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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
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© 2007 by Taylor & Francis Group, LLC
CRC Press
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© 2007 by Taylor & Francis Group, LLC
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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
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© 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
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© 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
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© 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
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© 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.
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© 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,
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© 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.
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© 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.
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© 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.
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[...]... 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. .. 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...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... 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... analog world in which we live For example, various sensors and actuators may be produced using MEMS technologies, and these sensors and actuators can then be used as interfaces between computers and the physical environment for the purposes of information processing and intelligent control In recent years, one of the most exciting progresses in MEMS applications is the rapid evolution of biological-microelectromechanical... to the basic lithography processing steps and optimal processing conditions, example applications in microfluidic devices and micro-optic devices are also presented Chapter 3 provides a very detailed presentation on the LIGA process Applications of LIGA technologies in fabricating polymer bio-MEMS are also introduced Nanoimprint lithography (NIL) is a low cost and flexible patterning technique particularly... 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 . (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 (Chapters. as surface
micromachining, and wet and dry etching technologies (RIE and DRIE pro-
cesses). As bio-MEMS technologies develop and many educational institu-
tions
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