CRC Press is an imprint of the Taylor & Francis Group, an informa business Boca Raton London New York Bio-MEMS Technologies and Applications EDITED BY Wanjun Wang • Steven A. Soper DK532X_C000.fm Page i Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2007 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number-10: 0-8493-3532-9 (Hardcover) International Standard Book Number-13: 978-0-8493-3532-7 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the conse- quences of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www. 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data BioMEMS : technologies and applications / edited by Wanjun Wang and Steven A. Soper. p. cm. Includes bibliographical references and index. ISBN 0-8493-3532-9 (alk. paper) 1. BioMEMS. I. Wang, Wanjun, 1958- II. Soper, Steven A. TP248.25.B54B56 2006 660.6 dc22 2006045665 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com DK532X_C000.fm Page ii Monday, November 13, 2006 7:24 AM copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) © 2007 by Taylor & Francis Group, LLC Table of Contents Preface v About the Editors vii Contributors ix 1 Introduction 1 Wanjun Wang and Steven A. Soper Part I Basic Bio-MEMS Fabrication Technologies 2 UV Lithography of Ultrathick SU-8 for Microfabrication of High-Aspect-Ratio Microstructures and Applications in Microfluidic and Optical Components 11 Ren Yang and Wanjun Wang 3 The LIGA Process: A Fabrication Process for High-Aspect-Ratio Microstructures in Polymers, Metals, and Ceramics 43 Jost Goettert 4 Nanoimprinting Technology for Biological Applications 93 Sunggook Park and Helmut Schift 5 Hot Embossing for Lab-on-a-Chip Applications 117 Ian Papautsky Part II Microfluidic Devices and Components for Bio-MEMS 6 Micropump Applications in Bio-MEMS 143 Jeffrey D. Zahn 7 Micromixers 177 Dimitris E. Nikitopoulos and A. Maha DK532X_C000.fm Page iii Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC 8 Microfabricated Devices for Sample Extraction, Concentrations, and Related Sample Processing Technologies 213 Gang Chen and Yuehe Lin 9 Bio-MEMS Devices in Cell Manipulation: Microflow Cytometry and Applications 237 Choongho Yu and Li Shi Part III Sensing Technologies for Bio-MEMS Applications 10 Coupling Electrochemical Detection with Microchip Capillary Electrophoresis 265 Carlos D. García and Charles S. Henry 11 Culture-Based Biochip for Rapid Detection of Environmental Mycobacteria 299 Ian Papautsky and Daniel Oerther 12 MEMS for Drug Delivery 325 Kabseog Kim and Jeong-Bong Lee 13 Microchip Capillary Electrophoresis Systems for DNA Analysis 349 Ryan T. Kelly and Adam T. Woolley 14 Bio-MEMS Devices for Proteomics 363 Justin S. Mecomber, Wendy D. Dominick, Lianji Jin, and Patrick A. Limbach 15 Single-Cell and Single-Molecule Analyses Using Microfluidic Devices 391 Malgorzata A. Witek, Mateusz L. Hupert, and Steven A. Soper 16 Pharmaceutical Analysis Using Bio-MEMS 443 Celeste Frankenfeld and Susan Lunte DK532X_C000.fm Page iv Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC Preface Applications of microelectromechanical systems (MEMS) and microfabrica- tion have spread to different fields of engineering and science in recent years. Perhaps the most exciting development in the application of MEMS technol- ogy has occurred in the biological and biomedical areas. In addition to key fluidic components, such as microvalves, pumps, and all kinds of novel sensors that can be used for biological and biomedical analysis and mea- surements, many other types of so-called micro total analysis systems (TAS) have been developed. The advantages of such systems are that microvolumes of biological or biomedical samples can be delivered and processed for testing and analysis in an integrated fashion, thereby dramatically reducing the required human involvement in many steps of sample handling and processing. This helps to reduce the overall cost of measurement and time, while improving the sensitivity in most cases. Many books have been published on these subjects in recent years, but most of them have focused primarily on various fabrication technologies with a few application areas highlighted. Unfortunately, in this burgeoning area, only a couple of books have been directed specifically toward biomed- ical MEMS. As MEMS applications spread to all corners of science and engineering, more and more universities and colleges are offering courses in the bio-MEMS area. In comparison with other MEMS areas, which typi- cally involve different engineering