Micro/Nano Technology for Genomics and Proteomics

by Ferrari, Mauro; Ozkan, Mihrimah; Heller, Michael J.

• ISBN13: 9780387255644
• ISBN10: 0387255648
• Edition: 1st
• Format: Hardcover
• Copyright: 2007-01-30
• Publisher: Springer Verlag

Summary

Volume 2 of the multi-volume reference, BioMEMS and Biomedical Nanotechnology , includes contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices with applications to Genomics and Proteomics. Topics include gene expression profiling utilizing microarray technology; imaging and sensing for gene detection and use in DNA analysis; and coverage of advanced microfluidic devices and the Human Genome Project. This volume is very well illustrated with many of the figures in color.

Author Biography

Dr. Mihri Ozkan is currently an Assistant Professor in the Department of Electrical Engineering at UC-Riverside with a research focus in nanotechnology and its applications in biology and engineering. She received her Ph.D. degree in the Department of Electrical and Computer Engineering at UC-San Diego and her M.S. degree in the Department of Materials Science and Engineering at Stanford University. She has over four years of industrial experience including at Applied Materials, Analog Devices and at IBM Almaden Research Center. Her awards and honors include "Emerging Scholar Award of 2005" by the American Association of University Women, "Invited participant of Kecks Future Initiative" (2005) by the National Academy of Science, "Regents Faculty Excellence Award" (2001 and 2004), "Visionary Science Award" (2003), "Technical Ingenuity Award" (2003), "Research Leadership Award" (2003), "Selected US team member in US-Japan Nanotechnology Symposium" (2003), and "Best graduate student awards" from the Materials Research Society, the Society of Biomedical Engineering and Jacobs School of Engineering (1999, 2000, 2001). Dr. Ozkan's research is recognized as "frontier research" by the Virtual Journal of Nanoscale Science & Technology (edited by Dr. David Awschalom) and featured many times in public newspapers, on the cover of journals, online news sites and newsletters. She is an active board member and treasurer in the International Society for BioMEMS and Biomedical Nanotechnology. Her editorial activities include the Journal of Sensors and Actuators B and the Journal of Biomedical Microdevices. She holds more than 25 patent disclosures and about 8 US-patents.Professor Michael J. Heller began his position at University of California, San Diego in July 2001. He has a joint appointment between the departments of Bioengineering and Electrical and Computer Engineering (ECE). His experience (academic and industrial) includes many areas of biotechnology and biomedical instrumentation, with particular expertise in DNA synthesis, DNA microarray diagnostics and optoelectronic based biosensor technologies. Dr. Heller has been the co-founder of three high-tech companies: Nanogen, Nanotronics and Integrated DNA Technologies. Dr. Heller's most recent work involved the development of an integrated microelectronic array based system for genotyping, genetic and infectious disease diagnostics, protein analysis, cell separations and for nanofabrication applications. Dr. Heller has a respectable publication record, and has been an invited speaker to a large number of scientific conferences and meetings related to DNA microarrays, biosensors, lab-on-a-chip devices, bio-MEMS and nanotechnology. He has over 30 issued US patents related to microelectronic chips, microarrays and integrated devices for DNA hybridization, miniaturized sample to answer diagnostic devices, biosensors, genomics, proteomics, nanotechnology and nanofabrication, nano-based DNA optical storage and for fluorescent energy transfer in DNA nanostructures. Dr. Heller has been a panel member for the NAS(NAE) Review of National Nanotechnology Initiative 2001-2002; the NAS(NAE Engineer for the 2020 - 2001/2002; the White House (OSTP) National Nanotechnology Initiative 1999/2000; and has also been involved in a number of NSF Nanotechnology Workshops.Professor Mauro Ferrari is a pioneer in the fields of bioMEMS and biomedical nanotechnology. As a leading academic, a dedicated entrepreneur, and a vision setter for the Nation's premier Federal programs in nanomedicine, he brings a three-fold vantage perspective to his roles as Editor-in-Chief for this work. Dr. Ferrari has authored or co-authored over 150 scientific publications, 6 books, and over 20 US and International patents. Dr. Ferrari is also Editor-in-Chief of Biomedical Microdevices and series editor of the new Springer series on Emerging Biomedical Technologies.Several private sector companies originated from his laboratories at the Ohio State University and the University of California at Berkeley over the years. On a Federal assignment as Special Expert in Nanotechnology and Eminent Scholar, he has provided the scientific leadership for the development of the Alliance for Cancer Nanotechnology of the National Cancer Institute, the world-largest medical nanotechnology operation to date. Dr. Ferrari trained in mathematical physics in Italy, obtained his Master's and Ph.D. in Mechanical Engineering at Berkeley, attended medical school at The Ohio State University, and served in faculty positions in Materials Science and Engineering, and Civil and Environmental Engineering in Berkeley, where he was first tenured. At Ohio State he currently serves as Professor of Internal Medicine, Division of Hematology and Oncology, as Edgar Hendrickson Professor of Biomedical Engineering, and as Professor of Mechanical Engineering. He is Associate Director of the Dorothy M. Davis Heart and Lung Research Institute, and the University's Associate Vice President for Health Science, Technology and Commercialization.

