Integrated microfabricated biodevices : advanced technologies for genomics, drug discovery, bioanalysis, and clinical diagnostics

INTEGRATED MICROFABRICATED BIODEVICES: Advanced Technologies for Genomics, Drug Discovery, Bioanalysis, and Clinical Diagnostics......Page 1
Preface......Page 3
Contributors......Page 8
Contents......Page 5
1.1 INTRODUCTION......Page 11
1.2 CREATING MICROSTRUCTURES IN GLASS MICROCHIPS......Page 14
1.3 DIAGNOSTICALLY RELEVANT SEPARATIONS ON A MICROCHIP......Page 15
1.4 EXECUTING MULTICHANNEL SEPARATIONS ON MICROCHIPS......Page 21
1.5 INTEGRATING FUNCTIONALITY......Page 27
1.5.1 Cell Sorting......Page 30
1.5.2 Flow Control and Microreactors......Page 31
1.5.3 Amplification......Page 34
1.5.4 Purification/Extraction......Page 40
REFERENCES......Page 42
2.1 INTRODUCTION......Page 45
2.2 DESCRIPTION OF DEVICES......Page 46
Electrokinetics......Page 48
Surface Tension and Capillary Action......Page 51
2.3.2 Mixing......Page 52
2.3.3 Chip Length Scales......Page 54
2.4.1 Enzyme Assays......Page 55
2.4.2 Immunoassays......Page 58
2.4.4 PCR......Page 59
2.6 MICROFLUIDIC VERSUS ARRAY TECHNOLOGIES......Page 61
REFERENCES......Page 62
3.1 INTRODUCTION......Page 65
3.2 MICROFABRICATION......Page 66
3.3 MICRODEVICE DESIGN......Page 69
3.4 INSTRUMENTATION AND DEVICE OPERATION......Page 72
3.5 STR GENOTYPING APPLICATIONS......Page 75
REFERENCES......Page 79
4.2 CURRENT CHALLENGES......Page 81
4.3 CONVENTIONAL ORGANIC EXTRACTION......Page 82
4.4 CHROMATOGRAPHIC METHODS......Page 83
4.5 ANION EXCHANGE CHROMATOGRAPHY......Page 84
4.6 SILICA-BASED METHODS......Page 85
4.7 PLASMID DNA......Page 86
4.8 GENOMIC DNA TEMPLATES FOR PCR......Page 87
4.9 BLOOD AND BODY FLUID SAMPLES......Page 89
4.11 PLANT MATERIAL......Page 90
4.12 PCR FRAGMENTS......Page 91
4.13 AUTOMATION......Page 92
4.14 DNA QUALITY FOR CHIPS AND ARRAYS......Page 93
REFERENCES......Page 94
5.1 INTRODUCTION......Page 96
5.2 ONLINE SANGER REACTION AND DNA SEQUENCING......Page 100
5.3 ONLINE PCR ANALYSIS AND GENOTYPING......Page 106
5.4 MINIATURIZATION OF CE INTERFACE......Page 112
5.5 MINIATURIZATION OF SANGER REACTION......Page 114
5.6 MINIATURIZATION OF THE PURIFICATION COLUMN......Page 116
5.7 MULTIPLEXED ONLINE REACTION AND ELECTROPHORESIS FOR DNA SEQUENCING......Page 117
5.8 MULTIPLEXED ONLINE PCR ANALYSIS AND GENOTYPING FROM BLOOD......Page 127
ACKNOWLEDGMENTS......Page 132
REFERENCES......Page 133
6.1 INTRODUCTION......Page 137
6.2 SYSTEM DESIGN......Page 139
6.2.1 Rectangular Channels......Page 140
6.2.2 Sample Introduction......Page 141
Fiber Optics/Photodiode Array Detection......Page 143
Fluorescence Detection with a Charge Coupled Device......Page 145
Electrochemical Array Detection......Page 148
6.3.1 Channel Separation Techniques......Page 149
Flow Injection Analysis FIA......Page 150
Micellar Electrokinetic Channel Chromatography......Page 153
6.3.2 Applications......Page 155
Monitoring Release from Cells......Page 157
6.4 CAPILLARY SAMPLE INTRODUCTION FOR PLUG/PARALLEL DNA SEPARATIONS......Page 162
