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Showing papers on "Bioprocess published in 2000"


Journal ArticleDOI
TL;DR: The conversion of both cellulose and hemicellulose for the production of fuel ethanol is being studied intensively, with a view to developing a technically and economically viable bioprocess.

492 citations


Journal ArticleDOI
TL;DR: In this article, factorial design and response surface techniques were used in combination with modeling and simulation to design and optimize an industrial bioprocess with multiple stages, where the fermentation system is composed of four ideal continuous-stirred tank reactors (ICSTR), linked in series, with cell recycling.

399 citations


Journal ArticleDOI
TL;DR: This review discusses integrated processing for ethanol, butanol, organic acids, antibiotics, and other products, which has important advantages in improving yield and conversion relative to conventional processes.

128 citations


Journal ArticleDOI
TL;DR: Evidence is provided to support the fact that models built for the prediction of analytes in a commercial bioprocess that employs a physicochemically complex production medium can be robust in performance over an extended period of time and that simple models based on fewer terms or latent variables can perform well, even in the context of matrices that are relatively complex.
Abstract: Near-infrared spectroscopy (NIRS) is known to have potential for cost-effective monitoring of bioprocesses. Although this has been demonstrated in many instances and several models have been reported, information regarding the complexity of models required and their utility over extended periods of time is lacking. In the present study, the complexity of the models required for the NIRS prediction of substrate (oil) and product (tylosin) concentration in an industrial bioprocess that employs a physicochemically heterogeneous medium for antibiotic production was assessed. Measurements made by both the diffuse reflectance and transmittance modes were investigated. SEP values for the prediction of the analytes averaged 5% or less, for the successful models, when evaluated using an external validation set, 2 years after the initial model development exercise. Diffuse reflectance measurements showed poorer results, compared to transmittance measurements, especially for monitoring tylosin. In general, this investigation provides evidence to support the fact that models built for the prediction of analytes in a commercial bioprocess that employs a physicochemically complex production medium can be robust in performance over an extended period of time and that simple models based on fewer terms or latent variables can perform well, even in the context of matrices that are relatively complex. It also indicates that sample presentation is likely to be a critical factor in the successful application of NIRS in bioprocess monitoring, which merits further detailed investigation.

42 citations


Journal ArticleDOI
TL;DR: The biotechnological potential of marine hyperthermophiles from a biochemical engineering perspective and their use in ‘green chemistry’ applications are discussed from both a microbiological and chemical engineering perspective.
Abstract: Despite the increased interest in hyperthermophiles and the rate of discovery of new species, their potential within the biotechnology industry has not been fully realized to date. The physiological characterization and biochemical survival mechanisms of marine hyperthermophilic Bacteria and Archaea are currently under investigation. However, very little information on their application in bioprocess systems is available. Since only a fraction of the world's oceans has been explored, the potential for isolating novel strains of marine hyperthermophiles is significant and hence they represent an, as yet, untapped biotechnological resource. Although much research has focused on the extraction of thermoactive enzymes, whole cell applications have been relatively overlooked. Running bioprocess systems using marine hyperthermophiles poses an interesting set of objectives, such as high temperature bioreactor operation and corrosion reduction of materials, for bioreactor design and manipulation of their products. Here, we discuss the biotechnological potential of marine hyperthermophiles from a biochemical engineering perspective and their use in ‘green chemistry’ applications. Both the bioprocess intensification implications and problems associated with cultivating these microbes in industrially relevant bioreactor systems are discussed from both a microbiological and chemical engineering perspective. © 2000 Society of Chemical Industry

25 citations


Journal ArticleDOI
TL;DR: A biosensor based on chemiluminescence for determination of serum uric acid and two biosensors for glutamate- and penicillin-fermentation process monitoring and controlling have been developed.
Abstract: A biosensor based on chemiluminescence for determination of serum uric acid and two biosensors for glutamate- and penicillin-fermentation process monitoring and controlling have been developed. The preparations and some properties of these sensors have been described in detail. The sensor methods described have been compared with routine methods used and the good coincidences have been obtained.

