Biotechnology bioreactor operation

Bioprocess Control An industrial fermenter is a fairly sophisticated device with control of temperature, aeration rate, and perhaps pH, concentration of dissolved oxygen, or some nutrient concentration. There has been a strong trend to automated data collection and analysis. Analog control is stiU very common, but when a computer is available for on-line data collec tion, it makes sense to use it for control as well. More elaborate measurements are performed with research bioreactors, but each new electrode or assay adds more work, additional costs, and potential headaches. Most of the functional relationships in biotechnology are nonlinear, but this may not hinder control when bioprocess operate over a narrow range of conditions. Furthermore, process control is far advanced beyond the days when the main tools for designing control systems were intended for linear systems. 

BPD is a contract research facility, which started operations in 1996. From the storage of frozen materials, the customized laboratory services to the consulting in process development and scaling up, BPD has been accumulating useful experiences in the biotechnological scenario. Very flexible set of fermenters are used to satisfy customer needs, through very small and fast adaptation and modifications. Bioreactors productivity varies from 100 mg to 1000 mg scale. 

The use of hydrocyclones for separating mammalian cells from the culture medium opens the possibility of using them to perform perfusion in bioreactors. As hydrocyclones have no moving parts, they are ideally suited for operation under aseptic conditions as required by the biotechnology industry. 

Commercial manufacturing operations in biotechnology usually employ bioreactors or fermentors for product expression. In this discussion, the term fermentor will refer to bacterial or fungal processes and the term bioreactor to animal cell cultures. While extensive description of the operation... 

K Schugerl, J. Lticke, U Oels Bubble Column Bioreactors. Tower Bioreactors without Mechanical Agitation. - R. Acton, J.D.Lynn Description and Operation of a Large-Scale, Mammalian Cell, Suspensio Culture Facility. -S. Aiba, M. Okabe A Complementary Approach to Scale-Up Simulation and Optimization of Microbial Processes. - LKjaer-gaard The Redox Potential ItUseandControl in Biotechnology. 

The manipulation of this bioreactor is generally performed in a laminar-flow cabinet, and is thus an open and risky operation. This is probably a characteristic that differentiates this bioreactor type from the other homogeneous bioreactors, where reliability of all seals and connections can be ensured through the use of direct steam. Also, the large number of connections using flexible tubing makes the operation of this type of bioreactor more complicated than that of other bioreactors of the same class. Currently, the performance and application potential of these bioreactors are under evaluation by the biotechnological community. 

The use of biotechnology in the manufacture of pharmaceuticals is of increasing interest Consequently these techniques require attention in the planning of unit processes. Bioprocessing can be considered in terms of small-scale bioreactors, or fermenters, and the translation of such processes into large-scale economically viable production operations. ... 

The major difference between a biotechnological process and other pharmaceutical manufacturing operations is the need for a bioreactor (Fig. 8). These bioreactors may be required to produce expressed proteins utilizing bacteria, yeast, insect, or mammalian... 

C. B. Ersu and S. K. Ong, Operating Characteristics and Treatment Performance of a Membrane Bioreactor Using Tubular Ceramic Membrane, IWA Environmental Biotechnology Advancement on Water and Wastewater Applications in the Tropics, Kuala Lumpur, Malaysia, December 9-10, 2003. 

The rising need for new separation processes for the biotechnology industry and the increasing attention towards development of new industrial eruyme processes demonstrate a potential for the use of liquid membranes (LMs). This technique is particularly appropriate for multiple enzyme / cofactor systems since any number of enzymes as well as other molecules can be coencapsulated. This paper focuses on the application of LMs for enzyme encapsulation. The formulation and properties of LMs are first introduced for those unfamiliar with the technique. Special attention is paid to carrier-facilitated transport of amino acids in LMs, since this is a central feature involved in the operation of many LM encapsulated enzyme bioreactor systems. Current work in this laboratory with a tyrosinase/ ascorbate system for isolation of reactive intermediate oxidation products related to L-DOPA is discussed. A brief review of previous LM enzyme systems and reactor configurations is included for reference. 

This book covers several of the emerging areas of separations in biotechnology and is not intended to be a comprehensive handbook. It includes recent advances and latest developments in techniques and operations used for bioproduct recovery in biotechnology and applied to fermentation systems as well as mathematical analysis and modeling of such operations. The topics have been arranged in three sections beginning with product release from the cell and recovery from the bioreactor. This section is followed by one on broader separation and concentration processes, and the final section is on purification operations. The operations covered in these last two sections can be used at a number of different stages in the downstream process. 

Whitford (48) provides mnch more information that is of interest to chemical engineers involved in the design and operation of fed batch processes for culture of animal cells. Shukla and Thommes (49) discnssed additional aspects of fed batch culture of mammalian cells for large scale production of monoclonal antibodies and related proteins. Further information concerning the use of bioreactors for culture of mammalian cells is contained in the article Mammalian Cell Bioreactors by Zhou and co-workers in the Encyclopedia of Industrial Biotechnology (50). 

For this study, a bi-phasic bioreactor design was utilized, operating in a semi-continuous flow process, having a hydraulic retention time of four days. Groundwater, with contaminant concentrations as high as 7000 ppm creosote, was treated on-site. This demonstration achieved a removal efficiency of greater than 99% for total polynuclear aromatic hydrocarbons (PAHs). This includes a removal rate of 98% for the most recalcitrant, and most hazardous fraction of the PAHs, and 88% for PCP. The field test proved that biotechnology application for hazardous waste remediation can be effective at an actual waste site. 

Christi Y, Moo-Young M. Clean-in-place systems for industrial bioreactors Design, validation and operation. Journal of Industrial Microbiology and Biotechnology 1994 13 201-207. 

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