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Bioseparations Science and Engineering / Edition 1

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Designed for undergraduates, graduate students, and industry practitioners, Bioseparations Science and Engineering fills a critical need in the field. Current, comprehensive, and concise, it covers bioseparations unit operations in greater depth than other texts on this topic. 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 scaleup. Unique to this text is a chapter dedicated to bioseparations process design and economics, in which a process simular, SuperPro Designer® is used to analyze and evaluate the production of three important biological products. Other unique features include basic information about bioproducts and engineering analysis and a chapter with bioseparations laboratory exercises. Bioseparations Science and Engineering is ideal for students and professionals alike. Features

· Incorporates numerous example problems within the chapters

· Offers extensive sets of problems at the end of chapters

· Includes basic information about bioproducts

· Provides thorough coverage of analytical methods for bioproducts

· Uses the simulation software SuperPro Designer® to illustrate the analysis and evaluation of the production of citric acid, recombinant human insulin, and monoclonal antibodies

· Includes laboratory exercises that support text material

· Accompanied by a solutions manual available to instructors who adopt this text

· Supplemented by a website ( with new problems and examples and links to useful databases and manufacturers of bioseparations equipment and supplies

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Editorial Reviews

From the Publisher

"I'm glad I found this book! Unlike many other books of similar titles, this is one that I can really understand. Not too heavy dosage of biological terms. Provides good linkage between the biological science and engineering applications. Good for students who have chamical engineering backgrounds and want to venture into bioseparations. The additional chapter on plant design and economics is also very beneficial."
--reader review from

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Product Details

  • ISBN-13: 9780195123401
  • Publisher: Oxford University Press, USA
  • Publication date: 10/31/2002
  • Series: Topics in Chemical Engineering Series
  • Edition description: New Edition
  • Edition number: 1
  • Pages: 432
  • Sales rank: 748,197
  • Product dimensions: 9.40 (w) x 7.30 (h) x 1.10 (d)

Meet the Author

Roger G. Harrison is Professor in the College of Engineering at the University of Oklahoma.
Scott R. Rudge is Technical Leader at RMC Pharmaceutical Solutions, Inc.
Paul W. Todd is Chief Scientist at Techshot, Inc.
Demetri P. Petrides is President of Intelligen, Inc.

