Cell Analysis on Microfluidics (eBook)

Professor Jin-Ming Lin was born in 1963. He received his Bachelor of Science degree at Fuzhou University in 1984 and his PhD in analytical chemistry at Tokyo Metropolitan University, Japan in 1997. He studied and worked at Showa University, Japan and Tokyo Metropolitan University from 1992 to 2002. He was a professor at the Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences from 2002 to 2004, and has been a professor at Tsinghua University, China since 2004 and was selected as Cheung Kung Scholars Professor of Ministry of Education, China at 2008. He is a Fellow of Royal Chemical Society. He is a general secretary and deputy chair of Mass Spectrometry Committee, Chinese Chemical Society, a vice president Chinese Society of Mass Spectrometry, and a member of the council of the Chinese Society for Chromatography Science. He received several awards for his contributions in chemiluminescence and separation science: Outstanding Young Chemist Award (Chinese Chemical Society, 1992), Young Analyst Award for Flow Injection Analysis (Flow Injection Section, Japan Society of Analytical Chemistry, 2000), Kanton New Century Award (Japan Society of Analytical Chemistry, 2001), National Science Fund for Distinguished Young Scholars of China (National Natural Science Foundation of China, 2002), FIA Award for Science (Flow Injection Section, Japan Society of Analytical Chemistry, 2008), GC Contribution Award (GC Discussion Group, Japan Society of Analytical Chemistry, 2008, 2013), CAIA Awards (China Association for Instrumental Analysis, 2009, 2010 and 2015), Science and Censorship Award (General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China, 2010), Award for Science and Technology(Beijing City, 2013), Natural Science Award (Ministry of Education, China, 2015), Liang Shuquan Award for Analytical Chemistry (Chinese Chemical Society, 2015), and Silver Prize from The 10th Race Award for Innovation and Creative Patents (The Innovation Association of Beijing City, China, 2016). His current research is focused on sample pretreatment, chemiluminescence and microfluidic devices. He is the author and co-author of 388 original research papers published in international journals, 32 reviews, 4 books and 45 patents.

Preface 6
Contents 10
1 Design and Preparation of Microfluidics Device 12
Abstract 12
1.1 Introduction 12
1.2 Development of Microfluidic Chip Material 16
1.2.1 Inorganic Material in Chip Preparation 17
1.2.2 Silicon Elastomer 20
1.2.3 Thermoset and Thermoplastic Materials 21
1.2.4 Hydrogel Material 22
1.2.5 Paper Based Microfluidic Devices 22
1.2.6 Hybrid Material Chip 25
1.3 Chip Fabrication 26
1.3.1 Soft Lithography 26
1.3.2 Fabrication of Extended-Nano Channels 27
1.3.3 3D Printing Technology 28
1.3.3.1 Stereolithography 28
1.3.3.2 Fused Deposition Method 30
1.4 Integration of Microfluidics Functional Units 31
1.4.1 Flow Manipulation: Micropump, Microvalve and Mixer 31
1.4.2 Concentration Gradient Generator 33
1.4.3 Cell Culture Chamber 35
1.4.4 Integrated Biosensors 35
1.4.4.1 Enzyme Catalyzed Biosensor 35
1.4.4.2 Immune Sensor 36
