Microfluidics for biological applications

Microfluidics for Biological Applications provides researchers and scientists in the biotechnology, pharmaceutical, and life science industries with an introduction to the basics of microfluidics and also discusses how to link these technologies to various biological applications at the industrial and academic level. Readers will gain insight into a wide variety of biological applications for microfluidics.

The material presented here is divided into four parts, Part I gives perspective on the history and development of microfluidic technologies, Part II presents overviews on how microfluidic systems have been used to study and manipulate specific classes of components, Part III focuses on specific biological applications of microfluidics: biodefense, diagnostics, high throughput screening, and tissue engineering and finally Part IV concludes with a discussion of emerging trends in the microfluidics field and the current challenges to the growth and continuing success of the field.

Chapter 1 Introduction to Microfluidics	p. 1
Abstract	p. 1
1.1 Introduction to Microfluidics	p. 2
1.2 History of Microfluidics	p. 3
1.2.1 The beginning: Gas chromatography and capillary electrophoresis	p. 3
1.2.2 The microfluidic advantage	p. 5
1.2.3 Modular separation, reaction and hybridization systems	p. 7
1.2.4 Integrated systems	p. 8
1.3 Fluidics and Transport Fundamentals	p. 10
1.3.1 The continuum approximation	p. 10
1.3.2 Laminar flow	p. 10
1.3.3 Diffusion in microfluidic systems	p. 12
1.3.4 Surface forces and droplets	p. 14
1.3.5 Pumps and valves	p. 16
1.3.6 Electrokinetics	p. 16
1.3.7 Thermal management	p. 18
1.4 Device Fabrication	p. 18
1.4.1 Materials	p. 19
1.4.2 Fabrication and assembly	p. 20
1.5 Biological Applications	p. 21
1.5.1 Genetic analysis (DNA/RNA)	p. 22
1.5.2 Proteomics	p. 22
1.5.3 Cellular assays	p. 23
1.5.4 Drug delivery and compatibility	p. 24
1.6 The Future	p. 26
1.6.1 Potential demand/market for microfluidic devices	p. 26
1.6.2 Current products	p. 27
1.6.3 Challenges and the future	p. 28
References	p. 29
Chapter 2 Materials and Microfabrication Processes for Microfluidic Devices	p. 35
Abstract	p. 35
2.1 Introduction	p. 36
2.2 Silicon Based Materials	p. 37
2.2.1 Micromachining of silicon	p. 39
2.2.2 Bulk micromachining	p. 39
2.2.3 Surface micromachining	p. 46
2.3 Glass Based Materials	p. 49
2.3.1 Microfabrication in glass	p. 51
2.4 Wafer Bonding	p. 56
2.4.1 Fusion bonding	p. 57
2.4.2 Anodic bonding	p. 57
2.4.3 Adhesive bonding	p. 58
2.5 Polymers	p. 59
2.5.1 Microfabrication	p. 59
2.5.2 Polymer materials	p. 64
2.6 Conclusion	p. 82
References	p. 82
Chapter 3 Interfacing Microfluidic Devices with the Macro World	p. 93
Abstract	p. 93
3.1 Introduction	p. 94
3.2 Typical Requirements for Microfluidic Interfaces	p. 94
3.3 Review of Microfluidic Interfaces	p. 95
3.3.1 World-to-chip interfaces	p. 95
3.3.2 Chip-to-world interfaces	p. 103
3.4 Future Perspectives	p. 112
References	p. 113
Chapter 4 Genetic Analysis in Miniaturized Electrophoresis Systems	p. 117
Abstract	p. 117
4.1 Introduction	p. 118
4.1.1 Status of genetic analyses	p. 118
4.1.2 Genetic analysis by miniaturized electrophoresis system	p. 119
4.2 Microchip Electrophoresis for Genomic Analysis	p. 122
4.2.1 Material and fabrication of electrophoresis microchips	p. 123
4.2.2 Theory of gel electrophoresis of DNA	p. 125
4.2.3 Gel matrices	p. 126
4.2.4 Novel DNA separation strategies on microchips	p. 130
4.2.5 Surface coating methods for microchannel walls	p. 134
4.3 Parallelization in Microchip Electrophoresis	p. 137
4.4 Integration in Microchip Electrophoresis for Genetic Analysis	p. 139
4.4.1 Sample preparation on microchip	p. 139
4.4.2 System integration	p. 141
4.5 Commercial Microfluidic Instruments for Genetic Analyses	p. 144
4.5.1 Commercial microchip electrophoresis instruments for genetic analysis	p. 145
4.5.2 Integrated microfluidic instruments for genetic analyses	p. 147
4.6 Microfluidic Markets and Future Perspectives	p. 150
References	p. 151
Chapter 5 Microfluidic Systems for Protein Separations	p. 165
Abstract	p. 165
5.1 Introduction	p. 166
5.1.1 Advantages of microfluidic chips for protein separations	p. 166
5.1.2 Limitations of microfluidic chips in proteomics applications	p. 167
5.1.3 Substrates used for proteomic analysis	p. 167
5.2 Microfluidic Chips for Protein Separation	p. 168
5.2.1 Microchip-based electrophoretic techniques	p. 169
5.2.2 Microchip chromatography	p. 172
5.3 Integrated Analysis in Microchips	p. 175
5.3.1 Integration of sample preparation with analysis	p. 175
5.3.2 Multi-dimensional separation in microchips	p. 177
