i Principles of Biomedical Instrumentation This accessible yet in-depth textbook describes the step-by-step processes involved in biomedical device design. Integrating microfabrication techniques, sensors and digital signal processing with key clinical applications, it covers: ■ the measurement, amplification and digitization of physiological signals, and the removal of interfering signals ■ the transmission of signals from implanted sensors through the body, and the issues concerning the powering of these sensors ■ networks for transferring sensitive patient data to hospitals for continuous home-monitoring systems ■ electrical and biological tests for ensuring patient safety ■ the cost–benefit and technological trade-offs involved in device design ■ current challenges in biomedical device design. With dedicated chapters on electrocardiography, digital hearing aids and mobile health, and including numerous end-of-chapter homework problems, online solu- tions and additional references for extended learning, it is the ideal resource for senior undergraduate students taking courses in biomedical instrumentation and clinical technology. Andrew G. Webb is Professor and Director of the C. J. Gorter Center for High Field Magnetic Resonance Imaging at the Leiden University Medical Center. He has authored or co-authored several books, including Introduction to Medical Imaging (Cambridge University Press, 2010) and Introduction to Biomedical Imaging(Wiley, 2002). ii CAMBRIDGE TEXTS IN BIOMEDICAL ENGINEERING Series Editors W. Mark Saltzman, Yale University Shu Chien, University of California, San Diego Series Advisors Jerry Collins, Alabama A & M University Robert Malkin, Duke University Kathy Ferrara, University of California, Davis Nicholas Peppas, University of Texas, Austin Roger Kamm, Massachusetts Institute of Technology Masaaki Sato, Tohoku University, Japan Christine Schmidt, University of Florida George Truskey, Duke University Douglas Lauffenburger, Massachusetts Institute of Technology Cambridge Texts in Biomedical Engineering provide a forum for high-quality textbooks targeted at undergraduate and graduate courses in biomedical engineer- ing. They cover a broad range of biomedical engineering topics from introductory texts to advanced topics, including biomechanics, physiology, biomedical instru- mentation, imaging, signals and systems, cell engineering and bioinformatics, as well as other relevant subjects, with a blending of theory and practice. While aiming primarily at biomedical engineering students, this series is also suitable for courses in broader disciplines in engineering, the life sciences and medicine. iii Principles of Biomedical Instrumentation Andrew G. Webb Leiden University Medical Center, The Netherlands iv University Printing House, Cambridge CB2 8BS, United Kingdom One Liberty Plaza, 20th Floor, New York, NY 10006, USA 477 Williamstown Road, Port Melbourne, VIC 3207, Australia 314–321, 3rd Floor, Plot 3, Splendor Forum, Jasola District Centre, New Delhi–110025, India 79 Anson Road, #06–04/06, Singapore 079906 Cambridge University Press is part of the University of Cambridge. It furthers the University’s mission by disseminating knowledge in the pursuit of education, learning, and research at the highest international levels of excellence. www.cambridge.org Information on this title: www.cambridge.org/9781107113138 DOI: 10.1017/9781316286210 © Andrew G. Webb 2018 This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published 2018 Printed in the United Kingdom by TJ International Ltd. Padstow, Cornwall A catalogue record for this publication is available from the British Library. Library of Congress Cataloging-in-Publication Data Names: Webb, Andrew (Andrew G.), author. Title: Principles of biomedical instrumentation / Andrew G. Webb. Other titles: Cambridge texts in biomedical engineering. Description: Cambridge, United Kingdom ; New York, NY, USA : Cambridge University Press, [2018] | Series: Cambridge texts in biomedical engineering | Includes bibliographical references and index. Identifiers: LCCN 2017024373 | ISBN 9781107113138 Subjects: | MESH: Equipment and Supplies | Equipment Design Classification: LCC R857.B54 | NLM W 26 | DDC 610.28/4–dc23 LC record available at https://lccn.loc.gov/2017024373 ISBN 978-1-107-11313-8 Hardback Additional resources available at www.cambridge.org/webb-principles Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. v Contents Preface page xi List of Abbreviations xvi 1 Biomedical Instrumentation and Devices 1 1.1 Classification of Biomedical Instruments and Devices 1 1.2 Outline of the Design Process: From Concept to Clinical Device 3 1.2.1 Engineering Design 4 1.3 Regulation of Biomedical Instrumentation and Devices 8 1.4 Safety of Biomedical Instrumentation and Devices 10 1.4.1 ISO and IEC Standards 10 1.4.2 Biological Testing 14 1.5 Evaluation of