1.4.5 Microfluidic Centrifuge Device 37
1.5 Development and Outlooks 38
1.5.1 Point of Care (POC) 38
1.5.2 Implantable Device 40
1.5.3 Smart Mobile Device 41
References 42
2 Recent Development of Cell Analysis on Microfludics 54
Abstract 54
2.1 Introduction 54
2.2 Cell Culture 56
2.2.1 3D Cell Culture 56
2.2.2 Cell Co-culture 57
2.2.3 Tissues/Organs-on-Chips 59
2.3 Cell Manipulation 60
2.3.1 Microstructures 60
2.3.2 Free-Flow Manipulation 61
2.3.3 Electrokinetic Operations 62
2.4 Cell Stimulation 63
2.4.1 Flow Control 64
2.4.2 Gradient Generation 65
2.4.3 Mechanical Stimuli 67
2.5 Cell Analysis 69
2.5.1 Sample Preparation 70
2.5.1.1 Cell Sorting 70
2.5.1.2 Cell Lysis 73
2.5.1.3 Sample Separation 75
2.5.2 Cell Analysis 78
2.5.2.1 Cell Morphology and Movement 78
2.5.2.2 Genetic Analysis 80
2.5.2.3 Protein Analysis 82
2.5.2.4 Metabolite Analysis 86
2.6 Conclusion and Perspective 87
References 88
3 Microfluidic Cell Isolation and Recognition for Biomedical Applications 105
Abstract 105
3.1 Introduction 105
3.2 Physical Approaches for Cell Isolation in Microfluidics 107
3.2.1 Microfabricated Structures for Cell Trap 107
3.2.2 Hydrodynamic Force for Cell Separation 109
3.2.3 Surface Acoustic Wave-Based Cell Isolation 110
3.2.4 Dielectrophoresis-Based Cell Sorting 111
3.3 Affinity-Based Cell Isolation in Microfluidics 113
3.3.1 Antibody-Based Cell Recognition 113
3.3.2 Aptamer-Specific Cell Capture 114
3.3.3 Cell Capture on Bio-Nano-Interfaces 115
3.4 Recent Technologies for Biomedical Applications 117
3.4.1 CTCs Isolation, Recognition and Detection 117
3.4.2 Cell-Based Biological Assays 119
3.4.3 Stem Cell Purification and Screening 119
3.5 Conclusion and Future Perspective 121
References 122
4 Cell Culture and Observation on Microfluidics 129
Abstract 129
4.1 Introduction 129
4.2 Types of Cell Culture 130
4.2.1 Two-Dimensional (2D) Culture 131
4.2.2 Three-Dimensional (3D) Culture 132
4.3 Cell Manipulation 134
4.4 Cellular Microenvironment Control 136
4.4.1 Gradient of Physical Factors 136
4.4.2 Gradient of Chemical Factors 139
4.4.3 Cell-Cell and Cell-Extracellular Matrix (ECM) Interactions 140
4.5 Non-destructive Observation Methods on Microfluidic Devices 142
4.5.1 Optical Methods 144
4.5.2 Electrochemical Methods 145
4.6 Applications in Cellular Biology and Metabolomics 146
4.6.1 Signal Transduction 146
4.6.2 Gene Expression 148
4.6.3 Metabolic Function Analysis 148
4.7 Perspectives 149
References 149
5 Cell Migration with Microfluidic Chips 158
Abstract 158
5.1 Introduction 158
5.2 Microfluidic-Based Chemotaxis Research 163
5.2.1 Microfluidic Gradient Generator 163
5.2.1.1 Convective Flow-Based Microfluidic Gradient Generator 164
5.2.1.2 Diffusion-Based Microfluidic Gradient Generator 167
5.2.2 Convective Flow- and Diffusion-Based Cell Chemotaxis Study 173
5.2.2.1 Convective Flow-Based Cell Chemotaxis Study 173
5.2.2.2 Diffusion-Based Cell Chemotaxis Study 176
5.3 Microfluidic-Based Electrotaxis Research 177
5.3.1 Microfluidic-Based Electrotaxis Research in Single Electric Field 179
5.3.2 Microfluidic-Based Electrotaxis Research in Multiple Electric Field 180
5.4 Conclusions 181
