Buch, Englisch, 536 Seiten, Format (B × H): 178 mm x 254 mm
Buch, Englisch, 536 Seiten, Format (B × H): 178 mm x 254 mm
ISBN: 978-0-19-767250-1
Verlag: Oxford University Press
Designed for undergraduates, graduate students, and industry practitioners, the third edition of Bioseparations Science and Engineering fills a critical need in the field. Current, comprehensive, and concise, it covers bioseparations unit operations in unprecedented depth. The unit operations covered are cell lysis, flocculation, filtration, sedimentation, extraction, liquid chromatography, liquid adsorption, precipitation, crystallization, evaporation, and drying.
In each of the chapters, the authors use a consistent method of explaining unit operations, starting with a qualitative description noting the significance and general application of the unit operation. They then illustrate the scientific application of the operation, develop the required mathematical theory, and finally, describe the applications of the theory in engineering practice, with an emphasis on design and scale-up. Unique to this text is a chapter dedicated to bioseparations process design and economics, in which a process simulator, SuperPro Designer®, is used to analyze and evaluate the production of six important biological products.
The third edition of the book has been completely updated and contains the addition of several topics, including the stability of bioproducts, electrophoretic analysis of DNA and RNA, separation by flow cytometry, continuous crystallization, batch crystallization by cooling, fluidized bed drying, and process design and economics of the production of messenger RNA vaccine, hyaluronic acid, and monosodium glutamate. Unique features include basic information about bioproducts, descriptions of analytical methods and bench scale separations of bioproducts, and a chapter with bioseparations laboratory exercises. Bioseparations Science and Engineering is ideal for students and professionals working in or studying bioseparations and is the premier text in the field.
Autoren/Hrsg.
Weitere Infos & Material
- Preface xix
- 1. Introduction to Bioproducts and Bioseparations
- 1.1 Instructional Objectives
- 1.2 Broad Classification of Bioproducts
- 1.3 Small Biomolecules
- 1.3.1 Primary Metabolites
- 1.3.2 Secondary Metabolites
- 1.3.3 Stability of Small Biomolecules
- 1.3.4 Summary of Small Biomolecules
- 1.4 Macromolecules: Proteins
- 1.4.1 Primary Structure
- 1.4.2 Secondary Structure
- 1.4.3 Tertiary Structure
- Example 1.1. Effect of a Reducing Agent on Protein Structure and Mobility
- 1.4.4 Quaternary Structure
- 1.4.5 Prosthetic Groups and Hybrid Molecules
- 1.4.6 Functions and Commercial Uses of Proteins
- 1.4.7 Stability of Proteins
- 1.4.8 Recombinant Protein Expression
- 1.5 Macromolecules: Nucleic Acids and Oligonucleotides
- 1.5.1 Structure of Nucleic Acids
- 1.5.2 Functions and Commercial Uses
- 1.5.3 Stability of Nucleic Acids
- 1.6 Macromolecules: Polysaccharides
- 1.7 Particulate Products
- 1.8 Introduction to Bioseparations: Engineering Analysis
