Microarray Technology and Its ApplicationsUwe R. Müller, Dan V. Nicolau Ithasbeenstatedthatourknowledgedoublesevery20years,butthatmaybe an understatement when considering the Life Sciences. A series of discoveries and inventions have propelled our knowledge from the recognition that DNA isthegeneticmaterialtoabasicmolecularunderstandingofourselvesandthe living world around us in less than 50 years. Crucial to this rapid progress was thediscoveryofthedouble-helicalstructureofDNA,whichlaidthefoundation forallhybridizationbasedtechnologies. Thediscoveriesofrestrictionenzymes, ligases, polymerases, combined with key innovations in DNA synthesis and sequencing ushered in the era of biotechnologyas a new science with profound sociological and economic implications that are likely to have a dominating in?uence on the development of our society during this century. Given the process by which science builds on prior knowledge, it is perhaps unfair to single out a few inventions and credit them with having contributed most to thisavalancheofknowledge. Yet,therearesurelysomethatwillberecognized as having had a more profound impact than others, not just in the furthering of our scienti?c knowledge, but by leveraging commercial applications that provide a tangible return to our society. The now famous Polymerase Chain Reaction, or PCR, is surely one of those, as it has uniquely catalyzed molecular biology during the past 20 years, and continues to have a signi?cant impact on all areas that involve nucleic acids, ranging from molecular pathology to forensics. Ten years ago micro- ray technology emerged as a new and powerful tool to study nucleic acid - quences in a highly multiplexed manner, and has since found equally exciting and useful applications in the study of proteins, metabolites, toxins, viruses, whole cells and even tissues. |
Contents
Array Formats | 3 |
12 Reasons to Use Arrays | 4 |
13 Arrays for Nucleic Acid Analysis | 6 |
14 Protein Arrays | 8 |
15 The ArrayPlate | 9 |
16 Conclusion | 19 |
References | 20 |
Biomolecules and Cells on Surfaces Fundamental Concepts | 23 |
102 Principles of Genotyping | 213 |
103 Performing the Assays in Practice | 217 |
104 Conclusion | 222 |
References | 223 |
High Sensitivity Expression Profiling | 229 |
112 Oligonucleotide Expression Arrays | 230 |
113 cDNAbased Expression Arrays | 239 |
114 Appendix | 244 |
23 DNA Immobilization on Surfaces | 28 |
24 Protein Immobilization on Surfaces | 32 |
25 Carbohydrate Immobilization | 36 |
26 Immobilization of Cells on Surfaces | 38 |
27 Conclusions | 41 |
References | 42 |
Surfaces and Substrates | 45 |
32 DNA Microarrays | 46 |
33 Protein Microarrays | 50 |
34 Conclusion | 55 |
References | 56 |
Reagent Jetting Based Deposition Technologies for Array Construction | 63 |
43 Thermal Jet Based Dispensing | 65 |
44 Piezo Jet Based Dispensing | 67 |
45 Solenoid Jet Based Dispensing | 68 |
References | 71 |
Manufacturing of 2D Arrays by Pinprinting Technologies | 73 |
53 Overview of Different Pin Technologies | 74 |
54 Other System Components and Environmental Factors | 79 |
55 Pin Printing Process | 81 |
56 Example of a High Throughput PinPrinting System for Manufacturing of 2D Arrays the Corning GENII System | 84 |
57 Conclusion | 86 |
References | 87 |
Nanoarrays | 89 |
62 Passive Nanoscale Arrays | 91 |
63 Computational Nanoarrays | 105 |
64 Dynamic Nanoarrays | 109 |
65 Conclusion | 115 |
The Use of Microfluidic Techniques in Microarray Applications | 119 |
72 Biochannel Hybridization Arrays | 120 |
73 Chips with Cavitation Microstreaming Mixers Kinetics Studies | 128 |
74 Integrated Microfluidic Reactors for DNA Amplification and Hybridization | 135 |
75 Summary and Conclusions | 142 |
Labels and Detection Methods | 147 |
82 Fluorophore Labelling and Detection Methods | 148 |
83 Enhanced FluorescenceBased Assays | 151 |
84 Phosphor Reporters | 154 |
85 Electrochemical Detection | 156 |
86 Metal Nanoparticle Labels and Metal Thin Films for Microarrays | 159 |
87 Conclusions | 172 |
References | 174 |
Markerfree Detection on Microarrays | 181 |
93 Intrinsic UV Fluorescence for Chip Analysis of Rare Proteins | 190 |
94 Genetic Diagnostics with Unlabelled DNA | 197 |
References | 204 |
DNA Microarrays | 209 |
Analysis of DNA Sequence Variation in the Microarray Format | 211 |
References | 245 |
Applications of MatrixCGH ArrayCGH for Genomic Research and Clinical Diagnostics | 251 |
122 Technical Aspects | 253 |
123 Applications | 256 |
References | 260 |
Analysis of Gene Regulatory Circuits | 265 |
132 An Experimental Protocol for Genome Wide Location Analysis | 268 |
Identifying the Target Genes of Human E2F4 | 273 |
134 Summary | 275 |
Protein Microarrays | 277 |
Protein Antibody and Small Molecule Microarrays | 279 |
142 Protein Microarrays | 280 |
143 Antibody Microarrays | 283 |
144 Peptide and Other Synthetic Arrays | 287 |
References | 290 |
Photoaptamer Arrays for Proteomics Applications | 297 |
152 Overview of Photoaptamer Discovery and High Throughput Production | 298 |
153 Using Photoaptamer Microarrays | 301 |
154 Discussion | 303 |
References | 305 |
Biological Membrane Microarrays | 309 |
162 Biospecific Binding Studies Using Membrane Microarrays | 313 |
163 Conclusions | 318 |
References | 319 |
Cell Tissue Microarrays | 321 |
Use of Reporter Systems for Reverse Transfection Cell Arrays | 323 |
172 Reporter Systems for Reverse Transfection | 325 |
173 Reagents and Protocols | 332 |
References | 333 |
Whole Cell Microarrays | 335 |
182 The Need | 336 |
184 Challenges and Opportunities for Cellular Micrroarrays | 341 |
References | 343 |
Tissue Microarrays for Miniaturized HighThroughput Molecular Profiling of Tumors | 345 |
192 The TMA Technology | 346 |
194 TMA Applications | 349 |
195 Future Directions | 351 |
196 Protocol | 352 |
References | 354 |
Application of Microarray Technologies for Translational Genomics | 361 |
202 High Throughput Clinical Target Validation Using Tissue Microarrays | 363 |
203 Examples of Studies Integrating DNA and Tissue Microarray Technologies for the Rapid Clinical Translation of Genomic Discoveries | 365 |
204 High Throughput Characterization of Gene Function Using Live Cell Microarrays | 368 |
205 Conclusions | 370 |
372 | |
375 | |
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Common terms and phrases
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