25 citations


Journal ArticleDOI
TL;DR: The validation studies show a satisfactory selectivity, linearity, accuracy, and recovery of the method, which could be an attractive choice for the analysis of glucose, methanol, and glycerol not only in fermentation media but also in biomedical and environmental samples.
Abstract: A reliable high-performance liquid chromatography-refractive index detection method for the simultaneous analysis of glucose, methanol, and glycerol in a bioprocess fermentation media using direct injection is presented. The validation studies show a satisfactory selectivity, linearity, accuracy, and recovery of the method. The lowest concentration detectable for glucose and methanol is 3.5 and 6.7 mg/100 mL, respectively. This method could be an attractive choice for the analysis of these compounds not only in fermentation media but also in biomedical and environmental samples.

24 citations



Journal ArticleDOI
TL;DR: An integrated bioprocess has been developed suitable for production of recombinant peptides using a gene multimerization strategy and site-specific cleavage of the resulting gene product using a fusion protein BB-C7 containing seven copies of the 31-residues C-peptide monomer.

17 citations


BookDOI
01 Jan 2000
TL;DR: Progress and Prospects of Ergot Alkaloid Research, Antimicrobial Peptides of Lactic Acid Bacteria, and Biochemical Engineering Aspects of Solid State Bioprocessing are studied.
Abstract: Progress and Prospects of Ergot Alkaloid Research.- Antimicrobial Peptides of Lactic Acid Bacteria: Mode of Action, Genetics and Biosynthesis.- Biochemical Engineering Aspects of Solid State Bioprocessing.- Multistage Magnetic and Electrophoretic Extraction of Cells, Particles and Macromolecules.- Recovery of Proteins and Microorganisms from Cultivation Media by Foam Flotation.

11 citations


Journal ArticleDOI
TL;DR: A method which combines the description of the evolution of components involved in the bioprocess including biomass and the physical environment generated mainly by the bioreactor characteristics and operational conditions is proposed.

Journal ArticleDOI
TL;DR: In this paper, the authors proposed to extend the dynamical analysis results on chemical tubular reactors presented in [5] to two linear distributed parameter models, in particular the linearized tangent models of two typical bioprocess models: a basic tubular bioreactor model and a denitrifying biofilter model.
Abstract: This paper proposes to extend the dynamical analysis results on chemical tubular reactors presented in [5] to two linear distributed parameter models. These are in particular the linearized tangent models of two typical bioprocess models: a basic tubular bioreactor model, and a denitrifying biofilter model. The tools used for the analysis are those of the infinite dimensional system theory (e.g., [2]). In the paper we show the existence of solutions for the studied models, and emphasize stability conditions.

Book ChapterDOI
01 Jan 2000
TL;DR: One of the most important goals in bioprocess automation is the manipulation of the process to meet desired performance criteria and typically the underlying model is highly dynamic in nature and typically a set of differential equations based on mass and energy balances is used for simulation of theprocess behavior.
Abstract: During the last decade, bioprocess development automation tasks have become more significant for overall process performance. Quality requirements on the one hand and growing process knowledge on the other have resulted in applied control strategies of increasing complexity. At the same time modern information technology facilitates higher flexibility of the technical systems used for practical realization of control tasks [1, 2]. Nevertheless, one of the most important goals in bioprocess automation is the manipulation of the process to meet desired performance criteria. Examples are the control of p02 to a prescribed limit or the realization of an exponential substrate feeding strategy. In practice, the process and the controller form a closed loop, often realized in a feedback fashion (Fig.6.1a). For design and stability investigations of these control-loops both process and controller require treatment using a theoretical mathematical model (Fig.6.1b). Obviously the time-dependent changes of the relevant process variables are of major interest for these applications. Therefore the underlying model is highly dynamic in nature and typically a set of differential equations based on mass and energy balances is used for simulation of the process behavior.