6.4.1 Ultrathin Slab Gels......Page 163
6.4.2 Separations of DNA Restriction Fragments......Page 164
6.5 FUTURE DIRECTIONS......Page 168
REFERENCES......Page 169
7.1 INTRODUCTION......Page 172
7.2 SEPARATION PLATFORM......Page 176
7.3 OPTICAL PATHWAY......Page 177
7.4 PLANAR MICROGELS......Page 178
7.6 IN MIGRATIO FLUOROPHORE LABELING......Page 179
7.7 AGAROSE-BASED REPLACEABLE SEPARATION MATRIX......Page 180
7.8 CONCLUSION......Page 185
REFERENCES......Page 187
8.1 INTRODUCTION......Page 190
8.2 INSTRUMENTATION......Page 194
Reaction Chamber......Page 196
Temperature Sensor......Page 198
Focusing and Collecting Optics......Page 199
8.2.3 Software......Page 202
8.3 PERFORMANCE......Page 205
8.4 NEXT-GENERATION INSTRUMENT......Page 207
8.5 CONCLUSION......Page 211
REFERENCES......Page 212
9.1 INTRODUCTION......Page 214
Collection......Page 220
Collection......Page 221
Collection......Page 222
Purity Check of Collected DNA Samples See Note 17......Page 223
MALDI-TOF Mass Determination......Page 224
MALDI-TOF Mass Determination......Page 225
NOTES......Page 226
REFERENCES......Page 229
10.1 INTRODUCTION......Page 230
10.2 ACTIVE MICROELECTRONIC CHIPS AND ARRAYS......Page 231
10.3 CHIP/CARTRIDGE AND ELECTRONIC HYBRIDIZATION SYSTEM......Page 236
10.4 ASPECTS OF ELECTRONIC HYBRIDIZATION......Page 243
10.5.1 Single Nucleotide Polymorphisms......Page 247
10.5.2 Short Tandem Repeats......Page 251
10.5.3 Genotyping Accuracy and Reliability......Page 252
10.5.4 Combined SNP and STR Genotyping......Page 255
10.6.1 Immunoassays and Combined Assays......Page 259
10.6.2 Integrated Sample-to-Answer Systems......Page 261
10.7.1 Enabling Nanotechnology......Page 265
10.7.2 Electric Field Array Approach to Micro/Nanofabrication......Page 267
10.8 CONCLUSIONS......Page 272
REFERENCES......Page 274
11.1 INTRODUCTION......Page 277
11.2.1 The Flow-thru Concept......Page 280
Glass Capillary Arrays......Page 281
Macroporous Silicon......Page 283
Methods for Flow-thru Chip Preparation......Page 284
Flow-thru Chip Hybridization and Detection......Page 286
Increased Responsiveness and Dynamic Range......Page 287
Enhanced Reaction Rates......Page 289
Uniform Probe Distribution and Increased Spot Density......Page 290
11.3 FLOW-THRU CHIP INTEGRATED SYSTEM......Page 291
Single-Pass Assays......Page 293
11.3.2 The Flow-thru Chip Fluidics Station......Page 296
Integrated Bread Board Unit......Page 297
Uniform Fluid Distribution......Page 298
Temperature Control of Hybridization......Page 300
Analysis of Gene Expression Patterns......Page 302
11.4 CONCLUSION......Page 305
REFERENCES......Page 306
12.1 INTRODUCTION......Page 309
12.2 PLASTICS AS SUBSTRATES......Page 310
12.3 SURFACE MODIFICATION......Page 311
12.4.1 In Situ Oligonucleotide Array Synthesis System......Page 312
12.4.2 Quality Control......Page 316
12.4.3 Postimmobilization Processes......Page 317
12.5 TARGET LABELING STRATEGIES......Page 318
12.6 AUTOMATION AND SYSTEM INTEGRATION......Page 319
REFERENCES......Page 322
13.1 INTRODUCTION......Page 324