disciplines, such as the mechanical, elec- trical, and optical fields, the development of bio-MEMS devices and systems involves a truly interdisciplinary integration of basic sciences, medical sci- ences, and engineering. This is the primary reason bio-MEMS is still in the earliest stages of development in comparison with electrical and mechanical sensing devices and systems. Due to the complexity and interdisciplinary nature of bio-MEMS, it is critical to include a diverse range of expertise in the composition of a book that attempts to cover the bio-MEMS area from both a fabrication and application point of view. This is the reason we have assembled a large group of leading researchers actively working in basic science, engineering, and biomedical areas to contribute to this book. Bio- MEMS: Technologies and Applications is divided into three sections: 1. Basic Bio-MEMS Fabrication Technologies 2. Microfluidic Devices and Components for Bio-MEMS 3. Sensing Technologies and Bio-MEMS Applications The book targets audiences in the basic sciences and engineering, both indus- trial engineers and academic researchers. Efforts have been made to ensure DK532X_C000.fm Page v Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC that while enough topics on the cutting edge of bio-MEMS research are covered, the book is still easy to read. In addition to structurally organizing the book from basic materials to advanced topics, we have made sure that each chapter and subject area are covered beginning with basic principles and fundamentals. Because of the shortage of suitable textbooks in this area, this collection is designed to be reasonable for graduate education as well as working application engineers who are interested in getting into this exciting new field. DK532X_C000.fm Page vi Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC About the Editors Wanjun Wang received his B.S. in mechanical engineering from Xian Jiao- tong University of China in 1982. He received his M.S. and Ph.D. degrees in mechanical engineering from the University of Texas at Austin in 1986 and 1989, respectively. He joined the faculty of the mechanical engineering department of Louisiana State University, Baton Rouge, in 1994 and has been teaching and doing research in microfabrication and MEMS for more than 13 years. His main research specialty has been in UV-LIGA microfabrication technology, especially in the UV lithography of ultra-thick SU-8 resist and applications in microfluidics, micro-optics, and micro-sensors/actuators. In the last 10 years, he has received research funding in MEMS and microfab- rication from many state and federal agencies, such as the National Science Foundation, the National Institutes of Health, and the Board of Regents of Louisiana. Dr. Wang has authored or co-authored more than seventy papers in technical journals and proceedings of conferences. Dr. Wang has also received five patents for sensors and actuators, as well as for microfluidic and micro-optic components. He has also taught courses in the areas of sensors and actuators, instrumentations, MEMS and microfabrication tech- nologies for many years. He is currently a senior member of IEEE, and a member of ASME and SPIE. Prof. Steven A. Soper received his Ph.D. in bioanalytical chemistry from the University of Kansas (KU) in 1989. While at KU, he received several awards, such as the Huguchi Distinguished Doctoral Candidate Award and the American Chemical Society Award for research in analytical chemistry (sponsored by the Pittsburgh Conference). Following graduation, Dr. Soper accepted a postdoctoral fellowship at Los Alamos National Laboratory, where he worked on single molecule detection methods for the high-speed sequencing of the human genome. As a result of this work, he received an R&D 100 award in 1991. Dr. Soper joined the faculty at Louisiana State University (LSU) in the fall of 1991 as an assistant professor. He was promoted to associate professor in 1997 and to full professor in 2000. In 2002, Steven received a chaired professorship in chemistry at LSU (William L. & Patricia Senn, Jr. Chair). His research interests include micro- and nanofabrication of integrated sys- tems for biomedicine, chemical modification of thermoplastic materials, ultra-sensitive fluorescence spectroscopy (time-resolved and steady-state), high-resolution electrophoresis, sample preparation methods for clinical analyses, and microfluidics. As a result of his efforts, he has secured extra- mural funding