Microfluidics and Biomems Applications Microsystems

MICROFLUIDICS AND BIOMEMS APPLICATIONS MICROSYSTEMS

Volume 10

Series Editor Stephen D. Senturia Massachusetts Institute of Technology

Editorial Board

Roger T. Howe, University of California, Berkeley D. Jed Harrison, University of Alberta Hiroyuki Fujita, University of Tokyo Jan-Ake Schweitz, Uppsala University

OTHER BOOKS IN THE SERIES:

Methodology for the Modelling and Simulation of Microsystems Bartlomiej F. Romanowicz Hardbound, ISBN 0-7923-8306-0, October 1998 Microcantilevers for Atomic Force Microscope Data Storage Benjamin W. Chui Hardbound, ISBN 0-7923-8358, October 1998 Bringing Scanning Probe Microscopy Up to Speed Stephen C. Minne, Scott R. Manalis, Calvin F. Quate Hardbound, ISBN 0-7923-8466-0, February 1999 Micromachined Ultrasound-Based Proximity Sensors Mark R. Hornung, Oliver Brand Hardbound, ISBN 0-7923-8508-X, April 1999 Microfabrication in Tissue Engineering and Bioartificial Organs Sangeeta Bhatia Hardbound, ISBN 0-7923-8566-7, August 1999 Microscale Heat Conduction in Integrated Circuits and Their Constituent Films Y. Sungtaek Ju, Kenneth E. Goodson Hardbound, ISBN 0-7923-8591-8, August 1999 Scanning Probe Lithography Hyongsok T. Soh, Kathryn Wilder Guarini, Calvin F. Quate Hardbound, ISBN 0-7923-7361-8, June 2001 Optical MicroScanners and Microspectrometers using Thermal Bimoph Actuators Gerhard Lommel, Sandra Schweizer, Philippe Renaud Hardbound, ISBN 0-7923-7655-2, January 2002 Microfluidics and BioMEMS Applications

edited by

Francis E.H. Tay The National University of Singapore

SPRINGER-SCIENCE+BUSINESS MEDIA B.V. A C.l.P. Catalogue record for this book is available from the Library of Congress.

ISBN 978-1-4419-5316-2 ISBN 978-1-4757-3534-5 (eBook) DOI 10.1007/978-1-4757-3534-5

Printed on acid-free paper

No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. TABLE OF CONTENTS

Table of Contents ...... v List of Contributors ...... ix Foreword ...... xi Preface ...... xiii Acknowledgements ...... xxi

PART I ...... !

Chapter 1 Literature Review for Micropumps ••••••.•••••••••.••••••••. 3 1.1 Origins of Micropump Research ...... 3 1.2 Mechanical Micropumps ...... 5 1.2.1 Reciprocating Micro pumps ...... 8 1.2.1.1 Piezoelectric Actuation ...... 9 1.2.1.2 Thermo-pneumatic Actuation ...... 10 1.2.1.3 Electrostatic Actuation ...... 11 1.2.1.4 Pneumatic Actuation ...... 12 1.2.1.5 Shape Memory Alloy (SMA) Actuation ...... 13 1.2.2 Peristaltic Micro pumps ...... 14 1.2.2.1 Piezoelectric Actuation ...... 15 1.2.2.2 Thermo-pneumatic Actuation ...... 15 1.2.3 Reciprocating Micropumps With Dynamic Micro-valves 16 1.3 Non-mechanical Micropumps ...... 18 1.3.1 Electro-hydrodynamic (EHD) Micropumps ...... 18 1.3 .1.1 DC-charge injection EHD micropump ...... 18 1.3.1.2 Travelling wave voltage EHD micropump ...... 19 1.3.2 Electro-osmotic Micropumps ...... 20 1.3.3 Ultrasonic Micropumps ...... 21 1.3.4 Magneto-hydrodynamic (MHO) Micropumps ...... 22 1.4 Motivation ...... 23

