New instrument for on-line viscosity measurement of fermentation media

In an attempt to resolve the difficult problem of on-line determination of the viscosity of non-Newtonian fermentation media, the authors have used a vibrating rod sensor mounted on a bioreactor. The sensor signal decreases nonlinearly with increased apparent viscosity. Electronic filtering of the signal damps the interfering effect of aeration and mechanical agitation. Sensor drift is very low (0.03% of measured value per hour).On the rheological level the sensor is primarily an empirical tool that must be specifically calibarated for each fermentation process. Once this is accomplished, it becomes possible to establish linear or second-degree correlations between the electrical signal from the sensor and the essential parameters of the ferementation process in question (pH of a feremented milk during acidification, concentration of extra cellular polysaccharide). In addition, by applying the power law to describe the rheological behavior of fermentation media, we observe a second-order polynomial correlation between the sensor signal and the behavior index (n).     

Scale-up strategy for bioreactors with Newtonian and non-Newtonian broths

In the scale-up of bioreactors one of the most commonly used criteria for aerobic processes is to keep the oxygen transfer coefficient constant. Nevertheless, the reproduction of the behaviour of a cell population at different scales is not dependent just on the oxygen transfer capability but rather on the oxygen transfer rate, that must be high enough to cope with the oxygen demand of the culture. In this work a strategy of scale-up is proposed based in geometric similarity, constant impeller tip speed, and constant oxygen transfer rate. The effects of the dissolved oxygen concentration, the scale-up ratio and the rheology of the broth are analysed.     

Hydrodynamics of non-Newtonian liquids in external-loop airlift bioreactors

In order to obtain further information on the behaviour and optimal design of external-circulation-loop airlift bioreactors, the liquid circulating velocity was studied using highly viscous pseudoplastic solutions of starch and antibiotic biosynthesis liquids of Penicillium chrysogenum, Streptomyces griseus, Streptomyces erythreus, Bacillus licheniformis and Cephalosporium acremonium. Measurements of liquid circulation velocity were made in laboratory and pilot plant external-loop airlift bioreactors, under various conditions concerning gas flow rate, riser liquid height at constant downcomer height, A _D /A _R ratio, using the impulse-response technique. It has been found that these parameters had a significant effect on liquid circulation velocity together with the apparent viscosity and dry weight of the solid phase in the biosynthesis liquids. For the tested liquids, the superficial liquid velocity in the riser section of an external-loop airlift bioreactor may be described by the following equation: where the exponents and the constant c take different values depending on the liquid phase properties and flow regime.     

Hydrodynamics of non-Newtonian liquids in external-loop airlift bioreactors

Gas holdup investigation was performed in two external-loop airlift bioreactors of laboratory (V _L =1.189·10^?3? 1.880·10^?3 m³; H _R =1.16 ? 1.56 m; H _D = 1.10 m; A _D /A _R = 0.111 ? 1.000) and pilot scale (V _L =0.157?0.170 m³; H _R =4.3?4.7 m; H _D =4.0?4.4 m;A _D /A _R =0.04?0.1225), respectively, using as liquid phase non-Newtonian starch solutions of different concentration with K=0.061?3.518 Pa sⁿ and n=0.86?0.39 and fermentation broths of P. chrysogenum, S. griseus, S. erythreus, B. licheniformis and C. acremonium at different hours since inoculation and from different batches. The influence of bioreactor geometry, liquid properties and the amount of introduced compressed air was investigated. The effect of sparger design on gas holdup was found to be negligible. It was found that gas holdup depends on the flow media index, ?_GR decreasing with the increase of liquid pseudoplasticity, A _D /A _R ratio and H _R /H _D ratio. The experimental data are in agreement with those presented in literature by Popovic and Robinson, which take into account liquid properties, geometric parameters and gas superficial velocity, with a maximum error of ±30%. It was obtained a correlation for gas holdup estimation taking into account the non-Newtonian behaviour of the fermentation broths and the dry weight of the solid phase, as well. The concordance between the experimental data and those calculated with the proposed correlation was good, with a maximum error of ±17%. Also, a dimensionless correlation for gas holdup involving superficial velocities of gas and liquid, cross sectional areas ratio, dispersion height to riser diameter ratio, as well as Froude and Morton numbers, was obtained.     

