Table of Contents
PREFACE xiii
1 Introduction 1
1.1 Scope of Design / 1
1.2 Definition of Biomechatronic Products / 3
1.3 Principles of Biomechatronics / 4
1.4 Brief History of the Development of Biomechatronic Products and Engineering / 7
1.5 Aim of This Book / 9
References / 10
PART I FUNDAMENTALS 13
2 Conceptual Design Theory 15
2.1 Systematic Design / 15
2.1.1 Design for Products / 15
2.1.2 Origin of the Design Task / 18
2.1.3 Development of Design Thinking / 18
2.1.4 Recent Methods / 20
2.2 Basics of Technical Systems / 21
2.2.1 Energy, Material, and Signals and Their Conversion / 22
2.2.2 Interrelationships of Functions / 22
2.2.3 Interrelationship of Constructions / 25
2.2.4 Interrelationship of Systems / 25
2.3 Psychology in the Systematic Approach / 25
2.4 A General Working Methodology / 26
2.4.1 Analysis for Resolving Technical Problems / 27
2.4.2 Abstraction of Interrelationships of Systems / 28
2.4.3 Synthesis of the Technical System / 28
2.5 Conceptual Design / 28
2.6 Abstraction inOrder to Identify Essential Problems / 29
2.7 Developing the Concepts / 31
2.7.1 Organizing the Development Process / 33
2.8 Concluding Remarks / 34
References / 35
3 Biotechnology and Mechatronic Design 37
3.1 Transduction of the Biological Science into Biotechnology / 37
3.2 Biological Sciences and Their Applications / 39
3.3 Biotechnology and Bioengineering / 42
3.4 Applying Mechatronic Theory to Biotechnology: Biomechatronics / 44
3.5 Conclusions / 47
References / 48
4 Methodology for Utilization of Mechatronic Design Tools 49
4.1 Idea of Applying the Mechatronic Design Tools / 49
4.2 Table of User Needs / 51
4.3 List of Target Specifications / 52
4.4 Concept Generation Chart / 52
4.4.1 Basic Concept Component Chart / 53
4.4.2 Permutation Chart / 54
4.5 Concept Screening Matrix / 55
4.6 Concept Scoring Matrix / 56
4.7 Hubka–Eder Mapping / 57
4.7.1 Overview Hubka–Eder Map / 57
4.7.2 Zoom-in Hubka–Eder Mapping / 59
4.8 Functions Interaction Matrix / 60
4.8.1 Functions Interaction Matrix for Systems and Subsystems / 60
4.8.2 Functions Interaction Matrix for Systems and Transformation Process / 61
4.8.3 Design Structure Matrix / 61
4.9 Anatomical Blueprint / 62
4.10 Conclusions / 63
References / 63
PART II APPLICATIONS 65
5 Blood Glucose Sensors 67
5.1 Background of Blood Glucose Analysis / 67
5.2 Specification of Needs for Blood Glucose Analysis / 70
5.3 Design of Blood Glucose Sensors / 71
5.3.1 Generation of Sensor Concepts / 71
5.4 Description of the Systems Involved in the Design Concepts for Glucose Blood Sensors / 76
5.4.1 Biological Systems / 77
5.4.2 Technical Systems / 77
5.4.3 Information Systems / 78
5.4.4 Management and Goal Systems / 78
5.4.5 Human Systems / 79
5.4.6 Active Environment / 79
5.4.7 Interactions Between the Systems and Functions of the Design / 79
5.4.8 Anatomical Blueprints from the Functions Interaction Matrix Analysis / 81
5.5 Conclusions / 82
References / 82
6 Surface Plasmon Resonance Biosensor Devices 85
6.1 Introduction / 85
6.2 Design Requirements on SPR Systems / 88
6.2.1 Needs and Specifications of an SPR Design / 88
6.3 Mechatronic Design Approach of SPR Systems / 89
6.3.1 Generation of Design Alternatives / 89
6.3.2 Hubka–Eder Mapping of the Design Alternatives / 92
6.4 Detailed Design of Critical SPR Subsystems / 99
6.4.1 Design of the Sensor Surface / 100
6.4.2 Design of the Fluidic System / 103
6.5 Conclusions / 109
References / 109
7 A Diagnostic Device for Helicobacter pylori Infection 113
7.1 Diagnostic Principle of Helicobacter Infection / 113
7.2 Mechatronic Analysis of Urea Breath Test Systems / 117
7.2.1 Mission and Specification for a Urea Breath Tests / 117
7.2.2 Generation of UBT Design Concepts / 118
7.2.3 Screening and Scoring of UBT Design Concepts / 119
7.3 Description of the Systems Involved in the Design Concepts for the Urea Breath Tests / 124
7.3.1 Biological Systems Involved / 124
7.3.2 Technical Systems Alternatives / 126
7.3.3 Information Systems (SIS) Required / 127
7.3.4 Management and Goal Systems Required / 127
