Microfluidics www.ebook3000.com Microfluidics Fundamentals, Devices and Applications Edited by Yujun Song, Daojian Cheng, and Liang Zhao Editors All books published by Wiley-VCH are carefully produced. Nevertheless, authors, Professor Yujun Song editors, and publisher do not warrant the University of Science and Technology information contained in these books, Beijing including this book, to be free of errors. School of Mathematics and Physics Readers are advised to keep in mind that Beijing Key Laboratory of Magnetic statements, data, illustrations, procedural Optoelectronic Composites and Interface details or other items may inadvertently Science be inaccurate. 30 Xueyuan Road Haidian District Library of Congress Card No.: applied for 100083 Beijing PR China British Library Cataloguing-in-Publication Data Professor Daojian Cheng A catalogue record for this book is avail- Beijing University of Chemical able from the British Library. 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Print ISBN: 978-3-527-34106-1 ePDF ISBN: 978-3-527-80062-9 ePub ISBN: 978-3-527-80065-0 Mobi ISBN: 978-3-527-80066-7 oBook ISBN: 978-3-527-80064-3 Cover Design Adam-Design, Weinheim, Germany Typesetting SPi Global, Chennai, India Printing and Binding Printed on acid-free paper www.ebook3000.com v Contents 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 ()ofFluids 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 vi Contents 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 for Wetting 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 www.ebook3000.com Contents vii 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 Simulation Models 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 Analytical Models 184 5.6 Electrical Signals Used and Their 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 viii Contents 6 Microfluidics for Chemical Analysis 211 Peng Song, Adrian C. Fisher, Luwen Meng, 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 Inertial Methods 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 www.ebook3000.com Contents ix 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