- 1.8.1 Stages of Downstream Processing
- Example 1.2. Initial Selection of Purification Steps
- 1.8.2 Basic Principles of Engineering Analysis
- 1.8.3 Process and Product Quality
- 1.8.4 Criteria for Process Development
- 1.9 The Route to Market
- 1.9.1 The Chemical and Applications Range of the Bioproduct
- 1.9.2 Documentation of Pharmaceutical Bioproducts
- 1.9.3 GLP and cGMP
- 1.9.4 Formulation
- 1.10 Summary
- Nomenclature
- Problems
- References
- 2. Analytical Methods and Bench Scale Preparative Bioseparations
- 2.1 Instructional Objectives
- 2.2 Specifications
- 2.3 Assay Attributes
- 2.3.1 Precision
- 2.3.2 Accuracy
- 2.3.3 Specificity
- 2.3.4 Linearity, Limit of Detection, and Limit of Quantitation
- 2.3.5 Range
- 2.3.6 Robustness
- 2.4 Analysis of Biological Activity
- 2.4.1 Animal Model Assays
- 2.4.2 Cell-Line-Derived Bioassays
- 2.4.3 In vitro Biochemical Assays
- Example 2.1. Coupled Enzyme Assay for Alcohol Oxidase
- 2.5 Analysis of Purity
- 2.5.1 Electrophoretic Analysis
- Example 2.2. Estimation of the Maximum Temperature in an Electrophoresis Gel
- 2.5.2 High-Performance Liquid Chromatography (HPLC)
- 2.5.3 Mass Spectrometry
- 2.5.4 Coupling of HPLC with Mass Spectrometry
- 2.5.5 Ultraviolet Absorbance
- Example 2.3. Determination of Molar Absorptivity
- 2.5.6 CHNO/Amino Acid Analysis (AAA)
- Example 2.4. Calculations Based on CHNO Analysis
- 2.5.7 Protein Assays
- 2.5.8 Enzyme-Linked Immunosorbent Assay
- 2.5.9 Gas Chromatography
- 2.5.10 DNA Hybridization
- 2.5.11 ICP/MS (AES)
- 2.5.12 Dry Weight
- 2.5.13 Flow Cytometry
- 2.6 Microbiology Assays
- 2.6.1 Sterility
- 2.6.2 Bioburden
- 2.6.3 Endotoxin
- 2.6.4 Virus, Mycoplasma, and Phage
- 2.7 Bench Scale Preparative Separations
- 2.7.1 Preparative Electrophoresis
- 2.7.2 Magnetic Bioseparations
- 2.7.3 Cell Purification by Flow Cytometry
- 2.8 Summary
- Nomenclature
- Problems
- References
- 3. Cell Lysis and Flocculation
- 3.1 Instructional Objectives
- 3.2 Some Elements of Cell Structure
- 3.2.1 Prokaryotic Cells
- 3.2.2 Eukaryotic Cells
- 3.3 Cell Lysis
- 3.3.1 Osmotic and Chemical Cell Lysis
- 3.3.2 Mechanical Methods of Lysis
- 3.4 Flocculation
- 3.4.1 The Electric Double Layer
- Example 3.1. Dependence of the Debye Radius on the Type of Electrolyte
- 3.4.2 Forces Between Particles and Flocculation by Electrolytes
- Example 3.2. Sensitivity of Critical Flocculation Concentration to Temperature and Counterion Charge Number
- 3.4.3 The Schulze-Hardy Rule
- 3.4.4 Flocculation Rate
- 3.4.5 Polymeric Flocculants
- 3.5 Summary
- Nomenclature
- Problems
- References
- 4. Filtration
- 4.1 Instructional Objectives
- 4.2 Filtration Principles
- 4.2.1 Conventional Filtration
- Example 4.1. Batch Filtration
- 4.2.2 Crossflow Filtration
- Example 4.2. Concentration Polarization in Ultrafiltration
- Example 4.3. Comparison of Mass Transfer Coefficient Calculated by Boundary Layer Theory Versus by Shear-Induced Diffusion Theory
- 4.3 Filter Media and Equipment
- 4.3.1 Conventional Filtration
- 4.3.2 Crossflow Filtration
- 4.4 Membrane Fouling
