PrefaceAll chapters (except Chapter 12) end with the following sections: Summary, Nomenclature, Problems, and References.PrefaceChapter 1. Introduction to Bioproducts and Bioseparations1.1. Instructional Objectives1.2. Broad Classification of Bioproducts1.3.

Small Biomolecules1.3.1. Primary Metabolites1.3.2. Secondary Metabolites1.3.

3. Summary of Small Biomolecules1.4. Macromolecules: Proteins1.4.1. Primary Structure1.4.

2. Secondary Structure1.4.3. Tertiary StructureExample 1.1: Effect of a Reducing Agent on Protein Structure and Mobility: 1.4.4.

Quaternary Structure1.4.5. Prosthetic Groups and Hybrid Molecules1.4.6. Functions and Commercial Uses of Proteins1.4.

7. Stability of Proteins1.4.8. Recombinant Protein Expression1.5. Macromolecules: Nucleic Acids and Oligonucleotides1.6.

Macromolecules: Polysaccharides1.7. Particulate Products1.8. Introduction to Bioseparations: Engineering Analysis1.8.1. Stages of Downstream ProcessingExample 1.

2: Initial Selection of Purification Steps: 1.8.2. Basic Principles of Engineering Analysis1.8.3. Process and Product Quality1.8.

4. Criteria for Process Development1.9. The Route to Market1.9.1. The Chemical and Applications Range of the Bioproduct1.9.

2. Documentation of Pharmaceutical Bioproducts1.9.3. GLP and cGMP1.9.4. FormulationChapter 2.

Analytical Methods2.1. Instructional Objectives2.2. Specifications2.3. Assay Attributes2.3.

1. Precision2.3.2. Accuracy2.3.3. Specificity2.

3.4. Linearity, Limit of Detection, and Limit of Quantitation2.3.5. Range2.3.6.

Robustness2.4. Analysis of Biological Activity2.4.1. Animal Model Assays2.4.2.

Cell-Line-Derived Bioassays2.4.3. In Vitro Biochemical AssaysExample 2.1: Coupled Enzyme Assay for Alcohol Oxidase: 2.5. Analysis of Purity2.5.

1. Electrophoretic AnalysisExample 2.2: Estimation of the Maximum Temperature in an Electrophoresis Gel: 2.5.2. High Performance Liquid Chromatography (HPLC)2.5.3.

Mass Spectrometry2.5.4. Coupling of HPLC with Mass Spectrometry2.5.5. UV AbsorbanceExample 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 Assays2.5.

8. Enzyme-Linked Immunosorbent Assay2.5.9. Gas Chromatography2.5.10. DNA Hybridization2.

5.11. ICP/MS (AA)2.5.12. Dry Weight2.6. Microbiology Assays2.

6.1. Sterility2.6.2. Bioburden2.6.3.

Endotoxin2.6.4. Virus and PhageChapter 3. Cell Lysis and Flocculation3.1. Instructional Objectives3.2.

Some Elements of Cell Structure3.2.1. Prokaryotic Cells3.2.2. Eukaryotic Cells3.3.

Cell Lysis3.3.1. Osmotic and Chemical Cell Lysis3.3.2. Mechanical Methods of Lysis3.4.

Flocculation3.4.1. The Electric Double LayerExample 3.1: Dependence of the Debye Radius on the Type of Electrolyte: 3.4.2. Forces between Particles and Flocculation by ElectrolytesExample 3.

2: Sensitivity of Critical Flocculation Concentration to Temperature and Counter-Ion Charge Number: 3.4.3. The Schulze-Hardy Rule3.4.4. Flocculation Rate3.4.

5. Polymeric FlocculantsChapter 4. Filtration4.1. Instructional Objectives4.2. Filtration Principles4.2.

1. Conventional FiltrationExample 4.1: Batch Filtration: 4.2.2. Crossflow FiltrationExample 4.2: Concentration Polarization in Ultrafiltration: 4.3.

Filter Media and Equipment4.3.1. Conventional Filtration4.3.2. Crossflow Filtration4.4.

Membrane Fouling4.5. Scaleup and Design of Filtration Systems4.5.1. Conventional FiltrationExample 4.3: Rotary Vacuum Filtration: Example 4.4: Washing of a Rotary Vacuum Filter Cake: 4.

5.2. Crossflow FiltrationExample 4.5: Diafiltration Mode in Crossflow Filtration: Chapter 5. Sedimentation5.1. Instructional Objectives5.2.

Sedimentation Principles5.2.1. Equation of Motion5.2.2. Sensitivities5.3.

Methods and Coefficients5.3.1. Equilibrium Sedimentation5.3.2. Sedimentation CoefficientExample 5.1: Application of the Sedimentation Coefficient: 5.

3.3. Equivalent TimeExample 5.2: Scaleup Based on Equivalent Time: 5.3.4. Sigma Analysis5.4.

Production Centrifuges: Comparison and Engineering Analysis5.4.1. Tubular Bowl CentrifugeExample 5.3: Complete Recovery of Bacterial Cells in a Tubular Bowl Centrifuge: 5.4.2. Disk Centrifuge5.

5. Ultracentrifugation5.5.1. Determination of Molecular Weight5.6. Flocculation and Sedimentation5.7.

Sedimentation at Low Accelerations5.7.1. Diffusion, Brownian Motion5.7.2. Isothermal Settling5.7.