13.2.1 General Properties......Page 326
Duroplastic Polymers......Page 327
13.3 REPLICATION TECHNOLOGIES......Page 328
13.4.1 Micromachining Methods......Page 332
13.4.2 Electroplating Methods......Page 333
13.4.3 Silicon Micromachining......Page 334
13.5 HOT EMBOSSING PROCESS......Page 335
13.6 EXAMPLES......Page 340
Lamination......Page 346
Ultrasonic Welding......Page 347
13.7.2 Dicing and Hole Drilling......Page 349
13.7.3 Electrode Fabrication......Page 350
13.8 OUTLOOK AND CONCLUSIONS......Page 351
REFERENCES......Page 352
14.1 INTRODUCTION......Page 356
14.2.1 Microfabricated Gas-Phase Reactors......Page 357
14.2.2 Microfabricated Liquid-Phase Reactors......Page 358
14.2.3 Microfabricated Packed-Bed Reactors......Page 361
14.2.4 Unit Operations......Page 362
14.3 ANALYTICAL ASPECTS AND APPLICATIONS......Page 364
14.3.2 Microanalytical Devices......Page 365
14.4 MICROFABRICATION TECHNIQUES......Page 367
14.5 SIMULATION OF MICROREACTOR SYSTEMS......Page 368
14.7 CONCLUSION......Page 371
REFERENCES......Page 372
15.1 INTRODUCTION......Page 376
15.2.1 Compounds......Page 378
15.2.3 Consumables......Page 379
15.2.5 Equipment Costs......Page 380
15.2.7 Beginning the 1536 Transition......Page 381
Piezoelectric and Inkjet Microdispensing Systems......Page 382
Air Displacement Systems......Page 383
Pin Transfer Technologies......Page 385
Digital Imaging......Page 386
Scanning Confocal Imagers......Page 387
Single-Molecule Detection Systems Based on Confocal Optics......Page 388
15.3.3 Plate Formats......Page 389
15.3.4 Automation......Page 390
15.4 ASSAY DEVELOPMENT FOR MINIATURIZED SCREENING......Page 391
15.4.1 Biochemical Assays......Page 392
15.4.2 Cell-Based Assays......Page 394
15.5 DATA HANDLING FOR MINIATURIZED ULTRA-HTS......Page 396
15.5.1 Quality Control......Page 397
15.5.2 Data Volume......Page 398
15.5.3 Visualization and Data Mining......Page 399
15.6 APPLICATION OF BIOCHIP TECHNOLOGY TO HTS......Page 400
15.7 EXAMPLES OF MINIATURIZED HTS ASSAYS......Page 402
15.7.1 Mass-Dependent Assay: Fluorescence Polarization FP......Page 403
15.7.2 Proximity-Dependent Assay: Fluorescence Resonance Energy Transfer FRET......Page 404
15.7.3 Luminescence-Based Assay......Page 405
15.7.4 Bead-Staining Assays......Page 406
15.7.5 Agar-Embedded Bead Assays......Page 407
15.8.1 How Low Is Low Enough?......Page 408
15.8.2 Timing......Page 409
15.8.3 Productivity Measurement......Page 410
15.8.4 Education of Customers......Page 411
15.8.5 Obsolescence Cycles......Page 412
15.9 SUMMARY......Page 413
REFERENCES......Page 414
16.2 BACKGROUND?BREADTH OF ANALYSIS......Page 420
16.3.2 Temperature Control......Page 422
16.3.3 Shelf Life......Page 423
16.4.1 Cost Limits of Microsystems......Page 424
16.4.2 Device Reuse......Page 425
16.5.1 Sample Collection......Page 430
16.5.2 Sample Separation......Page 431
16.5.3 Sample Transfer and Loading......Page 433
16.6 VOLUME SENSITIVITY TRADEOFF......Page 434
16.8.1 Requirements......Page 435
16.8.2 Capability......Page 436
16.9 CONCLUSIONS......Page 438
REFERENCES......Page 439