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At least 307 records · Page 17Linked to original sources
PubMed2001

High-rate continuous production of lactic acid by Lactobacillus rhamnosus in a two-stage membrane cell-recycle bioreactor.

It is important to produce L(+)-lactic acid at the lowest cost possible for lactic acid to become a candidate monomer material for promising biodegradable polylactic acid. In an effort to develop a high-rate bioreactor that provides high productivity along with a high concentration of lactic acid, the performance of membrane cell-recycle bioreactor (MCRB) was investigated via experimental studies and simulation optimization. Due to greatly increased cell density, high lactic acid productivity, 21.6 g L(-1) h(-1), was obtained in the reactor. The lactic acid concentration, however, could not be increased higher than 83 g/L. When an additional continuous stirred tank reactor (CSTR) was attached next to the MCRB a higher lactic acid concentration of 87 g/L was produced at significant productivity expense. When the two MCRBs were connected in series, 92 g/L lactic acid could be produced with a productivity of 57 g L(-1) h(-1), the highest productivity among the reports of L(+)-lactic acid that obtained lactic acid concentration higher than 85 g/L using glucose substrate. Additionally, the investigation of lactic acid fermentation kinetics resulted in a successful model that represents the characteristics of lactic acid fermentation by Lactobacillus rhamnosus. The model was found to be applicable to most of the existing data with MCRBs and was in good agreement with Levenspiel's product-inhibition model, and the Luedeking-Piret equation for product-formation kinetics appeared to be effective in representing the fermentation kinetics. There was a distinctive difference in the production potential of cells (cell-density-related parameter in Luedeking-Piret equation) as lactic acid concentration increases over 55 g/L, and this finding led to a more precise estimation of bioreactor performance.

Bioreactors↗
PubMed2001

Bone tissue engineering in a rotating bioreactor using a microcarrier matrix system.

A novel approach was utilized to grow in vitro mineralized bone tissue using lighter-than-water, polymeric scaffolds in a high aspect ratio rotating bioreactor. We have adapted polymer microencapsulation methods for the formation of hollow, lighter-than-water microcarriers of degradable poly(lactic-co-glycolic acid). Scaffolds were fabricated by sintering together lighter-than-water microcarriers from 500 to 860 microm in diameter to create a fully interconnected, three-dimensional network with an average pore size of 187 microm and aggregate density of 0.65 g/mL. Motion in the rotating bioreactor was characterized by numerical simulation and by direct measurement using an in situ particle tracking system. Scaffold constructs established a near circular trajectory in the fluid medium with a terminal velocity of 98 mm/s while avoiding collision with the bioreactor wall. Preliminary cell culture studies on these scaffolds show that osteoblast-like cells readily attached to microcarrier scaffolds using controlled seeding conditions with an average cell density of 6.5 x 10(4) cells/cm(2). The maximum shear stress imparted to attached cells was estimated to be 3.9 dynes/cm(2). In addition, cells cultured in vitro on these lighter-than-water scaffolds retained their osteoblastic phenotype and showed significant increases in alkaline phosphatase expression and alizarin red staining by day 7 as compared with statically cultured controls.

Alkaline Phosphatase↗
PubMed2006

Bioreactor technology: a novel industrial tool for high-tech production of bioactive molecules and biopharmaceuticals from plant roots.

Plants are the richest source for different bioactive molecules. Because of the vast number of side effects associated with synthetic pharmaceuticals, medical biotechnologists turned to nature to provide new promising therapeutic molecules from plant biofactories. The large-scale availability of the disease- and pesticide-free raw material is, however, restricted in vivo. Many bioactive plant secondary metabolites are accumulated in roots. Engineered plants can also produce human therapeutic proteins. Vaccines and diagnostic monoclonal antibodies can be won from their roots, so that engineered plants hold immense potential for the biopharmaceutical industry. To obtain sufficient amounts of the plant bioactive molecules for application in human therapy, adventitious and hairy roots have to be cultured in in vitro systems. High-tech pilot-scale bioreactor technology for the establishment of a long-term adventitious root culture from biopharmaceutical plants has recently been established. In this review, I briefly discuss a technology for cultivating bioactive molecule-rich adventitious and hairy roots from plants using a high-tech bioreactor system, as well as the principles and application of genome-restructuring mechanisms for plant-based biopharmaceutical production from roots. High-tech bioreactor-derived bioactive phytomolecules and biopharmaceuticals hold the prospect of providing permanent remedies for improving human well-being.

