Showing papers on "Bioprocess published in 1998"

13C-NMR, MS and metabolic flux balancing in biotechnology research

Abstract: The European Federation of Biotechnology defines biotechnology as ‘the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services’. Biotechnology thus focuses on the industrial exploitation of biological systems and is based on their unique expertise in specific molecular recognition and catalysis. The enormous potential for drug synthesis, design of biomedical diagnostics, large-scale production of biochemicals including fuels, food production, degradation of resistant wastes and extraction of raw materials will very likely make biotechnology, along with electronics and material sciences, one of the key technologies of the 21st century. From the chemical engineer's point of view, the living system participating in a biotechnological process is the central unit that catalyses chemical reactions. It exhibits a complex dependence on the bioprocess parameters, and the engineer focuses on these parameters to achieve optimal control (Hamer, 1985; Bailey & Ollis, 1986). For the natural scientist, the living system itself is in the centre of interest, so that attempts to optimize a bioprocess aim at its appropriate redesign by genetic manipulations. The increase in penicillin production by strain improvement based on random mutagenesis, which was pursued from 1940 to the mid 1970s, represents an early contribution of life scientists to improve a bioprocess that is of utmost medical importance (Hardy & Oliver, 1985).

Two-Dimensional Fluorescence Spectroscopy: A New Tool for On-Line Bioprocess Monitoring

Abstract: Two-dimensional fluorescence spectroscopy is presented as a new method for bioprocess monitoring. It covers a wide range of excitation and emission wavelengths and is a further development of the fluorescence measurements performed so far, which concentrated mainly on NAD(P)H culture fluorescence. Biogenic fluorophores such as proteins, coenzymes, and vitamins can simultaneously be detected qualitatively and quantitatively inside and outside the cells. This optical method is noninvasive, suitable for in vivo measurements. One whole spectrum (excitation, 250-550 nm; emission, 260-600 nm) with the described parameters is performed within 1 min, which allows an almost continuous monitoring of the bioprocess. The technique is ideal for on-line, in situ measurements via fiber optical systems. Results are presented for cultivations of Claviceps purpurea, Escherichia coli, Saccharomyces cerevisiae, and Sphingomonas yanoikuyae. Cell growth and the metabolism of the cells (changes from aerobic to anaerobic conditions and uncoupling of the oxidative phosphorylation) could be detected.

A hybrid method of differential evolution with application to optimal control problems of a bioprocess system

Abstract: A hybrid method of differential evolution is developed in this study. Two additional operations (accelerated phase and migrating phase) are embedded into the original version of differential evolution. These two phases are used for improving the convergence speed without reducing the diversity among the individuals. The method of multiplier updating, incorporated in the proposed method, is introduced to solve the constrained optimization problems. The method is then extended to solve the simultaneous optimal control and optimal parameter selection problems of a bioprocess system.

Commercial biosensors : applications to clinical, bioprocess, and environmental samples

Abstract: APPLICATIONS TO CLINICAL SAMPLES. Biosensors for Personal Diabetes Management (T. Henning & D. Cunningham). Microfabricated Sensors and the Commercial Development of the i--Stat Point--of--Care System (G. Davis). Noninvasive Biosensors in Clinical Analysis (G. Palleschi, et al.). Surface Plasmon Resonance (R. Earp & R. Dessy). Biosensors Based on Evanescent Waves (D. Purvis, et al.). APPLICATIONS TO BIOPROCESS SAMPLES. Applications of Biosensor--Based Instruments to the Bioprocess Industry (J. Woodward & R. Spokane). APPLICATIONS TO ENVIRONMENTAL SAMPLES. Application of Biosensors to Environmental Samples (K. Riedel). Index.

