Showing papers on "Bioprocess published in 1996"

Role of hydrodynamic shear in the cultivation of animal, plant and microbial cells

Abstract: The rapid developments in biotechnology have resulted in the identification and use of a large variety of biologically active substances produced from microbial, plant and animal origin. These range from enzymes and antibiotics to highly complex molecules such as immunoglobulins, growth factors and hormones. The advances in bioprocess technology have enabled the cultivation of different micro-organisms, namely bacteria, yeast and fungi, on a large scale. The potential use of plant and animal cells has, however, not yet been completely realized. One of the major limitations in the scale-up of plant and animal cell culture is the shear sensitivity of these cells. This arises owing to the large size of the cells. In addition, animal cells are especially fragile because of the lack of cell walls.

Near-Infrared Spectroscopic Determination of Acetate, Ammonium, Biomass, and Glycerol in an Industrial Escherichia coli Fermentation

Abstract: By use of near-infrared (NIR) spectroscopy, simultaneous, multiple-con-stituent estimation of important bioprocess parameters can be obtained in a time frame (< 1 min assay) that was previously unattainable. Therefore, with NIR spectroscopy the opportunity exists to incorporate real-time chemical information into bioprocess monitoring or control strategies which will lead to significant bioproeess improvements. The NIR spectroscopic analysis of unmodified whole broth samples for acetate, ammonium, biomass, and glycerol is described for an industrial Escherichia coil fed-batch fermentation bioprocess. For acetate and glycerol, suitable results were obtained from multiple linear least-squares regression (MLR) analysis. A more sophisticated partial least-squares (PLS) regression analysis was necessary to adequately model ammonium and biomass. The respective prediction errors (1σ) of 0.7 g/L, 1.4 g/L, 0.7 g/L, and 7 mmol/L for acetate, biomass, glycerol, and ammonium compare well with the error of the wet chemical reference methods used to derive the calibration algorithms.

The use of windows of operation as a bioprocess design tool

Abstract: Bioprocess design problems are frequently multivariate and complex. However, they may be visualised by a graphical representation of the design constraints and correlations governing both the process and system under consideration, namely windows of operation. Windows of operation exist at all stages of process design and find use both in the identification of key constraints from limited information, and also, with more detailed knowledge, the sensitivity of a process to design or operating changes. In this way windows of operation may be used to help understand and optimise a bioprocess design. In this paper the formulation, development and application of windows of operation is discussed for a range of biological processes including fermentation, protein recovery and biotransformation.

Sol-gels and chemical sensors

Abstract: We review the principles of optical and electrochemical sensors based on the use of the sol-gel technique, in particular their fabrication, working principles, and various configurations. We also report on potential applications, e.g. to environmental and clinical analysis, to gas sensing, and to bioprocess monitoring. Methods are critically reviewed for making such sensors, how to encapsulate organic, inorganic and biological matter, and how to control the properties of the resulting materials. Specifically, sensors for gases, ions, and organic as well as bioorganic molecules are discussed in some detail.

Bioprocess intensification through bioreactor engineering

Abstract: An overview of methods for intensification of bioprocesses is presented. Schemes focused on bioreactor and bioreaction engineering are the primary means of commercially-relevant process intensification. Examples are used to illustrate some of the available options : improved oxygen transfer by use of static mixers and other means ; enhancement of heat transfer ; slurry bioreactors for improved solid-liquid mass transfer and efficient suspension of the biocatalyst ; modification of fermentation conditions to amplify productivity ; high density cell culture bioreactors ; design modifications for low-shear bulk mixing of shear-sensitive, viscous broths ; use of additives as shear protectants ; and high-efficiency airlift bioreactors. Methods that are commonly used for intensification of chemical processes are generally too severe for use with biocatalysts. Of the available strategies for bioprocess intensification, some, such as enhancement of oxygen transfer, have broader applicability than others. For the foreseeable future, empirical strategies are expected to remain the primary means of bioprocess intensification. Intensification goals are most effectively achieved through multidisciplinary approaches implemented at the earliest stages of process research.

Biosensors in analytical biotechnology

Abstract: Sampling modules, R. Freitag enzyme modified field-effect-transistors (EnFET) for bioprocess monitoring, T. Kullick and R. Ulber optical biosensors in bioprocess technology, O. Thorsden and R. Freitag flow injection analysis based in enzymatic reactions, B.Weigel immunoanalysis and immunosensors, R. Freitag neural networks as a tool for the evaluation of measurement signals of Bio-FET-FI-sensors, B. Hitzman et al online monitoring of animal cell cultivation, G. Kretzmer biosensors for monitoring of microbial processes, U. Bilitewski and I. Rohm.

