9 g/g, the highest final acetate concentration was approximately 46 g/L, and the overall productivity was approximately 0.12 g/(L.h). In the continuous fermentation with immobilized cells, the reactor productivity decreased from 3.2 to 1. 3 g/(L.h) as retention time increased from 16 to 72 h to reach 100% conversion. Compared to free-cell fermentations, the superior performance of the fibrous-bed bioreactor can be attributed to the high density (>30 g/L) of viable cells immobilized in the fibrous bed. The fermentation product, acetic acid, was found to be a noncompetitive inhibitor to the cells. However, the immobilized cells had a higher maximum production rate (pmax) and a higher value for the inhibition rate constant (Kp) than those for the free cells, suggesting that the immobilized cells in the fibrous-bed bioreactor were less sensitive to acetic acid inhibition than the free cells. This improvement in kinetic behaviors for immobilized cells confirms that the fibrous-bed bioreactor can be used as an effective tool for adapting and screening for acetate-tolerant strains.

Journal Article↗

PubMedDate not supplied

Perfusion bioreactor for small diameter tissue-engineered arteries.

A scaleable perfusion bioreactor has been developed for tissue engineering of small diameter arterial constructs. This modular bioreactor allows for dynamic sequential seeding of smooth muscle and endothelial cells, biomechanical stimulation of cells during culture, and monitoring of tissue growth and maturation. Bovine aortic smooth muscle and endothelial cells were seeded onto porous tubular poly(glycolic acid) nonwoven scaffolds and cultured in the bioreactor under pulsatile flow conditions for up to 25 days. Cell proliferation was more than 3-fold after 4 days, smooth muscle cells expressed differentiated phenotype after 16 days, and collagen and elastin were distributed throughout the construct after 25 days of culture. In bioreactor experiments in which the construct lumen was seeded with endothelial cells by perfusion after 13 days of smooth muscle cell culture, endothelial cell seeding efficiency was 100%, and a confluent monolayer was observed in the lumen within 48 h. These data demonstrate that this perfusion bioreactor supports sequential seeding of constructs with smooth muscle and endothelial cells. Dynamic culture under pulsatile flow leads to cellular expression of differentiated function and extracellular matrix deposition toward the development of tissue-engineered arterial constructs.

Animals↗

PubMed1990

Biodegradation of trichloroethylene in continuous-recycle expanded-bed bioreactors.

Experimental bioreactors operated as recirculated closed systems were inoculated with bacterial cultures that utilized methane, propane, and tryptone-yeast extract as aerobic carbon and energy sources and degraded trichloroethylene (TCE). Up to 95% removal of TCE was observed after 5 days of incubation. Uninoculated bioreactors inhibited with 0.5% Formalin and 0.2% sodium azide retained greater than 95% of their TCE after 20 days. Each bioreactor consisted of an expanded-bed column through which the liquid phase was recirculated and a gas recharge column which allowed direct headspace sampling. Pulses of TCE (20 mg/liter) were added to bioreactors, and gas chromatography was used to monitor TCE, propane, methane, and carbon dioxide. Pulsed feeding of methane and propane with air resulted in 1 mol of TCE degraded per 55 mol of substrate utilized. Perturbation studies revealed that pH shifts from 7.2 to 7.5 decreased TCE degradation by 85%. The bioreactors recovered to baseline activities within 1 day after the pH returned to neutrality.

Journal Article↗

PubMed2002

Characterization of membrane bioreactor for dry wine production.

Characteristics of yeast growth and ethanol fermentation were examined in membrane bioreactor using a grape juice. After inoculation, batch fermentation was carried out for 24 h. When yeast growth reached the stationary phase, continuous fermentation was initiated. In continuous fermentation, a linear relationship was observed between cell concentration and dilution rate. In single-vessel membrane bioreactor, the cell concentrations of 18.7 g/l and 76.9 g/l (15 and 60 times higher than that of the batch fermentation, respectively) were observed at dilution rates of 0.1 h(-1) and 0.3 h(-1), respectively. The residual sugar concentration was higher than 10 g/l at the dilution rate of 0.1 h(-1), 0.2 h(-1) or 0.3 h(-1), therefore the single-vessel membrane bioreactor was not suitable for producing dry wine (sugar concentration: 4 g/l or less). In the double-vessel membrane bioreactor, it is most suitable to set the recycle ratio at 0.15 for keeping the sugar concentration below 4 g/l. The productivity of dry wine in the double-vessel membrane bioreactor was 28 times higher than that in the batch fermentation.

Journal Article↗

PubMed2000

Decolorization of heat-treatment liquor of waste sludge by a bioreactor using polyurethane foam-immobilized white rot fungus equipped with an ultramembrane filtration unit.

A bench-scale bioreactor using immobilized fungal cells equipped with an ultramembrane filtration unit was developed as a means of decolorizing brown color components (melanoidins) arising from the heat-treatment liquor (HTL) of waste sludge. Artificial HTL containing 4200 color units of synthetic melanoidin supplemented with 1000 mg/l ethanol was first subjected to decolorization by the fungus Coriolus hirsutus IFO4917 immobilized onto polyurethane foam cubes. Then, the resultant biologically treated HTL was subjected to ultrafiltration to obtain the permeate (filtrate) as the effluent. The retentate (concentrate) of the filtration unit, containing the remaining melanoidin of high molecular weight and extracellular decolorizing enzymes, was returned to the fungal bioreactor to allow further decolorization. This system was operated in a sequencing batch mode under nonsterile conditions. Contamination of the bioreactor with air/water-born microbes markedly lowered the decolorization efficiency. However, this problem was solved by heating the returned concentrate at 50 degrees C for 10 min. Under the almost stable condition of a hydraulic retention time of 2 d in a 1-d cycle sequencing batch mode, about 70% decolorization was routinely achieved using the entire system (bioreactor + ultrafiltration), while the contribution of the fungal bioreactor alone to the decolorization was about 45%.

Journal Article↗