Preface xiii
Acknowledgments xv
Abbreviations xvii
1 Introduction: The Origin, Current Status, and Future of Microfluidics 1
Kin Fong Lei
1.1 Introduction 1
1.2 Development of Microfluidic Components 3
1.3 Development of Complex Microfluidic Systems 4
1.4 Development of Application-Oriented Microfluidic Systems 6
1.4.1 Applications of DNA Assays 6
1.4.2 Applications of Immunoassays 9
1.4.3 Applications of Cell-Based Assays 11
1.5 Perspective 14
References 14
2 Fundamental Concepts and Physics in Microfluidics 19
Yujun Song, Xiaoxiong Zhao, Qingkun Tian, and Hongxia Liang
2.1 Introduction 19
2.2 Basic Concepts of Liquids and Gases 21
2.2.1 Mean Free Path () in Fluids among Molecular Collisions 21
2.2.2 Viscosity () of Fluids 22
2.2.3 Mass Diffusivity (D) 29
2.2.4 Heat (Thermal) Capacity 34
2.3 Mass and Heat Transfer Principles for Fluid 41
2.3.1 Basic Fluidic Concepts and Law for Mass and Heat Transfer 42
2.3.1.1 Pascal's Law and Laplace's Law 42
2.3.1.2 Mass Conservation Principle (Continuity Equation) 44
2.3.1.3 Energy Conservation (Bernoulli's Equation) 44
2.3.1.4 Poiseuille's Law 45
2.3.1.5 Velocity Profile of Laminar Flow in a Circular Tube 46
2.3.2 Important Dimensionless Numbers in Fluid Physics 47
2.3.3 Other Dimensionless Numbers in Fluids 50
2.3.4 Diffusion Laws 56
2.3.5 Conversion Equation Based on Navier-Stokes Equations 59
2.3.5.1 Conservation of Mass Equation 60
2.3.5.2 Conservation of Momentum Equation (Navier-Stokes Equation) 61
2.3.5.3 Conservation of Energy Equation 62
2.4 Surfaces and Interfaces in Microfluidics 62
2.4.1 Surface/Interface and Surface Tension 62
2.4.2 Surface-/Interface-Induced Bubble Formation 66
2.4.3 Effect of Surfactants on the Surface/Interface Energy forWetting 68
2.4.4 Features of Surface and Interface in Microfluidics 69
2.4.5 Capillary Effects in Microfluidic Devices 70
2.4.6 Droplet Formation in Microfluidics 71
2.5 Development of Driving Forces for Microfluidic Processes 74
2.5.1 Fundamental in Electrokinetic Methods for Microfluidics 76
2.5.2 Basic Principles of Magnetic Field-Coupled Microfluidic Process 81
2.5.3 Basic Principles in Optofluidic Processes for Microfluidics 83
2.6 Construction Materials Considerations 94
Acknowledgments 100
References 100
3 Microfluidics Devices: Fabrication and Surface Modification 113
Zhenfeng Wang and Tao Zhang
3.1 Introduction 113
3.2 Microfluidics Device Fabrication 113
3.2.1 Silicon and Glass Fabrication Process 114
3.2.1.1 Photolithography 117
3.2.1.2 Etching 117
3.2.1.3 Metallization 117
3.2.1.4 Bonding 117
3.2.2 Polymer Fabrication Process 119
3.2.2.1 Patterning 119
3.2.2.2 Bonding 125
3.2.2.3 Metallization 128
3.2.2.4 3D Printing 128
3.2.2.5 Surface Treatment 129
3.2.3 Fabrication for Emerging Microfluidics Devices 129
3.3 Surface Modification in Microfluidics Fabrication 129
3.3.1 Plasma Treatment 132
3.3.2 Surface Modification Using Surfactant 134
3.3.3 Surface Modification with Grafting Polymers 135
3.3.3.1 Surface Photo-Grafting Polymerization 135
3.3.3.2 Surface-Initiated Atom Transfer Radical Polymerization (SI-ATRP) 137
3.3.3.3 Grafting-to Technique 142
3.3.4 Nanomaterials for Bulk Modification of Polymers 142
3.4 Conclusions and Outlook 143
References 144
