Cell-Based Biosensors Principles and Applications Artech House Series Bioinformatics & Biomedical Imaging Series Editors Stephen T. C. Wong, The Methodist Hospital and Weill Cornell Medical College Guang-Zhong Yang, Imperial College Advances in Diagnostic and Therapeutic Ultrasound Imaging, Jasjit S. Suri, Chirinjeev Kathuria, Ruey-Feng Chang, Filippo Molinari, and Aaron Fenster, editors Biological Database Modeling, Jake Chen and Amandeep S. Sidhu, editors Biomedical Informatics in Translational Research, Hai Hu, Michael Liebman, and Richard Mural Cell-Based Biosensors: Principles and Applications, Ping Wang and Qinjun Liu, editors Data Mining in Biomedicine Using Ontologies, Mihail Popescu and Dong Xu, editors Genome Sequencing Technology and Algorithms, Sun Kim, Haixu Tang, and Elaine R. Mardis, editors High-Throughput Image Reconstruction and Analysis, A. Ravishankar Rao and Guillermo A. Cecchi, editors Life Science Automation Fundamentals and Applications, Mingjun Zhang, Bradley Nelson, and Robin Felder, editors Microscopic Image Analysis for Life Science Applications, Jens Rittscher, Stephen T. C. Wong, and Raghu Machiraju, editors Next Generation Artifi cial Vision Systems: Reverse Engineering the Human Visual System, Maria Petrou and Anil Bharath, editors Systems Bioinformatics: An Engineering Case-Based Approach, Gil Alterovitz and Marco F. Ramoni, editors Text Mining for Biology and Biomedicine, Sophia Ananiadou and John McNaught, editors Translational Multimodality Optical Imaging, Fred S. Azar and Xavier Intes, editors Cell-Based Biosensors Principles and Applications Ping Wang Qingjun Liu Editors Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the U.S. Library of Congress. British Library Cataloguing in Publication Data A catalog record for this book is available from the British Library. ISBN-13: 978-1-59693-439-9 Cover design by Pilar Colleran © 2010 Artech House 685 Canton Street Norwood, MA 02062 All rights reserved. Printed and bound in the United States of America. No part of this book may be reproduced or utilized in any form or by any means, elec- tronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the publisher. All terms mentioned in this book that are known to be trademarks or service marks have been appropriately capitalized. Artech House cannot attest to the accuracy of this information. Use of a term in this book should not be regarded as affecting the validity of any trademark or service mark. 10 9 8 7 6 5 4 3 2 1 Contents Foreword xi Preface xiii Acknowledgments xvii CHAPTER 1 Introduction 1 1.1 Defi nition of Cell-Based Biosensors 1 1.2 Characteristics of Cell-Based Biosensors 3 1.3 Types of Cell-Based Biosensors 4 1.4 Summary 10 References 11 CHAPTER 2 Cell Culture on Chips 13 2.1 Introduction 13 2.2 Cell Immobilization Factors 14 2.2.1 Physical Factors 14 2.2.2 Chemical Factors 15 2.2.3 Biological Factors 15 2.3 Basic Surface Modifi cation Rules 16 2.3.1 Hydrophilicity Improving 17 2.3.2 Roughness Changing 18 2.3.3 Chemical Coating 18 2.4 Typical Methods 20 2.4.1 Special Physical Structure 22 2.4.2 Microcontact Printing 24 2.4.3 Fast Ink-Jet Printing 26 2.4.4 Perforated Microelectrode 27 2.4.5 Self-Assembled Monolayer 29 2.4.6 Microfl uidic Technology 30 2.5 Summary 33 References 33 v vi Contents CHAPTER 3 Mechanisms of Cell-Based Biosensors 37 3.1 Introduction 37 3.2 Metabolic Measurements 38 3.2.1 Cell Metabolism 38 3.2.2 Extracellular pH Monitoring 40 3.2.3 Other Extracellular Metabolite Sensing 43 3.2.4 Secondary Transducers 44 3.3 Action Potential Measurements 44 3.3.1 Action Potential 45 3.3.2 The Solid-Electrolyte Interface 47 3.3.3 Cell-Electrode Interface Model 52 3.3.4 Cell-Silicon Interface Model 54 3.3.5 Secondary Transducers 55 3.4 Impedance Measurements 56 3.4.1 Membrane Impedance 56 3.4.2 Impedance Model of Single Cells 57 3.4.3 Impedance Model of Populations of Cells 59 3.4.4 Secondary Transducers 61 3.5 Noise Sources 62 3.5.1 Electrode Noise 62 3.5.2 Electromagnetic Interference 63 3.5.3 Biological Noise 63 3.6 Summary 64 References 64 CHAPTER 4 Microelectrode Arrays (MEA) as Cell-Based Biosensors 65 4.1 Introduction 65 4.2 Principle 68 4.3 Fabrication and Design of MEA System 69 4.3.1 Fabrication 69 4.3.2 Different MEA Chips 74 4.3.3 Measurement Setup 77 4.4 Theoretical Analysis of Signal Process in MEA Systems 79 4.4.1 Equivalent Circuit Model of Signal Process 79 4.4.2 Impedance Properties Analysis of MEA 80 4.4.3 Analysis of Extracellular Signal 82 4.5 Application of MEA 84 4.5.1 Dissociated Neural Network on MEA 84 4.5.2 Slice on MEA 86 