Contents. Preface XI Nomenclature XIII. Part I Basic Concepts and Principles 1

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1 V Preface XI Nomenclature XIII Part I Basic Concepts and Principles 1 1 Introduction Background and Scope Dimensions and Units Intensive and Extensive Properties Equilibria and Rates Batch versus Continuous Operation Material Balance Energy Balance 9 References 11 2 Elements of Physical Transfer Processes Introduction Heat Conduction and Molecular Diffusion Fluid Flow and Momentum Transfer Laminar versus Turbulent Flow Transfer Phenomena in Turbulent Flow Film Coefficients of Heat and Mass Transfer 22 References 25 3 Chemical and Biochemical Kinetics Introduction Fundamental Reaction Kinetics Rates of Chemical Reaction Elementary Reaction and Equilibrium Temperature Dependence of Reaction Rate Constant k Rate Equations for First- and Second-Order Reactions Rates of Enzyme Reactions Kinetics of Enzyme Reaction 35 Biochemical Engineering: A Textbook for Engineers, Chemists and Biologists Shigeo Katoh and Fumitake Yoshida Copyright r 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN:

2 VI Evaluation of Kinetic Parameters in Enzyme Reactions Inhibition and Regulation of Enzyme Reactions 39 References 45 4 Cell Kinetics Introduction Cell Growth Growth Phases in Batch Culture Factors Affecting Rates of Cell Growth Cell Growth in Batch Fermentors and Continuous Stirred-Tank Fermentors (CSTF) Batch Fermentor Continuous Stirred-Tank Fermentor 54 References 55 Part II Unit Operations and Apparatus for Bio-Systems 59 5 Heat Transfer Introduction Overall Coefficients U and Film Coefficients h Mean Temperature Difference Estimation of Film Coefficients h Forced Flow of Fluids Through Tubes (Conduits) Forced Flow of Fluids Across a Tube Bank Liquids in Jacketed or Coiled Vessels Condensing Vapors and Boiling Liquids Estimation of Overall Coefficients U 68 References 71 6 Mass Transfer Introduction Overall Coefficients k and Film Coefficients k of Mass Transfer Types of Mass Transfer Equipment Packed Column Plate Column Spray Column Bubble Column Packed (Fixed-)-Bed Column Other Separation Methods Models for Mass Transfer at the Interface Stagnant Film Model Penetration Model Surface Renewal Model Liquid-Phase Mass Transfer with Chemical Reactions 82

3 VII 6.6 Correlations for Film Coefficients of Mass Transfer Single-Phase Mass Transfer Inside or Outside Tubes Single-Phase Mass Transfer in Packed Beds J-Factor Performance of Packed Columns Limiting Gas and Liquid Velocities Definitions of Volumetric Coefficients and HTUs Mass Transfer Rates and Effective Interfacial Areas 91 References 95 7 Bioreactors Introduction Some Fundamental Concepts Batch and Continuous Reactors Effects of Mixing on Reactor Performance Uniformly Mixed Batch Reactor Continuous Stirred-Tank Reactor (CSTR) Plug Flow Reactor (PFR) Comparison of Fractional Conversions by CSTR and PFR Effects of Mass Transfer Around and Within Catalyst or Enzymatic Particles on the Apparent Reaction Rates Liquid Film Resistance Controlling Effects of Diffusion Within Catalyst Particles Effects of Diffusion Within Immobilized Enzyme Particles Bubbling Gas Liquid Reactors Gas Holdup Interfacial Area Mass Transfer Coefficients Definitions Measurements of k L a Mechanically Stirred Tanks General Power Requirements of Stirred Tanks Ungassed Liquids Gas-Sparged Liquids k L a in Gas-Sparged Stirred Tanks Liquid Mixing in Stirred Tanks Suspending of Solid Particles in Liquid in Stirred Tanks Gas Dispersion in Stirred Tanks Bubble Columns General Performance of Bubble Columns Gas Holdup k L a Bubble Size 122

4 VIII Interfacial Area a k L Other Correlations for k L a k L a and Gas Holdup for Suspensions and Emulsions Airlift Reactors IL Airlifts EL Airlifts Packed-Bed Reactors Microreactors [29] 127 References Membrane Processes Introduction Dialysis Ultrafiltration Microfiltration Reverse Osmosis Membrane Modules Flat Membrane Spiral Membrane Tubular Membrane Hollow-Fiber Membrane 142 References Cell Liquid Separation and Cell Disruption Introduction Conventional Filtration Microfiltration Centrifugation Cell Disruption 151 References Sterilization Introduction Kinetics of the Thermal Death of Cells Batch Heat Sterilization of Culture Media Continuous Heat Sterilization of Culture Media Sterilizing Filtration 162 References Adsorption and Chromatography Introduction Equilibria in Adsorption Linear Equilibrium Adsorption Isotherms of Langmuir-Type and Freundlich-Type 166

5 IX 11.3 Rates of Adsorption into Adsorbent Particles Single- and Multi-Stage Operations for Adsorption Adsorption in Fixed Beds Fixed-Bed Operation Estimation of the Break Point Separation by Chromatography Chromatography for Bioseparation General Theories on Chromatography Equilibrium Model Stage Model Rate Model Resolution Between Two Elution Curves Gel Chromatography Affinity Chromatography 181 References 183 Part III Practical Aspects in Bioengineering Fermentor Engineering Introduction Stirrer Power Requirements for Non-Newtonian Liquids Heat Transfer in Fermentors Gas Liquid Mass Transfer in Fermentors Special Factors Affecting k L a Effects of Electrolytes Enhancement Factor Presence of Cells Effects of Antifoam Agents and Surfactants k L a in Emulsions k L a in Non-Newtonian Liquids Desorption of Carbon Dioxide Criteria for Scaling-Up Fermentors Modes of Fermentor Operation Batch Operation Fed-Batch Operation Continuous Operation Operation of Enzyme Reactors Fermentors for Animal Cell Culture 207 References Downstream Operations in Bioprocesses Introduction Separation of Microorganisms by Filtration and Microfiltration Dead-End Filtration 214

6 X Cross-Flow Filtration Separation by Chromatography Factors Affecting the Performance of Chromatography Columns Velocity of Mobile Phase and Diffusivities of Solutes Radius of Packed Particles Sample Volume Injected Column Diameter Scale-Up of Chromatography Columns Separation in Fixed Beds Sanitation in Downstream Processes 224 References Medical Devices Introduction Blood and Its Circulation Blood and Its Components Blood Circulation Oxygenation of Blood Use of Blood Oxygenators Oxygen in Blood Carbon Dioxide in Blood Types of Blood Oxygenator Oxygen Transfer Rates in Blood Oxygenators Laminar Blood Flow Turbulent Blood Flow Carbon Dioxide Transfer Rates in Blood Oxygenators Artificial Kidney Human Kidney Functions Artificial Kidneys Hemodialyzer Hemofiltration Peritoneal Dialysis Mass Transfer in Hemodialyzers (cf. Section 8.2) Bioartificial Liver Human Liver Bioartificial Liver Devices 251 References 254 Appendix 255 Index 257