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Table of Contents

All chapters (except Chapter 12) end with the following sections: Summary, Nomenclature, Problems, and References.
Chapter 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. 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
1.6. 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
Chapter 2. Analytical Methods
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. UV 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 (AA)
2.5.12. Dry Weight
2.6. Microbiology Assays
2.6.1. Sterility
2.6.2. Bioburden
2.6.3. Endotoxin
2.6.4. Virus and Phage
Chapter 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 Counter-Ion Charge Number
3.4.3. The Schulze-Hardy Rule
3.4.4. Flocculation Rate
3.4.5. Polymeric Flocculants
Chapter 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
4.3. Filter Media and Equipment
4.3.1. Conventional Filtration
4.3.2. Crossflow Filtration
4.4. Membrane Fouling
4.5. Scaleup and Design of Filtration Systems
4.5.1. Conventional Filtration
Example 4.3: Rotary Vacuum Filtration
Example 4.4: Washing of a Rotary Vacuum Filter Cake
4.5.2. Crossflow Filtration
Example 4.5: Diafiltration Mode in Crossflow Filtration
Chapter 5. Sedimentation
5.1. Instructional Objectives
5.2. Sedimentation Principles
5.2.1. Equation of Motion
5.2.2. Sensitivities
5.3. Methods and Coefficients
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: Scaleup 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 Peclet Analysis
5.7.4. Inclined Sedimentation
5.7.5. Field-Flow Fractionation
5.8. Centrifugal Elutriation
Chapter 6. Extraction
6.1. Instructional Objectives
6.2. Extraction Principles
6.2.1. Phase Separation and Partitioning Equilibria
6.2.2. Countercurrent Stage Calculations
Example 6.1: Separation of a Bioproduct and an Impurity by Countercurrent Extraction
Example 6.2: Effect of Solvent Rate in Countercurrent Staged Extraction of an Antibiotic
6.3. Scaleup and Design of Extractors
6.3.1. Reciprocating-Plate Extraction Columns
Example 6.3: Scaleup of a Reciprocating-Plate Extraction Column
6.3.2. Centrifugal Extractors
Chapter 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 Curves
7.3.2. Agitated-Bed Adsorption
7.4. Chromatography Column Dynamics
7.4.1. Plate Models
7.4.2. Chromatography Column Mass Balance with Negligible Dispersion
Example 7.2: Chromatographic Separation of Two Solutes
Example 7.3: Calculation of the Shock Wave Velocity for a Non-Linear Isotherm
Example 7.4: Calculation of the Elution Profile
7.4.3. Dispersion Effects in Chromatography
7.4.4. Gradients and Modifiers
Example 7.5: Equilibrium for a Protein Anion in the Presence of a Chloride Ion
7.5. Adsorbent Types
7.5.1. Silica Based Resins
7.5.2. Polymer Based Resins
7.5.3. Ion Exchange Resins
7.5.4. Reversed Phase Chromatography
7.5.5. Hydrophobic Interaction Chromatography
7.5.6. Affinity Chromatography
7.5.7. Immobilized Metal Affinity Chromatography
7.5.8. Size Exclusion Chromatography
7.6. Particle Size and Pressure Drop in Fixed Beds
7.7. Equipment
7.7.1. Columns
7.7.2. Chromatography Column Packing Procedures
7.7.3. Detectors
7.7.4. Chromatography System Fluidics
7.8. Scaleup
7.8.1. Adsorption
Example 7.6: Scaleup of the Fixed-Bed Adsorption of a Pharmaceutical Product
7.8.2. Chromatography
Example 7.7: Scaleup of a Protein Chromatography
Example 7.8: Scaleup of a Protein Chromatography Using Standard Column Sizes
Example 7.9: Scaleup of Elution Buffer Volumes in Protein Chromatography
Example 7.10: Consideration of Pressure Drop in Column Scaling
Chapter 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. Precipitation 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
Chapter 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
9.4. Process Crystallization of Proteins
9.5. Crystallizer Scaleup and Design
9.5.1. Experimental Crystallization Studies as a Basis for Scaleup
9.5.2. Scaleup and Design Calculations
Example 9.2: Scaleup of Crystallization Based on Constant Power per Volume
Chapter 10. Drying
10.1. Instructional Objectives
10.2. Drying Principles
10.2.1. Water in Biological Solids and in Gases
Example 10.1: Drying of Antibiotic Crystals
10.2.2. Heat and Mass Transfer
Example 10.2: Conductive Drying of Wet Solids in a Tray
Example 10.3: Mass Flux during the Constant Rate Drying Period in Convective Drying
Example 10.4: Time to Dry Nonporous Solids by Convective Drying
10.3. Dryer Description and Operation
10.3.1. Vacuum-Shelf Dryers
10.3.2. Batch Vacuum Rotary Dryers
10.3.3. Freeze Dryers
10.3.4. Spray Dryers
10.4. Scaleup and Design of Drying Systems
10.4.1. Vacuum-Shelf Dryers
10.4.2. Batch Vacuum Rotary Dryers
10.4.3. Freeze Dryers
10.4.4. Spray Dryers
Example 10.5: Sizing of a Spray Dryer
Chapter 11. Bioprocess Design
11.1. Instructional Objectives
11.2. Definitions and Background
11.3. Synthesis of Bioseparation Processes
11.3.1. Primary Recovery Stages
11.3.2. Intermediate Recovery Stages
11.3.3. Final Purification Stages
11.3.4. Pairing of Unit Operations in Process Synthesis
11.4. Process Analysis
11.4.1. Spreadsheets
11.4.2. Process Simulators
11.4.3. Using a Biochemical Process Simulator
11.5. Process Economics
11.5.1. Capital Cost Estimation
11.5.2. Operating Cost Estimation
11.5.3. Profitability Analysis
11.6. Illustrative Examples
11.6.1. Citric Acid Production
11.6.2. Human Insulin Production
11.6.3. Therapeutic Monoclonal Antibody Production
Chapter 12. Laboratory Exercises in Bioseparations
12.1. Flocculant Screening
12.1.1. Background
12.1.2. Objectives
12.1.3. Procedure
12.1.4. Report
12.1.5. Some Notes and Precautions
12.2. Crossflow Filtration
12.2.1. Background
12.2.2. Objectives
12.2.3. Procedure
12.2.4. Report
12.3. Centrifugation of Flocculated and Unflocculated Particulates
12.3.1. Background
12.3.2. Objectives
12.3.3. Procedure
12.3.4. Report
12.4. Aqueous Two-Phase Extraction
12.4.1. Physical Measurements
12.4.2. Procedure
12.4.3. Calculations and Report
12.4.4. Inverse Lever Rule
12.5. Chromatography Scaleup
12.5.1. Background
12.5.2. Objectives
12.5.3. Procedure
Appendix. Table of Units and Constants

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