Showing papers in "Bioprocess Engineering in 1992"
TL;DR: In this paper, the scale-up of aerobic fermentations is often carried out on the basis of a constant oxygen transfer coefficient, i.e., k ≥ 1, to ensure the same oxygen supply rate to support normal growth and metabolism of the desired high cell populations.
Abstract: Effective scale-up is essential for successful bioprocessing While it is desirable to keep as many operating parameters constant as possible during the scale-up, the number of constant parameters realizable is limited by the degrees of freedom in designing the large-scale operation Scale-up of aerobic fermentations is often carried out on the basis of a constant oxygen transfer coefficient, k
L
a, to ensure the same oxygen supply rate to support normal growth and metabolism of the desired high cell populations In this paper, it is proposed to replace the scale-up criterion of constant k
L by a more direct and meaningful criterion of equal oxygen transfer rate at a predetermined value of dissolved oxygen concentration This can be achieved by using different oxygen partial pressures in the influent gas streams for different scales of operation One more degree of freedom, ie, gas-phase oxygen partial pressure, is thus added to the process of scale-up Accordingly, one more operating factor can be maintained constant during scale-up It can be used to regulate the power consumption in large-scale fermentors for economical considerations or to describe the fluid mixing more precisely Examples are given to show that the results of optimization achieved in the bench-scale study can be translated to the production-scale fermentor more successfully with only a small change in the gas-phase oxygen partial pressure employed in the bench-scale operation
105 citations
TL;DR: The optimization of fed-batch culture of hybridoma cells is accomplished on a mathematical model using dynamic programming and optimal trajectories can improve the final MAb concentration by 11 % for the single feed case and by 20% for the multifeed case.
Abstract: The optimization of fed-batch culture of hybridoma cells is accomplished on a mathematical model using dynamic programming. Optimal feed trajectories are found using a seventh order model for a single feed stream containing both glucose and glutamine and for two separate feed streams of glucose and glutamine. Compared to a constant feed rate, optimal trajectories can improve the final MAb concentration by 11 % for the single feed case and by 20% for the multifeed case. Higher MAb concentrations can be expected for fed-batch optimization with feed enriched in nutrients.
99 citations
TL;DR: The biological process for OMW treatment is based on an aerobic detoxification step followed by methanization step and aerobic post-treatment as discussed by the authors, which is called OMW post treatment.
Abstract: The biological process for OMW treatment is based on an aerobic detoxification step followed by methanization step and aerobic post-treatment.
83 citations
TL;DR: In this article, Eucalyptus globulus wood samples were treated with NaOH solutions in order to obtain substrates highly susceptible to enzymatic hydrolysis, and experiments performed in the extraction and Hydrolysis stages followed an incomplete factorial design.
Abstract: Eucalyptus globulus wood samples were treated with NaOH solutions in order to obtain substrates highly susceptible to enzymatic hydrolysis. The experiments performed in the extraction and hydrolysis stages followed an incomplete factorial design. Temperature, NaOH concentration and extraction time were considered as independent variables. Their influence on five dependent variables (defined to measure the extraction yield, the chemical composition of processed samples and the enzymatic conversion) was assessed using second order, empirical models. In addition to the experimental results, other aspects related to the extraction selectivity are discussed.
63 citations
TL;DR: In this article, a disc stack centrifuge may be scaled-down by up to 10-fold of its separation capacity by reducing the number of discs available for separation purposes and careful positioning of these discs in the overall disc stack.
Abstract: The means are described whereby a disc stack centrifuge may be scaled-down by up to 10-fold of its separation capacity. The centrifuge separation characteristics so measured are suitable for direct scale-up predictions of centrifuge performance where only small volumes of particle suspension are available for study. Such an ability to scale-down is especially important in the processing of biological particles where for example, in the early stage of process development, there is often insufficient fermentation broth for fullscale studies. Scale-down is achieved by the reduction of the number of discs available for separation purposes and by the careful positioning of these discs in the overall disc stack. A combination of dye tracer and particle separation studies are used to optimise the disc stack configuration. The resulting grade efficiency curve is an accurate reflection of the curve for the full-scale centrifuge especially in the critical design region specifying centrifuge throughput for near complete particle recovery.