Biopharmaceutics↗
PubMed2001

Measurement of bioreactor perfusion using dynamic contrast agent-enhanced magnetic resonance imaging.

Dynamic magnetic resonance imaging was used to monitor solute diffusion through aggregates of Chinese hamster ovary cells growing on macroporous carriers in a fixed-bed bioreactor. Diffusion-weighted (1)H magnetic resonance imaging (MRI) and scanning electron microscopy demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the periphery of the carriers. T(1)-weighted magnetic resonance imaging measurements of the inflow of a commonly used magnetic resonance contrast agent, gadolinium-diethylenetriaminopentaacetic acid (Gd-DTPA), showed that migration of the agent through the peripheral cell masses could be explained by diffusion. However, appearance of the contrast agent in the center of the carriers was too fast to be explained by simple diffusion and indicated that these regions were perfused by convective flow. The average diffusivity of Gd-DTPA through the cell mass was found to be (2.4 +/- 0.2) x 10(-10) m(2) sec(-) (mean +/- SEM). This technique will be useful in the characterization and development of high-cell-density bioreactor systems, in which solute transport plays a critical role in cell growth and physiology.

Animals↗
PubMed2001

Enzyme microgels in packed-bed bioreactors with downstream amperometric detection using microfabricated interdigitated microsensor electrode arrays.

In this article, we describe the use of pH- responsive hydrogels as matrices for the immobilization of two enzymes, glucose oxidase (GOx) and glutamate oxidase (GlutOx). Spherical hydrogel beads were prepared by inverse suspension polymerization and the enzymes were immobilized by either physical entrapment or covalent immobilization within or on the hydrogel surface. Packed-bed bioreactors were prepared containing the bioactive hydrogels and these incorporated into flow injection (FI) systems for the quantitation of glucose and monosodium glutamate (MSG) respectively. The FI amperometric detector comprised a microfabricated interdigitated array within a thin-layer flow cell. For the FI manifold incorporating immobilized GOx, glucose response curves were found to be linear over the concentration range 1.8-280 mg dL(-1) (0.1-15.5 mM) with a detection limit of 1.4 mg dL(-1) (0.08 mM). Up to 20 samples can be manually analyzed per hour, with the hydrogel-GOx bioreactor exhibiting good within-day (0.19%) precision. The optimized FI manifold for MSG quantitation yielded a linear response range of up to 135 mg dL(-1) (8 mM) with a detection limit of 3.38 mg dL(-1) (0.2 mM) and a throughput of 30 samples h(-1). Analysis of commercially produced soup samples gave a within-day precision of 3.6%. Bioreactors containing these two physically entrapped enzymes retained > 60% of their initial activities after a storage period of up to 1 year.

Aspergillus niger↗
PubMed2002

A novel multi-coaxial hollow fiber bioreactor for adherent cell types. Part 1: hydrodynamic studies.

A novel multi-coaxial bioreactor for three-dimensional cultures of adherent cell types, such as liver, is described. It is composed of four tubes of increasing diameter placed one inside the other, creating four spatially isolated compartments. Liver acinar structure and physiological parameters are mimicked by sandwiching cells in the space between the two innermost semi-permeable tubes, or hollows fibers, and creating a radial flow of media from an outer compartment (ECC), through the cell mass compartment, and to an inner compartment (ICC). The outermost compartment is created by gas-permeable tubing, and the housing is used to oxygenate the perfusion media to periportal levels in the ECC. Experiments were performed using distilled water to correlate the radial flow rate (Q(r)) with (1) the pressure drop (DeltaP) between the media compartments that sandwich the cell compartment and (2) the pressure in the cell compartment (P(c)). These results were compared with the theoretical profile calculated based on the hydraulic permeability of the two innermost fibers. Phase-contrast velocity-encoded magnetic resonance imaging was used to visualize directly the axial velocities inside the bioreactor and confirm the assumptions of laminar flow and zero axial velocity at the boundaries of each compartment in the bioreactor. Axial flow rates were calculated from the magnetic resonance imaging results and were similar to the measured axial flow rates for the previously described experiments.