- 4.5 Scale-up and Design of Filtration Systems
- 4.5.1 Conventional Filtration
- Example 4.4. Rotary Vacuum Filtration
- Example 4.5. Washing of a Rotary Vacuum Filter Cake
- 4.5.2 Crossflow Filtration
- Example 4.6. Diafiltration Mode in Crossflow Filtration
- 4.6 Summary
- Nomenclature
- Problems
- References
- 5. Sedimentation
- 5.1 Instructional Objectives
- 5.2 Sedimentation Principles
- 5.2.1 Equation of Motion
- 5.2.2 Sensitivities
- 5.3 Methods for Analysis of Sedimentation
- 5.3.1 Equilibrium Sedimentation
- 5.3.2 Sedimentation Coefficient
- Example 5.1. Application of the Sedimentation Coefficient
- 5.3.3 Equivalent Time
- Example 5.2. Scale-up Based on Equivalent Time
- 5.3.4 Sigma Analysis
- 5.4 Production Centrifuges: Comparison and Engineering Analysis
- 5.4.1 Tubular Bowl Centrifuge
- Example 5.3. Complete Recovery of Bacterial Cells in a Tubular Bowl Centrifuge
- 5.4.2 Disk Centrifuge
- 5.5 Ultracentrifugation
- 5.5.1 Determination of Molecular Weight
- 5.6 Flocculation and Sedimentation
- 5.7 Sedimentation at Low Accelerations
- 5.7.1 Diffusion, Brownian Motion
- 5.7.2 Isothermal Settling
- 5.7.3 Convective Motion and Péclet Analysis
- 5.7.4 Inclined Sedimentation
- 5.7.5 Field-Flow Fractionation
- 5.8 Centrifugal Elutriation
- 5.9 Summary
- Nomenclature
- Problems
- References
- 6. Extraction
- 6.1 Instructional Objectives
- 6.2 Extraction Principles
- 6.2.1 Phase Separation and Partitioning Equilibria
- Example 6.1 Process for Large-Scale Isolation of ?-Galactosidae from E. coli in an Aqueous Two-Phase Sytstem
- 6.2.2 Countercurrent Stage Calculations
- Example 6.2. Separation of a Bioproduct and an Impurity by Countercurrent Extraction
- Example 6.3. Effect of Solvent Rate in Countercurrent Staged Extraction of an Antibiotic
- 6.3 Scale-up and Design of Extractors
- 6.3.1 Reciprocating-Plate Extraction Columns
- Example 6.4. Scale-up of a Reciprocating-Plate Extraction Column
- 6.3.2 Centrifugal Extractors
- Example 6.5. Increase in Feed Rate to a Podbielniak Centrifugal Extractor
- 6.4 Summary
- Nomenclature
- Problems
- References
- 7. Liquid Chromatography and Adsorption
- 7.1 Instructional Objectives
- 7.2 Adsorption Equilibrium
- 7.3 Adsorption Column Dynamics
- 7.3.1 Fixed-Bed Adsorption
- Example 7.1. Determination of the Mass Transfer Coefficient from Adsorption Breakthrough Data
- 7.3.2 Agitated-Bed Adsorption
- 7.4 Chromatography Column Dynamics
- 7.4.1 Plate Models
- 7.4.2 Moment Analysis
- Example 7.2 Calculation of the HETP Using the Method of Moments
- 7.4.3 Chromatography Column Mass Balance with Negligible Dispersion
- Example 7.3. Chromatographic Separation of Two Solutes
- Example 7.4. Calculation of the Shock Wave Velocity for a Nonlinear Isotherm
- Example 7.5. Calculation of the Elution Profile
- 7.4.4 Dispersion Effects in Chromatography
- 7.4.5 Computer Simulation of Chromatography Considering Axial Dispersion, Fluid-Phase Mass Transfer, Intraparticle Diffusion, and Nonlinear Equilibrium
- Example 7.6 Computer Simulation of a Chromatography Process
- 7.4.6 Gradients and Modifiers