Investigation of the structure of two-phase flow fermentation model media in bubble-column bioreactors

Summary Electrical conductivity microprobes have been used to estimate the transverse variation of bubble size, local gas holdup and local specific gas/liquid interfacial area in bench scale bubble column bioreactors containing fermentation model media. Inserted O₂-electrodes and plane parallel windows alter the structure of the two phase flow. Even slight tilting of the column strongly influences the transverse profiles of the bubble size and local gas holdup. The larger bubbles are collected at the wall, where they can be redispersed. These observations open up new possibilities for the construction of bubble column bioreactors.     

Two-phase partitioning bioreactors in fermentation technology

The two-phase partitioning bioreactor concept appears to have a great potential in enhancing the productivity of many bioprocesses. The proper selection of an organic solvent is the key to successful application of this approach in industrial practice. The integration of fermentation and a primary product separation step has a positive impact on the productivity of many fermentation processes. The controlled substrate delivery from the organic to the aqueous phase opens a new area of application of this strategy to biodegradation of xenobiotics. In this review, the most recent advances in the application of two-liquid phase partitioning bioreactors for product or substrate partitioning are discussed. Modeling and performance optimization studies related to those bioreactor systems are also reviewed.     

合成气厌氧发酵生物反应器的研究进展

对合成气厌氧发酵生物反应器的研究进展进行综述,包括生物反应器操作原理、类型、构造、应用和对发酵过程的影响等,并对其未来的发展作出展望。     

A mathematical model for solid state fermentation in tray bioreactors

A simple mathematical model for the interaction of mass transport with biochemical reaction in solid state fermentations (SSF) in static tray type bioreactors under isothermal conditions has been developed. The analysis has enabled scientific explanations to a number of practical observations, through the concept of critical substrate bed thickness. The model will be most useful in the prediction of the concentration gradients as also in efficient design of these bioreactors.List of Symbols C g/cm³ Oxygen concentration in the bed - C _g g/cm³ Atmospheric oxygen concentration - C ^* Dimensionless oxygen concentration, C/C _g - D _e cm²/h Effective diffusivity - H cm Bed thickness or height - H _c cm Critical bed thickness or height - H _m cm Maximum height of zone of zero oxygen concentration - p _i mg/(g · h) Productivity (Eq. 13) - R g/(cm³ · h) Biochemical reaction rate - t h Fermentation time - t ^* Dimensionless time, D _e t/H² - X mg/cm³ Biomass concentration - X _max mg/cm³ Maximum biomass concentration - y Dimensionless thickness or height, (y = z/H) - y cm Thickness of zone of zero oxygen concentration (Eq. 12) - Y Yield coefficient - z cm Bed thickness or height along tray axis - Bed void fraction - _max h^–1 Specific growth rate - Thiele modulus      

Penicillin fermentation: mechanisms and models for industrial-scale bioreactors

Even after many years of research and industrial practice, the production of penicillin G in fed-batch fermentation by Penicillium crysogenum continues to attract research interest. There are many reasons: the commercial and therapeutic importance of penicillin and its derivatives, the complexity of cell growth, and the impact of engineering variables, the last of which are significant in large bioreactors but are not yet fully understood. Extensive research has generated new information on the mechanisms of cellular reactions and morphological features of the mycelia and their role in the synthesis of the product. Given a choice of mechanisms, models of different degrees of complexity, for both cellular differentiation and bioreactor performance, have been proposed. The more complex models require and provide more information. They are also more difficult to evaluate and apply in automatic control systems for production-scale bioreactors. The present review considers the evolution of recent knowledge and models from this perspective.     

