Fundamentals and Applications

of Microfluidics
Second Edition

Nam-Trung Nguyen
Steven T. Wereley

ARTECH
HOUSE
BOSTON|LONDON
artechhouse.com
Contents

Preface xi

Acknowledgments xiii

Chapter 1 Introduction 1
1.1 What Is Microfluidics? 1
1.1.1 Relationships Among MEMS, Nanotechnology, and Microfluidics 1
1.1.2 Commercial Aspects 4
1.1.3 Scientific Aspects 5
1.2 Milestones of Microfluidics 6
1.2.1 Device Development 6
1.2.2 Technology Development . 8
1.3 Organization of the Book - 8
References 9

Chapter 2 Fluid Mechanics Theory 11

2.1 Introduction 11
2.1.1 Intermolecular Forces 12
2.1.2 The Three States of Matter 14
2.1.3 Continuum Assumption 15
2.2 Continuum Fluid Mechanics at Small Scales 18
2.2.1 Gas Flows 19
2.2.2 Liquid Flows 23
2.2.3 Boundary Conditions 25
2.2.4 Parallel Flows 30
2.2.5 Low Reynolds Number Flows 33
2.2.6 Entrance Effects , 36
2.2.7 Surface Tension ' 37
2.3 Molecular Approaches 39
2.3.1 MD 40
2.3.2 DSMC Technique 42
2.4 Electrokinetics 44
2.4.1 Electro-osmosis 44
2.4.2 Electrophoresis 47
2.4.3 Dielectrophoresis 49
2.5 Conclusion 51
VI Fundamentals and Applications of Microfluidics

Problems 52
References 53

Chapter 3 Fabrication Techniques for Microfluidics 55

3.1 Basic Microtechniques 55
3.1.1 Photolithography 55
3.1.2 Additive Techniques 57
3.1.3 Subtractive Techniques 59
3.1.4 Pattern Transfer Techniques 61
3.2 Functional Materials 62
3.2.1 Materials Related to Silicon Technology 62
3.2.2 Polymers 67
3.3 Silicon-Based Micromachining Techniques 69
3.3.1 Silicon Bulk Micromachining 69
3.3.2 Silicon Surface Micromachining 76
3.4 Polymer-Based Micromachining Techniques 81
3.4.1 Thick Resist Lithography 82
3.4.2 Polymeric Bulk Micromachining 86
3.4.3 Polymeric Surface Micromachining 87
3.4.4 Microstereo Lithography 91
3.4.5 Micromolding 95
3.5 Other Micromachining Techniques 100
3.5.1 Subtractive Techniques 101
3.5.2 Additive Techniques 103
3.6 Assembly and Packaging of Microfluidic Devices 104
3.6.1 Wafer Level Assembly and Packaging 104
3.6.2 Device Level Packaging 106
3.7 Biocompatibility . 108
3.7.1 Material Response 108
3.7.2 Tissue and Cellular Response 109
3.7.3 Biocompatibility Tests 109
Problems 109
References 110

Chapter 4 Experimental Flow Characterization 117

4.1 Introduction 117
4.1.1 Pointwise Methods 117
4.1.2 Full-Field Methods 118
4.2 Overview of uPIV 122
4.2.1 Fundamental Physics Considerations of uPIV 122
4.2.2 Special Processing Methods for uPIV Recordings; 138
4.2.3 Advanced Processing Methods Suitable for Both Micro/Macro-PIV
Recordings 141
4.3 uPIV Examples 144
4.3.1 Flow in a MicroChannel 144
4.3.2 Flow in a Micronozzle 146
4.3.3 Flow Around a Blood Cell 149
4.3.4 Flow in Microfluidic Biochip 151
4.3.5 Conclusions 153
4.4 Extensions of the uPIV Technique 153
 Contents vu

4.4.1 Microfluidic Nanoscope 153

4.4.2 Microparticle Image Thermometry 158
4.4.3 Infrared uPIV 167
4.4.4 Particle Tracking Velocimetry 169
Problems 172
References 172

Chapter 5 Microfluidics for External Flow Control 177

5.1 Velocity and Turbulence Measurement 177
5.1.1 Velocity Sensors 177
5.1.2 Shear Stress Sensors 181
5.2 Turbulence Control 189
5.2.1 Microflaps 190
5.2.2 Microballoon 191
5.2.3 Microsynthetic Jet 192
5.3 Microair Vehicles 193
5.3.1 Fixed-Wing MAV 194
5.3.2 Flapping-Wing MAV 195
5.3.3 Microrotorcraft 197
5.3.4 Microrockets 198
Problems 207
References 208

