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BioMEMS and Biomedical Nanotechnology Volume II Micro/Nano Technology for Genomics and Proteomics BioMEMS and Biomedical Nanotechnology Mauro Ferrari, Ph.D., Editor-in-Chief Professor, Brown Institute of Molecular Medicine Chairman Department of Biomedical Engineering University of Texas Health Science Center, Houston, TX Professor of Experimental Therapeutics University of Texas M.D. Anderson Cancer Center, Houston, TX Professor of Bioengineering Rice University, Houston, TX Professor of Biochemistry and Molecular Biology University of Texas Medical Branch, Galveston, TX President, the Texas Alliance for NanoHealth Houston, TX Volume II Micro/Nano Technology for Genomics and Proteomics Edited by Mihrimah Ozkan Dept. of Electrical Engineering University of California, Riverside Riverside, California USA Michael J. Heller Dept. of Bioengineering University of California, San Diego La Jolla, California USA Mihrimah Ozkan University of California, Riverside Riverside, California Michael Heller University of California, Riverside Riverside, California Mauro Ferrari Ohio State University Columbus, Ohio Library of Congress Cataloging-in-Publication Data Volume II ISBN-10: 0-387-25564-8 ISBN-13: 978-0387-25564-4 Set ISBN-10: 0-387-25661-3 ISBN-13: 978-0387-25561-3 e-ISBN 10: 0-387-25843-4 e-ISBN-13: 978-0387-25843-0 Printed on acid-free paper. e-ISBN:10: 0-387-25749-7 e-ISBN:13: 978-0387-25749-5
C 2006 Springer Science+Business Media, LLC All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. 9 8 7 6 5 4 3 2 1 springer.com SPIN 11407157 Dedicated to Richard Smalley (1943–2005), in Memoriam To Rick, father founder of nanotechnology prime inspiration for its applications to medicine gracious mentor to its researchers our light—forever in the trenches with us (Rick Smalley received the 1996 Chemistry Nobel Prize for the co-discovery of carbon-60 buckeyballs) Contents List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxi Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxiii I. Application of Microarray Technologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Electronic Microarray Technology and Applications in Genomics and Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ying Huang, Dalibor Hodko, Daniel Smolko, and Graham Lidgard 1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Overview of Electronic Microarray Technology . . . . . . . . . . . . . . . . . . . . . . . . . r r 1.2.1 NanoChip
Array and NanoChip
Workstation . . . . . . . . . . . . . . . . . . r
1.2.2 Capabilities of the NanoChip Electronic Microarrays . . . . . . . . . . . . . 1.3 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.1 Single Nucleotide Polymorphisms (SNPs)—Based Diagnostics . . . . . 1.3.2 Forensic Detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.3 Gene Expression Profiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.4 Cell Separation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.5 Electronic Immunoassays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.6 Miniaturization of Electronic Microarray Technology and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.7 Applications in Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Summary and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References................................................................................. 2. Gene Expression Profiling Utilizing Microarray Technology and RT-PCR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Dominick Sinicropi, Maureen Cronin, and Mei-Lan Liu 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Real-Time PCR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.1 Detection Systems.............................................................. 2.2.2 Real-Time RT-PCR Data Analysis .......................................... 2.2.3 Qualification of Gene Panels Using Real-Time RT-PCR................ 2.2.4 Real-Time RT-PCR Summary................................................ 1 3 3 4 5 7 10 10 10 12 12 14 15 18 19 19 23 23 25 25 31 32 34 viii CONTENTS 2.3 Microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.1 Technology Platforms ......................................................... 2.3.2 Target Amplification and Labeling .......................................... 2.3.3 Applications ..................................................................... 2.4 Comparison of Gene Expression Profiling Methods . . . . . . . . . . . . . . . . . . . . . 2.4.1 Comparison of cDNA Arrays with Other Gene Expression Profiling Methods .............................................................. 2.4.2 Comparison of Oligonucleotide Arrays with Other Gene Expression Profiling Methods................................................ 2.4.3 Comparison of cDNA and Oligonucleotide Microarray Expression Profiles............................................................. 2.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements .................................................................... References ............................................................................... 35 35 37 40 41 3. Microarray and Fluidic Chip for Extracellular Sensing . . . . . . . . . . . . . . . . . . . Mihrimah Ozkan, Cengiz S. Ozkan, Shalini Prasad, Mo Yang, and Xuan Zhang 3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Antibody Based Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Nucleic Acid Based Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Ion Channel Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 Enzyme Based Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Cell Based Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Cellular Microorganism Based Sensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Fluorescence Based Cell Biosensors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Cellular Metabolism Based Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Impedance Based Cellular Sensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Intracellular Potential Based Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.12 Extracllular Potential Based Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.13 Cell Patterning Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.14 Dielectrophoresis for Cell Patterning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.15 Basis of Dielectrophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.16 Microelectrodes and Dielectrophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.17 Dielectric Properties of Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.18 Effect of Electric Fields on Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.19 Cell Types and the Parameters for Dielectrophoretic Patterning . . . . . . . . . . 