Bio-MEMS: Technologies and Applications

✍ Scribed by Wanjun Wang, Steven A. Soper

• Publisher: CRC Press
• Year: 2006
• Tongue: English
• Leaves: 463
• Edition: 1
• Category: Library

✦ Synopsis

Microelectromechanical systems (MEMS) are evolving into highly integrated technologies for a variety of application areas. Add the biological dimension to the mix and a host of new problems and issues arise that require a broad understanding of aspects from basic, materials, and medical sciences in addition to engineering. Collecting the efforts of renowned leaders in each of these fields, BioMEMS: Technologies and Applications presents the first wide-reaching survey of the design and application of MEMS technologies for use in biological and medical areas. This book considers both the unique characteristics of biological samples and the challenges of microscale engineering. Divided into three main sections, it first examines fabrication technologies using non-silicon processes, which use materials that are appropriate for medical/biological analyses. These include UV lithography, LIGA, nanoimprinting, injection molding, and hot-embossing. Attention then shifts to microfluidic components and sensing technologies for sample preparation, delivery, and analysis. The final section outlines various applications and systems at the leading edge of BioMEMS technology in a variety of areas such as genomics, drug delivery, and proteomics. Laying a cross-disciplinary foundation for further development, BioMEMS: Technologies and Applications provides engineers with an understanding of the biological challenges and biological scientists with an understanding of the engineering challenges of this burgeoning technology.