Chapter 6 Microfluidics for Internal Flow Control: Microvalves 211

6.1 Design Considerations 213
6.1.1 Actuators 213
6.1.2 Valve Spring 234
6.1.3 Valve Seat 237
6.1.4 Pressure Compensation Design 238
6.2 Design Examples 239
6.2.1 Pneumatic Valves 239
^ 6.2.2 Thermopneumatic Valves 240
6.2.3 Thermomechanical Valves 242
6.2.4 Piezoelectric Valves 244
6.2.5 Electrostatic Valves 245
6.2.6 Electromagnetic Valves 247
6.2.7 Electrochemical and Chemical Valves 248
6.2.8 Capillary-Force Valves 250
6.3 Summary 250
Problems 251
References • 251

Chapter 7 Microfluidics for Internal Flow Control: Micropumps 255

7.1 Design Considerations 256
7.1.1 Mechanical Pumps 256
7.1.2 Nonmechanical Pumps 269
7.2 Design Examples 288
7.2.1 Mechanical Pumps 288
7.2.2 Nonmechanical Pumps 298
7.3 Summary 303
viii Fundamentals and Applications of Microfluidics

Problems 303
References 304

Chapter 8 Microfluidics for Internal Flow Control: Microflow Sensors 311

8.1 Design Considerations 311
8.1.1 Design Parameters 311
8.1.2 Nonthermal Flow Sensors 312
8.1.3 Thermal Flow Sensors 317
8.2 Design Examples 324
8.2.1 Nonthermal Flow Sensors 324
8.2.2 Thermal Flow Sensors 327
8.3 Summary 335
Problems 336
References 336

Chapter 9 Microfluidics for Life Sciences and Chemistry: Microneedles 339

9.1 Design Considerations 341
9.1.1 Mechanical Design 341
9.1.2 Delivery Modes 346
9.2 Design Examples 348
9.2.1 Solid Microneedles 348
9.2.2 Hollow Microneedles 349
9.3 Summary 352
Problems 353
References 353

Chapter 10 Microfluidics for Life Sciences and Chemistry: Micromixers 357

10.1 Design Considerations 359
10.1.1 Parallel Lamination 360
10.1.2 Sequential Lamination 363
10.1.3 Sequential Segmentation 364
10.1.4 Segmentation Based on Injection 366
10.1.5 Focusing of Mixing Streams 369
10.1.6 Formation of Droplets and Chaotic Advection 372
10.2 Design Examples 374
10.2.1 Passive Micromixers 374
10.2.2 Active Micromixers 383
10.3 Summary 386
Problems 388
References 389

Chapter 11 Microfluidics for Life Sciences and Chemistry: Microdispensers 395

11.1 Design Considerations 395
11.1.1 Droplet Dispensers 395
11.1.2 In-Channel Dispensers 404
11.2 Design Examples 408
11.2.1 Droplet Dispensers 408
11.2.2 In-Channel Dispensers 412
11.3 Summary 414
Problems 415
 Contents

References 416

Chapter 12 Microfluidics for Life Sciences and Chemistry: Microfilters and Microseparators 419
12.1 Microfilters , 419
12.1.1 Design Considerations 421
12.1.2 Design Examples 423
12.2 Microseparator 425
12.2.1 Cell and Particle Sorter 426
12.2.2 Chromatography 431
12.3 Summary 438
Problems 439
References 439

Chapter 13 Microfluidics for Life Sciences and Chemistry: Microreactors 443

13.1 Design Considerations 444
13.1.1 Specification Bases for Microreactors 444
13.1.2 Miniaturization of Chemical Processes 445
13.1.3 Functional Elements of a Microreactor 446
13.2 Design Examples 449
13.2.1 Gas-Phase Reactors 449
13.2.2 Liquid-Phase Reactors 457
13.2.3 Multiphase Reactors 464
13.2.4 Microreactors for Cell Treatment 468
13.2.5 Hybridization Arrays 470
13.3 Summary 472
Problems 472
References 473

Appendix A List of Symbols 479

Appendix B Resources for Microfluidics Research 483

Appendix C Abbreviations of Different Plastics 485

Appendix D Linear Elastic Deflection Models 487

About the Authors 489

Index 491