60 citations
TL;DR: In this article, the homogeneity-time criterion is defined and introduced as the criterion for mixing quality in bioreactors, in the case when more than one measuring point (sensors) is included in the measuring system.
Abstract: “Homogeneity-time” is defined and introduced as the criterion for mixing quality in bioreactors. The criterion could replace the mixing time, in the case, when more than one measuring point (sensors) is included in the measuring system. Results based on the homogeneity-time and the temperature pulse method, achieved in stirred tank reactors under aerated conditions as well as in a jet-mixed tank, are presented.
53 citations
TL;DR: In this article, an integrated process of ethanol recovery by pervaporation was coupled with glucose fermentations by baker's yeast, and three different types of process configurations were investigated, two of these configurations also included cell retention by microfiltration, in order to optimize the productivity.
Abstract: In ethanol fermentations inhibition of the microorganism by ethanol limits the amount of substrate in the feed that can be converted. In a process high feed concentrations are desirable to minimize the flows. Such high feed concentrations can be realized in integrated processes in which ethanol is recovered from the fermentation broth as it is formed. In this study ethanol recovery by pervaporation was coupled to glucose fermentations by baker's yeast. Pervaporation was carried out with commercial silicone based hollow-fibre membrane modules with relatively high fluxes. Three different types of process configurations with pervaporation were investigated. Two of these configurations also included cell retention by microfiltration, in order to optimize the productivity. In the systems with pervaporation a feed containing 360 kg/m3 glucose could be converted almost completely. This feed concentration is a factor three higher than in a process without ethanol recovery. The productivity was 14 kg/m3 h in a system with pervaporation only, and could be increased to 43 kg/m3 h in the system with all recycle by microfiltration. The kinetic data suggest that accumulation of inhibitory compounds occurs in the integrated system. The integrated process was relatively easy in operation.
43 citations
TL;DR: In this paper, a methodology for the design of reactors using immobilized enzymes as catalysts is presented, based on material balances and rate equations for enzyme action and decay and considering the effect of mass transfer limitations on the expression of enzyme activity.
Abstract: A comprehensive methodology is presented for the design of reactors using immobilized enzymes as catalysts. The design is based on material balances and rate equations for enzyme action and decay and considers the effect of mass transfer limitations on the expression of enzyme activity. The enzymatic isomerization of glucose into fructose with a commercial immobilized glucose isomerase was selected as a case study. Results obtained are consistent with data obtained from existing high-fructose syrup plants. The methodology may be extended to other cases, provided sound expressions for enzyme action and decay are available and a simple flow pattern within the reactor might be assumed.
41 citations
TL;DR: A mathematical model for simultaneous saccharification and ethanol fermentation of sago starch using amyloglucosidase (AMG) and Zymomonas mobilis is described in this paper.
Abstract: A mathematical model is described for the simultaneous saccharification and ethanol fermentation (SSF) of sago starch using amyloglucosidase (AMG) and Zymomonas mobilis. By introducing the degree of polymerization (DP) of oligosaccharides produced from sago starch treated with α-amylase, a series of Michaelis-Menten equations were obtained. After determining kinetic parameters from the results of simple experiments carried out at various substrate and enzyme concentrations and from the subsite mapping theory, this model was adapted to simulate the SSF process. The results of simulation for SSF are in good agreement with experimental results.
34 citations
TL;DR: In this study microfiltration was used for cell retention in a fermentation of glucose to ethanol by baker's yeast, and the results in the integrated system could be described reasonably well with a mathematical model based on a different linear inhibition kinetics for growth and substrate consumption.