Artificial Organs↗
PubMed2002

Inline characterization of cell concentration and cell volume in agitated bioreactors using in situ microscopy: application to volume variation induced by osmotic stress.

A new in situ microscope (ISM) was developed and tested to perform in-line monitoring of average cell volume and cell concentration in agitated cultures subjected to osmotic stress. The ISM is directly immersed into the agitated broth in a bioreactor and generates still images of cells by using pulsed luminescent diode illumination and a virtual probe volume defined by depth of focus. This technique allows the acquisition of microscopic still images without mechanical sampling techniques. The front end of the sensor fits into a standard 25-mm port and it can be steam sterilized together with the bioreactor. The automatic image evaluation generates signals of the cell concentration and the average cell volume with a time resolution of a few minutes per data point (if a 200 MHz PC is used). Without the need for evaluation, the images can be acquired and stored at a rate of one image per 0.6 s. Hansenula anomala was cultivated as batch fermentation and monitored inline with the ISM. The ISM signal of the cell concentration agreed well with referential growth curves that were obtained from counting with a hemocytometer. The ISM signal of the average cell volume shows a gradual volume reduction as a result of the aging of the culture, and it monitors an abrupt and strong cell contraction if osmotic shocks are generated in the bioreactor. Systematic in vitro studies of osmotic shocks were performed by applying the ISM to agitated culture samples of H. anomala. The volume signal of H. anomala during osmotic shocks showed a very fast cell contraction within less than a second. Within half an hour after the shocks, no signal drifts were observed, which would indicate volume restoration. These findings suggest that the ISM volume signal can be used as an inline indicator of osmotic stress in cell cultures.

Bioreactors↗
PubMed2001

Indirect measurement of water content in an aseptic solid substrate cultivation pilot-scale bioreactor.

A lack of models and sensors for describing and monitoring large-scale solid substrate cultivation (SSC) bioreactors has hampered industrial development and application of this type of process. This study presents an indirect dynamic measurement model for a 200-kg-capacity fixed-bed SSC bioreactor under periodic agitation. Growth of the filamentous fungus Gibberella fujikuroi on wheat bran was used as a case study. Real data were preprocessed using previously reported methodology. The model uses CO2 production rate and inlet air conditions to estimate average bed water content and average bed temperature. The model adequately reproduces the evolution of the average bed water content and can therefore be used as an on-line estimator in pilot-scale SSC bioreactors. To obtain a reasonable fit of the bed temperature, however, inlet air humidity measurements will have to be adjusted with a data reconciliation algorithm. Good estimation of temperature is important for the future design of improved water content estimation using state observers. The model also provides insight into understanding the complex behavior of the dynamic system, which could prove useful when establishing advanced model-based operational and control strategies.

Bioreactors↗
PubMed2003

Effect of mixing rate on beta-carotene production and extraction by dunaliella salina in two-phase bioreactors.

beta-Carotene has many applications in the food, cosmetic, and pharmaceutical industries; Dunaliella salina is currently the main source for natural beta-carotene. We have investigated the effect of mixing rate and whether it leads to the facilitated release of beta-carotene from the cells of Dunaliella salina in two-phase bioreactors. Three pairs of bioreactors were inoculated at the same time, operated at 100, 150, and 170 rounds per minute, respectively, and illuminated with a light intensity of 700 micromol m(-2) s(-1). Each pair consisted of one bioreactor containing only aqueous phase for the blank and one containing the water phase together with dodecane, which is biocompatible with the cells. Comparison of the viability and growth of the cells grown under different agitation rates shows that 170 rpm and 150 rpm are just as good as 100 rpm. The presence and absence of the organic phase also has no influence on the viability and growth of the cells. In contrast to the growth rate, the extraction rate of beta-carotene is influenced by the stirrer speed. The extraction rate increases at a higher stirring rate. The effectiveness of extraction with respect to power input is comparable for all the applied mixing rates, even though it is slightly lower for 100 rpm than the others. The chlorophyll concentration in the organic phase remained very low during the experiment, although at higher mixing rates, chlorophyll impurity increased up to 3% (w/w) of the total extracted pigments. At 170 rpm carotenoid and chlorophyll undergo the highest extraction rate for both pigments-0.5% of the chlorophyll and 6% of the carotenoid is extracted.

