Interpretation of the gas residence time distributions in large stirred tank reactors

The behaviour of dispersed gas in large aerated stirred tank reactors is modelled by means of a Markov-process, which distinguishes between small recirculation bubbles with stagnant gas content, large rising bubbles with active gas content and exchange of stagnant and active gas contents, the gas exchange region at the impeller. The measurements of the gas residence time distributions (RTDs) in an 1.5 m³ aerated stirred tank reactor with water and Penicillium chrysogenum cultivation medium are interpreted by this model.List of Symbols CPR CO₂ production rate - OTR oxygen transfer rate - PRS pseudo random signal - RTD residence time distribution - V gas volume - recirculation coefficient - mean gas residence time Indices act active gas - ex gas exchange - stagn stagnant gas - tot total gas Dedicated to the 65th birthday of Professor Fritz Wagner.The authors thank Hoechst AG for the strain and the medium components, the GBF for the support of the experiments and H.M. Rüffer thanks the Verband der Chemischen Industrie for a Fond-der-Chemie scholarship.     

Comparison of the performances of stirred tank and airlift tower loop reactors.

Following a consideration of the prerequisites for reactor comparison and the fundamental differences between stirred tank and airlift tower loop reactors, their performances are compared for the production of secondary metabolites: penicillin V by Penicillium chrysogenum, cephalosporin C by Cephalosporium acremonium, and tetracycline by Streptomyces aureofaciens. In stirred tank reactors, cell mass concentrations, volumetric productivities, and specific power inputs are higher than in airlift tower loop reactors. In the latter, efficiencies of oxygen transfer are higher, and specific productivities with regard to power input, substrate and oxygen consumptions, and yield coefficients of product formation with regard to substrate and oxygen consumptions are considerably higher than in stirred tank reactors. The prerequisites for improved performance are discussed.     

Substrate effects in tower loop reactors

Summary Hansenula polymorpha was cultivated in a bubble column loop bioreactor employing ethanol and/or glucose as substrates. By varying the substrate concentration, the cultivations were carried out in non-limited, substrate limited and oxygen transfer limited growth ranges. The influence of the transitions from one range to another on reactor performance (OTR,k _L a, a) and cell productivity () were investigated. When employing ethanol as a substrate, the concentration considerably influences the fluid dynamics, mass transfer phenomena and cell productivity. When employing glucose as a substrate, glucose repression occurs. At high glucose concentrations no transition into the oxygen transfer limited growth is possible. The ethanol produced during the glucose repression influences the fluid dynamics, mass transfer phenomena and productivity. With decreasing glucose concentration the glucose repression can be gradually eliminated.     

A simplified model of hydrodynamics in airlift loop reactors

As a function of the gas throughput the following parameters were measured in an external loop reactor with a riser diameter of 0.6 m and a gassed liquid height of 8.6 m: integral and local values of gas hold-up; liquid velocities; mixing times and axial dispersion coefficients of the liquid phase. The height of the reactor could be altered by reconstruction. Measurements were also carried out with lower heights than 8.6 m. Besides pure water, aqueous solutions of coalescing, non-coalescing and viscosity-increasing substances were used as model systems. With the results a general relationship between superficial gas velocity, gas hold-up and liquid velocity was established. This hydrodynamic model uses the relative velocity between gas and liquid phase as the fundamental parameter. The generally valid model consists of one term for the homogeneous and of two additional terms for the heterogeneous flow regime.     

Cultivation of Hansenula polymorpha in tower loop reactors

Summary Hansenula polymorpha was cultured for extended periods in an air lift tower loop reactor (15 cm in diameter with a 275 cm bubbling layer height) with ethanol and/or glucose as the substrates. At constant operation conditions variations of the following parameters were measured: the consumption of the substrate and oxygen, the production of CO₂ and biomass, the longitudinal concentration profile of dissolved oxygen, the oxygen and substrate yield coefficients, the respiratory quotient and the specific interfacial area and volumetric mass transfer coefficient. The influence of the microorganisms on the oxygen transfer rate is discussed especially in the case of glucose repression.     