Abstract: The productivity of a fermentation is proportional to the biomass concentration. The productivity can therefore be increased by retention of the cells in the fermentor. In this study microfiltration was used for cell retention in a fermentation of glucose to ethanol by baker's yeast. Compared to a system without cell retention the productivity could be increased 12-fold to 55 kg/m3 h at a biomass concentration of 135 kg/m3. Maximal ethanol concentrations of 76 kg/m3 were obtained at conditions of growth. At zero growth conditions in the integrated system the ethanol concentration could be increased to about 115 kg/m3, and could be produced for at least 10 hours. The fermentation results in the integrated system could be described reasonably well with a mathematical model based on a different linear inhibition kinetics for growth and substrate consumption.
33 citations
TL;DR: In this article, the authors reported experimental observations on the oxygen and carbon dioxide concentration gradients in a tray-type solid state fermentation system and showed that steep gradients are experienced in deep beds making large portions of the bioreactor ineffective.
Abstract: In aerobic solid state fermentation systems, interaction of mass transfer effects with bioreaction plays an important role on the yields and productivities of the bioreactors. Experimental observations on the oxygen and carbon dioxide concentration gradients in a tray type solid state fermentation system are reported in this paper. Steep gradients are experienced in deep beds making large portions of the bioreactor ineffective. The results are useful in the design of the bioreactor in terms of efficient mass transfer as well as critical thickness of the substrate bed to be used.
TL;DR: Experiments indicate considerable potential advantages to the pellet morphology from the standpoint of oxygen transport processes in Aspergillus terreus fermentation.
Abstract: The cholesterol lowering drug, Lovastatin (Mevacor), acts as an inhibitor of HMGCoA reductase, and is produced from an Aspergillus terreus fermentation.
TL;DR: Effect of additional chemicals at different culture conditions was studied in detail on newly isolated Rhizopus oryza to maximize protease synthesis and a 2.5 fold increase in the protease production was possible by optimizing the two variable inducers system.
Abstract: Effect of additional chemicals at different culture conditions was studied in detail on newly isolated Rhizopus oryza (RO, IIT KGP) to maximize protease synthesis. The surfactants and metal ions when added to the basal medium individually were acted as inducers. The combined effect of these inducers on protease production was also studied in detail and a semiempirical mathematical model based on the data obtained was proposed to optimize their effects. A 2.5 fold increase in the protease production was possible by optimizing the two variable inducers system.
TL;DR: A comparative study between two reactors, one using microorganisms entrapped in calcium alginate gel, and the other using micro organisms attached on the surface of a membrane to biodegrade phenol indicates that a combined reactor system can be more effective for bioremediation than either separate or attached microbial reactors.
Abstract: A comparative study between two reactors, one using microorganisms entrapped in calcium alginate gel, and the other using microorganisms attached on the surface of a membrane (polymeric microporous sheeting, MPSTM) to biodegrade phenol is performed. Results indicate that the alginate bead bioreactor is efficient at higher phenol concentrations while the membrane bioreactor shows better performance at lower phenol concentrations. This unique response is primarily attributed to the different techniques by which the microorganisms are immobilized in the two reactors.
TL;DR: The production of gluconic acid was carried out with high catalase containing Aspergillus niger mutant, which enables to convert the concentrated solutions of D-glucose to D-gluconic acids without gasing using hydrogen peroxide as oxygen source.
Abstract: The production of gluconic acid was carried out with high catalase containing Aspergillus niger mutant. This osmofil strain enables to convert the concentrated solutions of D-glucose (300g/l) to D-gluconic acid without gasing using hydrogen peroxide as oxygen source. A controlled addition of hydrogen peroxide based on the pO2 measurement was performed. The conversion of 300g/l glucose solution was achieved with 7 hours and triple conversion (with biomass recycling) within 27 hours with yield with regard to the substrate over 98%. Kinetics of inactivation of glucose oxidasecatalase complex as a whole was examined. Some general factors influencing the inactivation of glucose oxidase and catalase in mycelium are discussed.