4 Numerical Simulation in Microfluidics and the Introduction of the Related Software 147
Zheng Zhao, Adrian Fisher, and Daojian Cheng
4.1 Introduction 147
4.2 Numerical SimulationModels in Microfluidics 148
4.2.1 Molecular Dynamics (MD) 148
4.2.2 The Direct Simulation Monte Carlo (DSMC) Method 151
4.2.3 The Dissipative Particle Dynamics (DPD) 153
4.2.4 Continuum Method (CM) 155
4.2.5 The Lattice Boltzmann Method (LBM) 158
4.2.6 Computational Fluid Dynamics (CFD) 160
4.3 Numerical Simulation Software in Microfluidics 161
4.3.1 CFD-ACE+ Software: Microfluidics Applications 162
4.3.2 CFX Software: Microfluidics Applications 162
4.3.3 FLOW-3D Software: Microfluidics Applications 164
4.3.4 Other Software: Microfluidics Applications 166
4.4 Conclusions 166
Acknowledgments 167
References 168
5 Digital Microfluidic Systems: Fundamentals, Configurations, Techniques, and Applications 175
Mohamed Yafia, Bara J. Emran, and Homayoun Najjaran
5.1 Introduction to Microfluidic Systems 175
5.2 Types of Digital Microfluidic Systems 177
5.3 DMF Chip Fabrication Techniques 179
5.4 Different Electrode Configurations in DMF Systems 181
5.5 Digital Microfluidic Working Principle 183
5.5.1 Electromechanical and Energy-Based Models 183
5.5.2 Numerical Models 184
5.5.3 AnalyticalModels 184
5.6 Electrical Signals Used andTheir Effect on the DMF Operations 185
5.6.1 Types of the Signals Used in Actuation 185
5.6.2 The Effect of Changing the Frequency 187
5.7 Droplet Metering and Dispensing Techniques in DMF Systems 188
5.8 The Effect of the Gap Height between the Top Plate and the Bottom Plate in DMF Systems 189
5.9 Modeling and Controlling Droplet Operations in DMF Systems 192
5.9.1 Feedback Control in DMF Systems 192
5.9.2 Droplet Sensing Techniques in DMF Systems 195
5.9.3 Droplet Routing in DMF Systems 195
5.9.4 Controlling and Addressing the Signals in DMF Systems 197
5.10 Prospects of Portability in DMF Platforms 199
5.11 Examples for Chemical and Biological Applications Performed on the DMF Platform 199
References 203
6 Microfluidics for Chemical Analysis 211
Peng Song, Adrian C. Fisher, LuwenMeng, and Hoang V. Nguyen
6.1 Introduction 211
6.2 Microfluidics for Electrochemical Analysis 212
6.2.1 Voltammetric Analysis 212
6.2.2 Amperometric Protocol 216
6.2.3 Potentiometric Protocol 219
6.2.4 Conductivity Protocol 221
6.3 Advanced Microfluidic Methodologies for Electrochemical Analysis 223
6.3.1 The Rotating Microdroplet 223
6.3.2 The Microjet Electrode 224
6.3.3 Channel Multiplex 225
6.4 Numerical Modeling of Electrochemical Microfluidic Technologies 226
References 229
7 Microfluidic Devices for the Isolation of Circulating Tumor Cells (CTCs) 237
Caroline C. Ahrens, Ziye Dong, and Wei Li
7.1 Introduction 237
7.2 Affinity-Based Enrichment of CTCs 241
7.2.1 CTC-Chip 243
7.2.2 Geometrically Enhanced Differential Immunocapture (GEDI) 243
7.2.3 Herringbone (HB)-Chip 244
7.2.4 CTC-iChip 244
7.2.5 High-Throughput Microsampling Unit (HTMSU) 245
7.2.6 OncoBean Chip 246
7.2.7 NanoVelcro Rare Cell Assays 246
7.2.8 GO Chip 246
7.2.9 CTC Subpopulation Sorting 247
7.3 Nonaffinity-Based Enrichment of CTCs 247
7.3.1 Microfluidic Filtration 249
7.3.2 InertialMethods 250
7.3.2.1 Deterministic Lateral Displacement (DLD) 250
7.3.2.2 Microfluidic Spiral Separation 250