v Vl Microjluidics and BioMEMS Applications

Chapter 2 Design Rules for Micropumps...... 25 2.1 Preliminary Design ...... 25 2.1.1 Piezoelectric Actuation ...... 26 2.2 Compression Ratio ...... 29 2.2.1 Determination of Volume Stroke ...... 30 2.2.1.1 Analytical Model ...... 31 2.2.1.2 Finite Element Model...... 35 2.2.2 Determination of Dead Volume ...... 42 2.2.3 Determination of Compression Ratio ...... 43 2.3 Criterion for Switching of Valve ...... 43 2.3 .1 Surface Energy Consideration ...... 44 2.3.2 Elasto-mechanical Consideration ...... 46 2.4 Criterion for Self-priming Capability ...... 48 2.5 Criterion for Bubble Tolerance ...... 50

Chapter 3 Modelling and Simulation ...... 53 3.1 Background ofMicrofluidics Systems Modelling ...... 53 3.2 Governing Equation for Micro-pumps ...... 54 3.3 Modelling of the Actuator Unit...... 57 3.4 Modelling of the Inlet Valve ...... 61 3.5 Modelling of the Outlet Valve ...... 64 3.6 System Model of Proposed Micro-pump ...... 65

Chapter 4 Process Development and Fabrication ...... 69 4.1 Bulk Silicon Micromachining ...... 70 4.1.1 Photolithography ...... 70 4.1.2 Thin Film Deposition ...... 72 4.1.2.1 Oxidation of Silicon ...... 72 4.1.2.2 Low Pressure Chemical Vapour Deposition of Silicon Nitride ...... 74 4.1.3 Wet Etching ...... 74 4.1.3.1 Concave Mask Geometry ...... 76 4.1.3.2 Convex Mask Geometry ...... 78 4.1.4 Dry Etching ...... 81 4.2 Process Flow ...... 82 4.2.1 Silicon Process ...... 82 4.2.2 Glass Process For Top Glass Wafer...... 92 4.2.3 Glass Process For Bottom Glass Wafer ...... 93 4.2.4 Wafer Bonding ...... 95

Chapter 5 Verification and Testing ...... 101 5.1 Experimental Set-up ...... 101 5.2 Piezoelectric Actuator Unit Model Verification ...... 104 Table of Contents Vll

5.2.1 Analytical Model Verification ...... 104 5.2.2 FEM Model Verification ...... 107 5.3 Preliminary Functional Tests ...... 109 5.4 Conclusions And Recommendations ...... 111 5.4.1 Conclusions ...... 111 5.4.2 Recommendations ...... 112

References ...... 115

Appendices ...... 121 Appendix A ...... 121 Appendix B ...... 128 Appendix C ...... 133 Appendix 0 ...... 138

PART II •••...•••.••••••.••••.••••.••••••••••••••••••.•••••.•••••.•••••.•••••.••••• 141

Chapter 6 Development of Integrated Microfluidic Devices for Genetic Analysis

Robin H. Liu and Piotr Grodzinski ...... 143

Chapter 7 Microfluidic Devices on Printed Circuit Board

Stefan Richter, Nam-Trung Nguyen, Ansgar Wego, and Lienhard Pagel ...... 185

Chapter 8 Nano and Micro Channel Flows of Rio• Molecular Suspension

Fan Xijun, Nhan Phan-Thien, Ng Teng Yong, Wu Xuhong, and Xu Diao ...... 219

Chapter 9 Transport of Liquid in Rectangular Micro• Channels by Electroosmotic Pumping

Chun Yang ...... 265

Chapter 10 A Development of Slip Model and Slip• Corrected Reynolds Equation for Gas Lubrication in Magnetic Storage Device viii Microjluidics and BioMEMS Applications

Eddie Yin-Kwee Ng, Ningyu Liu, and Xiaohai Mao ...... 287

Chapter 11 Short Notes on Particle Image Velocimetry for Micro/Nano Fluidic Measurements

Chee Yen Lim and Francis E. H. Tay ...... 307

Index ...... 331 LIST OF CONTRIBUTORS

PART I by Francis E. H. Tay and W. 0. Choong PART II

Chapter6 Development of Integrated Microfluidic Devices for Genetic Analysis by Robin H. Liu and Piotr Grodzinski; Microfluidics Laboratory, PSRL, Motorola Labs, USA.