TL;DR: A mathematical model developed here has described performance of an ultrafiltration reactor (UFR) system by considering effects of product inhibition, enzyme deactivation, and formation of side-product.
Abstract: Kinetics of enzymatic hydrolysis of starch to high maltose syrup (by simultaneous use of β-amylase and isoamylase) has been studied here. Main product of dual-enzyme system, maltose, showed a competitive inhibition effect on apparent overall activity of enzymes. Thermal inactivation behavior could be expressed by an empirical exponential function. A mathematical model developed here has described performance of an ultrafiltration reactor (UFR) system by considering effects of product inhibition, enzyme deactivation, and formation of side-product. Effects of concentrations in substrate and enzymes, with residence time of substrate on the performance of UFR has been investigated. Proposed model has been successfully verified in simulating experimental data under various conditions. Operation stability of UFR has also been studied.
TL;DR: In this article, an adaptive discrete-time control strategy is proposed based on recursive least squares identification of the model coefficients, where continuous and discrete versions are treated as well, and the control laws are carried out by a variation calculus problem and a polynomial pole placement synthesis solution.
Abstract: The problem of looking for high efficient modern control strategies in fermentation technology is very urgent, nowdays. Particular attention should be paid to the processes in fed-batch mode. Both, optimal feedforward and feedback control approaches are suggested. A contribution is considered to have been made in the feedback control where continuous and discrete versions are treated as well. The control laws are carried out by a variation calculus problem and a polynomial pole placement synthesis solution, respectively. All the algorithms result in an optimal substrate feed rate profile. On the basis of recursive least squares identification of the model coefficients an adaptive discrete-time control strategy is proposed. Some satisfying simulation results are dealt with.
TL;DR: In this paper, a comprehensive model consisting of sub-models for the enzyme adsorption, enzymatic hydrolysis and recycling of enzymes was set up comprising of non-linear systems of ordinary differential and algebraic equations.
Abstract: Characteristics of cellulase adsorption on cellulosic substrates and their recycling during the hydrolysis of cellulose were studied. On the basis of the experimental data, a comprehensive model was set up comprising of sub-models for the enzyme adsorption, enzymatic hydrolysis and recycling of enzymes. The model equations consist of non-linear systems of ordinary differential and algebraic equations. The model parameters were identified by means of the experimental results of Singh et al. [1] and Bader et al. [2]. The simulation results with the model corresponded well with the experimental data. Thus, the good agreement between simulated and measured process variables indicates that the model is suitable for description of cellulase adsorption and recycling during hydrolysis of cellulosic substrates.
TL;DR: In this article, specific rates of growth, substrate consumption and product formation were used to diagnose microbial activities during a lactic acid fermentation using on-line measured cell mass, and substrate and product concentrations.
Abstract: The on-line calculated specific rates of growth, substrate consumption and product formation were used to diagnose microbial activities during a lactic acid fermentation. The specific rates were calculated from on-line measured cell mass, and substrate and product concentrations. The specific rates were more sensitive indicators of slight changes in fermentation conditions than such monitored data as cell mass or product concentrations.
TL;DR: A model adequately describing the lipase production by Candida rugosa has been developed, calibrated and validated using new experimental data, and diauxic behavior is successfully characterized.
Abstract: A model adequately describing the lipase production by Candida rugosa has been developed, calibrated and validated using new experimental data. Process modelling has been done using CAMBIO software (Computer Aided Modelling of BIOprocesses), allowing to easy and interactively test various hypothesis and reaction schemes.
TL;DR: A model of multiple sugars uptake has been developed that utilizes a switching concept during the course of batch experiment, the consequences of which are discussed.
Abstract: Recent studies into the mechanisms of uptake of glucose and fructose in S. cerevisiae suggest the existence of at least two transport systems. Based on novel results from our work with glucose, fructose and sucrose, a model of multiple sugars uptake has been developed. This model utilizes a switching concept during the course of batch experiment, the consequences of which are discussed.