7.3.2.3 Vortex Platform 251
7.3.2.4 Multiorifice Flow Fractionation (MOFF) 251
7.3.3 Dielectrophoresis and Acoustophoresis 251
7.4 Conclusions and Outlook 252
References 254
8 Microfluidics for Disease Diagnosis 261
Jun-Tao Cao
8.1 Introduction 261
8.2 Protein Analysis 261
8.2.1 Secreted Proteins in Biological Fluids 261
8.2.2 Membrane Protein 264
8.3 Nucleic Acid Analysis 267
8.4 Cell Detection 269
8.5 Other Species 272
8.6 Summary and Overlook 275
References 275
9 Gene Expression Analysis on Microfluidic Device 279
Liang Zhao
9.1 Introduction 279
9.2 Analysis Cell Population Gene Expression on Chip 281
9.2.1 Nucleic Acid Analysis 281
9.2.2 Protein Level Analysis of Gene Expression 283
9.3 Single-Cell Gene Expression Profiling 288
9.3.1 Imaging-Based Single-Cell Analysis on Microfluidics 289
9.3.2 Microfluidic Methods to Single-Cell Nucleic Acid Analysis 292
9.3.3 Next-Generation Sequencing Platforms Based on Miniaturized Systems 301
9.4 Conclusion 305
Acknowledgment 306
References 306
10 Computational Microfluidics Applied to Drug Delivery in Pulmonary and Arterial Systems 311
Clement Kleinstreuer and Zelin Xu
10.1 Introduction 311
10.2 Modeling Methods 312
10.2.1 Governing Equations 312
10.2.2 Model Closure 312
10.2.3 Turbulence Modeling 313
10.2.4 Fluid-Particle Dynamics Modeling 313
10.2.5 Ferrofluid Dynamics 315
10.2.6 Nonspherical Particle Dynamics 316
10.2.7 Flow through Porous Media 316
10.2.8 Fluid-Structure Interaction 317
10.3 Pulmonary Drug Delivery 318
10.3.1 Inhalers and Drug-Aerosol Transport 319
10.3.2 Drug-Aerosol Dynamics 322
10.3.3 Methodologies and Design Aspects for Direct Drug Delivery 323
10.3.3.1 Smart Inhaler System Methodology 325
10.3.3.2 Enhanced Deeper Lung Delivery of Drug Aerosols via Condensational Growth 326
10.3.3.3 Shape Engineering for Novel Drug Carriers 326
10.3.3.4 Multifunctional Nanoparticles 327
10.3.3.5 Particle Absorption and Translocation 328
10.4 Intravascular Drug Delivery 328
10.4.1 Nanoparticle-Based Targeted Drug Delivery 329
10.4.2 Catheter-Based Intravascular Drug Delivery 330
10.4.2.1 Particle Hemodynamics 331
10.4.2.2 Tissue Heat and Mass Transfer 332
10.4.3 Magnetic Drug Delivery 333
10.4.4 Direct Drug Delivery 335
10.5 Conclusions and FutureWork 338
References 339
11 Microfluidic Synthesis of Organics 351
Hongxia Liang and Yujun Song
11.1 Introduction 351
11.2 Microfluidic Nebulator for Organic Synthesis 355
11.3 Coiled Tubing Microreactor for Organic Synthesis 356
11.4 Chip-Based Microfluidic Reactor for Organic Synthesis 360
11.5 Packed-Bed Microreactors for Organic Synthesis 363
11.6 Ring-Shaped (Tube-in-Tube) Microfluidic Reactor for Organic Synthesis 365
11.7 Summary and Outlook 368
Acknowledgments 369
References 369
12 Microfluidic Approaches for Designing Multifunctional PolymericMicroparticles from Simple Emulsions to Complex Particles 375
Jongmin Kim and Chang-Soo Lee
12.1 Introduction 375
12.2 Flow Regimes in Microfluidics: Dripping, Jetting, and Coflowing 376
12.2.1 Dimensionless Numbers 377
12.2.2 T-Junction Microfluidics 377
12.2.3 Flow-Focusing Microfluidics 378
12.2.4 Coflowing Microfluidics 379
12.3 Design of Multifunctional Microparticles from Emulsions 380
12.3.1 Microfluidic Approaches with Control of the Hydrodynamic Parameters 380