Identification of mass-transfer parameters and process simulation of SCP production process in airlift tower reactors with an external loop

A distributed parameter model for simulation of SCP-production processes in tower reactors with an outer loop was developed by considering substrate, cell, and CO(2) balances in the liquid phase, and O(2) and CO(3) balances in the ges phase and taking into account variations of dissolved oxygen concentration, pressure, and k(L)a along the column, as well as double substrate Monod kinetics. This model was used to describe the cultivation of Hansenula polymorpha in a tower-loop reactor (height 275 cm, diameter 15 cm). Parameter identification and process simulation were carried out by a hybrid computer. The variation of identified mass transfer parameters with fermentation time and operation mode is considered employing ethanol and glucose substrate, respectively. Relationships among k(L)a, substrate concentration, and superficial gas velocity were developed to facilitate the layout and simulation of pilot-plant reactors.     

Investigations of cephalosporin C production in an airlift tower loop reactor

Summary Cephalosporin C was produced by Cephalosporium acremonium in a 60 l airlift loop reactor on complex medium (with 30 kg/m³ peanut flour) in fed-batch operation. A final product concentration of 5 kg/m³ and a maximum productivity of 45 g/m³ h were attained. On-line analysis was used to determine ammonia, methionine, phosphate, reducing sugar and cephalosporin C by an autoanalyser, glucose by a flow injection analyser and cephalosporin C, penicillin N, deacetoxycephalosporin C, deacetylce-phalosporin C and methionine by HPLC. The volumetric productivity of the stirred tank reactor was higher than that of the airlift reactor because of differences in cell concentration. Specific productivities in relative to cell mass were similar in the two reactors. The substrate yield coefficient in the airlift reactor was twice that in the stirred tank reactor.Nomenclature E _o2 efficiency of oxygen transfer with regard to the specific power input - K _La volumetric mass transfer coefficient - OTR oxygen transfer rate - P power input - PR volumetric productivity of CPC - q _a volumetric aeration rate/broth volume (vvm) - SPR specific productivity with regard to RNA - V _L broth volume in reactor - z relative height of the aerated reactor     

Comparison of single- and three-stage tower loop reactors

Summary Hansenula polymorpha was cultured for long periods in 254 cm high single and three-stage countercurrent tower loop reactors 20 cm in diameter using ethanol as a substrate in the absence and presence of antifoam agents (Desmophen 3600 and/or soy oil). In the absence of antifoam agents in the three-stage column, much higher volumetric mass transfer coefficients were attained than in the corresponding single-stage column. The cell productivity in the former, however, was only slightly higher than in the single-stage column due to considerable enrichment of the cells in the foam and nonuniform cell concentration distribution in the three-stage column. In the presence of antifoam agents the three-stage column has a higher cell productivity, OTR, k_L a and a lower specific energy requirement with regard to the absorbed oxygen and/or produced cell mass than the single stage column. The reactor performance is especially high if the bubbling layer height is reduced to 20 cm. Soy oil has considerably less foam eliminating property than Desmophen. Since the soy oil is metabolized by the yeast, large amounts are needed to operate these reactors.     

Mixing time in airlift reactors during citric acid fermentation

Citric acid fermentations using strain Aspergillus niger were carried out in three airlift reactors of volumes of 10, 35 and 200 liters. Mixing times were measured at the beginning and the end of fermentation. It has been shown that the mixing time at the end of fermentation is approximately equal to the duration of one circulation period. This was due to the flow regime transition caused by the change of rheological properties of the mould broth during fermentation.     

Fluiddynamic characterization of airlift tower loop bioreactors with and without motionless mixtures

