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Animal cell cultures are being developed for the production of a variety of valuable biochemical products. Largescale in vitro culture methods which are being applied include free-cell suspension cultures'.* and immobilizedcell cultures .3,4 The hollow-fiber bioreactor (HFBR)5-7 is an immobilized-cell reactor. In this article, we present experimental results for hybridoma cultures grown in a modified design of the hollow-fiber reactor. The new design is intended to minimize the mass-transfer and scale-up problems often encountered with cell cultures.The monoclonal antibodies (Mabs) produced by hybridomas have found a variety of uses, including diagnostics, purification, and therapeutics. Current and projected applications call for facilities capable of producing gram or even kilogram quantities of individual Mabs . 2 Large-scale culture in immobilized-cell reactors has distinct advantages over free-cell suspension reactors .8 The cells are protected from the high shear that is found in stirred suspension cultures. Immobilized cells pack into dense colonies with cell concentrations two orders of magnitude higher than in suspensions. At such density, cells are able to stay viable for long periods of time in a stationary phase with low nutrient consumption and often exhibit increased antibody productivity and reduced serum requirement.An HFBR is a bundle of hollow fibers sealed inside a tube, separating the lumen side from the shell side. in the conventional operation, cells are confined to the shell. Medium flows axially through the lumen of each fiber (Fig. 1). Supply of nutrients to the cells and removal of waste products from their vicinity occurs by diffusive transport across the fiber membrane between the lumen and the shell space. The major problems associated with this system are mass transfer resistance and axial pressure
Animal cell cultures are being developed for the production of a variety of valuable biochemical products. Largescale in vitro culture methods which are being applied include free-cell suspension cultures'.* and immobilizedcell cultures .3,4 The hollow-fiber bioreactor (HFBR)5-7 is an immobilized-cell reactor. In this article, we present experimental results for hybridoma cultures grown in a modified design of the hollow-fiber reactor. The new design is intended to minimize the mass-transfer and scale-up problems often encountered with cell cultures.The monoclonal antibodies (Mabs) produced by hybridomas have found a variety of uses, including diagnostics, purification, and therapeutics. Current and projected applications call for facilities capable of producing gram or even kilogram quantities of individual Mabs . 2 Large-scale culture in immobilized-cell reactors has distinct advantages over free-cell suspension reactors .8 The cells are protected from the high shear that is found in stirred suspension cultures. Immobilized cells pack into dense colonies with cell concentrations two orders of magnitude higher than in suspensions. At such density, cells are able to stay viable for long periods of time in a stationary phase with low nutrient consumption and often exhibit increased antibody productivity and reduced serum requirement.An HFBR is a bundle of hollow fibers sealed inside a tube, separating the lumen side from the shell side. in the conventional operation, cells are confined to the shell. Medium flows axially through the lumen of each fiber (Fig. 1). Supply of nutrients to the cells and removal of waste products from their vicinity occurs by diffusive transport across the fiber membrane between the lumen and the shell space. The major problems associated with this system are mass transfer resistance and axial pressure
The article contains sections titled: 1. Introduction 2. Immobilization Techniques 2.1. Introduction 2.2. Methods of Enzyme Immobilization 2.2.1. Carriers for Enzyme Immobilization 2.2.2. Methods for Insoluble Enzymes 2.2.2.1. Carrier Binding 2.2.2.2. Cross‐Linking 2.2.2.3. Enzyme Copolymerization 2.2.2.4. Entrapment 2.2.3. Methods for Soluble Enzymes 2.3. Methods of Cell Immobilization 2.3.1. Introduction 2.3.2. Cell Supports 2.3.3. Immobilization Techniques 2.3.3.1. Cell Immobilization without a Support 2.3.3.2. Binding of Cells to a Carrier 2.3.3.3. Immobilization of Cells by Entrapment 2.4. Methods of Organelle Immobilization 2.5. Coimmobilization of Biocatalysts 3. Activity and Kinetics of Immobilized Biocatalysts 3.1. Effects of Immobilization on Enzyme Activity 3.2. Kinetics of Immobilized Biocatalysts 3.3. Assay of Immobilized Biocatalysts 4. Mass Transfer in Immobilized Biocatalyst Systems 4.1. External Mass Transfer 4.2. Prediction and Correlation of External Mass‐Transfer Coefficients 4.2.1. Catalyst Beds 4.2.2. Particles in an Agitated Tank 4.3. Internal Mass Transfer 5. Design of Immobilized Biocatalyst Reactors 5.1. Batch Stirred‐Tank Reactor 5.2. Plug‐Flow Tubular Reactor 5.3. Continuous Stirred‐Tank Reactor 5.4. Packed‐ or Fixed‐Bed Reactors 5.5. Fluidized‐Bed Reactors 5.6. Membrane Reactor Systems 5.7. Laboratory Reactors for Kinetic Measurements 5.7.1. Batch and Continuous Tank Reactors 5.7.2. Experimental Differential Recycle Reactor 6. Immobilization Media 6.1. Characteristics of Solid Supports 6.2. Characteristics of Semipermeable Separators 7. Application of Immobilized Biocatalysts 7.1. Analysis 7.2. Immobilized Enzymes in Therapeutic Medicine 7.3. Ethanol Production Using Immobilized Cells 7.4. Industrial Applications of Immobilized Biocatalysts 7.4.1. Production of High‐Fructose Corn Syrup 7.4.2. Amino Acid Production 7.4.3. Environmental Applications 8. Economic Aspects 9. Safety, Environmental, and Legal Aspects 9.1. Immobilized Enzymes 9.2. Immobilized Cells
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