12.3.2 Microfluidic Approaches with Phase Separation 393
12.3.3 Microfluidic Approaches with Spreading Coefficients 397
12.4 Conclusions and Outlooks 398
References 399
13 Synthesis of Magnetic Nanomaterials 405
Ali Abou-Hassan
13.1 Introduction 405
13.2 Synthesis of Magnetic Nanomaterials Using Microreactors 406
13.2.1 Magnetic Iron Oxide-Based Nanomaterials 406
13.2.2 Synthesis of Metallic and Magnetic Nanomaterials 412
13.2.3 Synthesis of Core-Shell Magnetic Nanomaterials 414
13.3 Conclusion 416
References 416
14 Microfluidic Synthesis of Metallic Nanomaterials 419
Jugang Ma and Yujun Song
14.1 Introduction 419
14.2 Microfluidic Processes for Metallic Nanomaterial Synthesis 421
14.3 Crystal Structure-Controlled Synthesis of Metallic Nanocrystals 422
14.4 Size- and Shape-Controlled Synthesis of Metallic Nanocrystals 426
14.5 Multi-Hierarchical Microstructure- and Composition-Controlled Synthesis of Metallic Nanocrystals 434
14.6 Summary and Outlook 437
Acknowledgments 439
References 439
15 Microfluidic Synthesis of Composites 445
JunmeiWang and Yujun Song
15.1 Introduction 445
15.2 Microfluidic Synthesis Systems and the Design Principles 447
15.3 The Formation Mechanism of Composites 451
15.4 Microfluidic Synthesis of Composites 452
15.4.1 Composites Composed of Nonmetal Inorganics 452
15.4.1.1 Microfluidic Synthesis of Oxide-Coated Multifunctional Composites 453
15.4.1.2 Microfluidic Synthesis of Semiconductor-Semiconductor Composites 455
15.4.2 Composites Composed of Metal and Nonmetal Inorganics 457
15.4.2.1 Microfluidic Synthesis of Dielectric-Plasmonic Composites 457
15.4.2.2 Microfluidic Synthesis of Plasmonic-Semiconductor Composites 459
15.4.2.3 Microfluidic Synthesis of Carbon-Supported Composites 461
15.4.3 Composites Composed of Polymers and Metals 464
15.4.4 Composites Composed of Metal or Metal Alloy Materials 464
15.4.5 Composites Composed of Polymer and Organic Molecular 466
15.4.6 Composites Composed of Two or More Polymers 469
15.4.7 Microfluidic Synthesis of Metal-Organic Frameworks (MOFs) 470
15.5 Summary and Perspectives 471
Acknowledgments 472
References 472
16 Microfluidic Synthesis of MOFs and MOF-Based Membranes 479
Fernando Cacho-Bailo, Carlos Tellez, and Joaquin Coronas
16.1 Microfluidic Synthesis of Metal-Organic Frameworks (MOFs) 479
16.1.1 Zeolite Background 479
16.1.2 Microfluidic MOF Synthesis 480
16.2 Microfluidic Synthesis of MOF-Based Membranes 488
16.2.1 Context 488
16.2.2 MOF Membranes by Microfluidics 489
16.2.3 Inorganic versus Polymeric Supports: Intensification of Processes 501
16.2.4 Support Influence on MOF Synthesis Method 504
16.2.5 Advantages of Inner MOF Growth 506
16.3 Conclusions and Outlook 507
Acknowledgments 508
References 508
17 Perspective for Microfluidics 517
Yujun Song and Daojian Cheng
17.1 Design, Fabrication, and Assemble of Microfluidic Systems 518
17.2 Precise Control of Critical Device Features for Chemical Analysis and Biomedical Engineering 521
17.3 Control of Critical Kinetic Parameters for Chemical and Materials Synthesis 522
17.4 Development of FundamentalTheory at Micro-/Nanoscale and Fluid Mechanism at Nanoliter Picoliter for Microfluidic Systems 525
Acknowledgments 529
References 529
Index 541