- Example 7.7. Equilibrium for a Protein Anion in the Presence of Chloride Ion
- 7.5 Membrane Chromatography
- Example 7.8. Comparison of Time for Diffusion Mass Transfer in Conventional Chromatography and Membrane Chromatography
- 7.6 Simulated Moving Bed Chromatography
- 7.7 Adsorbent Types
- 7.7.1 Silica-Based Resins
- 7.7.2 Polymer-Based Resins
- 7.7.3 Ion Exchange Chromatography and Adsorption
- 7.7.4 Reversed-Phase Chromatography
- 7.7.5 Hydrophobic Interaction Chromatography
- 7.7.6 Affinity Chromatography
- 7.7.7 Immobilized Metal Affinity Chromatography (IMAC)
- 7.7.8 Size Exclusion Chromatography
- 7.8 Particle Size and Pressure Drop in Fixed Beds
- 7.9 Equipment
- 7.9.1 Columns
- 7.9.2 Chromatography Column Packing Procedures
- 7.9.3 Detectors
- 7.9.4 Chromatography System Fluidics
- 7.10 Scale-up
- 7.10.1 Adsorption
- Example 7.9. Scale-up of the Fixed-Bed Adsorption of a Pharmaceutical Product
- 7.10.2 Chromatography
- Example 7.10. Scale-up of a Protein Chromatography
- Example 7.11. Scale-up of Protein Chromatography Using Standard Column Sizes
- Example 7.12. Scale-up of Elution Buffer Volumes in Protein Chromatography
- Example 7.13. Consideration of Pressure Drop in Column Scaling
- 7.11 Summary
- Nomenclature
- Problems
- References
- 8. Precipitation
- 8.1 Instructional Objectives
- 8.2 Protein Solubility
- 8.2.1 Structure and Size
- 8.2.2 Charge
- 8.2.3 Solvent
- Example 8.1. Salting Out of a Protein with Ammonium Sulfate
- 8.3 Precipitate Formation Phenomena
- 8.3.1 Initial Mixing
- 8.3.2 Nucleation
- 8.3.3 Growth Governed by Diffusion
- Example 8.2. Calculation of Concentration of Nuclei in a Protein Precipitation
- Example 8.3. Diffusion-Limited Growth of Particles
- 8.3.4 Growth Governed by Fluid Motion
- Example 8.4. Growth of Particles Limited by Fluid Motion
- 8.3.5 Precipitate Breakage
- 8.3.6 Precipitate Aging
- 8.4 Particle Size Distribution in a Continuous-Flow Stirred Tank Reactor
- Example 8.5. Dependence of Population Density on Particle Size and Residence Time in a CSTR
- 8.5 Methods of Precipitation
- 8.6 Design of Precipitation Systems
- 8.7 Summary
- Nomenclature
- Problems
- References
- 9. Crystallization
- 9.1 Instructional Objectives
- 9.2 Crystallization Principles
- 9.2.1 Crystals
- 9.2.2 Nucleation
- 9.2.3 Crystal Growth
- 9.2.4 Crystallization Kinetics from Batch Experiments
- 9.3 Batch Crystallizers
- 9.3.1 Analysis of Dilution Batch Crystallization
- Example 9.1. Batch Crystallization with Constant Rate of Change of Diluent Concentration
- 9.3.2 Cooling Batch Crystallization
- Example 9.2 Batch Crystallization by Cooling
- 9.4 Continuous Crystallization
- Example 9.3 Calculation of the Population Density and the Growth and Nucleation Rates for a MSMPR Crystallizer
- 9.5 Process Crystallization of Proteins
- 9.6 Crystallizer Scale-up and Design
- 9.6.1 Experimental Crystallization Studies as a Basis for Scale-up
- 9.6.2 Scale-up and Design Calculations
- Example 9.4. Scale-up of Crystallization Based on Constant Power per Volume
- 9.7 Summary
- Nomenclature
- Problems
- References