2-Dimensional fluorescence spectroscopy for on-line bioprocess monitoring

Abstract: The technique of two-dimensional (2D-) fluorescence spectroscopy covers a wide range of excitation and emission wavelengths. Several biogenic fluorophors (proteins, vitamins and coenzymes) can be detected simultaneously. The development of an optical sensor for on-line measurement of 2D-fluorescence spectra at biotechnological processes is described. This sensor is very well suited for in vivo measurements, because it is non-invasive and the on-line data can be performed in-situ using an optical light guide system. This instrumentation was used at cultivations of Saccharomyces cerevisiae to show the potential and also the reliability of 2D-fluorescence spectroscopy for bioprocess monitoring. Changes in cell metabolism (aerobicanaerobic transitions), cell growth, medium composition and also turbidity could be detected.

On-line bioprocess monitoring – an academic discipline or an industrial tool?

Abstract: Bioprocess monitoring capabilities are gaining increasing importance both in physiological studies and in bioprocess development. The present article focuses on on-line analytical systems since these represent the backbone of most bioprocess monitoring systems, both in academia and in industry. We discuss advantages and drawbacks of various of the most frequently used components (sampling units, flow systems and detection unit) and analytical techniques. The differences between academia and industry in the use of bioprocess monitoring are discussed, based on the key drivers determining implementation of analytical systems in each of these fields.

Advanced instrumentation, data interpretation, and control of biotechnological processes

Abstract: I: Hardware Sensors. 1. Flow Injection Analysis for On-Line Monitoring of a Waste-Water Treatment Plant. 2. On-Line Measurement of Viable Biomass. 3. Membrane Inlet Mass Spectrometry for the Characterization and Monitoring of Biotechnological Processes. 4. Flow Cytometry. 5. Microcalorimetric Characterization of Bacterial Inocula. II: Model Based Control. 6. On- Line Data Acquisition. 7. Data Processing for System Identification. 8. Error Diagnosis and Data Reconciliation Using Linear Conservation Relations. 9. General Concepts of Bioprocess Modeling. 10. Bioprocess Model Identification. 11. Optimal Control of Fed-Batch Fermentation Processes. 12. Monitoring and Adaptive Control of Bioprocesses. 13. Optimal Adaptive Control of Fed-Batch Fermentation Processes. 14. Predictive Control in Biotechnology Using Fuzzy and Neural Models.

Sniffing Out Trouble: Use of an Electronic Nose in Bioprocesses

Abstract: Given the considerable time and expense invested in a single bioprocess (fermentation) batch, variability and losses must be identified quickly. We propose that “sniffing” the odor of cultivation media and broth using instruments could provide a rapid and early indication of bioprocess performance. The human sensation of odor is related to the molecular composition of the vapor phase. The traditional approach to characterize volatile compounds has been sample extraction followed by GC−MS analysis. This approach is very tedious and requires some knowledge of the molecules involved. A new, alternate approach based on an “electronic nose” is now available which, like the human nose, can directly characterize the odor without reference to chemical composition. Here, an array of “conductive polymer” sensors with different chemical sensitivities produces a set of different responses to the same odor. The responses are analyzed mathematically, using pattern recognition techniques, to differentiate between different odors with a high level of sensitivity. In this report, we demonstrate the feasibility of using a commercially available electronic nose for the following applications: monitoring lot-to-lot variation in bioprocess medium ingredients, detecting microbial contamination early, and evaluating bioprocess performance during cultivation of microorganisms at inoculum and production stages.

Improvement of heterologous protein productivity using recombinant Yarrowia lipolytica and cyclic fed-batch process strategy.

Abstract: A cyclic fed-batch bioprocess is designed and a significant improvement of rice alpha-amylase productivity of recombinant Yarrowia lipolytica is illustrated. A bioprocess control strategy developed and reported here entails use of a genetically stable recombinant cloned for heterologous protein, use of optimized media for cell growth and enzyme production phases, and process control strategy enabling high cell-density culture and high alpha-amylase productivity. This process control can be achieved through maintaining a constant optimal specific cell growth rate at a predetermined value (i.e., 0.1 h-1), controlling medium feed rate commensurate with the cell growth rate, and maintaining a high cell-density culture (i.e., 60-70 g/L) for high productivity of cloned heterologous protein. The volumetric enzyme productivity (1, 960 units/L. h) achieved from the cyclic fed-batch process was about 3-fold higher than that of the fed-batch culture process (630 units/L. h).