3. Convective Motion and Peclet Analysis5.7.4. Inclined Sedimentation5.7.5. Field-Flow Fractionation5.

8. Centrifugal ElutriationChapter 6. Extraction6.1. Instructional Objectives6.2. Extraction Principles6.2.

1. Phase Separation and Partitioning Equilibria6.2.2. Countercurrent Stage CalculationsExample 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 Extractors6.3.1. Reciprocating-Plate Extraction ColumnsExample 6.3: Scaleup of a Reciprocating-Plate Extraction Column: 6.3.2. Centrifugal ExtractorsChapter 7.

Liquid Chromatography and Adsorption7.1. Instructional Objectives7.2. Adsorption Equilibrium7.3. Adsorption Column Dynamics7.3.

1. Fixed-Bed AdsorptionExample 7.1: Determination of the Mass Transfer Coefficient from Adsorption Breakthrough Curves: 7.3.2. Agitated-Bed Adsorption7.4. Chromatography Column Dynamics7.

4.1. Plate Models7.4.2. Chromatography Column Mass Balance with Negligible DispersionExample 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 Chromatography7.4.4. Gradients and ModifiersExample 7.5: Equilibrium for a Protein Anion in the Presence of a Chloride Ion: 7.

5. Adsorbent Types7.5.1. Silica Based Resins7.5.2. Polymer Based Resins7.

5.3. Ion Exchange Resins7.5.4. Reversed Phase Chromatography7.5.5.

Hydrophobic Interaction Chromatography7.5.6. Affinity Chromatography7.5.7. Immobilized Metal Affinity Chromatography7.5.

8. Size Exclusion Chromatography7.6. Particle Size and Pressure Drop in Fixed Beds7.7. Equipment7.7.1.

Columns7.7.2. Chromatography Column Packing Procedures7.7.3. Detectors7.7.

4. Chromatography System Fluidics7.8. Scaleup7.8.1. AdsorptionExample 7.6: Scaleup of the Fixed-Bed Adsorption of a Pharmaceutical Product: 7.

8.2. ChromatographyExample 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. Precipitation8.

1. Instructional Objectives8.2. Protein Solubility8.2.1. Structure and Size8.2.

2. Charge8.2.3. SolventExample 8.1: Salting-Out of a Protein with Ammonium Sulfate. 8.3.

Precipitation Formation Phenomena8.3.1. Initial Mixing8.3.2. Nucleation8.3.

3. Growth Governed by DiffusionExample 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 MotionExample 8.4: Growth of Particles Limited by Fluid Motion: 8.

3.5. Precipitate Breakage8.3.6. Precipitate Aging8.4. Particle Size Distribution in a Continuous Flow Stirred Tank ReactorExample 8.

5: Dependence of Population Density on Particle Size and Residence Time in a CSTR: 8.5. Methods of Precipitation8.6. Design of Precipitation SystemsChapter 9. Crystallization9.1. Instructional Objectives9.

2. Crystallization Principles9.2.1. Crystals9.2.2. Nucleation9.

2.3. Crystal Growth9.2.4. Crystallization Kinetics from Batch Experiments9.3. Batch Crystallizers9.

3.1. Analysis of Dilution Batch CrystallizationExample 9.1: Batch Crystallization with Constant Rate of Change of Diluent Concentration: 9.4. Process Crystallization of Proteins9.5. Crystallizer Scaleup and Design9.

5.1. Experimental Crystallization Studies as a Basis for Scaleup9.5.2. Scaleup and Design CalculationsExample 9.2: Scaleup of Crystallization Based on Constant Power per Volume: Chapter 10. Drying10.

1. Instructional Objectives10.2. Drying Principles10.2.1. Water in Biological Solids and in GasesExample 10.1: Drying of Antibiotic Crystals: 10.

2.2. Heat and Mass TransferExample 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 Operation10.

3.1. Vacuum-Shelf Dryers10.3.2. Batch Vacuum Rotary Dryers10.3.3.

Freeze Dryers10.3.4. Spray Dryers10.4. Scaleup and Design of Drying Systems10.4.1.

Vacuum-Shelf Dryers10.4.2. Batch Vacuum Rotary Dryers10.4.3. Freeze Dryers10.4.

4. Spray DryersExample 10.5: Sizing of a Spray Dryer: Chapter 11. Bioprocess Design11.1. Instructional Objectives11.2. Definitions and Background11.

3. Synthesis of Bioseparation Processes11.3.1. Primary Recovery Stages11.3.2. Intermediate Recovery Stages11.

3.3. Final Purification Stages11.3.4. Pairing of Unit Operations in Process Synthesis11.4. Process Analysis11.

4.1. Spreadsheets11.4.2. Process Simulators11.4.3.

Using a Biochemical Process Simulator11.5. Process Economics11.5.1. Capital Cost Estimation11.5.2.

Operating Cost Estimation11.5.3. Profitability Analysis11.6. Illustrative Examples11.6.1.

Citric Acid Production11.6.2. Human Insulin Production11.6.3. Therapeutic Monoclonal Antibody ProductionChapter 12. Laboratory Exercises in Bioseparations12.

1. Flocculant Screening12.1.1. Background12.1.2. Objectives12.

1.3. Procedure12.1.4. Report12.1.5.

Some Notes and Precautions12.2. Crossflow Filtration12.2.1. Background12.2.2.

Objectives12.2.3. Procedure12.2.4. Report12.3.

Centrifugation of Flocculated and Unflocculated Particulates12.3.1. Background12.3.2. Objectives12.3.

3. Procedure12.3.4. Report12.4. Aqueous Two-Phase Extraction12.4.

1. Physical Measurements12.4.2. Procedure12.4.3. Calculations and Report12.

4.4. Inverse Lever Rule12.5. Chromatography Scaleup12.5.1. Background12.

5.2. Objectives12.5.3.