- 10. Evaporation
- 10.1 Instructional Objectives
- 10.2 Evaporation Principles
- 10.2.1 Heat Transfer
- Example 10.1. Evaporation of a Butyl Acetate Stream Containing a Heat-Sensitive Antibiotic in a Falling-Film Evaporator
- 10.2.2 Vapor-Liquid Separation
- 10.3 Evaporation Equipment
- 10.3.1 Climbing-Film Evaporators
- 10.3.2 Falling-Film Evaporators
- 10.3.3 Forced-Circulation Evaporators
- 10.3.4 Agitated-Film Evaporators
- 10.4 Scale-up and Design of Evaporators
- 10.5 Summary
- Nomenclature
- Problems
- References
- 11. Drying
- 11.1 Instructional Objectives
- 11.2 Drying Principles
- 11.2.1 Water in Biological Solids and in Gases
- Example 11.1. Drying of Antibiotic Crystals
- 11.2.2 Heat and Mass Transfer
- Example 11.2. Conductive Drying of Wet Solids in a Tray
- Example 11.3. Mass Flux During the Constant Rate Drying Period in Convective Drying
- Example 11.4. Time to Dry Nonporous Biological Solids by Convective Drying
- 11.3 Dryer Description and Operation
- 11.3.1 Vacuum-Shelf Dryers
- 11.3.2 Batch Vacuum Rotary Dryers
- 11.3.3 Freeze Dryers
- 11.3.4 Spray Dryers
- 11.5 Fluidized Bed Dryers
- 11.4 Scale-up and Design of Drying Systems
- 11.4.1 Vacuum-Shelf Dryers
- 11.4.2 Batch Vacuum Rotary Dryers
- 11.4.3 Freeze Dryers
- 11.4.4 Spray Dryers
- Example 11.5. Sizing of a Spray Dryer
- 11.4.5 Fluidized Bed Dryers
- Example 11.6 Scale-up of a Fluidized Bed Dryer
- 11.5 Summary
- Nomenclature
- Problems
- References
- 12. Bioprocess Design and Economics
- 12.1 Instructional Objectives
- 12.2 Definitions and Background
- 12.3 Synthesis of Bioseparation Processes
- 12.3.1 Primary Recovery Stages
- 12.3.2 Intermediate Recovery Stages
- 12.3.3 Final Purification Stages
- 12.3.4 Pairing of Unit Operations in Process Synthesis
- 12.4 Process Analysis
- 12.4.1 Spreadsheets
- 12.4.2 Process Simulators and Their Benefits
- 12.4.3 Using a Biochemical Process Simulator
- 12.5 Process Economics
- 12.5.1 Capital Cost Estimation
- 12.5.2 Operating Cost Estimation
- 12.5.3 Profitability Analysis
- 12.6 Illustrative Examples
- 12.6.1 Citric Acid Production
- 12.6.2 Human Insulin Production
- 12.6.3 Therapeutic Monoclonal Antibody Production
- 12.6.4 RNA (mRNA) Vaccine Production
- 12.6.5 Hyaluronic Acid Production
- 12.6.6 Monosodium Glutamate (MSG) Production
- 12.7 Summary
- Problems
- References
- 13. Laboratory Exercises in Bioseparations
- 13.1 Flocculant Screening
- 13.1.1 Background
- 13.1.2 Objectives
- 13.1.3 Procedure
- 13.1.4 Report
- 13.1.5 Some Notes and Precautions
- 13.2 Crossflow Filtration
- 13.2.1 Background
- 13.2.2 Objectives
- 13.2.3 Procedure
- 13.2.4 Report
- 13.3 Centrifugation of Flocculated and Unflocculated Particulates
- 13.3.1 Background
- 13.3.2 Objectives
- 13.3.3 Procedure
- 13.3.4 Report
- 13.4 Aqueous Two-Phase Extraction
- 13.4.1 Physical Measurements
- 13.4.2 Procedure
- 13.4.3 Calculations and Report
- 13.4.4 Inverse Lever Rule
- 13.5 Chromatography Scale-up
- 13.5.1 Background
- 13.5.2 Objectives
- 13.5.3 Procedure
- 13.5.4 Report References
- APPENDIX: Table of Units and Constants
- Index