Chapter7 Microfluidic Devices on Printed Circuit Board by Stefan Richter, Nam-Trung Nguyen, Ansgar Wego, and Lienhard Pagel; University of Rostock, Germany; Nanyang Technological University, Singapore.

ChapterS Nano and Micro Chamiel Flows ofBio-Molecular Suspension by Fan Xijun, Nhan Phan-Thien, Ng Teng Yong, Wu Xuhong, and Xu Diao; Institute of High Performance Computing, Singapore; Bioengineering Division, Natinal University of Singapore, Singapre.

Chapter9 Transport of Liquid in Rectangular Micro-Channels by Electroosmotic Pumping by Chun Yang; School of Mechanical and Production Engineering, Nanyang Technological University, Singapore.

Chapter 10 A Development of Slip Model and Slip-Corrected Reynolds Equation for Gas Lubrication in Magnetic Storage Device

lX X Microjluidics and BioMEMS Applications by Eddie Yin-Kwee Ng, Ningyu Liu, and Xiaohai Mao; Nanyang Technological University, Singapore.

Chapter 11 Short Notes on Particle Image Velocimetry for Micro/Nano Fluidic Measurements by Chee Yen Lim and Francis E. H. Tay; Institute of Materials Research and Engineering, Singapore. FOREWORD

The past 10-15 years have shown an explosive growth in research on and development of BIOMEMS, Micro Total Analysis Systems (J..LTAS), or Lab• on-Chip devices. The field emerged as a promising marriage between the well-established area of MEMS and that of bio-analytical chemistry, and was in particular driven by the immense efforts put in the Human Genome Project and related, mostly US-based, funding. The field was originally constituted by researchers from micromechanical and analytical chemistry, as rapid amino acid and DNA separations carried out in micromachined channels in quartz were the most powerful demonstration of the potential of the Lab-on-Chip concept. More recently the field has enormously widened, comprising areas such as protein analysis, genomics and proteomics, cell analysis, DNA diagnostics, environmental assays, drug discovery, chemistry on chips, and biochemical arrays. A very important common aspect in all of these applications, however, remains the handling and control of extremely small amounts of fluids (mostly liquids), also called microfluidics. After the first demonstration of a micromachined piezo-actuated pump in our institute in the late '90's (van Lintel et al.) it became clear that fluid flow control on a small scale was possible. Nowadays, the area of microfluidics is considered crucial for development of Lab-on-Chip applications, as it enables careful handling and treatment of minuscule amounts of precious biochemical samples. Unfortunately up to now no textbooks exist that could serve to introduce students in this multidisciplinary field. In this book a two-track approach has been chosen: in the first part a case study, the development of a micropump, is systematically worked out. This will be a great help for those researchers that focus on efficiently developing particular, well-defmed microfluidic devices using all modem techniques and tools currently available. The second part of the book forms a very useful complement to the first part, as it presents a variety of examples of microfluidics theory, phenomena, techniques and concepts authored by international leading experts. Here you fmd a book that will undoubtedly help to develop skills needed for the design and realization of microfabricated fluid devices whereas it provides at the same time an introduction to the world of microfluidics in all

xi xii Microjluidics and BioMEMS Applications its aspects. All people working in the area of microfabricated fluid devices, should consider this book as an indispensable and very valuable tool.