Table of Contents

List of Contributors	p. xvii
Foreword	p. xxi
Preface	p. xxiii
Application of Microarray Technologies	p. 1
Electronic Microarray Technology and Applications in Genomics and Proteomics	p. 3
Introduction	p. 3
Overview of Electronic Microarray Technology	p. 4
NanoChip Array and NanoChip Workstation	p. 5
Capabilities of the NanoChip Electronic Microarrays	p. 7
Applications	p. 10
Single Nucleotide Polymorphisms (SNPs)-Based Diagnostics	p. 10
Forensic Detection	p. 10
Gene Expression Profiling	p. 12
Cell Separation	p. 12
Electronic Immunoassays	p. 14
Miniaturization of Electronic Microarray Technology and Applications	p. 15
Applications in Proteomics	p. 18
Summary and Outlook	p. 19
References	p. 19
Gene Expression Profiling Utilizing Microarray Technology and RT-PCR	p. 23
Introduction	p. 23
Real-Time PCR	p. 25
Detection Systems	p. 25
Real-Time RT-PCR Data Analysis	p. 31
Qualification of Gene Panels Using Real-Time RT-PCR	p. 32
Real-Time RT-PCR Summary	p. 34
Microarrays	p. 35
Technology Platforms	p. 35
Target Amplification and Labeling	p. 37
Applications	p. 40
Comparison of Gene Expression Profiling Methods	p. 41
Comparison of cDNA Arrays with Other Gene Expression Profiling Methods	p. 41
Comparison of Oligonucleotide Arrays with Other Gene Expression Profiling Methods	p. 42
Comparison of cDNA and Oligonucleotide Microarray Expression Profiles	p. 44
Summary	p. 44
Acknowledgements	p. 45
References	p. 45
Microarray and Fluidic Chip for Extracellular Sensing	p. 47
Introduction	p. 47
Antibody Based Biosensors	p. 50
Nucleic Acid Based Biosensors	p. 51
Ion Channel Biosensors	p. 51
Enzyme Based Biosensors	p. 51
Cell Based Biosensors	p. 52
Cellular Microorganism Based Sensors	p. 52
Fluorescence Based Cell Biosensors	p. 53
Cellular Metabolism Based Biosensors	p. 55
Impedance Based Cellular Sensors	p. 56
Intracellular Potential Based Biosensors	p. 57
Extracllular Potential Based Biosensors	p. 58
Cell Patterning Techniques	p. 60
Dielectrophoresis for Cell Patterning	p. 61
Basis of Dielectrophoresis	p. 62
Microelectrodes and Dielectrophoresis	p. 63
Dielectric Properties of Cells	p. 64
Effect of Electric Fields on Cells	p. 64
Cell Types and the Parameters for Dielectrophoretic Patterning	p. 65
Biosensing System	p. 66
Chip Assembly	p. 66
Environmental Chamber	p. 67
Experimental Measurement System	p. 67
Cell Culture	p. 67
Neuron Culture	p. 67
Primary Osteoblast Culture	p. 68
Signal Processing	p. 68
Selection of Chemical Agents	p. 69
Ethanol	p. 69
Hydrogen Peroxide	p. 69
Pyrethroid	p. 70
Ethylene Diamene Tetra Acetic Acid (EDTA)	p. 70
Chemical Agent Sensing	p. 70
Signature Pattern for Control Experiments	p. 70
Electrical Sensing Cycle	p. 70
Ethanol Sensing	p. 71
Single Neuron Sensing	p. 71
Single Osteoblast Sensing	p. 71
Hydrogen Peroxide Sensing	p. 72
Single Neuron Sensing	p. 72
Single Osteoblast Sensing	p. 73
Pyrethroid Sensing	p. 74
Single Neuron Sensing	p. 74
Single Osteoblast Sensing	p. 75
EDTA Sensing	p. 76
Single Neuron Sensing	p. 76
Single Osteoblast Sensing	p. 76
