Microfluidics for Biologists (eBook)

Chandra Dixit is in the Department of Chemistry at the University of Connecticut.Ajeet Kaushik is in the Department of Immunology at Florida International University.Gerson Aguirre is in the Biomedical Engineering Department at McGill University.

Preface 5
Salient Features of This Book 6
Contents 7
Chapter 1: Fundamentals of Fluidics 8
1 Introduction 8
2 Microfluidic Physics 8
2.1 Hierarchy of Dimensions 9
2.2 Non-dimensionalization and Dimensionless Numbers 10
2.3 Hydrostatics: Physics of the Stagnant 11
Pascal´s Law 13
2.3.1 Pressure and Pumping 14
2.3.2 Buoyancy and the Problem of Microfluidic Mixing 15
2.4 Hydrodynamics: Physics of the Flows 16
2.4.1 Concept of Continuum 17
2.4.2 Important Intrinsic Properties 17
2.4.3 Types of Fluids Based on Intrinsic Properties 19
Newtonian vs. Non-newtonian: Case of Whole Blood Analysis in Microfluidics 19
Compressible and Incompressible Fluids 20
2.4.4 Other Important Properties 21
Importance of Surface Tension in Microfluidics 22
Critical Thinking 22
2.4.5 Laws Governing Dynamics 23
Basic Law 23
Equations of Motion 24
Conservation of Mass 25
Conservation of Linear Momentum/Inertia 26
Conservation of Energy 26
Important Concepts 27
Applications of Stokes Law 28
2.5 Key Dimensionless Numbers Explained 34
2.5.1 Reynolds Number: Inertial Focusing to Separate Plasma from Whole Blood 34
2.5.2 Pclet Number: Diffusivities Across Channel Width and No-Membrane Dynamic Filtering 35
3 Conclusion 37
Further Reading 38
Recommended reviews and articles 38
Recommended Books and Lecture Notes 39
Chapter 2: Microfluidics Overview 40
1 Introduction 40
2 Basic Fabrication Techniques 42
2.1 LASER 42
2.1.1 Application of Laser Machining for micro-channel making 43
2.1.2 Application of LASER Machining for Mask Making 44
2.2 Photo-Lithography 45
2.2.1 Pattern Transfer 45
2.2.2 Alignment 46
2.2.3 Exposure 47
2.3 Soft Lithography 47
2.4 Micro-Scale Replication by Double Inversion (MRDI) Process 48
2.5 Embedded Structures with Replication and Moulding Processes 49
3 Microfluidics for Flow Control and Some Novel Effects 51
3.1 Micro-mixer Design and Characterization 52
3.2 Bilayer Staggered Herringbone Micromixers (BSHM) 53
3.3 Long Microchannel Arrays as Vibration Pads 53
3.4 Micro-pump 55
3.4.1 Micro-pumping System with Peristaltic Motion 56
3.5 Micro-valve 58
4 Micro-cantilevers for Mass Based Sensing and Diagnostics 59
5 Applications in Clinical Diagnostics 64
5.1 Paper Microfluidics: Applications in Clinical Diagnostics 64
5.1.1 Basic Principles of Fluid Flow in Paper Micro-fluidics 67
5.2 Electrophoresis 69
5.3 Dielectrophoresis 72
5.4 Polymerase Chain Reaction Microchips 75
5.5 Gene Delivery Using Nanoscale Material and Electrophoretic Transport of DNA 79
6 Various Sensing and Detection Techniques 79
6.1 Electrochemical Sensing 80
6.2 Optical Sensing 82
6.3 Mass Based Sensing 83
References 84
Chapter 3: Manufacturing Methods Overview for Rapid Prototyping 91
1 Motivation 91
2 Selecting a Fabrication Method 91
2.1 Photolithography and Mask Design 93
2.2 Moulding and Casting 97
2.3 Hot Embossing 98
2.4 Micromilling 100
2.5 Choice of Instrument and Relation to Material 100
2.6 Laser Ablation 102
3 Packaging and Bonding 105
3.1 Thermal Bonding 105
3.2 Chemical Bonding 105
3.3 Bonding Through Pressure Sensitive Adhesive 106
3.4 Plasma Bonding of PDMS 106
References 107
Chapter 4: 3D Printed Microfluidic Devices 109
1 Introduction 109
2 3D Printing Techniques 110
2.1 Extrusion-Based Methods 110
2.2 Methods Based on Photocuring 111
2.3 Cost and Materials 112
3 3D-Printed Microfluidics 112
3.1 Molds and Scaffolds for Fluidic Channels 113
3.2 Fluidic Devices Prepared by Direct Printing 114
4 3D-Printed Fluidics and Bioanalysis 115
5 Outlook and Prospects 117
References 117
Chapter 5: The Centrifugal Microfluidic: Lab-on-a-Disc Platform 120
1 Introduction 120
2 Centrifugal Microfluidics 121
2.1 Centrifugal Hydrodynamics 121
