Microdevices in Biology and Medicine (Artech House Methods in Bioengineering)

273 Pages·2009·7.06 MB·English

by  Yaakov Nahmias

Methods in Bioengineering
Microdevices in Biology and Medicine
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. Zahnand Luke P. Lee, editors
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
Microdevices in Biology and Medicine
YaakovNahmias
Massachusetts General Hospital, Harvard Medical School
Bioengineering Program, Hebrew University of Jerusalem
SangeetaN.Bhatia
Department of Electrical Engineering, Massachusetts Institute of Technology
Howard Hughes Medical Institute
Editors
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: 978-1-59693-404-7
Cover design byYekaterinaRatner
© 2009ArtechHouse.
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mark.
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Contents
Preface xi
CHAPTER 1
ImmunoaffinityCapture of Cells from Whole Blood 1
1.1 Introduction 2
1.2 Experimental Design 3
1.3 Materials 4
1.4 Methods 5
1.4.1 Device fabrication 5
1.4.2 Fluidicport punching 8
1.4.3 Surface modification 9
1.4.4 Cell capture 11
1.4.5 Injecting blood into cassette 13
1.4.6 Washingnoncapturedcells with PBS 15
1.4.7 Postcaptureprocessing 16
1.4.8 Immunofluorescence staining 17
1.4.9 Giemsastaining protocol 17
1.4.10 Cell lysis forgenomicapplications 19
1.5 Data Acquisition, Anticipated Results, and Interpretation 20
1.6 Discussion and Commentary 21
1.7 Application Notes 21
1.8 Summary Points 23
Acknowledgments 23
References 23
CHAPTER 2
Dynamic Gene-Expression Analysis in aMicrofluidicLiving Cell Array (mLCA) 25
2.1 Introduction 26
2.2 Materials 29
2.2.1 Reagents 29
2.2.2 Fabrication facilities 29
2.2.3 Imaging equipment 29
2.2.4 Perfusion components 30
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Contents
2.3 Methods 30
2.3.1 GFPreporter cell line construction 30
2.3.2 Microfluidiccell array fabrication 31
2.3.3 Microfluidicarray pretreatment and seeding 33
2.3.4 Stimulation and reporter imaging 34
2.4 Data Acquisition, Anticipated Results, and Interpretation 34
2.5 Discussion 36
2.6 Application Notes 39
2.7 Summary Points 39
Acknowledgments 39
References 40
CHAPTER 3
MicromechanicalControl of Cell-Cell Interactions 43
3.1 Introduction 44
3.1.1 Cell-cell interactions 44
3.1.2 Conventionalcocultivationmodels 44
3.1.3 Micromechanicalreconfigurable culture 45
3.1.4 Application examples 46
3.2 Experimental Design 51
3.2.1 Experimental variables 51
3.2.2 Readout 51
3.3 Materials 52
3.3.1 Reagents/supplies 52
3.3.2 Facilities/equipment 52
3.4 Methods 53
3.4.1 Device handling and actuation 53
3.4.2 Preparing devices for cell culture 54
3.4.3 Cell seeding 58
3.4.4 Assay preparation 59
3.5 Discussion 59
3.6 Summary Points 60
Acknowledgments 61
References 61
Related sources 61
CHAPTER 4
Mechanotransductionand the Study of Cellular Forces 63
4.1 Introduction 64
4.1.1 Cellular forces: Functions and underlying mechanisms 64
4.1.2 Techniques for studying traction forces 65
4.2 Materials 67
4.2.1 Reagents and supplies 67
vi
Contents
4.2.2 Facilities, equipment, and software 68
4.3 Methods 68
4.3.1 Microfabricationofmicropostarrays 68
4.3.2 Analysis of traction forces withmicropostarrays 74
4.4 Discussion 76
4.4.1 Applications and enhancements of themicropostarrays 76
4.4.2 Potential pitfalls ofmicropostarrays 77
4.4.3 Biological insights from usingmicropostarrays 80
4.4.4 Future innovations for studying cellular forces 82
4.5 Summary Points 82
References 84
CHAPTER 5
AMicrofluidicTool for ImmobilizingC. elegans 87
5.1 Introduction 88
5.2 Materials 89
5.3 Methods 89
5.3.1 Overview andtimeline 89
5.3.2 Designing the device and ordering thephotomask 90
5.3.3 Fabricating the master for the device 93
5.3.4 Replica-molding the master inPDMS 96