In a 60 l airlift tower reactor with outer loop fluiddynamical measurements were carried out in presence of three motionless mixer modules (Type SMV, Sulzer) in water, 0.6%, 0.9% and 1.2% CMC solutions. The global mixing properties were determined in the liquid and gas phases by tracers. Detailed local measurements revealed differences of local flow patterns and mixing properties in the unhindered riser and in the immediate wake of the mixer module. The local liquid velocities were measured by the pseudorandom heat pulse technique. The local bubble velocities were determined by the ultrasound Doppler technique. The dependence of liquid velocity, gas velocity and gas holdup on the superficial gas velocity were determined. The radial profiles of the mean liquid velocities and their standard deviations were evaluated in water and CMC solutions upstream and downstream of the motionless mixer modules. The radial profiles of the mean large-bubble velocities and mean small-bubble velocities and their standard deviations were determined as well. The influence of the presence of the motionless mixers in the riser on these properties was evaluated.List of Symbols Bo _L w _L L/D _L liquid Bo number - Bo _G w _G L/D _G ,gas Bo number - c tracer concentration - CMC carboxymelthylcellulose - D _G gas dispersion coefficient - D ₁ local liquid dispersion coefficient - D _L liquid dispersion coefficient - D _r riser diameter - d distance between transmitter and detector of the heat pulse probe - E _G gas holdup - HBV horizontal bubble velocity - HLBV horizontal large-bubble velocity - HSBV horizontal small-bubble velocity - L length of the column - l relative distance of the detector position from the tracer injection with respect to L - LBV large-bubble velocity - n number of circulations - OHBV overall horizontal bubble velocity - OVBV overall vertical bubble velocity - P power input - Pe ₁ w ₁d/D₁, local liquid Peclet number - SBV small-bubble-velocity - V _L liquid volume - VBV vertical bubble velocity - VLBV vertical large-bubble velocity - VSBV vertical small-bubble velocity - w _G gas velocity - w ₁ local liquid velocity - w _L liquid velocity - w _SG superficial gas velocity - w _SL superficial liquid velocity - mean residence time of the liquid in the riser H.M.R. thank the Verband der Chemischen Industrie for a Fund der Chemie scholarship     

Cultivation of recombinant E. coli and production of fusion protein in 60-1 bubble column and airlift tower loop reactors.

E. coli K12 with multicopy plasmid (lambda PR-promoter and temperature-sensitive lambda cI 857 repressor) was cultivated in 60-l bubble column and airlift tower loop reactors. The medium composition, cell concentration, and intracellulary enzyme activity were monitored on-line during batch, fed-batch, and continuous cultivations. The specific growth rates, cell mass yield coefficients, plasmid stabilities, productivities of the amount of active fusion protein (beta-galactosidase activity), concentrations and yields of acetic acid, and volumetric oxygen transfer coefficient were evaluated for different medium compositions and cultivation conditions. The enzyme activity was also monitored during the temperature induction. The results evaluated in the 60-l bubble column and airlift tower loop reactors are compared with those evaluated in a 1-1 stirred-tank reactor.     

Liquid residence time distributions in immobilized cell bioreactors

Previous work has demonstrated that high ethanol productivities can be achieved using yeast or bacterial cells adsorbed onto the surface of ion exchange resin in vertical packed bed bioreactors. The present work quantitatively characterizes the overall degree of backmixing in such reactors at two scales of operation: 2.0 and 8.0 L. Stimulus-response experiments, using two solvents (2,3-butanediol and 2-ethoxyethanol) as tracers, were performed to measure the liquid phase residence time distribution (RTD) during continuous ethanol fermentations using the yeast Saccharomyces cerevisiae and the bacterium Zymomonas mobilis at the 2-L scale, and with S. cerevisiae at the 8-L scale. In order to separately determine the effects of liquid flow rate and gas evolution on the degree of mixing, stimulus-response experiments were also performed in the systems without microbial cells present. The evolution of CO(2) was found to dramatically increase the extent of mixing; however, the tanks-in-series model for non-ideal flow represented the systems adequately. The packed beds were equivalent to over 70 tanks-in-series during abiotic operation while during fermentations, with similar liquid flow rates, they ranged in equivalence from 35 to 15 tanks-in-series. This increased knowledge of the overall degree of mixing in packed bed, immobilized cell bioreactors will allow for more accurate kinetic modelling and efficient scale up of the process.     

Effect of scale-up on average shear rates for aerated non-Newtonian liquids in external loop airlift reactors

Average shear rates have been estimated experimentally in a 700-dm3 external loop airlift reactor. Aqueous pseudoplastic carboxymethylcellulose and xanthan gum solutions were used to simulate non-Newtonian behavior of biological media. Average shear rates of non-Newtonian solutions were found by analogy with Newtonian glycerol solutions using downcomer liquid velocity as the measurable parameter. Due to the complexity of local shear rate measurement, an average shear rate was assumed to exist and is proportional to superficial gas velocity. The data from this work and those in the literature were used in producing a new correlation for estimating average shear rates as a function of superficial gas velocity, geometry, and dispersion height. Wall shear rates were found to be significant. The ratio of wall shear rates to bulk shear rates were varied from 5% to 40%. Furthermore, it has been found that shear rates generated in airlift loop reactors are lower than those generated in bubble columns. Copyright 1999 John Wiley & Sons, Inc.     

