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Bioprocess Engineering Principles
The emergence and refinement of techniques in molecular biology has changed our perceptions of medicine, agriculture, and environmental management. Scientific breakthroughs in gene expression, protein engineering, and cell fusion are being translated by a strengthening biotechnology industry into revolutionary new products and services. Many a student has been enticed by the promise of biotechnology and the excitement of being near the cutting edge of scientific advancement. However, graduates trained in molecular biology and cell manipulation soon realize that these techniques are only part of the picture. Reaping the full benefits of biotechnology requires manufacturing capability involving the large-scale processing of biological material. Increasingly, biotechnologists are being employed by companies to work in cooperation with chemical engineers to achieve pragmatic commercial goals. For many years, aspects of biochemistry and molecular genetics have been included in chemical engineering curricula, yet there has been little attempt until recently to teach aspects of engineering applicable to process design to biotechnologists.
This textbook is the first to present the principles of bioprocess engineering in a way that is accessible to biological scientists. Other texts on bioprocess engineering currently available assume that the reader already has engineering training. On the other hand, chemical engineering textbooks do not consider examples from bioprocessing, and are written almost exclusively with the petroleum and chemical industries in mind. This publication explains process analysis from an engineering point of view, but refers exclusively to the treatment of biological systems. Over 170 problems and worked examples encompass a wide range of applications, including recombinant plant and animal cell cultures, immobilized catalysts, as well as traditional fermentation systems.
Introduction: Bioprocess Development: An Interdisciplinary Challenge: Steps in Bioprocess Development: A Typical New Product from Recombinant DNA. A Quantitative Approach. Introduction to Engineering Calculations: Physical Variables, Dimensions and Units. Units. Force and Weight. Measurement Conventions. Standard Conditions and Ideal Gases. Physical and Chemical Property Data. Stoichiometry. Presentation and Analysis of Data: Errors in Data and Calculations. Presentation of Experimental Data. Data Analysis. Graph Paper with Logarithmic Coordinates. General Procedures for Plotting Data. Process Flow Diagrams. Material and Energy Balances: Material Balances: Thermodynamic Preliminaries. Law of Conservation of Mass. Procedure for Material-Balance Calculations. Material-Balance Worked Examples. Material Balances with Recycle, By-Pass and Purge Streams. Stoichiometry of Growth and Product Formation. Energy Balances: Basic Energy Concepts. General Energy-Balance Equations. Enthalpy Calculation Procedures. Enthalpy Change in Non-Reactive Processes. Steam Tables. Procedure for Energy-Balance Calculations without Reaction. Energy-Balance Worked Examples without Reaction. Enthalpy Change Due to Reaction. Heat of Reaction for Processes with Biomass Production. Energy-Balance Equation for Cell Culture. Fermentation Energy-Balance Worked Examples. Unsteady-State Material and Energy Balances: Unsteady-State Material-Balance Equations. Unsteady-State Energy-Balance Equations. Solving Differential Equations. Solving Unsteady-State Mass Balances. Solving Unsteady-State Energy Balances. Physical Processes: Fluid Flow and Mixing: Classification of Fluids. Fluids in Motion. Viscosity. Momentum Transfer. Non-Newtonian Fluids. Viscosity Measurement. Rheological Properties of Fermentation Broths. Factors Affecting Broth Viscosity. Mixing. Power Requirements for Mixing. Scale-Up of Mixing Systems. Improving Mixing in Fermenters. Effects of Rheological Properties on Mixing. Role of Shear in Stirred Fermenters. Heat Transfer: Heat Transfer-Equipment. Mechanisms of Heat Transfer. Conduction. Heat Transfer between Fluids. Design Equations for Heat-Transfer Systems. Application of the Design Equations. Mass Transfer: Molecular Diffusion. Role of Diffusion in Bioprocessing. Film Theory. Convective Mass-Transfer. Oxygen Uptake in Cell Cultures. Oxygen Transfer in Fermenters. Measuring Dissolved-Oxygen Concentrations. Estimating Oxygen Solubility. Mass-Transfer Correlations. Measurement of kLa . Oxygen Transfer in Large Vessels. Unit Operations: Filtration. Centrifugation. Cell Disruption. The Ideal-Stage Concept. Aqueous Two-Phase Liquid Extraction. Adsorption. Chromatography. Reactions and Reactors: Homogenous Reactions: Basic Reaction Theory. Calculation of Reaction Rates from Experimental Data. General Reaction Kinetics for Biological Systems. Determining Enzyme Kinetic Constants from Batch Data. Kinetics of Enzyme Deactivaton. Yields in Cell Culture. Cell Growth Kinetics. Growth Kinetics with Plasmid Instability. Production Kinetics in Cell Culture. Kinetics of Substrate Uptake in Cell Culture. Effect of Culture Conditions on Cell Kinetics. Determining Cell Kinetic Parameters from Batch Data. Effect of Maintenance on Yields. Kinetics of Cell Death. Heterogenous Reactions: Heterogeneous Reactions in Bioprocessing. Concentration Gradients and Reaction Rates in Solid Catalysts. Internal Mass-Transfer and Reaction. The Thiele Modulus and Effectiveness Factor. External Mass-Transfer. Liquid-Solid Mass-Transfer Correlations. Experimental Aspects. Minimising Mass-Transfer Effects. Evaluating True Kinetic Parameters. General Comments on Heterogeneous Reactions in Bioprocessing. Reaction Engineering: Reactor Engineering in Perspective. Bioreactor Configurations. Practical Considerations for Bioreactor Construction. Monitoring and Control of Bioreactors. Ideal Reactor Operation. Sterilisation. Appendices: Conversion Factors. Physical and Chemical Property Data. Steam Tables. Mathematical Rules. Chapter Summaries, Problems, References, and Suggestions for Further Reading. List of Symbols. Index.