Methods in Bioengineering: Biomicrofabrication and Biomicrofluidics (Artech House Methods in Bioengineering Series)

367 Pages·2009·8.16 MB·English

by  Jeffrey D. Zahn

Methods in Bioengineering
Biomicrofabrication and Biomicrofluidics
The Artech House Methods in Bioengineering Series
Series Editors-in-Chief
Martin L.Yarmush, M.D., Ph.D.
Robert S.Langer, Sc.D.
Methods in Bioengineering:BiomicrofabricationandBiomicrofluidics,
Jeffrey D. Zahn, editor
Methods in Bioengineering:Microdevicesin Biology and Medicine,
YaakovNahmiasand Sangeeta N.Bhatia, editors
Methods in Bioengineering:NanoscaleBioengineering andNanomedicine,
KaushalRege and IgorMedintz, editors
Methods in Bioengineering: Stem Cell Bioengineering,
BijuParekkadanand Martin L.Yarmush, editors
Methods in Bioengineering: Systems Analysis of Biological Networks,
ArulJayaramanand Juergen Hahn, editors
Methods in Bioengineering
Biomicrofabrication and Biomicrofluidics
Jeffrey D. Zahn
Department of Biomedical Engineering
Rutgers University
Editor
artechhouse.com
Library of Congress Cataloging-in-Publication Data
A catalog record for this book is available from the U. S. Library of Congress.
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library.
ISBN-13: 978-1-59693-400-9
Cover design by Greg Lamb
Text design by Darrell Judd
© 2010 Artech House. All rights reserved.
Printed and bound in the United States of America. No part of this book may be reproduced or
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mark.
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Contents
Preface xiii
CHAPTER 1
Microfabrication Techniques for Microfluidic Devices 1
1.1 Introduction to microsystems and microfluidic devices 2
1.2 Microfluidic systems: fabrication techniques 3
1.3 Transfer processes 4
1.3.1 Photolithography 4
1.3.2 Molding 6
1.4 Additive processes 6
1.4.1 Growth of SiO 6
2
1.4.2 Deposition techniques 7
1.5 Subtractive techniques 10
1.5.1 Etching 10
1.5.2 Chemical-mechanical polishing and planarization 13
1.6 Bonding processes 13
1.6.1 Lamination 13
1.6.2 Wafer bonding methods 14
1.7 Sacrificial layer techniques 16
1.8 Packaging processes 16
1.8.1 Dicing 16
1.8.2 Electrical interconnection and wirebonding 17
1.8.3 Fluidic interconnection in microfluidic systems 18
1.9 Materials for microfluidic and bio-MEMS applications 19
1.9.1 Glass, pyrex, and quartz 19
1.9.2 Silicon 19
1.9.3 Elastomers 20
1.9.4 Polydimethylsiloxane 20
1.9.5 Epoxy 20
1.9.6 SU-8 thick resists 20
1.9.7 Thick positive resists 21
1.9.8 Benzocyclobutene 21
1.9.9 Polyimides 21
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Contents
1.9.10 Polycarbonate 22
1.9.11 Polytetrafluoroethylene 22
1.10 Troubleshooting table 22
1.11 Summary 22
References 25
CHAPTER 2
Micropumping and Microvalving 31
2.1 Introduction 32
2.2 Actuators for micropumps and microvalves 33
2.2.1 Pneumatic actuators 35
2.2.2 Thermopneumatic actuators 36
2.2.3 Solid-expansion actuators 37
2.2.4 Bimetallic actuators 38
2.2.5 Shape-memory alloy actuators 38
2.2.6 Piezoelectric actuators 38
2.2.7 Electrostatic actuators 39
2.2.8 Electromagnetic actuators 39
2.2.9 Electrochemical actuators 40
2.2.10 Chemical actuators 41
2.2.11 Capillary-force actuators 42
2.3 Micropumps 42
2.3.1 Mechanical pump 43
2.3.2 Nonmechanical pump 48
2.4 Microvalves 51
2.4.1 Mechanical valve 52
2.4.2 Nonmechanical valve 54
2.5 Outlook 55
2.6 Troubleshooting 55
2.7 Summary points 56
References 56
CHAPTER 3
Micromixing Within Microfluidic Devices 59
3.1 Introduction 60
3.2 Materials 62
3.2.1 Microfluidic mixing devices 62
3.2.2 Microfluidic interconnects 62
3.2.3 Optical assembly 63
3.2.4 Required reagents 63
3.3 Experimental design and methods 64
3.3.1 Passive micromixers 64
3.3.2 Active micromixers 70
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Contents
3.3.3 Multiphase mixers 75
3.4 Data acquisition, anticipated results, and interpretation 77
3.4.1 Computer acquisition 77
3.4.2 Performance metrics, extent of mixing, reaction monitoring 78
3.5 Discussion and commentary 78
3.6 Troubleshooting 79