Bioreactors↗
PubMed2004

Milking microalga Dunaliella salina for beta-carotene production in two-phase bioreactors.

A new method was developed for production of beta-carotene from Dunaliella salina. Cells were grown in low light intensity and then transferred to a production bioreactor illuminated at a higher light intensity. It was a two-phase bioreactor consisting of an aqueous and a biocompatible organic phase. Mixing of the cells and extraction were performed by recirculation of the organic phase. Two experiments were performed. In the first experiment, bioreactors were operated at two different solvent recirculation rates of 150 and 200 mL min(-1). The beta-carotene extraction rate increased significantly at the higher recirculation rate, without exerting any influence on cell number and viability. A second experiment was carried out at a recirculation rate (200 mL min(-1)) appropriate for the study of long-term production of beta-carotene. The results show that D. salina at high light intensity remained viable for a long period (>47 days) in the presence of a biocompatible organic phase; however, cell growth was very slow. beta-Carotene could be continuously extracted to the organic phase; the cells continued to produce beta-carotene and the extracted molecules were continuously reproduced. As a result, beta-carotene was continuously removed ("milked") from the cells. beta-Carotene extraction efficiency in this system was >55%, and productivity was 2.45 mg m(-2) day(-1), much higher than that of commercial plants.

Bioreactors↗
PubMed2001

Optical method for the determination of the oxygen-transfer capacity of small bioreactors based on sulfite oxidation.

The growth of microorganisms may be limited by operating conditions which provide an inadequate supply of oxygen. To determine the oxygen-transfer capacities of small-scale bioreactors such as shaking flasks, test tubes, and microtiter plates, a noninvasive easy-to-use optical method based on sulfite oxidation has been developed. The model system of sodium sulfite was first optimized in shaking-flask experiments for this special application. The reaction conditions (pH, buffer, and catalyst concentration) were adjusted to obtain a constant oxygen transfer rate for the whole period of the sulfite oxidation reaction. The sharp decrease of the pH at the end of the oxidation, which is typical for this reaction, is visualized by adding a pH dye and used to measure the length of the reaction period. The oxygen-transfer capacity can then be calculated by the oxygen consumed during the complete stoichiometric transformation of sodium sulfite and the visually determined reaction time. The suitability of this optical measuring method for the determination of oxygen-transfer capacities in small-scale bioreactors was confirmed with an independent physical method applying an oxygen electrode. The correlation factor for the maximum oxygen-transfer capacity between the chemical model system and a culture of Pseudomonas putida CA-3 was determined in shaking flasks. The newly developed optical measuring method was finally used for the determination of oxygen-transfer capacities of different types of transparent small-scale bioreactors.

Bioreactors↗
PubMed2004

Evaluation of baculovirus expression vectors with enhanced stability in continuous cascaded insect-cell bioreactors.

Continuous protein production with baculovirus expression vectors in insect-cell bioreactors is characterized by a dramatic drop in heterologous protein production within a few weeks. This is mainly due to the spontaneous deletion of the heterologous gene(s) from the baculovirus genome and/or to the rapid accumulation of defective interfering baculoviruses (DIs). Cell culture experiments with bacmid-derived baculoviruses showed that spontaneous deletions in the foreign bacterial artificial chromosome (BAC) sequences readily occurred. These deletions correlated with a low density of baculovirus homologous (repeat) regions (hrs), which are located dispersed throughout the baculovirus genome and are believed to act as origins of viral DNA replication (oris). To test the hypothesis that deletions are more likely to occur in regions with a low ori density, the properties of bacmid-derived baculoviruses with an additional hr in the unstable BAC sequences were compared to the standard bacmid-derived baculovirus in a continuous cascaded insect-cell bioreactor configuration. All viruses were equipped with a green fluorescent protein (GFP) gene and a gene encoding the classical swine fever virus E2 glycoprotein (CSFV-E2). The insertion of an extra hr in the BAC vector led to improved genetic stability of adjacent sequences, resulting in prolonged protein expression. The maintenance of the BAC sequences appeared to be dependent on the orientation of the inserted hr. The advantages of the utilization of hrs to improve the stability of baculovirus expression vectors for the large-scale protein production in insect-cell bioreactors are discussed.