A method for analyzing non-Newtonian blood viscosity data in low shear rates

Viscosity measurements were made using a coaxial rotating cylinder viscometer for blood having various volume fractions of red cells. A method is described for analyzing non-Newtonian blood viscosity in low shear rates by taking account of an increase or a decrease in size of red cell aggregates induced by shear. Our results are compared with empirical formulae presented by Scott Blair, Weaver-Evans-Walder and Thurston.     

Concentration-dependent, temperature-dependent non-Newtonian viscosity of lung surfactant dispersions

The bulk shear viscosities of aqueous dispersions of lavaged calf lung surfactant (LS) and its chloroform:methanol extract (CLSE) were measured as a function of concentration, shear rate and temperature. At 10-mg phospholipid per milliliter, dispersions of LS and vortexed CLSE in 0.15 M NaCl (saline) had low viscosities near 1 cp over a range of shear rates from 225 to 1125 s(-1). Lung surfactant viscosity increased with phospholipid concentration and became strongly non-Newtonian with higher values at low shear rates. At 37 degrees C and 40 mg/ml, LS and vortexed CLSE in saline had viscosities of 38 and 34 cp (77 s(-1)) and 12 and 7 cp (770 s(-1)), respectively. Viscosity values for LS and CLSE were dependent on temperature and, at fixed shear, were lower at 23 degrees C than at 37 or 10 degrees C. Hysteresis was also present in viscosity measurements depending on whether shear rate was successively increased or decreased during study. Addition of 5 mM Ca(2+) at 37 degrees C markedly reduced CLSE viscosity at all shear rates and decreased LS viscosity at low shear rates. Dispersion by sonication rather than vortexing increased the viscosity of CLSE at fixed shear, while synthetic phospholipids dispersed by either method had low, relatively Newtonian viscosities. The complex viscous behavior of dispersions of LS and CLSE in saline results from their heterogeneous aggregated microstructure of phospholipids and apoproteins. Viscosity is influenced not only by the aggregate surface area under shear, but also by phospholipid-apoprotein interactions and aggregate structure/deformability. Similar complexities likely affect the viscosities of biologically-derived exogenous surfactant preparations administered to patients in clinical surfactant therapy.     

Baffles increase performance of solid-state fermentation in rotating drum bioreactors

Summary Rhizopus oligosporus grew better on wheat bran in a rotating drum when baffles were fitted. The maximum O₂ uptake rates for the baffled and unbaffled runs were 9.0 and 5.7 mmol/min.kg initial dry substrate respectively. The RQ remained at 1.0 throughout the baffled run but varied between 1.0 and 1.2 for the unbaffled run.     

External-circulation-loop airlift bioreactors: study of the liquid circulating velocity in highly viscous non-Newtonian liquids

In order to obtain further information on the behavior and optimal design of external-circulation-loop airlift (ECL-AL) bioreactors, the liquid circulating velocity, gas holdup and average bubble diameter in the downcomer were studied using highly viscous pseudoplastic solutions of various types of CMC. A few comparative measurements also were made using a viscous Newtonian aqueous sucrose solution. For the liquid velocity measurements, an ultrasonic flow meter (Doppler frequency shift principle) was applied for the first time to the gas/non-Newtonian liquid dispersion in downward flow and satisfactory results were obtained. For viscous liquids, the circulating liquid velocity in the riser section of an ECL-AL (u(LR)) is shown to be dependent mainly on the downcomer-to-riser cross-sectional area ratio (A(d)/A(r)), the effective viscosity (eta(eff)) and the gas superficial velocity (u(GR)) as described by the following equation \documentclass{article}\pagestyle{empty}\begin{document}$$ u_{LR} = 0.23u_{GR};{0.32} (A_d /A_r);{0.97} \eta _{eff};{ - 0.39} $$\end{document} The circulating liquid velocity exerts opposing effects on the mass transfer and liquid-phase mixing performances of ECL-AL fermentors. Therefore, it is proposed that the optimum operating conditions for a given fermentation may be best achieved by means of independently regulating the circulating liquid velocity.     