Apoptosis and Bioprocess Technology

Abstract: Optimisation of the production of biopharmaceuticals in animal cell lines has become a key area of research. The identification of apoptosis as the major mechanism of cell death during such processes has raised the importance of studies of cell death when implementing culture optimisation strategies. In this article we present an overview of the studies which have demonstrated the induction of apoptosis during the cultivation of industrially important animal cell lines. We also discuss studies which have shown that deprivation of factors such as amino acids, glucose, serum and oxygen are potent inducers of apoptosis in industrial cultures. The suppression of apoptosis under these conditions has been demonstrated by a number of recent reports, and we describe ways in which this knowledge may be applied in the development of novel solutions to some of the technical problems associated with the development of successful large scale culture process. The article concludes with a discussion of future directions for apoptosis research in bioprocess technology.

Recombinant bioprocess optimization for heterologous protein production using two-stage, cyclic fed-batch culture.

Abstract: A two-stage, cyclic fed-batch bioprocess was designed, and its performance evaluated to improve rice α-amylase productivity by the yeast Yarrowia lipolytica SMY2 (MatA, ade1, ura3, xpr2), ATCC 201847, containing a replicative plasmid coding for a rice α-amlyase. Transcription of the recombinant gene is controlled by the XPR2 promoter. The first stage (or growth stage) was operated in the fed-batch mode, and the growth medium, designed to maintain a constant high cell density (i.e., 60 g/l), was fed according to a predetermined and preprogrammed optimal feed rate which, in turn, maintained the specific cell growth rate at an optimal value (i.e., 0.1 h−1). Typically, when the volume in the first stage reached a preset value, a portion of culture broth (i.e., 55%) was transferred to the second stage (or production stage). The remaining cells in the growth stage were then fed with fresh growth medium according to the bioprocess control strategy developed, while induction of α-amylase expression and its production was taking place in the second stage. The second stage was also operated in the fed-batch mode, and the production medium designed to maintain a constant high cell density and high productivity of heterologous protein was fed at a predetermined and preprogrammed rate, which maintained the specific cell growth rate at an optimal level. The volumetric α-amylase productivity achieved (1835 units l−1 h−1) from the two-stage, cyclic fed-batch culture process was twofold higher than that of the fed-batch culture process. The genetic stability of the recombinant strain and the design of optimal media for growth and production stages are also critically important to a successful implementation of the two-stage, cyclic fed-batch process for production of heterologous protein.

Opportunities for Marine Bioprocess intensification using novel bioreactor design: Frequency of barotolerance in microorganisms obtained from surface waters.

Abstract: Abstract In the context of marine biochemical systems, opportunities exist for the development of novel reactors, with optimization and conversion of current technologies having the potential to yield more efficient units. A limiting factor in the widespread commercial acceptance of a large range of marine metabolites is the efficient production of, for example, sufficient quantities of antibiotics and nutraceuticals to allow for structural analysis and clinical testing. Conventional methods utilised for physical and chemical process intensification require careful analysis of their potential application to shear-sensitive bioprocess systems. Stress induction, for example, provides one route to marine bioprocess intensification due to the expression of metabolites not otherwise possible. Use of high pressure as a stressing agent and/or intensification tool is discussed, and its potential, demonstrated by showing the existence of barotolerant (at 120 MPa) marine microorganisms obtained from shallow surface waters (

On-line state estimation of biomass based on acid production in Zymomonas mobilis cultures

Abstract: The concentrations of biomass, substrate and product are very important state variables of almost every bioprocess and generally unable to be measured directly in␣situ due to the lack of reliable sensors. In this paper, an adaptive observer of the biomass concentration is proposed for an anaerobic fermentation process where only the measurement of the acid product is available on-line. The observer was tested to be effective by several experiments under various operating conditions. In this experimental system, an auto-sampling device was connected between the bioreactor for the fermentation of Zymomonas mobilis and a HPLC so that the concentrations of glucose and ethanol could be directly measured through such implementation.