TL;DR: In this paper, the authors measured gas holdup and liquid circulation time in a down flow jet loop bioreactor with a non-Newtonian fluid and found that the circulation time decreases with increase in nozzle diameter, draft tube to column diameter ratio and shear thinning of the media.
Abstract: Gas holdup and liquid circulation time were measured in a down flow jet loop bioreactor with a non-Newtonian fluid. It was observed that the circulation time decreases with increase in nozzle diameter, draft tube to column diameter ratio and shear thinning of the media. The gas holdup increases with increase in gas and liquid velocities. The optimum draft tube to column diameter ratio was found to be 0.438. Correlations for gas holdup and circulation time involving operational and geometrical variables were presented.
TL;DR: In this paper, the concept of separation of stages coupled with novel design of reciprocating jet bioreactor have been incorporated in this research for the development of high efficiency treatment system for contaminated wastewaters.
Abstract: Concept of separation of stages coupled with novel design of reciprocating jet bioreactor have been incorporated in this research for the development of high efficiency treatment system for contaminated wastewaters.
TL;DR: The LAexpert is a supervisor for a process control system and assists operators in fault diagnosis and was implemented using a fuzzy expert system shell based on the object oriented programming tool Smalltalk V/Mac running in a Macintosh II computer.
Abstract: A knowledge based system, LAexpert, was developed to diagnose microbial activities during a fermentation process on the basis of specific rates determined on-line. The LAexpert is a supervisor for a process control system and assists operators in fault diagnosis. The LAexpert was implemented using a fuzzy expert system shell based on the object oriented programming tool Smalltalk V/Mac running in a Macintosh II computer. The shell can handle uncertainties both in the measurements and knowledge by fuzzy reasoning.
TL;DR: A new and cheap support, vermiculite was successfully used to immobilize neutral protease by adsorption and hexamethylene diamine mediated coupling using glutaraldehyde as a bifunctional agent.
Abstract: A new and cheap support, vermiculite was successfully used to immobilize neutral protease by adsorption and hexamethylene diamine mediated coupling using glutaraldehyde as a bifunctional agent. Neutral protease immobilized on vermiculite by adsorption showed maximum retained activity than HMD mediated coupling. The optimum temperature for both free and immobilized neutral protease was found to be 45°C. However, the pH and thermal stabilities of immobilized neutral protease was observed to be better than that of the free enzyme. The storage stability of the immobilized enzyme was also studied.
TL;DR: In this paper, a methanol sensor was constructed to detect methanols on-line by combining membrane separation and semiconductor gas sensor technology, which demonstrated excellent ability in following methanolic concentrations during the batch production of a polysaccharide by the organism Methylomonas mucosa.
Abstract: Combining principles of membrane separation and semiconductor gas sensor technology, we constructed a methanol sensor to follow methanol concentrations on-line. A length of silicone tubing allowed for mass transfer of methanol from the fermentation medium to a carrier gas which then flowed over a semiconductor gas sensor for detection. The sterilizable sensor demonstrated excellent ability in following methanol concentrations during the batch production of a polysaccharide by the organism Methylomonas mucosa, even as the fermentation broth became increasingly viscous. During fed-batch control by feeding methanol to the fermentation to maintain setpoint methanol levels, a drift in the sensor signal was noted and quantified. A drift factor was determined which, after it was incorporated into the calibration calculations, improved methanol concentration control greatly. Methanol concentration was held constant over a range of set point concentrations during fedbatch fermentations.
TL;DR: Two optimised, inexpensive and easy to scale-up processes for the simultaneous separation and purification of l-lactate dehydrogenase (LDH) and pyruvate kinase (PK) from rabbit muscles were designed and the following factors were proven to be important: Extract pretreatment, ionic strength and pH, amount loaded on the adsorbent, and elution conditions.