References 182
6 Biomaterial-Based Microfluidics for Cell Culture and Analysis 189
Abstract 189
6.1 Introduction 189
6.2 Materials of Making Microfluidic Chips 190
6.2.1 Inorganic Materials 190
6.2.2 Polymeric Materials 192
6.2.2.1 Plastics 192
6.2.2.2 Elastomers 194
6.2.3 Hydrogels and Papers 195
6.2.3.1 Hydrogels 195
6.2.3.2 Papers 196
6.3 Cell Culture 197
6.3.1 Plane Cell Culture 198
6.3.2 3D Cell Culture 201
6.4 Organ-on-Chip System 206
6.5 Simulation and Manipulation of Cell Microenvironment on Chips 210
6.6 On-Chip Cell Observation 212
6.6.1 Cell Immobilization 213
6.6.2 Cell Imaging 215
6.7 On-Chip Cell Analysis 217
6.7.1 Population Cell Analysis 217
6.7.2 Single Cell Analysis 219
6.7.3 Chip-MS Technology 221
6.8 Summary 224
References 225
7 Droplet-Based Microfluidic Technology for Cell Analysis 233
Abstract 233
7.1 Introduction 233
7.2 Principles of Droplet Generation 238
7.2.1 Surface Tension ? 238
7.2.2 Dimensionless Numbers 239
7.3 Methods for Droplet Generation 240
7.3.1 T-junction 241
7.3.2 Flow Focusing Structure 241
7.3.3 Co-flowing Structure 243
7.3.4 Other Methods 243
7.4 Analytical Methods in Droplet Microfluidic 244
7.4.1 Fluorescence 244
7.4.2 Mass Spectrometry (MS) 246
7.4.3 Electrochemical Detection and Capillary Electrophoresis 248
7.4.4 Other Methods 248
7.5 Single Cell Analysis 249
7.5.1 Encapsulation of Single Cells 249
7.5.2 Droplet Sorting 251
7.5.3 Protein Analysis 254
7.5.4 Single Cell PCR 255
7.6 Cell Manipulation 256
7.7 Summary and Prospect 259
References 261
8 Single Cell Analysis on Microfluidic 271
Abstract 271
8.1 Introduction 271
8.1.1 Lab on a Chip 271
8.1.2 Single Cell Analysis and Microfluidic 272
8.2 Tissue Dissociation 273
8.2.1 Conventional Approaches of Tissue Dissociation 273
8.2.2 Tissue Dissociation on Microfluidic 274
8.3 Cell Sorting 275
8.3.1 Conventional Approaches of Cell Sorting 275
8.3.2 Cell Sorting on Microfluidic 275
8.3.2.1 Electrophoresis and Dielectrophoresis 276
8.3.2.2 Electro-Osmotic Flow 277
8.3.2.3 Acoustic 277
8.3.2.4 Optical 280
8.3.2.5 Other Approaches 282
8.3.3 Outlook for Cell Sorting on Microfluidic 282
8.4 Single Cell Isolation 282
8.4.1 Conventional Approaches of Single Cell Isolation 282
8.4.2 Single Cell Isolation on Microfluidic 283
8.4.2.1 Valves 284
8.4.2.2 Dielectrophoretic 284
8.4.2.3 Microwells 285
8.4.2.4 Hydrodynamic 285
8.4.2.5 Droplets 287
8.5 Single Cell Lysis 288
8.5.1 Conventional Approaches of Single Cell Lysis 288
8.5.2 Single Cell Lysis on Microfluidic 289
8.5.2.1 Mechanical 289
8.5.2.2 Thermal 290
8.5.2.3 Chemical 290
8.5.2.4 Electrical 291
8.6 Single Cell Analysis 292
8.6.1 Single Cell Fluorescence Imaging 292
8.6.2 Single Cell Electrochemical Analysis 292
8.6.3 Single Cell Mass Spectrometry 293
8.7 Future Outlook 293
References 294
9 Microfluidics-Mass Spectrometry for Cell Analysis 299
Abstract 299
9.1 Introduction 299
9.2 Mass Spectrometer Interface 301
9.2.1 ESI Interface 302
9.2.2 MALDI Interface 304
9.3 On-Chip Sample Pretreatment 305
9.3.1 Sample Preconcentration 305
9.3.2 Sample Separation 307
9.4 Analytical Application 308
9.4.1 Proteomics 308
9.4.2 Metabolomics 309
9.4.3 Glycomics 311