Journal Article
Parrer G1, Gerhard Schroll1, Gapes, Werner Lubitz, Schuster Kc 
TL;DR: The use of acetate and butyrate from an AB process is expected to provide a higher return-on-investment than the combustion of biogas to help meet energy demands.
Abstract: In a bioconversion study based on utilisation of by-products from the AB- (acetone - butanol) bioprocess a new isolated gram-negative solvent tolerant bacterium was used to convert the AB process residue after removal of the major part of the solvents. The bacterium identified as a representative of the genus Alcaligenes (designated as Alcaligenes sp. G) was capable of growth up to optical densities ranging from 8 to 20 and simultaneously of polyhydroxyalkanoate-(PHA-)accumulation up to 40% per dry weight. A standardised medium based on AB by-products containing 7 g/l of butyrate and 5 g/l of acetate at pH 7.5 was used in our studies for bioconversion into PHAs. Concentrations of 1-butanol, which is known for its membrane damaging properties in microorganisms, were tolerated in the AB by-products medium up to 4 g/l without significant inhibition of cellular growth. No inhibition of growth was observed, when the medium was adjusted to 40 g/l butyrate. Due to the toxicity of the remaining 1-butanol maintenance of sterility is of no high priority during the process. The use of acetate and butyrate from an AB process is expected to provide a higher return-on-investment than the combustion of biogas to help meet energy demands.


Book ChapterDOI
01 Jan 2000
TL;DR: In Japan, the fuzzy control has already been applied to practical industrial productions, such as pravastatin precursor, vitamin B2, and Japanese sake mashing process, and these industrial approaches of fuzzy control are introduced.
Abstract: Process control of bioprocess has been carried out by the judgment of the experts, who are the skilled operators and have lots of experiences for the control of the process. In almost all cases, those experiences are described linguistic IF-THEN rules. Fussy inference is one of the powerful tools to incorporate the linguistic rules to the computer for process control. Fuzzy control are divided into two types; one is the direct fuzzy control of process variables such as sugar feed rate in fed-batch culture and fermentation temperature in batch operation. The other is the indirect control of bioprocess, in which at first the phase recognition is carried out by fuzzy inference and the control strategies constructed in each phase are used for the control of process variables. In Japan, the fuzzy control has already been applied to practical industrial productions, such as pravastatin precursor, vitamin B2, and Japanese sake mashing process. In this review, these industrial approaches of fuzzy control are introduced.

Journal ArticleDOI
TL;DR: Bhowmik et al. as discussed by the authors proposed a software-based method for contamination detection in a fermentation process, where the state variables of the process are used to detect contamination of the processes.
Abstract: By Ujjal Kr. Bhowmik, Goutam Saha, Alok Barua, and Satyabroto Sinha*Fermentationisaveryimportantbioprocessfortheproductionofdrugs,foodproducts,beverageandforanimalcelllinecultureetc. The substrates used in these processes are expensive. So on-line monitoring of contamination in a fermentation process isvery essential in industries. A new method for contamination detection is being proposed in this paper. This is a software-basedmethod. In this new method, the state variables of the process are used to detect contamination of the process.

Journal ArticleDOI
TL;DR: In this article, a simple user friendly mathematical modelling tool was developed on the basis of MATLAB software, which provides the possibility of solving differential equation system with the aid of an easy-to-use graphical surface.
Abstract: A simple user friendly mathematical modelling tool was developed on the basis of MATLAB software. The program system provides the possibility of solving differential equation system with the aid of an easy-to-use graphical surface. It is suitable for bioprocess engineering simulations to describe the dynamic behaviour of a great series of various enzyme, fermentation and environmental bioreaction systems. It is especially beneficial that non-time interventions can also be modelled and graphical representations can be realized on a wide palette.