Optimization of bioprocess conditions for exopolysaccharide production by Klebsiella oxytoca

Abstract: Optimization of bioprocess conditions increased exopolysaccharide production by a strain of Klebsiella oxytoca from 6g/l to 15g/l; this corresponded to an increase in medium viscosity from 36cP at 12s−1 to 20,000 cP at 0.6 s−1. A combination of equal proportions of tryptone nitrogen and urea nitrogen proved to be the best nitrogen source. Lactose was shown to be the preferred carbon source. At an optimum temperature of 25°C, a pH of 7 was found to be the best for exopolysaccharide production. The concentration of exopolysaccharide produced on whey, enriched whey, enriched whey permeate and lactose-rich medium was comparable.

Fermentation odor and bioprocess scale-up

Abstract: During scaleup of Streptomyces avermitilis batch culture based on similarity of geometry, aeration and mixing conditions, the production of avermectins was proportional to the intensity of fermentation odor represented by geosmin. The active stimulatory role of odor component on antibiotic production was detected after addition of volatile compounds separated from the fermentation liquor by steam distillation.

Integrated system for bioprocess monitoring and diagnosis using a local area network

Abstract: Bioprocess monitoring and data analysis utilizing a local area network (LAN) is described in which an integrated computer environment provides for real-time monitoring from several remote personal computers with easy evaluation of the current process status and providing a common utilization of fermentation data. The computer network also enhances the decision-making process in the management of the production plant. Bioprocess control utilizing a LAN environment is expected to promote better utilization of fermentation data accumulated through repeated operations and to realize advanced control of fermentation processes. © Rapid Science Ltd. 1998

[Testing the osmotic-diffusion properties for the membranous dressing Bioprocess].

Abstract: In order to determine of the osmotic-diffusive properties of membranous dressing Bioprocess, which is a microfibrous network of homogeneous cellulose produced in biosynthesis by Acetobacter, the hydraulic permeability (Lp), reflection (sigma) and diffusive permeability (omega) coefficients were measured. The values of these coefficients showed that this membrane possess a low selectivity. This amount it easy permeable for solvent (water) as well as for solutions (aqueous solutions of glucose, sucrose, ethanol, NaCl or KCl). Thus, it attend a demands make for polymeric materials used in therapy of scald and ulceration.

Computer applications in biotechnology 1998, (CAB7) : horizon of bioprocess systems engineering in 21st century : a proceedings volume from the 7th IFAC International Conference, Osaka, Japan, 31 May-4 June 1998

Abstract: Computer application in bio-process engineering in Japan (T. Yoshida). Modeling, Simulation, Design and Optimization of Bioprocesses. Improving the estimation of parameters of penicillin fermentation models (M.T. Syddall et al. ). Modeling and simulation of gas-liquid-liquid extractive cultivation processes - biodegradation of xenobiotics (K. Bagherpour et al. ). Model discrimination and parameter identification by an experimental design strategy (R. Takors et al. ). Robotics in Biotechnology. Automated synthesis apparatus for pharmaceuticals (T. Sugawara). Knowledge Engineering Approaches for Bioprocess Operation. Stress monitoring in recombinant fermentations for artificial neural network control (A.J. Austin et al. ). Design of an expert system for selection of protein purification processes: comparison between different selection criteria (M.E. Lienqueo et al. ). Computer Application in Metabolic Engineering. Optimization and control of metabolic systems (R. Heinrich). Instrumentation and Data Processing. On-line monitoring and optimal adaptive control of the fed-batch baker's yeast fermentation (J.E. Claes, J.F. Van Impe). Database mining tools for bioprocess analysis (R.T. Kamimura et al. ). Cell Culture Engineering and Clinical Application. Modeling of multiple steady states in mammalian cells. A cybernetic approach (M.J. Guardia et al. ). Cell therapy by using genetic engineered glomerular cells to remove immune complex deposited on kidney (P.C. Wang et al. ). Application to Environmental Engineering. Process simulation of desulfurization from pyrite by thiobacillus ferrooxidans in a packed-bed medium-recirculating bioreactor under different recirculation rates (D-D. Xu et al. ). Equilibrium model for an anaerobic fixed-film reactor (H. Chua).