Characterisation of liquid and gas flow in jet loop reactors

The fluid dynamics in jet loop fermenters has been subject to experimental and theoretical investigation. It is demonstrated that by determination of Euler number, Bodenstein number, and residence time distribution for the gas phase it is possible to perform a reliable characterization of the fermenters. It can be shown that the investigated jet loop fermenters with internal loop closely resemble ideally mixed tanks.     

Influence of bovine serum albumin on the growth of hybridoma cells in airlift loop reactors using serum-free medium

Summary Hybridoma cells were grown in serum-free media using different culture systems: stationary culture, spinner flask and a laboratory-scale airlift loop reactor. Influence of bovine serum albumin (BSA) on growth and product formation was only found in the airlift loop reactor.     

Characterization of a pilot plant airlift tower loop bioreactor: II. Evaluation of global mixing properties of the gas phase during yeast cultivation

Saccharomyces cerevisiae was cultivated in a 4-m(3) pilot plant airlift tower loop reactor with a draft tube in batch and continuous operations and for comparison in a laboratory airlift tower loop reactor of 0.08 m(3) volume. The reactors were characterized during and after the cultivation by measuring the distributions of the residence times of the gas phase with pseudostochastic tracer signals and mass spectrometer and by evaluating the mixing in the liquid phase with a pulse-shaped volatile tracer signal and mass spectrometer as a detector. The mean residence times and the intensities of the axial mixing in the riser and downcomer, the circulation times of the gas phase, and the fraction of the recirculated gas phase were evaluated and compared.     

Dynamics of biofilm detachment in biofilm airlift suspension reactors

The dynamic change in the overall detachment rate of spherical biofilms in a biofilm airlift suspension reactor was measured after a downshift of the substrate loading rate to zero while all other conditions remained constant. In contrast to the expectations, the overall detachment rate decreased rapidly to a nearly stable level. Correlations available from literature were not able to describe this phenomenon. Concepts were formulated which can describe the observations from this study. Research under dynamic conditions and careful monitoring of the biofilm surface area and biofilm morphology are necessary to elucidate and discriminate biofilm detachment mechanisms. (c) 1995 John Wiley & Sons, Inc.     

Mixing in liquid-impelled loop reactors

The liquid-impelled loop reactor is a new column-type bioreactor. The design of this device is based on the principle of the air-lift loop reactor. In the external-loop configuration used in this work, descending perfluorochemical drops bring about circulation of the continuous aqueous phase. Mixing of this continuous phase is characterized per section of the rector. Axial-dispersion coefficients for the tube with two-phase flow are determined and correlated with the energy dissipation in the tube. Comparisons with similar systems such as bubble columns and air-lift loop reactors are made. Overall mixing parameters are derived and used for calculation of the number of circulatins needed to achieve a certain degree of mixing. The hydrodynamic model from previous work is tested for the reactor configurations of this work. It can be useful to calculate circulation times.     

Characterization of a pilot plant airlift tower loop reactor: III. Evaluation of local properties of the dispersed gas phase during yeast cultivation and in model media

The local properties of the dispersed gas phase (gasholdup, bubble diamater, and bubble velocity) were measured and evaluated at different positions in the riser and downcomer of a pilot plant reactor and, for comparison, in a laboratory reactor. These were described in Parts I and II of this series of articles during yeast cultivation and with model media. In the riser of the pilot plant reactor, the local gas holdup and bubble velocities varied only slightly in axial direction. The gas holdup increased considerably, while the bubble velocity increased only slightly with aeration rate. The bubble size diminished with increasing distance from the aerator in the riser, since the primary bubble size was larger than the equilibrium bubble size. In the downcomer, the mean bubble size was smaller than in the riser. The mean bubble size varied only slightly, the bubble velocity was accelerated, and the gas holdup decreased from top to bottom in the downcomer. In pilot plant at constant aeration rate, the properties of the dispersed phase were nearly constant during the batch cultivation, i.e., they depended only slightly on the cell concentration. In the laboratory reactor, the mean bubble sizes were much larger than in the pilot plant reactor. In the laboratory reactor, the bubble velocities in the riser and downcomer increased, and the mean gas holdup and bubble diameter in the downcomer remained constant as the aeration rate was increased.