7.3.5 Human Systems Involved in the Testing / 127
7.3.6 Active Environment That Can Influence / 128
7.4 Aspects of the Design for Efficient Manufacture / 128
7.5 Conclusions / 131
References / 131
8 Microarray Devices 135
8.1 Principles, Methods, and Applications of Microarrays / 135
8.1.1 Principles and Technology / 135
8.1.2 Fabrication Methods / 136
8.1.3 Companies Developing Microarrays / 138
8.1.4 Applications of DNA Microarrays / 139
8.2 Specification of Needs / 141
8.3 Design of Microarrays / 142
8.3.1 Generation of cDNA Microarray Concepts / 142
8.4 Description of the Systems Involved in the Design Concepts / 145
8.4.1 Biological Systems / 146
8.4.2 Technical Systems / 147
8.4.3 Information System / 147
8.4.4 Management and Goal Systems and the Human Systems / 147
8.4.5 Active Environment / 147
8.4.6 Interaction Analysis / 148
8.5 Conclusions / 149
References / 149
9 Microbial and Cellular Bioreactors 153
9.1 Bioreactor Development During the 1970s–1990s / 153
9.2 Missions, User Needs, and Specifications for Bioreactors / 158
9.2.1 Design Mission and User Needs / 158
9.2.2 Target Specifications / 158
9.3 Analysis of Systems for Conventional Bioreactors / 161
9.3.1 Biological Systems in the Bioreactor / 161
9.3.2 Technical Systems / 164
9.3.3 Studying the Interactions of the Systems / 166
9.3.4 Penicillin Production in a Metabolically Engineered Penicillium strain (Case 1) / 168
9.3.5 A Bioreactor System Producing a Recombinant Protein in CHO Cell Culture (Case 2) / 171
9.3.6 Information Systems / 173
9.3.7 Management and Goal Systems / 177
9.3.8 Human Systems / 179
9.3.9 Active Environment / 179
9.4 Novel Bioreactor Designs / 180
9.4.1 Microbioreactors / 180
9.4.2 Bioreactors with Immobilized Cells / 183
9.4.3 Bioreactors for Tissue and Stem Cell Cultures / 185
9.4.4 Bioreactors for Plant Cell Cultures / 186
9.5 Conclusions / 187
References / 187
10 Chromatographic Protein Purification 193
10.1 Background of Chromatographic Protein Purification / 193
10.2 Specification of Needs for Protein Purification Systems / 197
10.3 Design of Purification Systems / 199
10.3.1 Generation of Design Alternatives / 199
10.3.2 Screening the Design Alternatives / 201
10.3.3 Analysis of the Generated Alternatives for a Chromatography System / 202
10.3.4 Interactions Between Key Systems and the Transformation Process / 206
10.4 Unit Operation Purification in a FVIII Production Process (Case 1) / 208
10.5 Micropurification System Based on a Multichip Device (Case 2) / 209
10.6 Conclusions / 211
References / 212
11 Stem Cell Manufacturing 215
11.1 State of the Art of Stem Cell Manufacturing / 215
11.2 Needs and Target Specifications for Scaled-Up Stem Cell Manufacturing / 218
11.3 Setting Up an Efficient Manufacturing System by Using Biomechatronic Conceptual Design / 220
11.3.1 Generating Process Alternatives / 220
11.3.2 Hubka–Eder Map for a Human Embryonic Stem Cell Process / 220
11.4 Conclusions / 225
References / 226
12 Bioartificial Organ-Simulating Devices 229
12.1 Introduction / 229
12.2 Design of Bioartificial Organ-Simulation Devices / 232
12.2.1 Needs and Specifications / 232
12.2.2 Evaluation of the Design Concepts / 236
12.3 Analysis of Bioartificial Liver Systems / 239
12.3.1 Biological Systems / 239
12.3.2 Technical Systems / 241
12.3.3 Information Systems / 242
12.3.4 Management and Goals Systems / 243
12.3.5 Human Systems / 243
12.4 Conclusions / 244
References / 244
13 Applications to Process Analytical Technology and Quality by Design 249
13.1 PAT and QbD Concepts / 249
13.2 Needs of the PAT/QbD Players and Resulting Specifications / 253
13.3 Application of Design Methodology to PAT/QbD / 255
13.3.1 Concept Generation for a PAT/QbD System Structure / 255
13.3.2 Hubka–Eder Mapping of the PAT/QbD Transformation Process for a Pharmaceutical
Process / 257
13.3.3 Analysis of Effects / 259
13.4 Applying Mechatronic Design on a PAT System for Online Software Sensing in a Bioprocess (Case) / 260
13.5 Conclusions / 263
References / 263
GLOSSARY 267
INDEX 275