Immunohistochemistry	p. 77
Visualization of Physiological Changes Due to the Effect of the Chemical Analytes	p. 80
Effect of Ethanol on Neurons	p. 80
Effect of Ethanol on Osteoblasts	p. 80
Effect of Hydrogen Peroxide on Neurons	p. 83
Effect of Hydrogen Peroxide on Osteoblasts	p. 84
Effect of Pyrethroid on Neurons	p. 86
Effect of Pyrethroid on Osteoblasts	p. 88
Effect of EDTA on Neurons	p. 89
Effect of EDTA on Osteoblasts	p. 91
Discussion and Conclusions	p. 93
References	p. 98
Cell Physiometry Tools based on Dielectrophoresis	p. 103
Introduction	p. 103
Dielectrophoresis	p. 104
Dielectric Polarizability of Bioparticles	p. 107
Dynamics of Interfacial Polarization	p. 107
Surface Charge Effects	p. 113
Other Physiometric Effects	p. 116
Traveling Wave Dielectrophoresis	p. 118
Controlling Possible DEP-Induced Damage to Cells	p. 120
Concluding Comments	p. 123
References	p. 124
Hitting the Spot: The Promise of Protein Microarrays	p. 127
Introduction	p. 127
Generation of Protein Microarrays	p. 128
Content	p. 128
Surface Chemistry	p. 129
Microarray Production	p. 129
Detection	p. 130
Protein Arrays for Analysis of Proteins Involved in Recombination & DNA Repair	p. 130
Protein Expression Microarrays	p. 130
Protein Interaction Arrays	p. 132
Summary: Protein arrays-Hope or hype?	p. 133
Acknowledgements	p. 133
References	p. 133
Use of Electric Field Array Devices for Assisted Assembly of DNA Nanocomponents and Other Nanofabrication Applications	p. 137
Introduction	p. 138
Active Microelectronic Array Hybridization Technology	p. 141
Electric Field Assisted Nanofabrication Process	p. 146
Integration of Optical Tweezers for Manupilation of Live Cells	p. 153
Conclusions	p. 156
Abbreviations	p. 156
Acknowledgements	p. 157
References	p. 157
Peptide Arrays in Proteomics and Drug Discovery	p. 161
Introduction	p. 161
Generation of Peptide Arrays	p. 162
Coherent Surfaces and Surface Modification	p. 163
Generation of Micro-Structured Surfaces	p. 173
Peptide Array Preparation	p. 182
Techniques for Array Production with Pre-Synthesized Peptides	p. 200
Library Types	p. 203
Protein Sequence-Derived Libraries	p. 204
De Novo Approaches	p. 210
Assays for Peptide Arrays	p. 214
Screening	p. 215
Read-Out	p. 219
Applications of Peptide Arrays	p. 221
Antibodies	p. 222
Protein-Protein Interactions	p. 224
Enzyme-Substrate and Enzyme-Inhibitor Interactions	p. 226
Application of Peptide Arrays: Miscellaneous	p. 228
Peptidomimetics	p. 231
Bibliography	p. 231
References	p. 265
From One-Bead One-Compound Combinatorial Libraries to Chemical Microarrays	p. 283
Introduction	p. 283
OBOC Peptide Libraries	p. 284
Encoded OBOC Small Molecule Combinatorial Libraries	p. 287
Peptide and Chemical Microarrays	p. 289
Immobilization Methods for Pre-Synthesized Libraries	p. 289
In Situ Synthesis of Microarrays	p. 292
CD, Microfluidics, Fiber Optic Microarray, Multiplex Beads	p. 295
Detection Methods in Chemical Microarrays	p. 296
Identification and Characterization of Bound Proteins	p. 296