5.3.5 PreparingC. elegansfor loading 97
5.3.6 Assembling themicrofluidicdevice 98
5.3.7 Preparing the device for loading 100
5.3.8 Loading worms into the device 101
5.3.9 Unloading worms from the device 102
5.4 Data Acquisition, Anticipated Results, and Interpretation 102
5.5 Discussion and Commentary 104
5.6 Application Notes 105
5.7 Summary Points 107
Acknowledgments 108
Annotated References 108
Supplementary electronic materials and resources 108
CHAPTER 6
OsmolalityControl forMicrofluidicEmbryo Cell Culture Using Hybrid
Polydimethylsiloxane(PDMS)–ParyleneMembranes 109
6.1 Introduction 110
6.2 Experimental Design 111
6.2.1 Hypothesis 111
6.3 Materials 111
6.3.1 Reagents 111
6.3.2 Equipment 112
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Contents
6.4 Methods 112
6.4.1 PDMS-Parylene-PDMSmembrane preparation 112
6.4.2 Preparation of glass slides and bonding to hybrid membranes 113
6.4.3 Embryo preparation 114
6.4.4 Osmolalitymeasurements 114
6.5 Data Acquisition, Anticipated Results, and Interpretation 116
6.6 Discussion and Commentary 118
6.7 Application Notes 122
6.8 Summary Points 124
Acknowledgments 125
References 126
CHAPTER 7
Image-Based Cell Sorting UsingMicroscaleElectrical and Optical Actuation 129
7.1 Introduction 130
7.1.1 Electrical and opticalmicroscalecell manipulation 131
7.2 Materials 134
7.2.1 Materials formicrofabrication 134
7.2.2 Cell lines and culture 134
7.2.3 Buffers and reagents 135
7.2.4 Staining 135
7.2.5 Equipment 135
7.3 Experimental Design 135
7.4 Methods 136
7.4.1 Material choices and fabrication 136
7.4.2 Packaging and experimental setup 139
7.5 Data Acquisition, Anticipated Results, and Interpretation 142
7.5.1 Cell culture and assay 142
7.5.2 Imaging and sorting 144
7.6 Discussion and Commentary 146
7.7 Summary Points 147
Acknowledgments 147
References 147
CHAPTER 8
Pharmacokinetic-PharmacodynamicModels on a Chip 149
8.1 Introduction 150
8.2 Pharmacokinetic-PharmacodynamicModeling 151
8.2.1 Basic concept 151
8.2.2 Pharmacokineticmodel 152
8.2.3 Pharmacodynamicmodel 154
8.2.4 IntegratedPK-PDmodeling 159
8.3 Micro Cell Culture Analog ((cid:2)CCA) 160
viii
Contents
8.3.1 Design of aμCCAand calculation of flow rates 164
8.3.2 Fabrication of aμCCA 165
8.3.3 Cell seeding and assembly of the device 167
8.3.4 Data acquisition, anticipated results, and interpretation 170
8.3.5 Discussion and commentary 171
8.4 Application Notes 178
8.5 Summary Points 179
Acknowledgments 180
References 180
CHAPTER 9
Lab-on-a-Chip Impedance Detection of Microbial and Cellular Activity 185
9.1 Introduction 186
9.2 Lab-on-a-Chip for Monitoring Microbial Metabolic Activity 187
9.2.1 “Impedance microbiology-on-a-chip” for bacterial
concentration and detection 187
9.2.2 Microfluidicbiochipsfor impedance detection ofBacillus
anthracisspore germination 192
9.3 Lab-on-a-Chip for Impedance Detection of Cell Concentration
Based on Ion Release from Cells 197
9.3.1 Microchips for impedance detection of CD4+ T lymphocytes 197
9.3.2 Interdigitatedmicroelectrodechip for impedance detection
of bacterial cells 202
9.4 Conclusion 207
9.5 Summary Points 208
Acknowledgments 208
References 209
CHAPTER 10
Controlling the CellularMicroenvironment 211
10.1 Introduction 212
10.2 MicroenvironmentalControl of Cell-Cell Interactions 213
10.2.1 Surface patterning for cellcoculture 213
10.2.2 Microfluidicsystems for cardiacorganoidformation 216
10.2.3 3-D patterning of embryonic stem cells 220
10.3 Interactive Use of Substrate Topography and Electrical Stimulation
for the Control of Cell Alignment 223
10.3.1 Materials 224
10.3.2 Methods 224
10.3.3 Data acquisition, anticipated results, and interpretation 228
10.3.4 Discussion and commentary 230
10.3.5 Summary points 233
Acknowledgments 233
References 233
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