Model development and simulation of membrane separation systems for the recovery of intracellular protein products from crude biological feedstocks

Abstract: The definition of a microfiltration operation for the recovery of protein products from complex biological feedstocks requires an understanding of a large number of operating variables including the permeate flux rate and transmission characteristics of the membrane. This thesis examines the use of computer-based simulation techniques, accompanied with experimental studies, for the rapid design and evaluation of crossflow microfiltration systems for use in the bioprocess industries. The thesis sets out to test the hypothesis that single laboratory tests of permeate flux rate and transmission, accompanied by selected laboratory-scale characterisations, may be used to define the operating characteristics of a membrane separation process and hence allow the evaluation of the effect of a range of operating variables including the recirculation rate and the concentration factor on process performance. The results of single microfiltration experiments have been used to establish a relationship between the rejection of soluble species as a function of their molecular weight and the membrane operating conditions. Verification trials have been conducted to test the accuracy of the model predictions. Microfiltration experiments have also been conducted on biological systems including polyethleneimine flocculated yeast homogenate and Escherichia coli cell lysate. The results of experiments indicate that the use of physical property characterisations as a generic basis for the prediction of membrane performance is limited by the highly specific nature of biological feed-streams and their interaction with the membrane. Simulations studies were conducted on a 3-stage filtration process for the recovery of alcohol dehydrogenase from yeast homogenate. The studies assessed the impact of the recirculation rate, the membrane module length, the starting cell concentration and diafiltration volumes on the product yield and product purity. The benefits of simulation were further illustrated through a realistic case study where the objective was to specify the design and operating conditions for a membrane separation process leading to the lowest overall cost for a fermentation-based product manufactured to a specified level. The work highlighted the high degree of specific interactions between membranes and typical bioprocess feed-streams making statistical modelling approaches most appropriate for describing membrane filtration. The importance of simulation as an efficient tool to aid process development work was also illustrated.

Near infrared spectroscopy technique for bioprocess monitoring and control.

Abstract: The thesis described an application of near infrared (NIR) spectroscopy to a specific characterisation of a complex biological process stream. Its use is for the monitoring and control of a downstream process in which alcohol dehydrogenase (ADH) is to be recovered from a broth of homogenised yeast. Other than the product ADH, the yeast homogenate consists of contaminants such cell debris, protein, nucleic acids, lipids and others. While the first two represented a large fraction of the total contaminant and could be removed sufficiently by centrifugation and fractional precipitation, respectively. The remains residuals of contaminants often poses a fouling problem to the final stage of hydrophobic interaction chromatography (HIC) purification. The fouling has been minimised by the inserting a flocculation process at the early stage of recovery so that the problem contaminants are removed and the overall recovery is enhanced. A low budget instrument has been developed for sensitivity in the region of the NIR spectrum (from 1900 to 2500 nm) where preliminary work found distinctive NIR signatures from cell debris, protein and RNA in the yeast homogenate. The instrument is configured as a scanning spectrophotometer. Multivariate calibration technique with partial least squares (PLS) has been used for the three mentioned contaminants calibration. Two types of samples are used for calibrating the NIR instrument. In one case samples are prepared by adding materials representative of the contaminates to clarified yeast homogenate. In the other samples are taken from the process stream after flocculation and floe removal. In the former case the contaminant levels are well known but are outside the range of interest; in the latter there is uncertainty of analysis of contaminant level but the calibration is in the range of interest. The NIR instrument together with the calibration models has demonstrated potential in rapid monitoring of contaminants.