5.3.3 Chips integrated with mass spectrometry	p. 180
5.4 Future Directions	p. 180
References	p. 181
Chapter 6 Microfluidic Systems for Cellular Applications	p. 185
Abstract	p. 185
6.1 Introduction	p. 186
6.1.1 Physiological advantages	p. 188
6.1.2 Biological advantages	p. 189
6.1.3 Economical advantages	p. 191
6.2 Microfluidic Technology for Cellular Applications	p. 191
6.2.1 Microfluidic cell isolation/separation	p. 191
6.2.2 Microfluidic cell culture	p. 200
6.2.3 Microfluidic cell analysis	p. 208
6.3 Commercialization of Microfluidic Technology	p. 211
6.4 Concluding Remarks	p. 214
References	p. 215
Chapter 7 Microfluidic Systems for Engineering Vascularized Tissue Constructs	p. 223
Abstract	p. 224
7.1 Introduction	p. 224
7.2 Generating 2D Vascularized Tissue Constructs Using Microfluidic Systems	p. 226
7.3 Generating 3D Vascularized Tissue Constructs Using Microfluidic Systems	p. 230
7.4 Hydrogel-based Microfluidic Systems for Generating Vascularized Tissue Constructs	p. 232
7.5 Mathematical Modeling to Optimize the Microfluidic Systems for Generating Vascularized Tissue Constructs	p. 235
7.6 Future Challenges	p. 237
7.7 Conclusions	p. 237
References	p. 237
Chapter 8 High Throughput Screening Using Microfluidics	p. 241
Abstract	p. 241
8.1 Introduction	p. 242
8.2 Cell-Based Assays	p. 244
8.2.1 High throughput cell culture	p. 245
8.2.2 Cell sorting for high throughput applications	p. 252
8.3 Biochemical Assays	p. 254
8.3.1 PCR	p. 254
8.3.2 Electrophoresis	p. 255
8.3.3 Others	p. 255
8.4 Drug Screening Applications	p. 258
8.5 Users and Developers of [mu]F HTS Platforms	p. 259
8.5.1 Users: Research labs, academic screening facilities, and pharmaceutical	p. 260
8.5.2 Commercialized products in HTS	p. 261
8.6 Conclusion	p. 262
8.7 Acknowledgements	p. 263
References	p. 263
Chapter 9 Microfluidic Diagnostic Systems for the Rapid Detection and Quantification of Pathogens	p. 271
Abstract	p. 271
9.1 Introduction	p. 272
9.1.1 Infectious pathogens and their prevalence	p. 272
9.1.2 Traditional pathogen detection methods	p. 274
9.1.3 Microfluidic techniques	p. 276
9.2 Review of Research	p. 277
9.2.1 Pathogen detection/quantification techniques based on detecting whole cells	p. 277
9.2.2 Pathogen detection/quantification techniques based on detecting metabolites released or consumed	p. 294
9.2.3 Pathogen detection/quantification through microfluidic immunoassays and nucleic acid based detection platforms	p. 297
9.3 Future Research Directions	p. 305
References	p. 307
Chapter 10 Microfluidic Applications in Biodefense	p. 323
Abstract	p. 323
10.1 Introduction	p. 324
10.2 Biodefense Monitoring	p. 326
10.2.1 Civilian biodefense	p. 326
10.2.2 Military biodefense	p. 328
10.3 Current Biodefense Detection and Identification Methods	p. 330
10.3.1 Laboratory detection	p. 331
10.3.2 Field detection	p. 332
10.4 Microfluidic Challenges for Advanced Biodefense Detection and Identification Methods	p. 333
10.5 Microscale Sample Preparation Methods	p. 335
10.5.1 Spore disruption	p. 336
10.5.2 Pre-separations	p. 336
10.5.3 Nucleic acid purifications	p. 337
10.6 Immunomagnetic Separations and Immunoassays	p. 339
10.6.1 Immunomagnetic separations	p. 340
10.6.2 Immunoassays	p. 341
10.7 Proteomic Approaches	p. 345
10.8 Nucleic Acid Amplification and Detection Methods	p. 346
10.8.1 PCR and qPCR detection of pathogens for biodefense	p. 347
10.8.2 Miniaturized and Microfluidic PCR	p. 348
10.8.3 Heating and cooling approaches	p. 349
10.8.4 Miniaturized PCR and qPCR for biodefense	p. 350
10.8.5 Other Nucleic acid amplification methods	p. 351
10.9 Microarrays	p. 352
10.9.1 Microarrays and microfluidics	p. 353
10.10 Microelectrophoresis and Biodefense	p. 354
10.10.1 Microelectrophoresis technologies	p. 356
10.11 Integrated lab-on-a-chip systems and biodefense	p. 358
10.11.1 Full microfluidic integration for biodefense	p. 363
10.12 Summary and Perspectives	p. 363
References	p. 365
Chapter 11 Current and Future Trends in Microfluidics within Biotechnology Research	p. 385
Abstract	p. 385
11.1 The Past - Exciting Prospects	p. 386
11.2 The Present - Kaleidoscope-like Trends	p. 388
11.2.1 Droplet microfluidics	p. 389
11.2.2 Integrating Active Components in Microfluidics	p. 391
11.2.3 Third world - paper microfluidics - George Whitesides	p. 394
11.2.4 Microfluidic solutions for enhancing existing biotechnology platforms	p. 395
11.2.5 Microfluidics for cell biology - seeing inside the cell with molecular probes	p. 400
11.2.6 Microfluidics for cell biology - high throughput platforms	p. 401
11.3 The Future - Seamless and Ubiquitous MicroTAS	p. 403
References	p. 405
Index	p. 413

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