9.4.4 Single Cell Analysis 312
9.5 Conclusion and Future Perspective 313
References 314
10 Biochemical Analysis Techniques Integrated on Microfluidic Chips and Their Applications 320
Abstract 320
10.1 Introduction 320
10.2 Biochemical Analysis Techniques Integrated on Chips 321
10.2.1 Optical Detector 321
10.2.2 Electronic Manipulation 324
10.2.3 Magnetic Operation 327
10.2.4 Surface Acoustic Wave 329
10.3 Applications 332
10.4 Genetic Analysis 332
10.5 Protein Analysis 335
10.6 Conclusions and Outlooks 338
References 338
11 Microfluidic Cell Culture Systems for Drug Research 346
Abstract 346
11.1 Introduction 347
11.2 Microfluidic Chip 347
11.2.1 Cell-Based Microfluidic Model Systems 348
11.2.2 3D Cell Culture in Microfluidic Chip 350
11.2.3 Organs on a Chip 352
11.2.3.1 Liver 354
11.2.3.2 Intestine 355
11.2.3.3 Lung 358
11.2.3.4 Vasculature 358
11.2.3.5 Kidney 361
11.2.3.6 Brain 361
11.2.3.7 Multi-Organ-on-a-Chip 361
11.2.4 Whole Organisms on a Chip 362
11.3 Chip-MS Platform 364
11.4 Application in Drug Research 366
11.4.1 Drug Delivery 367
11.4.2 Drug Metabolism and Toxicity 367
11.4.3 Oral Drug Pharmacokinetics System 368
11.4.4 Drug-Droplet Technology 370
11.5 Challenges and Prospects 371
References 372
12 Cell Metabolite Analysis on Microfluidic Platform 378
Abstract 378
12.1 Introduction 379
12.2 Models of Cell Culture on Microfluidic Platform 381
12.2.1 Cell Culture Models in Microfluidic Systems 381
12.2.1.1 2D Cell Culture 381
12.2.1.2 3D Cell Culture 383
12.2.1.3 Organ-on-Chip System 384
12.2.2 Controlling the Microenvironment In Vitro by Microfluidic Technology 385
12.2.2.1 Controlled Chemical Microenvironment 385
12.2.2.2 Controlled Mechanical Microenvironment 388
12.3 Strategy for Cell Metabolite Analysis on Microfluidic Platform 389
12.3.1 Sample Separation on Microfluidic Platform for Cell Metabolite Analysis 389
12.3.1.1 LC Technology 389
12.3.1.2 Droplet Technology 391
12.3.1.3 Microdialysis 391
12.3.1.4 Microchip Electrophoresis 392
12.3.2 Cell Metabolite Detection Systems 392
12.3.2.1 Antibody-Based Immunoassays for Cell Metabolite 393
12.3.2.2 Nucleic Acid-Based Biosensors for Cell Metabolite Analysis 395
12.3.2.3 Enzyme-Based Biosensors for Cell Metabolite Analysis 396
12.4 Application 396
12.4.1 Clinical Diagnostics 396
12.4.2 Drug Research and Development 397
12.4.3 Toxicology Study 398
12.5 Conclusions and Perspectives 399
References 399
13 Microfluidic Platforms for Microbial 404
Abstract 404
13.1 Introduction 404
13.2 Microbial Characteristics 406
13.2.1 Traditional Methods of Analysis and Research 407
13.2.2 New Technologies for the Study of Microorganisms 407
13.3 Basic Research Methods 409
13.3.1 Channel Culture 410
13.3.1.1 Diffusion Culture 410
13.3.1.2 Liquid Flow Culture 411
13.3.2 Chamber Culture 412
13.3.3 Agar Package 413
13.4 Single Cell Analysis 413
13.5 Applied Technology 415
13.5.1 Basic Sciences 415
13.5.2 Resistance Detection 417
13.5.3 Toxicity Test 417
13.5.4 Cancer Surveillance and Treatment 419
13.5.5 Microfluidic for Fuel Cell 419
13.5.6 Food-Brone Bacteria Detection 421
13.6 Opportunities and Challenges 422
References 424
Index 431