Albert van den Berg Enschede, July 1011\2002. PREFACE

The idea of writing this book comes as a result of frequent enquiries about the possibility of publishing a book on documenting MEMS problems in its golden era. A first round survey of the literature showed that abundant researches on almost every aspect of MEMS have been carried out in recent years, so that any of the books can no longer give a comprehensive and balanced picture of the field. As a result, it was felt that a direct collection of peer-reviewed papers was hardly adequate; instead a new book based on substantially new concept was prepared, which is now placing before the reader. In planning this book, it soon became apparent that even if only the most important developments and relevant problems which took place from recent publications were documented, the book would seem impracticably thick. It was, therefore, necessary to restrict its scope to a narrower field. These subjects can be treated more appropriately if only the central ideas of MEMS development are tackled. The fact would be that, even after this limitation, the book would have been much larger than that in our expectation, giving some implication about the extent of the researches that have been carried out in MEMS related fields in recent times. We have envisaged that by demonstrating a comprehensive development of a micro pump, which is the heart of most lab-on-a-chip or BioMEMS devices for delivering fluid flows, we can illustrate the overall picture in the research and development of these tiny devices. We have also incorporated several selected articles that we think are useful in microfluidics and BioMEMS applications, hovering around the idea that MEMS devices are mostly associated with microfluidic flows; this is especially true for biomedical related devices, which have gained popularity and attention for their various miniaturization effects. These miniaturization effects include strict tolerance of high-yield, hatched processes in fabrication, quick mechanical response due to small inertia, maximum saving on chemicals and reagents, minimum waste on samples, etc. We have aimed at providing, within the skeleton we just outlined, a reasonably self-contained picture of our present knowledge and compilation that are separated into two parts in the book. In the first part, we have

xiii XIV Microjluidics and BioMEMS Applications attempted to present the approach of tackling a research problem in MEMS device development from the fundamentals, including a complete literature survey, modelling and simulation, process development and fabrication, and verification and testing. We have intentionally left out packaging and commercialisation stages for their industrial and commercial complexities. The second part of the book incorporates some valuable articles that are related to microfluidics and its applications, mostly of biomedical use or the related advanced modellings. The purpose of their incorporation as a separate part in the book serves the purpose of complementing the subject discussed in Part I, whose central idea is tackling a MEMS development problem. A specific device - the micro pump, deemed to be the most appropriate and relevant being the heart for any biomedical related and lab• on-a-chip products, has been exploited for this demonstration purpose. Flowchart I below depicts the concept of the presentation of the book, showing how the second part of article collection complement the first part of the book, which weighs equally with its counterpart in terms of length and importance:

r------Pa•·t I

Literature Rc\-icw~ Design ~ Proce!ii Developrmni Bnd t~abricabon~ Verification &. Tc~ling

Flowchart I. Complementary relationship between Part I and Part II Preface XV

As stated above, this book is divided into two parts. Part I consists of five chapters that deal with conception, design, fabrication and testing of a MEMS device. Chapter 1 presents a detailed literature review for a micro• pump, which is always a primary and mandatory step in performing any research irrespective of their nature. It categorizes micro pump into mechanical and non-mechanical categories (without moving parts, see Flowchart ll). The development trend for micro pump and its respective pumping principles are also studied and reported. The last portion of this chapter discusses the motivation of this entire part of the book.

I ' Nleto-Pumps I I l PuiJIMI Piloclples I I l Mechanlcat J Non-mechanical j

I Rotarv I j Reciorocatinc I I Peristallic I Electro- Eieetro- Traveling h~rodynamic osmotic Flexural I Wave I Valve Strucwre I

I Active I I Passive I

Dynamic Check Valves I "Valve· less" I I I

Flowchart II. Micro pumps categories by their pumping principles

Chapter 2 presents the design rules which are applicable to other development projects, reporting some mandatory steps in preliminary designing and consideration for a micro pump. In this chapter, compression ratio, valve switching criteria, self-priming capability and bubble tolerance are discussed. While the approach is limited to designing a micro pump, it is the author wish that the reader can realize the general rules of thumb in designing similar devices by induction. Chapter 3 is mainly concerned with modelling and simulation, which is often necessary before any fabrication of real prototype. It covers some governing equations based on Navier-Stokes equations, individual modellings of actuator, inlet valve and exit valve, and construction of a complete model. Again, by the demonstration of micro pump, the message behind the text is clear, and realization of the hidden application idea is quite clear in applying to other MEMS development projects. xvi Microjluidics and BioMEMS Applications

