- ホーム
- > 洋書
- > 英文書
- > Science / Mathematics
Full Description
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.
Contents
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