✦ Table of Contents

Bio-Mems: Technologies and Applications......Page 1
Table of Contents......Page 3
Preface......Page 5
About the Editors......Page 7
Contributors......Page 9
CONTENTS......Page 11
1.1.1 Microfabrication Technologies......Page 14
1.1.2 Microfluidic Devices and Components for Bio-MEMS......Page 15
1.1.3 Sensing Technologies and Bio-MEMS Applications (Chapters 10, 11, 12, 13, 14, 15, and 16)......Page 16
1.2 Suggestions for Using This Book as a Textbook......Page 17
Part I: Basic Bio-MEMS Fabrication Technologies......Page 18
CONTENTS......Page 19
2.1 Introduction......Page 20
2.2.1 Diffraction Caused by Air Gap and Wavelength Dependence of the UV Absorption Rate of SU-8......Page 21
2.2.2 Numerical Analysis of Diffraction and the Absorption Spectrum on UV Lithography of Ultrathick SU-8 Resist......Page 23
2.2.3 Development with One-Direction Agitation Force......Page 28
2.3 Experimental Results Using Filtered Light Source and Air Gap Compensation for Diffraction......Page 29
2.4.1 Pretreat for the Substrate......Page 33
2.4.2 Spin-Coating SU-8......Page 34
2.4.3 Soft Bake......Page 35
2.4.4 Exposure......Page 36
2.4.6 Development......Page 37
2.5 Tilted Lithography of SU-8 and Its Application......Page 38
2.5.1 Micromixer/Reactor......Page 40
2.5.2 Three-Dimensional Hydrofocus Component for Microcytometer......Page 42
2.5.3 Out-of-Plane Polymer Refractive Microlens, Microlens Array, Fiber Bundle Aligner......Page 45
References......Page 48
CONTENTS......Page 51
3.1 The LIGA Process: A Brief History......Page 52
3.2 The LIGA Process: A Brief Introduction......Page 53
3.3.1 Synchrotron Light, Beamlines, and Scanner......Page 54
3.3.2 X-Ray Mask......Page 57
3.3.3 Resist Application and X-Ray Exposure......Page 60
3.4 High-Aspect-Ratio LIGA Structures......Page 64
3.4.1.1 Basic Principle of Electrodeposition......Page 67
3.4.1.1.1 Galvanostatic and Potentiostatic Plating......Page 68
3.4.1.2 Electroplating Rate and Calculation of the Deposition Thickness......Page 69
3.4.1.2.1 Surface Uniformity of Electroplated Metals......Page 70
3.4.2 Nickel Electroplating and Solutions......Page 71
3.4.3.1.1 Current Density......Page 72
3.4.3.1.5 Filtration......Page 73
3.5 Molding of LIGA Microstructures......Page 74
3.6 Application of LIGA Microstructures......Page 78
3.6.1 Mold Insert Fabrication......Page 79
3.6.2.1 Safety-and-Arming Switch......Page 80
3.6.2.2 Nanobarcodes......Page 82
3.6.2.3 Harmonic Drive® Microgears......Page 83
3.6.2.4 Polymer Chips for Bio-MEMS Applications......Page 84
3.6.2.5 Regenerators for Cryocoolers and Stirling Cycle Heat Engines......Page 85
3.6.2.6 Examples of Precision Parts (HT Micro)......Page 87
3.7 Summary......Page 90
Acknowledgment......Page 91
References......Page 92
CONTENTS......Page 100
4.1 Introduction......Page 101
4.2.1 NIL Process......Page 102
4.2.2 Polymer Flow during NIL......Page 104
4.2.3 Biocompatibility of the Resist......Page 107
4.2.4 Stamps with Nanostructures......Page 108
4.2.5 Antiadhesive Layer Coating......Page 109
4.3.1 Nanofluidic Devices......Page 110
4.3.2 Engineering Nanopores......Page 112
4.3.3 Chemical Nanopatterning......Page 114
4.3.4 Protein Nanopatterning......Page 116
4.4 Outlook......Page 118
References......Page 119
5.1 Introduction......Page 123
5.2.1 Material Properties......Page 126
5.2.2 Polymethylmethacrylate and Polycarbonate......Page 127
5.2.3 Cyclic Olefin Copolymer......Page 128
5.3.1 Micromachining Methods......Page 130
5.3.2 Bulk Micromachining......Page 131
5.3.3 Surface Micromachining......Page 133
5.4.1 Conventional Hot Embossing Process......Page 136
5.4.2 Examples of Embossed Structures......Page 138
5.4.3 Hot Embossing with Polymer Masters......Page 140
5.5 Conclusions......Page 143
References......Page 144
Part II: Microfluidic Devices and Components for Bio-MEMS......Page 147
CONTENTS......Page 148
6.1 Introduction......Page 149
6.2 Background......Page 150
6.3 Fabrication Processes......Page 153
6.4.1.2 Electromagnetic Actuation......Page 155
6.4.1.3 Piezoelectric Actuation......Page 156
6.4.1.8 Thermopneumatic Actuation......Page 158
6.4.2 Positive Displacement Pumps......Page 159
6.4.2.1 Positive Displacement Pumps with Integrated Check Valves......Page 160
6.4.3 Fixed-Geometry Rectification Micropumps......Page 161
6.4.4 Peristaltic Pumps......Page 167
6.4.5 Acoustic Streaming......Page 169
6.5.1 Electroosmotic Flow Micropumps......Page 171
6.5.2 Electrowetting......Page 173
6.5.3 Marangoni Pumps......Page 174
6.5.4 Buoyancy-Driven Flows......Page 176
References......Page 177
7.1 Introduction......Page 181
7.2 Some Basic Considerations......Page 182
7.3.1 Pressure-Driven Passive Micromixers......Page 185
7.3.2 Electrically Driven Passive Micromixers......Page 189
7.4 Active Micromixers......Page 192
7.5 Multiphase Micromixers......Page 195
7.6 Performance Metrics for Microscale Mixer Design and Evaluation......Page 196
7.7 Design Methodology for Optimal Diffusion-Based Micromixers for Batch Production Applications......Page 199
References......Page 210
CONTENTS......Page 216
8.2 Sample Extraction and Concentrations......Page 217