Detection Methods to Identify Post-Translational Modification of Proteins or to Quantitate Enzyme Activity in Analytes	p. 297
Application of Chemical Microarray	p. 297
Protein Binding Studies	p. 298
Post-Translational Modification, Enzyme-Substrate and Inhibitor Studies	p. 299
Cell-Binding Studies	p. 300
Drug Discovery and Cell Signaling	p. 300
Diagnostic Studies	p. 301
Non-Biological Applications	p. 301
Future Directions	p. 302
Acknowledgements	p. 303
Abbreviations	p. 303
References	p. 304
Advanced Microfluidic Devices and Human Genome Project	p. 309
Plastic Microfluidic Devices for DNA and Protein Analyses	p. 311
Introduction	p. 311
Detection	p. 311
Materials	p. 312
Electrokinetic Pumping	p. 312
Plastic Devices	p. 314
Pumping and Detection	p. 315
Device Fabrication	p. 316
DNA Analyses	p. 318
Integrating PCR and DNA Fragment Separations	p. 318
DNA Sequencing	p. 320
DNA Sample Purification	p. 321
Protein Analyses	p. 322
Isoelectric Focusing for Studying Protein Interactions	p. 323
Enzymatic Digestion for Protein Mapping	p. 324
Concluding Remarks	p. 326
Acknowledgements	p. 326
References	p. 326
Centrifuge Based Fluidic Platforms	p. 329
Introduction	p. 329
Why Centrifuge as Fluid Propulsion Force?	p. 330
Compact Disc or Micro-Centrifuge Fluidics	p. 333
How it Works	p. 333
Some Simple Fluidic Function Demonstrated on a CD	p. 334
Mixing of Fluid	p. 334
Valving	p. 335
Volume Definition (Metering) and Common Distribution Channels	p. 338
Packed Columns	p. 339
CD Applications	p. 339
Two-Point Calibration of an Optode-Based Detection System	p. 339
CD Platform for Enzyme-Linked Immunosorbant Assays (ELISA)	p. 340
Multiple Parallel Assays	p. 341
Cellular Based Assays on CD Platform	p. 342
Automated Cell Lysis on a CD	p. 344
Integrated Nucleic Acid Sample Preparation and PCR Amplification	p. 356
Sample Preparation for MALDI MS Analysis	p. 358
Modified Commercial CD/DVD Drives in Analytical Measurements	p. 359
Conclusion	p. 361
Acknowledgements	p. 362
References	p. 362
Sequencing the Human Genome: A Historical Perspective On Challenges For Systems Integration	p. 365
Overview	p. 365
Approaches Used to Sequence the Human Genome	p. 366
Overview	p. 366
Strategy Used for Sequencing Source Clones	p. 368
Construction of the Chromosome Tiling Paths	p. 379
Data Sharing	p. 379
Challenges for Systems Integration	p. 380
Methodological Challenges for Sequencing Source Clones: 1990-1997	p. 381
Challenges for Sequencing the Entire Human Genome: 1998-2003	p. 386
Are there Lessons to be Learned from the Human Genome Project?	p. 395
Acknowledgements	p. 397
References	p. 398
Nanoprobes for Imaging, Sensing and Therapy	p. 401
Hairpin Nanoprobes for Gene Detection	p. 403
Introduction	p. 403
Nanoprobe Design Issues for Homogeneous Assays	p. 405
In Vitro Gene Detection	p. 408
Pathogen Detection	p. 409
Mutation Detection and Allele Discrimination	p. 409
Intracellular RNA Targets	p. 411
Cytoplasmic and Nuclear RNA	p. 411
RNA Secondary Structure	p. 418
Living Cell RNA Detection	p. 418
Cellular Delivery of Probes	p. 419
Intracellular Probe Stability	p. 424