Journal ArticleDOI
TL;DR: Anhand eines Prozessmodells und einiger verfügbarer Messungen sind Zustandsbeobachter in der Lage, nicht gemessene Zustände online zu rekonstruieren, werden die unbekannten Parameter gewöhnlich mit Hilfe der Methode der kleinsten Fehlerquadrate oder der Maximum-Likelihood-Methode identif
Abstract: Anhand eines Prozessmodells und einiger verfügbarer Messungen sind Zustandsbeobachter in der Lage, nicht gemessene Zustände online zu rekonstruieren. Wenn das zugrundeliegende Prozessmodell aufgestellt ist, werden die unbekannten Parameter gewöhnlich mit Hilfe der Methode der kleinsten Fehlerquadrate oder der Maximum-Likelihood-Methode identifiziert, die von Offline-Messungen des gesamten Zustandsvektors Gebrauch machen. Diese herkömmlichen Methoden bringen jedoch nicht zum Ausdruck, dass das Modell des nicht gemessenen Teils des Zustandsvektors mit dem gemessenen in einer sensitiven Abhängigkeit stehen soll. Um eine höhere Modellsensitivität zu erzielen, wird in dieser Studie eine neue Kostenfunktion vorgeschlagen, die das klassische Maximum-Likelihood-Kriterium mit einem skalaren Maß der Modellsensitivität kombiniert.

Dissertation
01 Jan 2000
TL;DR: The aim of this work was to evaluate the processing options necessary to carry out a multi step biotransformation, undertake the decision-making stage of process design by following guidelines defined in a feasibility study, and put into practice the design of the bioprocess necessary to over accumulate a specific product using a model system.
Abstract: The majority of commercially used biotransformations tend to be single step involving the conversion of a substrate to a structurally similar compound. The exploitation of an existing host native pathway such that a novel compound is synthesised on the addition of a foreign gene is also possible. The cloning of a section of a foreign metabolic pathway in such a way that the enzymes synthesise a specific product on the addition of a substrate is a powerful technique that has been seldom investigated from a process design perspective. The aim of this work was to evaluate the processing options necessary to carry out a multi step biotransformation, undertake the decision-making stage of process design by following guidelines defined in a feasibility study, and put into practice the design of the bioprocess necessary to over accumulate a specific product using a model system. This research was based on the concept that a properly defined structured approach could be used to develop a particular biotransformation, and this approach could facilitate the development of any multi step biotransformation. The cloning of a whole section of a foreign metabolic pathway was possible due to the advent of metabolic pathway engineering using recombinant DNA technology. The distinguishing feature of this bioprocess when compared to other common biotransformations is the existence of pathway intermediates and pathway enzymes not naturally found in the host. The metabolic pathway used as the model system was the TOL meta-cleavage pathway, and the genes which convert benzoate to 2-hydroxymuconic semialdehyde in a linear three-step portion of the pathway were ligated into a host vector and used to transform an E. coli host strain JM107. This thesis describes the design of a fermentation protocol resulting in a biomass concentration of 18 - 22 g.L-1 and an investigation into the effect of induction on foreign gene expression including a long term induction experiment over a 20 hour period. A substrate feeding strategy was also designed and product yields as high as 17% during multi step biotransformations were compared to a single step counterpart with a yield of 22%. A method for the removal of the product using an Amberlite resin in a bisulphite form was proposed, and the resin was experimentally assessed for its use in this model system.


Journal Article
TL;DR: Based on McCarty's half reaction concept and Zhou's method, the stoichiometric equations of anaerobic oxidation of ammonium (AOA) are yielded in this article, where it is discovered that AOA process is a kind of autotrophic bioprocess.
Abstract: Based on McCarty's half reaction concept and Zhou's method, the stoichiometric equations of anaerobic oxidation of ammonium (AOA) are yielded. It is discovered that AOA process is a kind of autotrophic bioprocess. There are two possibilities of the nitrogen source for cell synthesis of AOA, i.e., NO - x or NH + 4. The alkalinity is necessary for AOA process when NH + 4 is used as the nitrogen source for cell synthesis. It is predicted that pH values will decrease if AOA processes are achieved.

Book ChapterDOI
01 Jan 2000
TL;DR: Measurements are not only a key issue in modern process development, but they also open the door to process supervision and control, and avoid restricted views when analyzing processes just through a keyhole.
Abstract: All measurements have the ultimate goal of creating information. Measurements are also the basis for new bioprocess development. The study of cell metabolism and regulation would be impossible without reliable analytical methods. Furthermore, process optimization and control are also based on reliable measurements. Bioprocess analyzers have the fundamental task to provide the information for optimizing microbial growth, yields, and product quality. Therefore, measurements are not only a key issue in modern process development, but they also open the door to process supervision and control, and avoid restricted views when analyzing processes just through a keyhole.