Animals↗
PubMed2004

Parameter oscillations in a very high gravity medium continuous ethanol fermentation and their attenuation on a multistage packed column bioreactor system.

The quasi-steady-states, marked by small fluctuations of residual glucose, ethanol, and biomass concentrations, and sustainable oscillations marked by big fluctuations of these monitored fermentation parameters were observed during the continuous ethanol fermentation of Saccharomyces cerevisiae when very high gravity media were fed and correspondingly high ethanol concentrations reached. A high ethanol concentration was shown to be one of the main factors that incited these oscillations, although the residual glucose level affected the patterns of these oscillations to some extent. The lag response of S. cerevisiae to high ethanol stress that causes the shifts of morphology, viability loss, and death of yeast cells is assumed to be one of the probable mechanisms behind these oscillations. It was predicted that the longer the delay of this response was, the longer the oscillation periods would be, which was validated by the experimental data and the comparison with the oscillatory behaviors reported for the ethanologen bacterium, Zymomonas mobilis. Furthermore, three tubular bioreactors in series were arranged to follow a stirred tank bioreactor to attenuate these oscillations. However, exaggerated oscillations were observed for the residual glucose, ethanol, and biomass concentrations measured in the broth from these tubular bioreactors. After the tubular reactors were packed with Intalox ceramic saddle packing, these oscillations were effectively attenuated and quasi-steady-states were observed during which there were very small fluctuations of residual glucose, ethanol, and biomass within the entire experimental run.

Apoptosis↗
PubMed2005

Development of a small-scale bioreactor: application to in vivo NMR measurement.

A perfused bioreactor allowing in vivo NMR measurement was developed and validated for Eschscholtzia californica cells. The bioreactor was made of a 10-mm NMR tube. NMR measurement of the signal-to-noise ratio was optimized using a sedimented compact bed of cells that were retained in the bioreactor by a supporting filter. Liquid medium flow through the cell bed was characterized from a mass balance on oxygen and a dispersive hydrodynamic model. Cell bed oxygen demand for 4 h perfusion required a minimal medium flow rate of 0.8 mL/min. Residence time distribution assays at 0.8-2.6 mL/min suggest that the cells are subjected to a uniform nutrient environment along the cell bed. Cell integrity was maintained for all culture conditions since the release of intracellular esterases was not significant even after 4 h of perfusion. In vivo NMR was performed for (31)P NMR and the spectrum can be recorded after only 10 min of spectral accumulation (500 scans) with peaks identified as G-6P, F-6P, cytoplasmic Pi, vacuolar Pi, ATP(gamma) and ADP(beta), ATP(alpha) and ADP(alpha), NADP and NDPG, NDPG and ATP(beta). Cell viability was shown to be maintained as (31)P chemical shifts were constant with time for all the identified nuclei, thus suggesting constant intracellular pH.

Bacterial Proteins↗
PubMed2005

Detoxification of organophosphate nerve agents by immobilized dual functional biocatalysts in a cellulose hollow fiber bioreactor.

A whole-cell technology for detoxification of organophosphates based on genetically engineered Escherichia coli cell expressing both cellulose-binding domain (CBD) and organophosphorus hydrolase (OPH) onto cell surface was reported recently (Wang et al., 2002). This study reports the application of these biocatalysts when immobilized in a cellulose hollow fiber bioreactor (HFB) for the biodetoxification of a model organophosphate, paraoxon, in a continuous flow mode. In 24 h, 0.79 mg wet cell/cm2 fiber surface were immobilized onto cellulose fibers specifically and strongly through the cellulose binding domain, forming a monolayer demonstrated by Scanning Electronic Micrograph, and essentially no cell was washed away by washing buffer. The immobilized biocatalyst had a high performance of detoxifying paraoxon solution of 5,220 mumol/h x L reactor or 990 mumol/h x m2 reactor. The immobilized biocatalysts maintained a stable degradation capacity for 15 uses over a period of 48 days with only 10% decline in degradation efficiency under operating and storage conditions. In addition, the bioreactor was easily regenerated by washing with 1% sodium dodecyl sulfate (SDS), with 86.7% immobilization capacity and 93.9% degradation efficiency recovery. This is the first report using the HFB in a non-traditional way, immobilizing whole-cell biocatalysts by specific adhesion thus rendering the catalysis operation the advantages of low pressure drop, low shear force, and low energy requirement. The successful application of this genetically engineered dual functional E. coli strain in a model bioreactor shows its promise in large-scale detoxification of organophosphate nerve agents in bulk liquid phase.