Intracellular mRNA Detection	p. 428
Opportunities and Challenges	p. 431
Acknowledgements	p. 433
References	p. 433
Fluorescent Lanthanide Labels with Time-Resolved Fluorometry In DNA Analysis	p. 437
Introduction	p. 437
Lanthanide Fluorescent Complexes and Labels	p. 438
Time-Resolved Fluorometry of Lanthanide Complexes	p. 441
DNA Hybridization Assay	p. 442
Conclusion	p. 445
References	p. 445
Role of SNPs and Haplotypes in Human Disease and Drug Development	p. 447
Introduction	p. 447
SNP Discovery	p. 448
Detection of Genetic Variation	p. 449
Disease Gene Mapping	p. 450
Evolution	p. 450
Haplotypes	p. 452
Drug Development	p. 452
Concluding Remarks	p. 454
References	p. 454
Control of Biomolecular Activity by Nanoparticle Antennas	p. 459
Background and Motivation	p. 459
ATP Synthase as a Molecular Motor	p. 459
Biological Self Assembly of Complex Hybrid Structures	p. 461
DNA as a Medium for Computation	p. 463
Light Powered Nanomechanical Devices	p. 463
Nanoparticles as Antennas for Controlling Biomolecules	p. 465
Technical Approach	p. 468
Dehybridization of a DNA Oligonucleotide Reversibly by RFMF Heating of Nanoparticles	p. 469
Determination of Effective Temperature by RFMF Heating of Nanoparticles	p. 469
Selective Dehybridization of DNA Oligos by RFMF Heating of Nanoparticles	p. 471
Conclusions and Future Work	p. 473
References	p. 474
Sequence Matters: The Influence of Basepair Sequence on DNA-protein Interactions	p. 477
Introduction	p. 477
Generalized Deformations of Objects	p. 481
Sequence Dependent Aspects to the Double Helix Elastic Constants	p. 484
Sequence Dependent Bending of the Double Helix and the Structure Atlas of DNA	p. 485
Some Experimental Consequences of Sequence Dependent Elasticity	p. 486
Phage 434 Binding Specificity and DNase 1 Cutting Rates	p. 486
Nucleosome Formation: Sequence and Temperature Dependence	p. 491
Conclusions	p. 494
References	p. 494
Engineered Ribozymes: Efficient Tools for Molecular Gene Therapy and Gene Discovery	p. 497
Introduction	p. 497
Methods for the Introduction of Ribozymes into Cells	p. 498
Ribozyme Expression Systems	p. 499
The Pol III System	p. 499
Relationship Between the Higher-Order Structure of Ribozymes and their Activity	p. 500
Subcellular Localization and Efficacy of Ribozymes	p. 501
Mechanism of the Export of tRNA-Ribozymes from the Nucleus to the Cytoplasm	p. 504
RNA-Protein Hybrid Ribozymes	p. 505
Accessibility to Ribozymes of their Target mRNAs	p. 505
Hybrid Ribozymes that Efficiently Cleave their Target mRNAs, Regardless of Secondary Structure	p. 505
Maxizymes: Allosterically Controllable Ribozymes	p. 508
Shortened Hammerhead Ribozymes that Function as Dimers	p. 508
Design of an Allosterically Controllable Maxizyme	p. 509
Inactivation of an Oncogene in a Mouse Model	p. 512
Generality of the Maxizyme Technology	p. 512
Identification of Genes Using Hybrid Ribozymes	p. 513
Summary and Prospects	p. 515
References	p. 516
About the Editors	p. 519
Index	p. 521
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