Chapter 4 deals with process development and fabrication of a micro pump, which involve mainly photolithography, thin film deposition, and wet etching. The entire process flow is also shown from silicon and glass processes, to wafer bonding. The last chapter in Part I, Chapter 5, contains the experimental verification and preliminary functional test for the micro pump developed based on previous chapters, which also includes some recommendations as fmal comments. Part II comprises six chapters, which are contributions from various prominent authors in the world. All but the last chapter were selected from contributions made to the International MEMS Workshop 2001, from 4th to 6th July 2001 at National University of Singapore, Singapore. Chapter 6, a contribution by Robin H. Liu and Piotr Grodzinski that bears the title "Development of integrated microfluidic devices for genetic analysis," discusses the design, fabrication, and testing of plastic microfluidic devices for on-chip genetic sample preparation and DNA microarray detection. Genetic analysis and microfluidics theory were included in its introduction, from which some beginners may find them very useful for quick references. Devices such as micromixers, microvalves, cell capture devices, on-chip micro-PCR, and other hybridization enhancements are also discussed in details. Chapter 7 "Microfluidic devices on printed circuit board," is contributed by Stefan Richter et al., revealing a new approach for fabrication of microfluidic devices based on printed circuit board (PCB) technology. Descriptions on the basic process steps in PCB fabrication considering the special needs of fluidic components to make it easier to understand the technological approach. Similar to Chapter 6, design, fabrication and characteristics of a number of sensors and actuators are also presented. Their Results of active components, including various types of pumps and sensors prove the feasibility of this new fabrication concept. Chapter 8 "Nano and micro channel flows of bio-molecular suspension," contributed by Xijun Fan et al., describes two particle methods, the molecular dynamics (MD) and dissipative particle dynamics (DPD), for simulating flow problems in micro and nano scales. Their simulation principles, governing equations and numerical implementations are presented in this paper, using molecular models that are used in polymer rheology to model bio-macromolecules. Results for both MD and DPD simulations are also presented and discussed. Chapter 9 "Transport of liquid in rectangular microchannels by electroosmotic pumping," contributed by Chun Yang, provides a theoretical framework for the phenomenon of electroosmotic flow in microchannels, in which the author analyses the characteristics of transient and steady-state Preface XVll electroosmotic flows in rectangular microchannels. An analytical solution to two-dimensional Poisson-Boltzmann equation that governs the electrical double-layer filed near the solid-liquid interface is developed here based on Debye-Hiickel approximation and Greens' function formula. Effects of various parameters on the electroosmotic velocity distributions in this chapter provide insights into the electroosmotic phenomenon. Chapter 10 "A development of slip model and slip-corrected Reynolds equation for gas lubrication in magnetic storage device," contributed by Eddie Yin-Kwee Ng et al., reports the implementation of direct simulation of Monte Carlo (DSMC) for ultra thin ftlm lubrication environment. The authors find that the slip velocity is affected not only by shear stress, but also by the density. Through this study, a new slip velocity model - stress-density ratio (SDR) model particularly suitable to the flows with large Knudsen numbers is developed, and a slip-corrected Reynolds equation is subsequently derived and solved numerically. Chapter 11 "Short notes on particle image velocimetry for micro/nano fluidic measurements," contributed by Chee Yen Lim and Francis Eng Hock Tay, discusses the application of a mature fluid visualization and measurement technique to measure fluidic flows in micro/nano scales. Several limiting issues, such as particle size, light diffraction limit, and the instrumentation were discussed. Some potential research directions were also included. Table I below summarises the central topics and key ideas of each chapter for both parts in the book:

Table I. Summary of chapters Ch. Title/Authors Central Methodo- Key Ideas Key words Topic logy

Literature Review Micro pump Complete Gathering, Micro pumps, development search on the understanding mechanical and literature and analysing pumps, non- categorization facts mechanical pumps 2 Design Rules Design Breakdown of Determining Piezoelectric consideration consideration criteria for dead actuation, s for factors and volume, valve compression piezoelectric design criteria switching, self- ratio, volume actuation priming capa- stroke, dead micro pump bility and bub- volume, finite ble tolerence element model, ABACUS, ANSYS 3 Modelling& Performing Computatio- Development Frequency Simulation simulations of nal, by and simulations mode shapes, components commercial of inlet and out- FEM and the entire software Jet valves, then simulations xviii Microjluidics arul. BioMEMS Applications