2.2 Metering 123
2.3 Mixing 124
2.4 Diagnostic Applications 125
2.4.1 Nucleic Acid Amplification 125
2.4.2 Immunoassays 125
3 Valving Technologies 126
3.1 Passive Valving 126
3.1.1 Capillary Valves 126
3.1.2 Siphon Valves 127
3.1.3 Centrifugo-Pneumatic Valving 129
3.1.4 Event Triggered Valving 129
3.1.5 Paper Imbibition Valves 130
3.2 Active Valving 130
3.2.1 Phase-Change Micro-valves 130
3.2.2 Electromechanical Pumping 131
4 Valving Design 131
5 Spin Stand 131
5.1 Operation 131
5.1.1 Signal from the Motor 132
5.1.2 Positional Triggering 134
5.1.3 Filtering the Camera Signal 134
5.2 Application Example: Automation of a Direct Bilirubin Test 135
5.2.1 Direct Bilirubin 135
5.3 Liquid Handling Protocol: Disc Architecture 135
6 Manufacturing Protocol 138
6.1 Designing the Lab-on-a-Disk 138
6.2 Cutting PSA 140
6.3 Dissolvable Film Tabs 140
6.4 Cutting PMMA 141
7 Assembly 142
7.1 Vents (PMMA) 143
7.2 Microchannels (PSA) 144
7.3 Microchambers (PMMA) 144
7.4 DF Cover (PSA) 144
7.5 DF Support (PSA) 145
7.6 Mid-Layer (PMMA) 145
7.7 Lower Channels (PSA) 145
7.8 Base Layer (PMMA) 145
7.9 Testing 145
8 Conclusion 146
References 147
Chapter 6: Materials and Surfaces in Microfluidic Biosensors 150
1 Introduction 150
1.1 Biosensors-Involvement of Microfluidics 151
2 Material Development for Microfluidic Systems 152
2.1 Inorganic Materials 152
2.1.1 Silicon 152
2.1.2 Glass 155
2.1.3 Ceramics 156
2.2 Elastomers and Plastics 156
2.2.1 Elastomers 158
2.2.2 Thermoplastics 159
2.3 Hydrogel 161
2.4 Paper 162
3 The Ideal Microfluidic System for POC Sensor Design 166
4 Conclusion 167
References 167
Chapter 7: Paper Microfluidics 170
1 Introduction 170
2 Application Areas 173
3 Physical Principles 174
3.1 Flow Through Paper 174
3.2 Spreading of Wax and Width of Patterned Channel 175
3.3 Transport Time 175
3.4 Signal Visibility 176
4 Main Formats of Paper Devices 176
5 Types of Paper and Its Functionalization 181
6 Existing Fabrication Technologies 183
6.1 Technologies for Patterning of Hydrophobic Barriers 183
6.1.1 Wax Printing 184
6.1.2 Screen-Printing 185
6.1.3 Inkjet-Printing 185
6.1.4 Flexographic Printing 186
6.1.5 Photolithography-Assisted Methods 186
6.1.6 Plasma Treatment 186
6.2 Technologies for Assembly of Devices 186
6.3 Technologies for Fabrication of Electrodes in Paper 187
7 Detection Methods 187
7.1 Colourimetric 187
7.2 Electrochemical 187
7.3 Chemiluminescence and Electrochemiluminescence 188
7.4 Fluorescence 188
7.5 Nanoparticles 188
7.6 Other Methods 188
References 189
Chapter 8: Biological Applications of Microfluidics System 196
1 Introduction 196
2 Microfluidics in Cell Biology 197
2.1 Stem Cell Research 198
2.2 Neurology 201
2.3 Drug Development 203
2.4 Organs on Chips 204
2.5 Single Cell Analysis 209
3 Microfluidics in Diagnostics 213
3.1 Molecular Diagnostics 216
3.2 Immunodiagnostics 217
3.3 Commercial Diagnostics 219
4 Present Challenges and Future Perspectives 220
5 Conclusion 221
References 222
Chapter 9: RETRACTED CHAPTER: On-Chip Immunoassay for Molecular Analysis 227
1 Introduction 227
1.1 Immunoassays 227
2 Immunoassay Formats in Microfluidic Systems 228
2.1 Homogeneous Immunoassays in Microfluidic Systems 229
2.2 Heterogeneous Immunoassays in Microfluidic Systems 230
2.2.1 Antibody Immobilization 230
2.2.2 Analyte Transport and Delivery 231
2.3 Heterogeneous Immunoassays on Microbeads 232
2.3.1 Magnetic Microbeads 232
2.3.2 Non-magnetic Microbeads 233
3 Fluid Driving and Handling Technologies in Microfluidic Systems 234
3.1 Electric Forces 234
3.2 Pressure-Driven Fluid Handling Modalities 236
3.3 Centrifugal Force-Driven Modalities 237
3.4 Passive, Capillary Force-Driven Modalities 239
4 Multiplexed Microfluidic Immunoassay Platforms 241
4.1 Surface Array-Based Multiplexing 241
4.2 Bead-Based Multiplexing 242
5 Conclusions 243
References 244
Chapter 10: Challenges and Future 250
RETRACTION NOTE TO: On-Chip Immunoassay for Molecular Analysis 252
Index 253