3.7 Application notes 79
3.8 Summary points 79
References 80
CHAPTER 4
On-Chip Electrophoresis and Isoelectric Focusing Methods for Quantitative Biology 83
4.1 Introduction 84
4.1.1 Microfluidic electrophoresis supports quantitative biology
4.1.1 and medicine 84
4.1.2 Biomedical applications of on-chip electrophoresis 88
4.2 Materials 89
4.2.1 Reagents 89
4.2.2 Facilities/equipment 91
4.3 Methods 91
4.3.1 On chip polyacrylamide gel electrophoresis (PAGE) 92
4.3.2 Polyacrylamide gel electrophoresis based isoelectric focusing 96
4.3.3 Data acquisition, anticipated results, and interpretation 102
4.3.4 Results and discussion 103
4.4 Discussion of pitfalls 105
4.5 Summary notes 105
Acknowledgments 108
References 108
CHAPTER 5
Electrowetting 111
5.1 Introduction 112
5.1.1 Electrowetting theory 112
5.1.2 Droplet manipulation using electrowetting 113
5.1.3 Digital microfluidic lab-on-a-chip for clinical diagnostics 115
5.2 Digital microfluidic lab-on-a-chip design 115
5.2.1 Fluidic input port 115
5.2.2 Liquid reservoirs 116
5.2.3 Droplet pathways 116
5.3 Materials 117
5.3.1 Chemicals 117
5.3.2 Fabrication materials 118
5.4 Device Fabrication 119
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Contents
5.4.1 Fabrication of single layer electrowetting chips 119
5.4.2 Fabrication of two layer electrowetting chips 119
5.4.3 Dielectric deposition 120
5.4.4 Fabrication of the top plate 121
5.4.5 Hydrophobic coating 121
5.5 Instrumentation and system assembly 121
5.5.1 Detection setup 121
5.5.2 System assembly 122
5.6 Methods 123
5.6.1 Automated glucose assays on-chip 123
5.6.2 Magnetic bead manipulation on-chip 123
5.6.3 Droplet-based immunoassay 125
5.7 Results and discussion 125
5.7.1 Testing of two layer electrowetting device 125
5.7.2 Automated glucose assay on-chip 126
5.7.3 Optimization of magnetic bead washing 127
5.8 Method challenges 129
5.9 Summary points 131
Acknowledgments 131
References 131
CHAPTER 6
Dielectrophoresis for Particle and Cell Manipulations 133
6.1 Introduction: physical origins of DEP 134
6.2 Introduction: theory of dielectrophoresis 135
6.2.1 Limiting assumptions and typical experimental conditions 138
6.3 Materials: equipment for generating electric field nonuniformities
6.3 and DEP forces 145
6.3.1 Electric field frequency 145
6.3.2 Electric field phase 147
6.3.3 Geometry 149
6.4 Methods: data acquisition, anticipated results, and interpretation 152
6.4.1 General considerations for dielectrophoretic devices 152
6.4.2 Electrode-based dielectrophoresis 156
6.4.3 Insulative dielectrophoresis 163
6.4.4 Summary of experimental parameters 168
6.5 Troubleshooting 169
6.6 Application notes 169
6.6.1 Particle trapping 169
6.6.2 Particle sorting and fractionation 172
6.6.3 Single-particle trapping 175
References 177
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Contents
CHAPTER7
Optical Microfluidics for Molecular Diagnostics 183
7.1 Introduction 184
7.2 Integrated optical systems 185
7.2.1 Absorbancedetection 185
7.2.2 Fluorescence detection 188
7.2.3 Chemiluminescencedetection 191
7.2.4 Interferometric detection 192
7.2.5 Surface plasmon resonance detection 194
7.3 Nanoengineered optical probes 195
7.3.1 Quantum dots 196
7.3.2 Up-converting phosphors 197
7.3.3 Silver-enhanced nanoparticle labeling 197
7.3.4 Localized surface plasmon resonance 198
7.3.5 SPR with nanohole gratings 200
7.3.6 Surface-enhanced Raman spectroscopy 200
7.4 Conclusions 203
7.5 Summary 203
Acknowledgments 204
References 204
CHAPTER 8
Neutrophil Chemotaxis Assay from Whole Blood Samples 209
8.1 Introduction 210
8.2 Device design 210
8.3 Materials 213
8.4 Methods 213
8.4.1 Device fabrication 213
8.4.2 Surface treatment 215
8.4.3 Chemotaxis assay 216
8.5 Data acquisition 220
8.6 Troubleshooting tips 220
Appendix 8A 221
References 223
CHAPTER 9
Microfluidic Immunoassays 225
9.1 Introduction 226
9.1.1 Microfluidic immunoassay design/operation considerations 227
9.1.2 Example microfluidic immunoassay formats 227
9.2 Materials 230
9.2.1 Microfluidic device 230
ix