Ch. Title/Authors Central Methodo- Key Ideas Key words Topic logy

system before the entire fabrication system 4 Process Prototype Process and Building the Bulk silicon Development & building fabrication pump by thin- micromachin- Fabrication film depositi- ing, photolitho- on, etching, and graphy, thin wafer bonding fibn deposition, wet etching, wafer bonding 5 Verification & Verifying the Experimental Pump Functional Testing fabricated functionality tests, FEM pump test and model characteriza- verifications tion 6 Robin H. Liu and Device Process Demonstrating Micro-mixers/ Piotr Grodzinski development, development plastic microvalves, cell and system and system fabrication, capture device, integration integration micromoulding, integrated for on-chip etc. for bio- microPCR functionalities technology device, and applications microchannel DNA hybrida- zation arrays 7 Stefan Richter et Fabrication of Design, fabri- Development of PCB, sensors, al. microfluidic cation, and micro pumps, actuators, devices by characteriza- pH, flow& micro pumps PCB tion; pressure sensors technology numerical on PCB simulations 8 Xijun Fan et al. Advanced Computatio- bnplementing Biomacromole- modelling on nal, using molecular mo- cular bio-molecular molecular dels for simple suspensions, suspension dynamics and suspended MD,DPD, (MD) and liquids in nano- nano-/micro- dissipative channel channel particle dynamics (DPD) 9 Chun Yang Advanced Computationa Analysing Electroosmotic modelling on I, based on characteristics flow, electroosmo- basic of transient/ BioMEMS tic pumping transport steady state pumping, equations electroosmotic rectangular flow in rectan- micro-channel, gular micro- Greens' channel function approach Preface XlX

Ch. Title/Authors Central Methodo- Key Ideas Key words Topic logy

10 Eddie Yin-Kwee Slip Computatio- Development of SDRmodel, Ngetal. consideration nal, by slip- Stress-Density DSMC, in film corrected ratio (SDR) Reynolds lubrication Reynolds model, and equation, slip equation comparisons to coefficient, various models film lubrication 11 Chee Yen lim Discussion on Experimental Flow ceo cameras, and Francis E. H. modem flow in nature, by visualization pulsed laser, Tay visualization particle image and character- microscope, technique velocimetry ization in nano-particles, app-lied to (PlY) rnicro-/nano- cross- rnicro-/nano- scales by nano- correlation, fast fluidic particles Fourier trans- measurements form (FFT)

Though we have produced a book which in its methods of presentation and general approach would seem micro pump orientated in Part I, it would be evident from its later part that the present book is neither a documentary about developing a micro pump nor entirely a compilation of prestigious articles. Flowchart I above illustrates how the second part of the book complements the first part by exhibiting its related applications in literature surveying, designing, fabrication, and testing. Some advanced numerical modellings and simulations are also included for this purpose. We hope the reader can benefit from a series of related chapters and gain proficiency in tackling other research projects with similar nature and capacity. The references that are given, which we hope to cover the most important and relevant papers, are to equip the reader with a starter kit, or to help them attain some bearings in the literature; an omission of any particular research work should not be interpreted as due to our lack of regard for its merit. We have not included in our consideration about attempting the task of referring to all the relevant publications, which will be extremely difficult if not impossible. Lastly, we have, not always been able to use the most elegant notation but we hope that we have succeeded, at least, in avoiding the use in any one section of the same symbol for different quantities.

Francis E. H. Tay Editor ACKNOWLEDGEMENTS

It is a pleasure to thank many friends and colleagues for advice and help. In the first place we wish to record our gratitude to Mr Andojo Ongkodjojo Ong and Mr Yen Peng Kong for useful advice and assistance in early stages of this project, as well as their support for coordinating the article contributions from various authors through communications. We are also greatly indebted to Mr Chee Yen Lim, who helped in final stages of coordination work and in preparing camera-ready draft, including the index of the book.

xxi