Microarrays Integrated Analytical Systems Series Editor: Radislav A. Potyailo GE Global Research Center Niskayana, NY For other titles published in this series, go to www.springer.com/series/7427 Kilian Dill (cid:129) Robin Hui Liu (cid:129) Piotr Grodzinski Editors Microarrays Preparation, Microfl uidics, Detection Methods, and Biological Applications Editors Dr. Kilian Dill Dr. Robin Hui Liu CombiMatrix Corporation, Inc. Osmetech Molecular Diagnostics 6500 Harbour Heights Parkway 757 S. Raymond Ave. Suite 301, Mukilteo, WA 98275 Pasadena, CA 91105 USA USA [email protected] [email protected] Dr. Piotr Grodzinski National Institutes of Health National Cancer Institute 31 Center Drive Bethesda, MD 20892 USA [email protected] ISBN: 978-0-387-72716-5 e-ISBN: 978-0-387-72719-6 DOI: 10.1007/978-0-387-72719-6 Library of Congress Control Number: 2008937468 © Springer Science+Business Media, LLC 2009 All rights reserved. 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Printed on acid-free paper springer.com Series Preface In my career I’ve found that “thinking outside the box” works better if I know what’s “inside the box.” Dave Grusin, composer and jazz musician Different people think in different time frames: scientists think in decades, engineers think in years, and investors think in quarters. Stan Williams, Director of Quantum Science Research, Hewlett Packard Laboratories Everything can be made smaller, never mind physics; Everything can be made more efficient, never mind thermodynamics; Everything will be more expensive, never mind common sense. Tomas Hirschfeld, pioneer of industrial spectroscopy Integrated Analytical Systems Series Editor: Dr. Radislav A. Potyrailo, GE Global Research, Niskayuna, NY The book series Integrated Analytical Systems offers the most recent advances in all key aspects of development and application of modern instrumentation for chemical and biological analysis. The key development aspects include: (i) innova- tions in sample introduction through micro- and nanofluidic designs, (ii) new types and methods of fabrication of physical transducers and ion detectors, (iii) materials for sensors that became available due to the breakthroughs in biology, combinato- rial materials science, and nanotechnology, and (iv) innovative data processing and mining methodologies that provide dramatically reduced rates of false alarms. A multidisciplinary effort is required to design and build instruments with previously unavailable capabilities for demanding new applications. Instruments with more sensitivity are required today to analyze ultratrace levels of environ- mental pollutants, pathogens in water, and low vapor pressure energetic materials in air. Sensor systems with faster response times are desired to monitor transient in vivo events and bedside patients. More selective instruments are sought to analyze specific proteins in vitro and analyze ambient urban or battlefield air. v vi Series Preface For these and many other applications, new analytical instrumentation is urgently needed. This book series is intended to be a primary source of both fundamental and practical information on where analytical instrumentation technologies are now and where they are headed in the future. Looking back over peer-reviewed technical articles from several decades ago, one notices that the overwhelming majority of publications on chemical analysis has been related to chemical and biological sensors and has originated from depart- ments of chemistry in universities and divisions of life sciences of governmental laboratories. Since then, the number of disciplines has dramatically increased because of the ever-expanding needs for miniaturization (e.g., for in vivo cell analysis, embedding into soldier uniforms), lower power consumption (e.g., har- vested power), and the ability to operate in complex environments (e.g., whole blood, industrial water or battlefield air) for more selective, sensitive, and rapid determination of chemical and biological species. Compact analytical systems that have a sensor as one of the system components are becoming more important than individual sensors. Thus, in addition to traditional sensor approaches, a variety of new themes has been introduced to achieve an attractive goal of analyzing chemical and biological species on the micro- and nanoscale. Preface The area of microarrays enjoyed unprecedented growth in the last two decades the. The early demonstration of the concept in the seminal work of Fodor et al. led to the formulation of new standards for gene expression studies and molecular diagnostics methodologies. The highly parallel microarray concept evolved from the initial area of genomic studies to proteomics and single-cell studies benefiting a multitude of fields from fundamental systems biology to practical diagnostic tests. In the mid 1980s, dot-blots and slot-blots were utilized in the earliest array experiments. These low-density and early-stage microarrays were used to assess the identity of the material present as well as the concentration of the constituents. Later, they evolved into modern DNA and protein microarrays mostly produced on membranes. In the late 1980s and early 1990s, DNA microarrays were devel- oped further and were either spotted or synthesized via photolithography on solid surfaces. Affymetrix developed photolithography synthesis method into a mature technology and relied upon a step-by-step base synthesis with “photomasks” and light-labile protecting groups on oligonucleotide synthetic blocks. With time, Affymetrix became one of the largest suppliers of commercial DNA microarrays. In parallel, spotting of presynthesized oligonucleotides on the surface, in predeter- mined two-dimensional patterns allowed for an inexpensive approach to building custom-designed, “home-made” arrays in many