from such agencies as the National Institutes of Health, DK532X_C000.fm Page vii Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC Whitaker Foundation, American Chemical Society, Department of Energy, and the National Science Foundation. Steven has published over 160 manu- scripts in various research publications and is the author of three patents. In addition, Steven has given approximately 165 technical presentations at national/international meetings and universities since 1995. Steven is now the director of a major multi-disciplinary research center at LSU, which is funded through the NSF. Prof. Soper has received several awards for his research accomplishments while at LSU, including the Outstanding Untenured Researcher (Physical Sciences, Louisiana State University, 1995) presented by Phi Kappa Phi; Outstanding Researcher in the College of Basic Sciences (Louisiana State University, 1996); and Outstanding Science/Engineering Research in the state of Louisiana (2001). In 2006, Dr. Soper was awarded the Benedetti- Pichler Award in Microchemistry. Prof. Soper is also involved in various national activities, such as serving on review panels for the National Institutes of Health, the Department of Energy, and the National Science Foundation. In addition, he serves on the advisory board for several technical journals including Analytical Chemistry (A-page editorial board), Journal of Fluorescence , and The Analyst. DK532X_C000.fm Page viii Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC Contributors Gang Chen Department of Chemistry, Fudan University, Shanghai, China Wendy D. Dominick Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, U.S.A. Celeste Frankenfeld Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas , U.S.A. Carlos D. García Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas, U.S.A. Jost Goettert The J. Bennett Johnston, Sr. Center for Advanced Microstructures and Devices, Louisiana State University, Baton Rouge, Louisiana, U.S.A. Charles S. Henry Department of Chemistry, Colorado State University, Fort Collins, Colorado, U.S.A. Mateusz L. Hupert Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana, U.S.A. Lianji Jin Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, U.S.A. Ryan T. Kelly Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, U.S.A. Kabseog Kim HT MicroAnalytical, Inc., Albuquerque, New Mexico, U.S.A. Jeong-Bong (J-B.) Lee Department of Electrical Engineering, University of Texas at Dallas, Richardson, Texas, U.S.A. Patrick A. Limbach Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio , U.S.A. Yuehe Lin Pacific Northwest National Laboratory, Richland, Washington, U.S.A. Susan Lunte Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas, U.S.A. DK532X_C000.fm Page ix Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC A. Maha Mechanical Engineering Department, Louisiana State University, Baton Rouge, Louisiana Justin S. Mecomber Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, U.S.A. Dimitris E. Nikitopoulos Professor, Mechanical Engineering Department, Louisiana State University, Baton Rouge, Louisiana, U.S.A. Daniel Oerther Department of Civil and Environmental Engineering, University of Cincinnati, Cincinnati, Ohio, U.S.A. Ian Papautsky Department of Electrical and Computer Engineering, University of Cincinnati, Cincinnati, Ohio, U.S.A. Sunggook Park Mechanical Engineering Department, Louisiana State University, Baton Rouge, Louisiana, U.S.A. Helmut Schift Laboratory for Micro- and Nanotechnology, Paul Scherrer Institut, Villigen, Switzerland Li Shi Mechanical Engineering Department, The University of Texas at Austin, Austin, Texas, U.S.A. Steven A. Soper Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana, U.S.A. Wanjun Wang Department of Mechanical Engineering, Louisiana State University, Baton Rouge, Louisiana, U.S.A. Malgorzata. A. Witek Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana, U.S.A. Adam T. Woolley Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, U.S.A. Ren Yang Department of Mechanical Engineering, Louisiana State University, Baton Rouge, Louisiana, U.S.A. Choongho Yu Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, U.S.A. Jeffrey D. Zahn Department of Bioengineering, Pennsylvania State University, University Park, Pennsylvania, U.S.A. DK532X_C000.fm Page x Monday, November 13, 2006 7:24 AM © 2007 by Taylor & Francis Group, LLC [...]... 