Degradation of pencillin-V in fermentation media

In Industrial production of penicillin there is a noticeable loss of the product through degradation reactions. It is shown that the degradation of penicillin-V, both in a complex and in a chemically defined medium, can be separated into a phosphate-catalyzed conversion of penicillin-V to penicilloic-V acid, overlaid by at least one other reaction in which penicillin V is degraded to as yet unknown products. Parameter values for the phosphatecatalyzed degradation are found to be independent of the type of fermentation medium. The rate of formation of other degradation products of penicillin-V is found to be significantly higher in a complex fermentation medium with corn-steep liquor in a chemically defined medium. (c) 1994 John Wiley & Sons, Inc.     

Growth ofRhizopus arrhizus in fermentation media

Summary Rhizopus arrhizus biomass attached itself to fermentor walls, baffles and impellers when grown in casein/ glucose media. In shake flasks, dispersed filamentous growth was produced in media containing certain concentrations of glucose and soya flour. Other media tested produced pelleted or clumpy growth. Medium initial pH did not affect morphology type. Dispersed growth could not be obtained by addition of detergents, oils and polymers to a clear glucose/soya peptone medium. Addition of maize solids to this medium resulted in dispersed growth which occurred even in the presence of calcium, which in most media caused pellet formation. Mycelia appeared to bind to the maize particles and use these as growth centres thereby preventing pellet or clump formation. Mycelial pellets appeared to originate either from a single spore or by interaction of branched hyphae from different spores. Medium composition and macro-morphology type correlate with differences in hyphal structures.     

A pulsing device for packed-bed bioreactors: II. Application to alcoholic fermentation

When the immobilized cells are employed in packed-bed bioreactors several problems appear. To overcome these drawbacks, a new bioreactor based on the use of pulsed systems was developed [1]. In this work, we study the glucose fermentation by immobilized Saccharomyces cerevisiae in a packed-bed bioreactor. A comparative study was then carried out for continuous fermentation in two packed-bed bioreactors, one of them with pulsed flow. The determination of the axial dispersion coefficients indicates that by introducing the pulsation, the hydraulic behaviour is closer to the plug flow model. In both cases, the residence time tested varied from 0.8 to 2.6 h. A higher ethanol concentration and productivity (increases up to 16%) were achieved with the pulsated reactors. The volumes occupied by the CO₂ were 5.22% and 9.45% for fermentation with/without pulsation respectively. An activity test of the particles from the different sections revealed that the concentration and viability of bioparticles from the two bioreactors are similar. From the results we conclude that the improvements of the process are attributable to a mechanical effect rather than to physiological changes of microorganisms.List of Symbols D m²/s dispersion coefficient - K _is l/g inhibition substrate constant - K _ip l/g inhibition ethanol constant - K _s g/l Apparent affinity constant - P g/l ethanol concentration - q _p g/(gh) specific ethanol productivity - Q _p g/(lh) overall ethanol productivity - q _s g/(gh) specific glucose consumption rate - Q _s g/(lh) glucose consumption rate - S g/l residual glucose concentration - S(in0) g/l initial glucose concentration - V _max g/(lh) maximum rate - Y _p/s g/g yield in product     

Valuation of bioreactors for low viscous media and high oxygen transfer demand

A strategy of a systematic comparison is developed in which the valuation parameters and the influencing parameters are put in order in a three dimensional matrix. The performance of a bioreactor construction is then evaluated with a biological test system that has representative medium properties and where all important parameters of microbial growth are known. This strategy is applied to four bioreactor constructions and to low viscous bacteria and yeast systems with and without foam formation. On the basis of this data set the performances of the different bioreactors are compared.The financial support of the Kommission zur Förderung der Wissenschaftlichen Forschung, Bern, is gratefully acknowledged.