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Cell culture bioprocess engineering / Wei-Shou Hu. -- 2nd ed. -- Boca Raton : CRC Press, c2020. – (58.221/H874/2nd ed.) |
Contents
Preface
1 Overview of Cell Culture Processes
An
Introduction to Cell Culture: A Historical Perspective
Cell Culture as Process Technology
Industrial Cell Lines
Other Production Systems
Manufacturing
Upstream Process
Product Quality in Cell Culture
Processing
Quality of the Product
From Discovery to Clinical Products
2 Cell Biology for Bioprocessing
Introduction
Tissue Cells and Their Isolation
Cell Membrane
Cytoplasm and Organelles
Protein Secretion through the ER and
Golgi Apparatus
Transport across Cellular Membranes
Cell Shape, Mechanics, and Movement
Growth Control
Concluding Remarks
3 Cell Physiology
Introduction
Glucose and Energy Metabolism
Regulation of Glucose Metabolism
Transport and Transporters
Metabolic Homeostasis and Lactate
Consumption
Amino Acid Metabolism
Lipid Metabolism
Glycan Biosynthesis and Protein Glycosylation
Concluding Remarks
4
Product Quality and Process
Introduction
Quality
of Protein Product
Structural
Homogeneity of the Product
Biological
Activities
Quality
by Design (QbD) of Cell Culture Products
QTPP
and CQAs
Quality
Risk Management
Design
Space and Control Strategy
QbD
in Different Stages of the Product's Life Cycle
Concluding
Remarks
5 Stoichiometry and the Kinetics of Cell
Cultivation
Introduction
Material
Conversion in Cell Culture
Material
Balance on Cell Growth
Kinetic Description of Cell Growth &
Product Formation
Kinetic
Model of Cell Growth
Modeling
Productivity
Modeling
a Cell Culture System
Concluding
Remarks
6 Cell Line Development
Introduction
Transient
Production vs. Stable Expression Cell Line
Host
Cells
Generating
a Recombinant Protein High-Producing Cell Line
Concluding
Remarks: Genomic Technology & Cell Line Development
7 Medium
Design for Cell Culture Processing
Introduction
Types
of Media and Classes of Medium Components
Process
Medium Design: Kinetics, Stoichiometry, Omics & Optimization
Components
of Basal Medium
High
Molecular Weight and Complex Supplements
Concluding
Remarks
8 Cell
Culture Bioreactors
Introduction
Basic Types of Bioreactors
Tissue Culture and Disposable Cell
Culture Systems
Adherent Cell Support Systems
Bioreactors Developed for Cell Culture
Concluding Remarks
9 Fed-Batch Culture Processes
Introduction
Batch Cultures
Fed-Batch Cultures
Stoichiometric Feeding
Delivery of Feed Medium
Product Quality in Fed-Batch Culture
Concluding Remarks
10 Continuous Cell Culture Processes
Introduction
Analysis of Continuous Culture and
Steady State
Methods of Cell Retention
Continuous Culture & Continuous
Process
Concluding Remarks
11 Oxygen Transfer in Cell Culture Bioreactors
Introduction
Oxygen Concentration across the
Gas-Liquid Interface
Oxygen Transfer the Gas-Liquid
Interface
Damage to Cells by Gas Sparging
Oxygen Transfer in Aggregates and Membrane
Bioreactors
Concluding Remarks
12
Scaling Up and Scaling Down for Cell Culture Bioreactors
Introduction
Mechanical Agitation
Power Consumption for Mixing Tanks
Mixing Time
Scaling Up and Mechanical Forces on
Cells
Oxygen and Carbon Dioxide Transfer
Process Scale-Up and Scale-Down Models
Concluding Remarks
Appendix
A: Cell Culture Process Data Analysis
Overview of Process Data
Data Processing Pipeline
Metabolic Flux Analysis
Time Series Data Analysis
Aggregation and Analysis of Process
Data
Concluding Remarks
Index