1.1 Main Contents and Organization of the Book The contents in this book can be generally divided into three basic sections: 1 Basic Bio-MEMS Fabrication Technologies (Chapters 2, 3, 4, and 5); 2 Microfluidic Devices and Components for Bio-MEMS (Chapters 6, 7, 8, and 9); 3 Sensing Technologies and Bio-MEMS Applications (Chapters 10, 11, 12, 13, 14, 15, and 16) 1.1.1 Microfabrication Technologies In this... of design and fabrication technologies of MEMS devices and systems Most of these books have focused on silicon-based technologies, such as surface micromachining, and wet and dry etching technologies (RIE and DRIE processes) As bio-MEMS technologies develop and many educational institutions begin to offer courses on this subject matter, textbooks covering both the fundamental fabrication technologies. ..DK532X_book.fm Page 1 Tuesday, November 14, 2006 10:41 AM 1 Introduction Wanjun Wang and Steven A Soper CONTENTS 1.1 Main Contents and Organization of the Book 4 1.1.1 Microfabrication Technologies 4 1.1.2 Microfluidic Devices and Components for Bio-MEMS 5 1.1.3 Sensing Technologies and Bio-MEMS Applications 6 1.2 Suggestions for Using This Book as a Textbook 7 The last decade... Tuesday, November 14, 2006 10:41 AM 2 Bio-MEMS: Technologies and Applications of such systems are the microvolumes of biological or biomedical samples that can be delivered and processed for testing and analysis in an integrated fashion, therefore dramatically reducing the required human involvement in many steps of sample handling and processing, and improving data quality and quantitative capabilities This... cytometry and a review of the state-of-the-art in this field 1.1.3 Sensing Technologies and Bio-MEMS Applications (Chapters 10, 11, 12, 13, 14, 15, and 16) Because of the enormous variations in biological and biomedical samples, the processing and detection principles required for the analysis of targets are often completely different There have been numerous bio-MEMS either in commercial applications. .. monochromatic source waves, r and r0 stand for positions of a point on the aperture relative to the screen and the source, respectively, (n, r) and (n, r0) © 2007 by Taylor & Francis Group, LLC DK532X_book.fm Page 16 Tuesday, November 14, 2006 10:41 AM 16 Bio-MEMS: Technologies and Applications denote the angles between the vectors and the normal to the surface of integration, and ds represents the integration... impossible to cover all of them in the limited space of this book In addition, bio-MEMS technologies are still in their early stages of development and as such new and novel technologies are constantly evolving with the potential for integration into bio-MEMS The seven chapters in this section cover some of the representative technologies in this rapidly developing area Chapter 11 focuses on the topic... Basic Bio-MEMS Fabrication Technologies © 2007 by Taylor & Francis Group, LLC DK532X_book.fm Page 11 Tuesday, November 14, 2006 10:41 AM 2 UV Lithography of Ultrathick SU-8 for Microfabrication of High-Aspect-Ratio Microstructures and Applications in Microfluidic and Optical Components Ren Yang and Wanjun Wang CONTENTS 2.1 Introduction 12 2.2 Numerical Study of Diffraction Compensation and. .. technologies and interested readers can always refer to these books Secondly, the current trends in bio-MEMS seem to be in the direction of using nonsilicon-based fabrication technologies and materials Because biologists and chemists have long used nonsilicon materials, such as glasses and polymers (PMMA, polycarbonate, etc.), various surface treatment technologies have been developed and processes... 6 Tuesday, November 14, 2006 10:41 AM 6 Bio-MEMS: Technologies and Applications it is necessary to integrate all of the components for sample preparation (including sample extraction, sample preconcentration, and sample derivatization), sample introduction, separation, and detection onto a single microchip made from either glass, silica, or polymers In most bio-MEMS, the sample usually undergoes some . AM Basic Bio-MEMS Fabrication Technologies (Chapters 2, 3, 4, and 5); Microfluidic Devices and Components for Bio-MEMS (Chapters 6, 7, 8, and 9); Sensing Technologies and Bio-MEMS Applications. Microfluidic Devices and Components for Bio-MEMS 3. Sensing Technologies and Bio-MEMS Applications The book targets audiences in the basic sciences and engineering, both indus- trial engineers and academic. Wanjun Wang and Steven A. Soper Part I Basic Bio-MEMS Fabrication Technologies 2 UV Lithography of Ultrathick SU-8 for Microfabrication of High-Aspect-Ratio Microstructures and Applications in