Abstract: Cibacron Blue 3GA-Sepharose CL6B was used to design two optimised, inexpensive and easy to scale-up processes for the simultaneous separation and purification of l-lactate dehydrogenase (LDH) and pyruvate kinase (PK) from rabbit muscles. The tissue was homogenised, filtered, and the liquid treated by DEAE-cellulose and Sephadex-G25 gel to obtain the “pre-treated” extract which was used in the dye-column. The first process, involving two identical dye-columns (1 ml each), afforded from the first column 2.3 mg PK-free LDH of specific activity (S.A.) 470 units/mg with 73% yield, and from the second column 1.9 mg LDH-free PK of S.A. 66 units/mg with 63% yield. The second process, involving only one dye-column (1 ml), afforded both enzymes in good yield (65–67%) but with less purity: S.A. 360 units/mg for LDH (0.1% PK) and 44 units/mg for PK (0.01–0.04% LDH). In both processes LDH was eluted biospecifically from both columns with NADH (5 mM), whereas, PK was eluted with KCl (0.15 M). Biospecific elution of PK from the blue adsorbent resulted in poor enzyme recovery (25%). The following factors were proven to be important: Extract pretreatment, ionic strength and pH, amount loaded on the adsorbent, and elution conditions.
TL;DR: A model of continuous acetonobutylic fermentation correctly portrays the predominantly solvents formation observed at acidic extracellular pH and predominantly acids production at more neutral pH, as well as observed effects of dilution rate and feed substrate on products' concentrations.
Abstract: A model of continuous acetonobutylic fermentation is proposed. This model correctly portrays the predominantly solvents formation observed at acidic extracellular pH and predominantly acids production at more neutral pH, as well as observed effects of dilution rate and feed substrate on products' concentrations. A fair agreement between experimental and theoretical predictions is achieved for a broad range of operating variables.
TL;DR: In this paper, the influence of polymeric additives on specific glucose uptake rate of flocs of a S. cerevisiae strain was studied and it was shown that poly-meric additives act on the reduction of diffusional limitations by increasing the available flux area for glucose inside the floc.
Abstract: The influence of several polymeric additives on specific glucose uptake rate of flocs of a S. cerevisiae strain - S. cerevisiae NRRL Y 265 was studied. A special continuous membrane micro- reactor was used to measure glucose uptake on the presence of cal- cium and of the tested additives - two cationic polymers - bis(poly- oxyethylene-bis(amine)) 20,000 and BPA 1,000 and one anionic polymer -- Magna Floc LT25. An increase on glucose uptake rate was always observed when comparing with calcium bound flocs. For bis(polyoxyethylene- bis(amine)) 20,000 the increase was only 19% but for BPA 1,000 a value of more than 50% was observed. For Magna Floc LT25 a two fold increase was measured. The determination of floc size and porosity in the presence of the additives indicated that, on the basis of these parameters, it was not possible to explain the observed glucose uptake rates. The floc porosites in additive bound flocs were similar and 10% larger than for calcium bound flocs and glucose uptake rate was larger for the largest flocs - Magna Floc LT25 bound flocs were the largest fol- lowed by BPA t,000, bis(polyoxyethylene-bis(amine)) 20,000 and calcium bound flocs. These values disagree with what should be expected in diffusion controlled processes. The calculation of intercellular floc distance indicated that poly- meric additives act on the reduction of diffusional limitations by increasing the available flux area for glucose inside the flocs. By analysing different kinds of packings, it was also observed that the packing arrangement for yeast cells in flocs is close to the cubic packing. The simulation of this arrangement for the obtained floc sizes confirmed that the 10% increase in floc porosity is sufficient to explain the increase in the available flux area.
TL;DR: This paper showed that at high substrate feed concentrations it is possible to obtain solvent productivities about 25-40% higher than in conventional systems with cell recycle if the biomass bleed rate is kept about one tenth of the value of D.
Abstract: Simulations of continuous ethanol or acetonobutylic fermentations in aqueous two-phase systems show that at high substrate feed concentrations it is possible to obtain solvent productivities about 25–40% higher than in conventional systems with cell recycle if the biomass bleed rate is kept about one tenth of the value of D.