research labs. Nowadays, DNA microarrays have become a widespread tool used in life sci- ences, drug screening, and diagnostic applications. With the abundant availability of gene targets and combinatorial chemistry/biology libraries, researchers leveraged the ability to study the effects of diseases, environmental factors, drugs, and other treatments on thousands of genes at once using microarrays. DNA microarrays are used in pharmacogenomic studies that include gene expression profiling, the meas- urement and analysis of regulated genes under various conditions, and genotyping, the detection of polymorphisms or mutations in a gene sequence. DNA microar- rays are also useful in molecular diagnostics, which includes genetic screening (e.g., detection of mutations or inherited disorders), identification of pathogens and resistance in infections, and molecular oncology (cancer diagnosis). Protein microarrays, on the other hand, consist of antibodies, proteins, or protein fragments and are used to screen and assess patterns of interaction with samples containing distinct proteins or classes of proteins. Similar to DNA systems developed earlier, vii viii Preface protein microarrays find their use in the identification of diagnostic targets and drug screening. Finally, cell arrays allow for the immobilization of single cells on the solid surface, while maintaining their viability and can be used in ion-channel studies and drug screening experiments as well as in monitored tissue growth. In this book, not only do we discuss the use of microarrays in DNA studies, but also include peptide arrays, protein arrays, combinatorial chemistry arrays, cell-based arrays, and glycoarrays, to name a few. The book is organized around several features of the microarray field: the biological material studied on the array, the detection methodology, and the application of the array toward specific study or diagnosis of the disease. This organization of the chapters demonstrates the advancement of the field in many different facets and shows the implementation of new technological advances into microarray systems and the subsequent expansion of possible utilization of these systems. Undoubtedly, we will witness further progress in microarrays due to the intro- duction of microtechnology, nanotechnology, and modern molecular biology into the field. This book will prove a useful source of current information for research- ers in the field of microarrays and for those who are just entering the field of microarray research. We wish to thank all of the contributing authors for their enthusiasm for the project and their commitment to provide high-quality manuscripts. We are also thankful to our families and coworkers for their patience and support during the course of completing this project. Kilian Dill Robin Hui Liu Piotr Grodzinski Contents Contributors ................................................................................................... xiii Part I Overview and New Detection Method 1 The Current Status of DNA Microarrays .............................................. 3 Leming Shi, Roger G. Perkins, and Weida Tong 2 Electrochemical Detection on Microarrays ........................................... 25 Kilian Dill and Andrey Ghindilis Part II Fluidic Manipulation and Microarrays 3 Fully Integrated Microfl uidic Device for Direct Sample-to-Answer Genetic Analysis ...................................................... 37 Robin H. Liu and Piotr Grodzinski 4 Integrated Microfl uidic Devices for Automated Microarray-Based Gene Expression and Genotyping Analysis ......................................................................... 67 Robin H. Liu, Mike Lodes, H. Sho Fuji, David Danley, and Andrew McShea Part III Statistical Data Evaluation on Microarrays 5 Intensity Concentration Relationships for Electrochemical Detection: Latin Square and Mixture Analysis ............................................................................... 97 Mervyn Thomas Part IV Applications 6 Genotyping Arrays ................................................................................... 121 ix x Contents Michael J. Lodes, Dominic Suciu, David Danley, and Andrew McShea 7 Peptide-Based Microarray .................................................................... 139 Resmi C. Panicker, Hongyan Sun, Grace Y. J. Chen, and Shao Q. Yao 8 Protein Microarrays for the Detection of Biothreats .......................... 169 Amy E. Herr 9 Photo-Generation of Carbohydrate Microarrays Gregory T. Carroll, Denong Wang, Nicholas J. Turro, and Jeffrey T. Koberstein 10 Expression Profi ling Using Microfl uidic Living Cell Arrays ................................................................................. 211 Kevin R. King, Martin L. Yarmush, and Arul Jayaraman 11 New Approaches to the Synthesis of Addressable Microarray Molecular Libraries .......................................................... 227 Karl Maurer and Kevin D. Moeller 12 eSensor®: A Microarray Technology Based on Electrochemical Detection of Nucleic Acids and Its Application to Cystic Fibrosis Carrier Screening .................................................................................. 247 Michael R. Reed and William A. Coty Part V Future Improvements in Microarray Sensing 13 Use of Redox Enzymes for the Electrochemical Detection of Sequence-Specifi c DNA and Immunochemical Entities ................ 263 Kilian Dill and Andrey Ghindilis 14 Biochip Platforms for Dna Diagnostics ................................................ 271 Anil K. Deisingh, Adilah Guiseppi-Wilson, and Anthony Guiseppi-Elie 15 MagArray Biochips for Protein and DNA Detection with Magnetic Nanotags: Design, Experiment, and Signal-to-Noise Ratio ..................................................................... 299 Sebastian J. Osterfeld and Shan X. Wang