Aryldialkylphosphatase↗
PubMed2005

A restructured framework for modeling oxygen transfer in two-phase partitioning bioreactors.

This communication proposes a mechanistic modification to a recently published method for analyzing oxygen mass transfer in two-phase partitioning bioreactors (Nielsen et al., 2003), and corrects an oversight in that paper. The newly proposed modification replaces the earlier empirical approach, which treated the two liquid phases as a single, homogeneous liquid phase, with a two-phase mass transfer model of greater fundamental rigor. Additionally, newly developed empirical models are presented that predict the mass transfer coefficient of oxygen absorption in both aqueous medium and an organic phase (n-hexadecane) as a function of bioreactor operating conditions. Experimental values and theoretical predictions of mass transfer coefficients in two-phase dispersions, k(L)a(TP), are compared. The revised approach more clearly demonstrates the potential for oxygen mass transfer enhancement by organic phase addition, one of the motivations for employing a distinct second phase in a partitioning bioreactor.

Absorption↗
PubMed2005

Continuous operation of foamed emulsion bioreactors treating toluene vapors.

Continuous operation of a new bioreactor for air pollution control called the foamed emulsion bioreactor (FEBR) has been investigated. The effect of several liquid feeding strategies was explored. The FEBR exhibited high and steady toluene removal performance (removal efficiency of 89%-94%, elimination capacity of 214-226 g/m3h at toluene inlet concentration of 1 g/m3) for up to 360 h, when 20% of the culture was replaced every 24 h by a nutrient solution containing 4 g/L of potassium nitrate as a nitrogen source. This feeding mode supported a high cell activity measured as INT reduction potential and active cell growth without being subject to nitrogen limitation. In comparison, operating the FEBR with the liquid in a closed loop (i.e., batch) resulted in a significant decrease of both the removal efficiency of toluene and INT reduction activity. Operation with feeding active cells resulted in stable and effective treatment, but would require a significant effort for mass culture preparation. Therefore, the continuous process with periodically feeding nutrients was found to be the most practical and effective operating mode. It also allows for stable operation, as was shown during removal of low concentration of toluene or after pollutant starvation. Throughout the study, INT reduction measurements provided insight into the process. INT reduction activity data proved that under normal operating conditions, the FEBR performance was limited by both the kinetics and by mass transfer. Overall, the results illustrate that engineered gas-phase bioreactors can potentially be more effective than conventional biofilters and biotrickling filters for the treatment of air pollutants such as toluene.

Air Pollutants↗
PubMed2005

Characterization of mixing in a novel wavy-walled bioreactor for tissue engineering.

The wavy-walled bioreactor (WWB) possesses a novel geometry comprised of walls with sinusoidal waves that mimic baffles in an effort to promote mixing. This geometry provides a unique hydrodynamic environment suitable for the cultivation of mammalian cells and tissues and the investigation of fluid mechanical effects on cell and tissue growth and development. In the present study, mixing in WWB was characterized and compared to that in a conventional spinner flask (SF). The key parameters included in this characterization were mixing time, residence time distribution (RTD), and dissolved oxygen concentration during engineered cartilage tissue cultivation. Factors that influenced mixing in WWB included wave amplitude, agitation rate, and the ratio of the impeller diameter to the tank diameter (D/T). Data obtained from RTD and acid base neutralization studies confirmed the presence of different mixing zones in WWB. A theoretical comparison of WWB to a baffled spinner flask (BSF) using computational fluid dynamics (CFD) modeling predicted that while enhanced mixing was achieved in wavy-walled and BSF bioreactors, the shear stresses applied on tissue constructs were 15% lower in WWB. Improved mixing was achieved in WWB compared to the SF at similar D/T ratios, verified by improved oxygen transport and increased dispersion. However, for lower D/T ratios mixing in WWB was not necessarily improved. This study demonstrated the importance of characterization of mixing by showing the impact of even minor changes in bioreactor geometry and operating conditions.

Bioreactors↗