8.2.1 Solid-Phase Extraction Techniques on Microchips......Page 218
8.2.3 Field-Amplified Injection on Microchips......Page 221
8.2.5 Isotachophoresis for Sample Preconcentration......Page 222
8.3.1 Labeling and Complexation on Microchips......Page 223
8.3.2 Postcolumn Reactors for Derivatization......Page 224
8.3.3 Precolumn Reactor Derivatization......Page 225
8.3.4 Postcolumn Reactors for Chemiluminescence on Microchips......Page 226
8.4.1 Microfabricated Single-Stage Microdialysis Device for Fast Desalting of Biological Samples......Page 227
8.4.2 Microfabrcated Dual-Stage Microdialysis Device for Rapid Fractionation and Cleanup of Complex Biological Samples......Page 230
8.4.3 Application to Complex Cellular Samples......Page 233
Acknowledgments......Page 235
References......Page 236
9.1 Conventional Cytometers......Page 239
9.2 Microflow Cytometers......Page 242
9.2.1.1 Hydrodynamic Focusing......Page 243
9.2.1.2 Small Constriction......Page 247
9.2.1.3 Dielectrophoretic Focusing......Page 248
9.2.2.1 Optical Detection......Page 257
9.2.2.2 Impedance Detection......Page 258
9.2.3 Sorting and Counting......Page 260
References......Page 261
Part III: Sensing Technologies for Bio-MEMS Applications......Page 265
CONTENTS......Page 266
10.1 Introduction......Page 267
10.3 Historical Development......Page 268
10.4 Instrumental Development......Page 269
10.5.1 Off-Chip Detection......Page 271
10.5.2 Microfabricated Electrodes......Page 273
10.5.3 Other Electrode Configurations......Page 274
10.6.1 Amperometry......Page 276
10.6.2 Pulsed Electrochemical Detection......Page 278
10.6.3 Conductivity......Page 279
10.7 Dual Electrochemical Detection and ECD Coupled to Other Detection Modes......Page 282
10.8 Decouplers......Page 283
10.9 Electrode Materials and Designs......Page 284
10.9.1 Thin-Film Metallic Electrodes......Page 285
10.9.2 Carbon Electrodes......Page 286
References......Page 289
11.1 Introduction......Page 299
11.2 Culture-Based Approach......Page 301
11.3.1 Paraffins......Page 303
11.3.2 Paraffin Deposition......Page 305
11.3.3 Paraffin Patterning......Page 306
11.4 Testing of Paraffin Surfaces with Microorganisms......Page 311
11.5.1 Microchannel Fabrication......Page 315
11.5.2 Adhesive Bonding......Page 317
11.5.3 Challenging Biochip with Mycobacteria......Page 318
References......Page 320
12.1 Introduction......Page 324
12.2 Human Skin and Microneedles......Page 325
12.3 In-Plane Silicon Microneedles......Page 327
12.4 In-Plane Metallic Microneedles......Page 330
12.5 Out-of-Plane Silicon Microneedles......Page 332
12.6 Out-of-Plane Metallic and Polymeric Microneedles......Page 337
12.7 Mechanical Robustness of the Microneedles......Page 339
12.8 Microreservoir Devices for Drug Delivery......Page 343
References......Page 345
13.1 Introduction......Page 348
13.2 Optimization of DNA Sequencing Separations......Page 349
13.3 Parallel DNA Separations in Microchips......Page 352
13.4 Integrated Microchips for DNA Analysis......Page 355
13.5 Phase-Changing Sacrificial Layers for Polymer Microchip Fabrication......Page 356
13.6 Conclusions......Page 358
References......Page 359
14.1 Introduction......Page 362
14.2.1 Peptide and Protein Microarrays......Page 364
14.2.2 Immunoassays......Page 365
14.3.1 Overview of Proteomics Methodologies......Page 369
14.3.2.1 One-Dimensional Analyte Separations......Page 370
14.3.2.2 Two-Dimensional Analyte Separations......Page 371
14.3.2.3 Modifications to Fluidic Networks......Page 372
14.3.2.4 Sample Purification and Preconcentration......Page 375
14.3.2.5 Bio-MEMS-Compatible Enzyme Reactors......Page 378
14.4 Integrated Bio-MEMS Approaches in Proteomics......Page 379
14.4.1 Integrated High-Throughput Devices Using MALDI-MS......Page 380
14.4.2 Integrated High-Throughput Devices Using ESI-MS......Page 381
14.5 Summary......Page 382
References......Page 383
15.1.1 What Is a Cell?......Page 390
15.1.2 The Molecular Makeup of Cells......Page 393
15.1.3 Single-Molecule Analysis......Page 394
15.1.4 Why Analyze Single Cells or Single Molecules?......Page 396
15.2 Single-Cell Analysis Using Microfluidic Devices......Page 397
15.2.1 Cell Sorting and Capture......Page 398
15.2.2 Cell Lysis......Page 401
15.2.3 Cellular Physiology and Signaling......Page 404
15.2.4 Molecular Analysis of Cells......Page 411
15.2.5 Organelle Manipulation in Microfluidics......Page 418
15.3 Single-Molecule Detection in Microfluidic Devices......Page 421
15.3.1 DNA Fragment Sizing......Page 422
15.3.2 Sequencing of Single DNA Molecules......Page 426
15.3.3 Other SMD Bioassays On-Chip......Page 427
15.3.4 Submicrometer-Sized Fluidic Channels......Page 429
15.3.5 Selection of the Right Substrate Material for SMD......Page 432
References......Page 434
16.1 Advantages of the Microworld for Pharmaceutical and Biomedical Analysis......Page 441
16.2 Basic Components of Bio-MEMS and Lab-on-a-Chip Devices for Pharmaceutical Analysis......Page 442
16.3 Challenges of Pharmaceutical Bio-MEMS......Page 446
16.4.1 Clinical Chemistry......Page 447
16.4.2 Therapeutic Drug Monitoring......Page 453
16.4.3 High-Throughput Screening......Page 455
16.5 Conclusion......Page 457
References......Page 458