Process integration aspects for the production of fine chemicals illustrated with the biotransformation of γ-butyrobetaine into l-carnitine

Abstract: l -carnitine is a fine chemical with pharmaceutical, nutritional and animal food applications. Thus, the product purification forms an essential part of the production process. Consequently, process optimization of biotransformation and downstream processing should be done in an integral way. There are several options for the process design of the biotransformation, e.g. chemostat with cell recycling, one-stage or multistage, fed-batch. Blackman kinetics for the product formation of the biotransformation of γ-butyrobetaine into l -carnitine provided adequate modelling of the bioprocess in order to define the optimal process design with respect to productivity, downstream processing and cost. With respect to these criteria, the fed-batch biotransformation of γ-butyrobetaine into l -carnitine appeared to be superior over several modes of operation of the continuous process with cell recycling. A lower productivity of the fed-batch process was compensated by a disproportionally cheaper downstream processing or a lower investment cost. Furthermore, process integration considerations determined the choice of raw materials for the biotransformation, such as carbon and nitrogen sources, resulting in optimized or even a reduced number of unit operations of the downstream processing.

A new version of an in situ sampling system for bioprocess analysis

Abstract: In this article, attention is focussed on an on-line sampling device for bioreactors and its characterization regarding sterility and response time. The integration of this device into analytical systems for biotechnology (FIA with biosensors) resulted in on-line analysis systems for bioprocess control. The new ESIP version of an in situ sampling system for bioprocess analysis produced by the EPPENDORF-NETHELER-HINZ GmbH, Germany, had a short response time of 8 min (99%), which was determined by means of conductivity measurement after an increase of the medium conductivity due to the gradual addition of KCl. Effectiveness and reliability of the module were tested by bubble point measurement resulting in a bubble point pressure of 2.1 bars. The sampling probe was tested successfully for use in a broad variety of microorganisms and cultivations.

Strategies for Bioreactor Scale-Up

Abstract: Scale-up has been one of the major problems in bioprocess technology. Earlier methods of trial-and-error have now been replaced by those which involve the understanding of the fundamental phenomena, at least for the simpler cases. For more complicated heterogeneous systems the employment of various rules of thumb is still widely practised. A summary of various strategies for bioreactor scale-up is given below.

Bioprocess design: study of a case

Abstract: We developed a scale-up process design for the production of the 18 kDa heat shock recombinant protein from Mycobacterium leprae cloned in Saccharomyces cerevisiae (1). Here we present some of the costs associated with running a process based in our laboratory and pilot scale data. Based on these values and assuming the demand of the 18kDa-hsp protein as 500g/year we can review costs at least on an approximate basis.

Bioprocess for production of dipeptide based compounds

Abstract: Bioprocesses are disclosed for the production of compounds which can be produced from a dipeptide intermediate. The process comprises production of a recombinant polypeptide which contains the dipeptide intermediate. The dipeptide intermediate is further processed to ultimately provide the finished product.

Control of Cell Protein Synthesis from Kluyveromyces Marxianus Var. Lactis MC5

Abstract: A bioprocess of transformation of lactose from natural substrate in batch fermentation of Kluyveromyces marxianus var lactis MC5 is considered in this paper A mathematical model which described the kinetics of the process is designed on the basis of experimental data The control of the batch fermentation process by flow rate of the influent substrate is determined so as to meet given technological requirements for maximum biomass yield, constant concentration of dissolved oxygen and preset yield coefficient

General Methodology in Bioprocess Engineering

Abstract: Commercialization of biotechnologies not only depends on intelligent products for the market but also on a rapid and secure methodology for bioprocess design & development. The “old” empirical way of trial & error is to be replaced by a more systematic procedure according to a recent methodology in bioprocess technology, called the “formal macroapproach”, based on a holistic mode of thinking, operating with interaction-networks (integration of biological and physical phenomena). It is based on macroscopic process variables and on formal analogies adapted to experiments, which are used for mathematical modeling. A better scale-up is achieved by a scale-down approach, where regime analysis is used to determine the process bottlenecks, which then are experimentally simulated in the scale-down “model-bioreactors”, representing the new integrating strategy. Mathematical modeling plays a central role representing a simplified but adequate approximation to real process behaviour.