4.5.3 Retina on MEA 88 4.5.4 Pharmacological Application 89 4.6 Development Trends 92 4.6.1 Lab on a Chip 92 4.6.2 Portable MEA System 92 Contents vii 4.6.3 Other Developmental Trends 92 4.7 Summary 93 References 93 CHAPTER 5 Field Effect Transistor (FET) as Cell-Based Biosensors 97 5.1 Introduction 97 5.2 Principle 98 5.3 Device and System 100 5.3.1 Fabrication of FET-Based Biosensor 100 5.3.2 FET Sensor System 102 5.4 Theoretical Analysis 103 5.4.1 Area-Contact Model 104 5.4.2 Point-Contact Model 105 5.5 Application 106 5.5.1 Electrophysiological Recording of Neuronal Activity 106 5.5.2 Two-Way Communication Between Silicon Chip and Neuron 108 5.5.3 Neuronal Network Study 109 5.5.4 Cell Microenvironment Monitoring 112 5.6 Development Trends 114 5.7 Summary 115 References 116 CHAPTER 6 Light Addressable Potentiometric Sensor (LAPS) as Cell-Based Biosensors 119 6.1 Introduction 119 6.2 Principle 121 6.2.1 Fundamental 121 6.2.2 Numerical Analysis 122 6.3 Device and System 124 6.3.1 Device 124 6.3.2 Microphysiometer System 126 6.3.3 Detecting System of Cell-Semiconductor Hybrid LAPS 129 6.4 Application 132 6.4.1 Signaling Mechanism Study 133 6.4.2 Functional Characterization of Ligand/Receptor Binding 134 6.4.3 Identifi cation of Ligand/Receptor 136 6.4.4 Drug Analysis 137 6.5 Developing Trend 143 6.5.1 LAPS Array System for Parallel Detecting 144 6.5.2 Multifunctional LAPS System 145 6.6 Summary 146 References 146 viii Contents CHAPTER 7 Electric Cell-Substrate Impedance Sensor (ECIS) as Cell-Based Biosensors 151 7.1 Introduction 151 7.2 Principle 152 7.2.1 Electrochemical Impedance 152 7.2.2 Cell-Substrate Impedance 154 7.2.3 AC Frequency and Sensitivity Characteristics of Interdigitated Electrodes 156 7.3 Device and System 160 7.3.1 Device Fabrication 160 7.3.2 Bioimpedance Measurement System 161 7.4 Theoretical Analysis 164 7.4.1 Lumped Model 164 7.4.2 Analytical Model 165 7.4.3 Data Calculation and Presentation 165 7.5 Applications 167 7.5.1 Monitoring of Cell Adhesion, Spreading, Morphology, and Proliferation 167 7.5.2 Monitoring of Cell Migration and Invasion 169 7.5.3 Monitoring of Cellular Ligand-Receptor Interactions 170 7.5.4 Cytotoxicity Assays 172 7.6 Development Trends 173 7.6.1 High-Throughput Screening 173 7.6.2 Integrated Chip 175 7.7 Summary 175 References 176 CHAPTER 8 Patch Clamp Chip as Cell-Based Biosensors 179 8.1 Introduction 179 8.2 Theory 179 8.2.1 Conventional Patch Clamp 179 8.2.2 Patch Clamp Chip 181 8.3 Sensor Device and System 182 8.3.1 Patch Clamp Chip Device 182 8.3.2 Patch Clamp Chip System 188 8.3.3 Cells Preparation 193 8.4 Biomedical Application 194 8.4.1 Ionic Channels Research 194 8.4.2 Drug Discovery 199 8.4.3 Drug Safety 200 8.5 Development Trends 202 8.6 Summary 203 References 203 Contents ix CHAPTER 9 Other Cell-Based Biosensors 207 9.1 Quartz Crystal Microbalance (QCM) as Cell-Based Biosensors 207 9.1.1 Introduction 207 9.1.2 Principle of QCM 208 9.1.3 QCM Sensors and Measurement System 210 9.1.4 Biomedical Application 211 9.2 Surface Plasmon Resonance (SPR) as Cell-Based Biosensors 217 9.2.1 Introduction 217 9.2.2 The Principle of SPR 219 9.2.3 SPR Sensors and Measurement System 220 9.2.4 Biomedical Application 221 9.3 Immune Cell-Based Biosensors 225 9.3.1 Introduction 225 9.3.2 Mast Cell–Based Biosensors 226 9.3.3 Dendritic Cell–Based Biosensors 227 9.3.4 B Cell–Based Biosensors 229 9.4 Summary 229 References 230 CHAPTER 10 Developments of Cell-Based Biosensors 233 10.1 Introduction 233 10.2 Cell-Based Biosensors with Integrated Chips 233 10.2.1 Integration Chip of the Same or Similar Functional Sensors 234 10.2.2 Multisensors Involve Sensing Elements with Different Functions 235 10.2.3 Multifunctional Chip Monitoring Different Parameters 236 10.3 Cell-Based Biosensors Using Nanotechnology 237 10.3.1 Nano-Micropatterned Cell Cultures 238 10.3.2 Nanoporous-Based Biosensor 239 10.3.3 Nanoprobes to Intracellular Nanosensors 240 10.4 Cell-Based Biosensors with Microfl uidic Chips 241 10.4.1 Microfl uidic Flow 242 10.4.2 Soft Lithography 243 10.4.3 Dielectrophoresis 245 10.5 Biomimetic Olfactory and Gustatory Cell-Based Biosensors 246 10.5.1 Bioelectronic Nose and Bioelectronic Tongue 247 10.5.2 Olfactory and Gustatory Biosensors with Special Receptors 247 10.5.3 Olfactory and Gustatory Cell-Based Biosensors 248 References 250 Glossary 255 About the Editors 261 List of Contributors 262 Index 263 Foreword The fi eld of biosensors and bioelectronics has enveloped many new areas such as molecularly sensitive receptors, biomimetic sensors, nanotechnology, and more.