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Microfluidics for Biological Applications

Wei-Cheng Tian · Erin Finehout Editors Microfluidics for Biological Applications 1 3

Editors Wei-Cheng Tian General Electric Global Research Center 1 Research Circle Niskayuna, NY 12309 Erin Finehout General Electric Global Research 1 Research Circle Niskayuna, NY 12309 ISBN: 978-0-387-09479-3 e-ISBN: 978-0-387-09480-9 Library of Congress Control Number: 2008930844  2008 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. Printed on acid-free paper springer.com

To my family Erin Finehout To Gan-Wu, Yu-Hsien, Wei-Hua, Kaitlyn, Darren, and Jennifer Wei-Cheng Tian

Preface In Nobel Prize winner Richard Feynman’s well-known 1959 speech “There’s Plenty of Room at the Bottom” [1] he marvels that although many biological systems, such as cells, are very small, they are active and perform a number of functions. He then poses the challenge “Consider the possibility that we too can make a thing very small which does what we want – that we can manufacture an object that maneuvers at that level!” [1] In this book we hope to show readers that we are getting closer to meeting this challenge. We have tools to manipulate and analyze small volumes of biomolecules (such as DNA and protein); we can manipulate and analyze individual cells; and we can create nanodrops, the size of a cell, to perform specific chemical reactions. All of these have been made possible by the application of microfluidics. This book consists of a selection of review articles that are intended to show how microfluidics is applied to solve biological problems; why mi- crofluidics continues to play an important role in this field; and what needs to be done next. We will introduce not only the various technologies of microfluidics but also how to link these technologies to different biological applications at the industrial and academic level. Chapters 1-3 give perspective on the history and development of microfluidic technolo- gies. They also serve to give a physical understanding of microfluidic de- vices. Chapter 1 covers the physics and fluid dynamics of microscale flows. Chapter 2 summarizes the materials and methods used to fabricate microfluidic devices in biological applications. Chapter 3 gives solutions to how these microscale devices can be interfaced with the macro scale world. Chapters 4-66 give overviews on how microfluidic systems have been used to study and manipulate specific classes of components. Microfluidic devices samples (Chapter 4); separate and analyze protein mixtures (Chapter 5); and culture, separate, and analyze cells (Chapter 6). Chapters 7-10 focus on specific biological applications of microfluidics: tissue engineering (Chap- ter 7), high throughput screening (Chapter 8), diagnostics (Chapter 9), and biodefense (Chapter 10). And finally, Chapter 11 discusses have been used to: prepare, amplify, and analyze DNA 6

viii emerging trends in the microfluidics field and the current challenges to the growth and continuing success of the field. In all the chapters, the authors give information on the biological problems that need to be solved, the current research that is being done to address them, and the obstacles that still remain. In addition, there are summaries of the types of products that have been commercialized in each area. This book is intended to be used at the senior undergraduate or graduate level for students. It will also be a great resource for researchers and scientists in the biotechnology, pharmaceutical, and life science industries. We hope to provide the readers with an overview of microfluidics and its current ap- plications to encourage readers to think about how these technologies could help them in their own fields. Reading through the chapters there are a few recurring themes that merit being mentioned here. The first is that the application of microfluidics isn’t just about saving time, cutting costs, and needing less reagents. Working in the microfluidic regime enables scientists to perform experiments and use techniques that simply aren’t possible at a larger scale. The second theme is that for the microfluidics field as a whole to continue to move forward in the biological area, it is vital that scientists from different fields (engineers, chemists, material scientists, biologist, etc.) work together. Only with such collaborations can one be sure that the right questions are being addressed, the right methods are being applied, and the optimal tools are being used. The editors would like to thank Steven Elliot and Angela DePina at Springer for their help in pulling this book together. We would also like to show our appreciation to the authors for all of the time and effort they put towards writing their chapters. Lastly, we’d like to thank our friends and family for their support and patience during this project. References: 1. Feynman RP (1960) There’s plenty of room at the bottom: An invitation to en- ter a new field of physics. Engineering and Science 23:22-36.

Contents Chapter 1 Introduction to Microfluidics ................................................ 1 Abstract...................................................................................................1 1 Introduction to Microfluidics...............................................................2 1.2 History of Microfluidics ...................................................................3 1.2.1 The beginning: Gas chromatography and capillary electrophoresis....................................................................................3 1.2.2 The microfluidic advantage....................................................... 5 1.2.3 Modular separation, reaction and hybridization systems ..........7 1.2.4 Integrated systems .....................................................................8 1.3 Fluidics and Transport Fundamentals.............................................10 1.3.1 The continuum approximation.................................................10 1.3.2 Laminar flow ...........................................................................10 1.3.3 Diffusion in microfluidic systems ...........................................12 1.3.4 Surface forces and droplets......................................................14 1.3.5 Pumps and valves ....................................................................16 1.3.6 Electrokinetics .........................................................................16 1.3.7 Thermal management ..............................................................18 1.4 Device Fabrication..........................................................................18

x 1.4.1 Materials..................................................................................19 1.4.2 Fabrication and assembly ........................................................20 1.5 Biological Applications ..................................................................21 1.5.1 Genetic analysis (DNA/RNA) .................................................22 1.5.2 Proteomics ...............................................................................22 1.5.3 Cellular assays .........................................................................23 1.5.4 Drug delivery and compatibility..............................................24 1.6 The Future.......................................................................................26 1.6.1 Potential demand/market for microfluidic devices..................26 1.6.2 Current products ......................................................................27 1.6.3 Challenges and the future ........................................................28 References ............................................................................................29 Chapter 2 Materials and Microfabrication Processes for Microfluidic Devices ...................................................................................................... 35 Abstract.................................................................................................35 2.1 Introduction ....................................................................................36 2.2 Silicon Based Materials ..................................................................37 2.2.1 Micromachining of silicon.......................................................39 2.2.2 Bulk micromachining ..............................................................39 2.2.3 Surface micromachining..........................................................46 2.3 Glass Based Materials.....................................................................49 2.3.1 Microfabrication in glass......................................................... 51 2.4 Wafer Bonding ............................................................................... 56 2.4.1 Fusion bonding ........................................................................ 57 2.4.2 Anodic bonding ....................................................................... 57 2.4.3 Adhesive bonding.................................................................... 58 2.5 Polymers ......................................................................................... 59 2.5.1 Microfabrication ...................................................................... 59 2.5.2 Polymer materials:...................................................................64 2.6 Conclusion......................................................................................82 References ............................................................................................82 Chapter 3 Interfacing Microfluidic Devices with the Macro World.. 93 Abstract.................................................................................................93 3.1 Introduction ....................................................................................94 3.2 Typical Requirements for Microfluidic Interfaces .........................94 3.3 Review of Microfluidic Interfaces..................................................95 3.3.1 World-to-chip interfaces..........................................................95 3.3.2 Chip-to-world interfaces........................................................103 3.4. Future Perspectives......................................................................112 References ..........................................................................................113

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