Book ChapterDOI
TL;DR: This chapter discusses the engineering process control of bioseparation, which is defined as process steps used to purify the products from bioreactors (such as fermentors) which may include extraction, precipitation, electrophoresis, and chromatography.
Abstract: Publisher Summary This chapter discusses the engineering process control of bioseparations. Bioseparation is defined as process steps used to purify the products from bioreactors (such as fermentors): downstream processing steps which may include extraction, precipitation, electrophoresis, and chromatography. It is suggested that these separation and purification steps comprise 40–80% of the total cost of a bioprocess. An example of the scale of the bioseparation portion of a processing sequence is the production of human insulin using fermentation and recombinant DNA technology. After the fermentor stage, this process requires cell harvesting and disruption, recovery and solubilization, enzymatic conversion, refolding, sulfitolysis, cleavage, purification, and crystallization. These steps involve the unit processes of centrifugation, reaction, adsorption, filtering, chromatography, and crystallization. Clearly, any steps to improve the efficiency of the process must address the downstream steps.

01 Jan 2000
TL;DR: The exploitation of in-situ mid-IR spectroscopy in combination with partial least-squares anal.
Abstract: Comprehensive and cGMP suitable bioprocess monitoring is still a challenge in microbial fermn. and cell culture process development. This paper discusses the exploitation of in-situ mid-IR spectroscopy in combination with partial least-squares anal. to monitor carbohydrate, amino acid, org. acid, pH, temp., and biomass content of Saccharomyces Cerevisiae, Phaffia rhodozyma, and CHO cell cultures. Reliability of the monitored values will be discussed for potential application in cGMP environments along with case studies to increase the productivity by using the information for controlling the processes. [on SciFinder (R)]

Book ChapterDOI
TL;DR: This paper uses ion exchange as a model process, and presents the principles and the practices involved in the chromatography validation, which is probably the most widely used unit operation in biologies manufacturing.
Abstract: Validation has become a key issue in the production of biopharmaceutics or biologies intended for therapeutic use. In addition to the validation of final product quality, manufacturing process validation is gaining wider attention. Bioprocesses are delicate and sensitive in nature, and thus careful planning and organization are required for any successful process validation. Bioprocess chromatography is probably the most widely used unit operation in biologies manufacturing. In this paper, using ion exchange as a model process, we present the principles and the practices involved in the chromatography validation.

01 Jan 2000
TL;DR: In this paper, the authors present a case study for use in the teaching of bioprocess design, taking the production and isolation of an intracellular protein from S. cerevisae, and demonstrate how undergraduates can use a range of data to construct and then to investigate the range of process flowsheet options available for such a process duty.
Abstract: This paper presents a case study for use in the teaching of bioprocess design. Taking the production and isolation of an intracellular protein from S. cerevisae , it demonstrates how undergraduates can use a range of data to construct and then to investigate the range of process flowsheet options available for such a process duty. The paper considers the role of newer operations, such as expanded bed technology, alongside more traditional process routes. An integrated view of bioprocess design is developed to demonstrate how unit operations interact and hence enable students to determine the eventual overall process performance that is achieved.


Journal ArticleDOI
TL;DR: In this article, the authors present a case study for use in the teaching of bioprocess design, taking the production and isolation of an intracellular protein from S. cerevisae, and demonstrate how undergraduates can use a range of data to construct and then to investigate the range of process flowsheet options available for such a process duty.
Abstract: This paper presents a case study for use in the teaching of bioprocess design. Taking the production and isolation of an intracellular protein from S. cerevisae , it demonstrates how undergraduates can use a range of data to construct and then to investigate the range of process flowsheet options available for such a process duty. The paper considers the role of newer operations, such as expanded bed technology, alongside more traditional process routes. An integrated view of bioprocess design is developed to demonstrate how unit operations interact and hence enable students to determine the eventual overall process performance that is achieved.