3.20 Biosensing System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.21 Chip Assembly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.22 Environmental Chamber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.23 Experimental Measurement System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.24 Cell Culture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.24.1 Neuron Culture ................................................................ 3.24.2 Primary Osteoblast Culture ................................................. 3.25 Signal Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.26 Selection of Chemical Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 41 42 44 44 45 45 47 50 51 51 51 52 52 53 55 56 57 58 60 61 62 63 64 64 65 66 66 67 67 67 67 68 68 69 CONTENTS ix 3.26.1 Ethanol.......................................................................... 3.26.2 Hydrogen Peroxide ........................................................... 3.26.3 Pyrethroid ...................................................................... 3.26.4 Ethylene Diamene Tetra Acetic Acid (EDTA)........................... Chemical Agent Sensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.27.1 Signature Pattern for Control Experiments............................... Electrical Sensing Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ethanol Sensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.29.1 Single Neuron Sensing....................................................... 3.29.2 Single Osteoblast Sensing ................................................... Hydrogen Peroxide Sensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.30.1 Single Neuron Sensing....................................................... 3.30.2 Single Osteoblast Sensing ................................................... Pyrethroid Sensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.31.1 Single Neuron Sensing....................................................... 3.31.2 Single Osteoblast Sensing ................................................... EDTA Sensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.32.1 Single Neuron Sensing....................................................... 3.32.2 Single Osteoblast Sensing ................................................... Immunohistochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Visualization of Physiological Changes Due to the Effect of the Chemical Analytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.34.1 Effect of Ethanol on Neurons............................................... 3.34.2 Effect of Ethanol on Osteoblasts ........................................... 3.34.3 Effect of Hydrogen Peroxide on Neurons ................................ 3.34.4 Effect of Hydrogen Peroxide on Osteoblasts ............................ 3.34.5 Effect of Pyrethroid on Neurons ........................................... 3.34.6 Effect of Pyrethroid on Osteoblasts........................................ 3.34.7 Effect of EDTA on Neurons................................................. 3.34.8 Effect of EDTA on Osteoblasts............................................. Discussion and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References ............................................................................... 69 69 70 70 70 70 70 71 71 71 72 72 73 74 74 75 76 76 76 77 4. Cell Physiometry Tools based on Dielectrophoresis . . . . . . . . . . . . . . . . . . . . . . . Ronald Pethig 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Dielectrophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Dielectric Polarizability of Bioparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Dynamics of Interfacial Polarization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Surface Charge Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6 Other Physiometric Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.7 Traveling Wave Dielectrophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.8 Controlling Possible DEP-Induced Damage to Cells . . . . . . . . . . . . . . . . . . . . . Concluding Comments.................................................................. References................................................................................. 103 3.27 3.28 3.29 3.30 3.31 3.32 3.33 3.34 3.35 80 80 80 83 84 86 88 89 91 93 98 103 104 107 107 113 116 118 120 123 124 x CONTENTS 5. Hitting the Spot: The Promise of Protein Microarrays . . . . . . . . . . . . . . . . . . . . Joanna S. Albala 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Generation of Protein Microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2.1 Content............................................................................. 5.2.2 Surface Chemistry ............................................................... 5.2.3 Microarray Production .......................................................... 5.2.4 Detection........................................................................... 5.3 Protein Arrays for Analysis of Proteins Involved in Recombination & DNA Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3.1 Protein Expression Microarrays ............................................... 5.3.2 Protein Interaction Arrays ...................................................... 5.4 Summary: Protein arrays-Hope or hype? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements...................................................................... References................................................................................. 6. Use of Electric Field Array Devices for Assisted Assembly of DNA Nanocomponents and Other Nanofabrication Applications . . . . . . . . . . . . . . . Michael J. Heller, Cengiz S. Ozkan, and Mihrimah Ozkan 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2 Active Microelectronic Array Hybridization Technology . . . . . . . . . . . . . . . . . 6.3 Electric Field Assisted Nanofabrication Process . . . . . . . . . . . . . . . . . . . . . . . . . 6.4 Integration of Optical Tweezers for Manupilation of Live Cells . . . . . . . . . . . Conclusions ............................................................................... Abbreviations ............................................................................. Acknowledgements...................................................................... References................................................................................. 7. Peptide Arrays in Proteomics and Drug Discovery . . . . . . . . . . . . . . . . . . . . . . . Ulrich Reineke, Jens Schneider-Mergener, and Mike Schutkowski 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 Generation of Peptide Arrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.1 Coherent Surfaces and Surface Modification ............................... 7.2.2 Generation of Micro-Structured Surfaces ................................... 7.2.3 Peptide Array Preparation ...................................................... 7.2.4 Techniques for Array Production with Pre-Synthesized Peptides....... 7.3 Library Types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.1 Protein Sequence-Derived Libraries.......................................... 7.3.2 De Novo Approaches............................................................ 7.4 Assays for Peptide Arrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4.1 Screening .......................................................................... 7.4.2 Read-Out........................................................................... 7.5 Applications of Peptide Arrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.5.1 Antibodies ......................................................................... 7.5.2 Protein-Protein Interactions .................................................... 7.5.3 Enzyme-Substrate and Enzyme-Inhibitor Interactions .................... 127 127 128 128 129 129 130 130 130 132 133 133 133 137 138 141 146 153 156 156 157 157 161 161 162 163 173 182 200 203 204 210 214 215 219 221 222 224 226 CONTENTS 7.5.4 Application of Peptide Arrays: Miscellaneous ............................. 7.5.5 Peptidomimetics.................................................................. 7.6 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References................................................................................. 8. From One-Bead One-Compound Combinatorial Libraries to Chemical Microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Kit S. Lam, Ruiwu Liu, Jan Marik, and Pappanaicken R. Kumaresan 8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2 OBOC Peptide Libraries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3 Encoded OBOC Small Molecule Combinatorial Libraries . . . . . . . . . . . . . . . . 8.4 Peptide and Chemical Microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.1 Immobilization Methods for Pre-Synthesized Libraries .................. 8.4.2 In Situ Synthesis of Microarrays .............................................. 8.4.3 CD, Microfluidics, Fiber Optic Microarray, Multiplex Beads ........... 8.5 Detection Methods in Chemical Microarrays . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.5.1 Identification and Characterization of Bound Proteins.................... 8.5.2 Detection Methods to Identify Post-Translational Modification of Proteins or to Quantitate Enzyme Activity in Analytes................ 8.6 Application of Chemical Microarray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.6.1 Protein Binding Studies......................................................... 8.6.2 Post-Translational Modification, Enzyme-Substrate and Inhibitor Studies ............................................................ 8.6.3 Cell-Binding Studies ............................................................ 8.6.4 Drug Discovery and Cell Signaling .......................................... 8.6.5 Diagnostic Studies ............................................................... 8.6.6 Non-Biological Applications .................................................. 8.7 Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements...................................................................... Abbreviations ............................................................................. References................................................................................. xi 228 231 231 265 283 283 284 287 289 289 292 295 296 296 297 297 298 299 300 300 301 301 302 303 303 304 II. Advanced Microfluidic Devices and Human Genome Project . . . . . . . . . . . . . . . . 309 9. Plastic Microfluidic Devices for DNA and Protein Analyses . . . . . . . . . . . . . . . Z. Hugh Fan and Antonio J. Ricco 9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.1.1 Detection........................................................................... 9.1.2 Materials........................................................................... 9.2 Electrokinetic Pumping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.3 Plastic Devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.3.1 Pumping and Detection ......................................................... 9.3.2 Device Fabrication ............................................................... 9.4 DNA Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.1 Integrating PCR and DNA Fragment Separations ......................... 311 311 311 312 312 314 315 316 318 318