a New Device 14 2 Sensors and Transducers 18 2.1 Micro-Electro-Mechanical Systems 19 2.1.1 Noise in MEMS Devices 22 2.2 Voltage Sensors: Example–Biopotential Electrodes 24 2.2.1 Clinical and Biomedical Voltage Measurements 24 2.2.2 Action Potentials and Cellular Depolarization 24 2.2.3 Surface Electrode Design 28 2.3 Optical Sensors: Example–a Pulse Oximeter 31 2.3.1 Clinical Blood Oxygenation Measurements 31 2.3.2 Measurement Principle Using an Optical Sensor 33 2.3.3 Optical Transmitter and Detector Design 35 2.4 Displacement/Pressure Sensors and Accelerometers 37 2.4.1 Clinical Pathologies Producing Changes in Internal Pressure 38 2.4.2 Resistive and Piezoresistive Transducers 38 2.4.3 Piezoelectric Sensors 42 vi Contents 2.4.4 Capacitive Transducers 45 2.4.5 Inductive Transducers: the Linear Voltage Differential Transformer 48 2.5 Chemical Sensors: Example–a Glucose Monitor 49 2.5.1 Clinical Need for Glucose Monitoring 49 2.5.2 System Requirements for Glucose Monitoring 49 2.5.3 Basic Detection Principles of Glucose Monitoring 50 2.5.4 Designing a Portable Device for Glucose Monitoring 52 2.6 Acoustic Sensors: Example–a Microphone for Hearing Aids 53 2.6.1 Clinical Need for Hearing Aids 53 2.6.2 Microphone Design for Hearing Aids 54 3 Signal Filtering and Amplification 62 3.1 Frequency-Dependent Circuit Characteristics: Bode Plots 63 3.2 Passive Filter Design 71 3.2.1 First-Order Low-Pass and High-Pass Filters 72 3.2.2 Higher Order High-Pass, Low-Pass, Band-Pass and Band-Stop Filters 73 3.2.3 Resonant Circuits as Filters 77 3.3 Operational Amplifiers 79 3.3.1 Circuit Analysis Rules for Op-Amps 80 3.3.2 Single Op-Amp Configurations 80 3.3.3 The Instrumentation Amplifier 87 3.4 Active Filters 89 3.4.1 First-Order Low-Pass, High-Pass and Band-Pass Active Filters 89 3.4.2 Higher Order Butterworth, Chebyshev and Sallen–Key Active Filters 92 3.5 Noise in Electrical Circuits 95 3.6 Examples of Signal Amplification and Filtering 97 3.6.1 Signal Conditioning in the Pulse Oximeter 98 3.6.2 Amplification and Filtering in a Glucose Sensor 100 4 Data Acquisition and Signal Processing 106 4.1 Sampling Theory and Signal Aliasing 108 4.2 Dynamic Range, Quantization Noise, Differential and Integrated Non-Linearity 108 vii Contents 4.3 Electronic Building Blocks of Analogue-to-Digital Converters 112 4.3.1 Sample-and-Hold Circuits 113 4.3.2 Comparator Circuits 115 4.3.3 Shift Register Circuits 116 4.4 Analogue-to-Digital Converter Architectures 117 4.4.1 Flash ADCs 118 4.4.2 Successive Approximation Register ADCs 119 4.4.3 Pipelined ADCs 121 4.4.4 Oversampling ADCs 122 4.5 Commercial ADC Specifications 127 4.5.1 ADC for a Pulse Oximeter 127 4.5.2 ADC for a Glucose Meter 128 4.6 Characteristics of Biomedical Signals and Post-Acquisition Signal Processing 128 4.6.1 Deterministic and Stochastic Signals 128 4.6.2 The Fourier Transform 131 4.6.3 Cross-Correlation 133 4.6.4 Methods of Dealing with Low Signal-to-Noise Data 135 5 Electrocardiography 140 5.1 Electrical Activity in the Heart 141 5.2 Electrode Design and Einthoven’s Triangle 145 5.2.1 Standard Twelve-Lead Configuration 146 5.3 ECG System Design 149 5.3.1 Common-Mode Signals and Other Noise Sources 150 5.3.2 Reducing the Common-Mode Signal 152 5.3.3 Design of Lead-Off Circuitry 154 5.3.4 Filtering and Sampling 155 5.4 Signal Processing of the ECG Signal and Automatic Clinical Diagnosis 156 5.4.1 University of Glasgow (Formerly Glasgow Royal Infirmary) Algorithm 157 5.5 Examples of Abnormal ECG Recordings and Clinical Interpretation 158 5.6 ECG Acquisition During Exercise: Detection of Myocardial Ischaemia 161 5.7 High-Frequency (HF) ECG Analysis 163 viii Contents 6 Electroencephalography 169 6.1 Electrical Signals Generated in the Brain 171 6.1.1 Postsynaptic Potentials 171 6.1.2 Volume Conduction Through the Brain 173 6.2 EEG System Design 175 6.2.1 Electrodes and their Placement on the Scalp 176 6.2.2 Amplifiers/Filters and Digitizing Circuitry 178 6.3 Features of a Normal EEG: Delta, Theta, Alpha and Beta Waves 180 6.4 Clinical Applications of EEG 182 6.4.1 EEG in Epilepsy 182 6.4.2 Role of EEG in Anaesthesia: the Bispectral Index 183 6.5 EEG Signals in Brain–Computer Interfaces for Physically Challenged Patients 187 6.5.1 Applications of BCIs to Communication Devices 188 6.5.2 Applications of BCIs in Functional Electrical Stimulation and Neuroprostheses 190 6.6 Source Localization in EEG Measurements (Electrical Source Imaging) 191 7 Digital Hearing Aids 196 7.1 The Human Auditory System 198 7.2 Causes of Hearing Loss 201 7.3 Basic Design of a Digital Hearing Aid 202 7.4 Different Styles of Hearing Aid 202 7.5 Components of a Hearing Aid 203 7.5.1 Earmoulds and Vents 204 7.5.2 Microphones 207 7.6 Digital Signal Processing 213 7.6.1 Feedback Reduction 216 7.6.2 Adaptive Directionality and Noise Reduction 216 7.6.3 Wind-Noise Reduction 218 7.6.4 Multi-Channel and Impulsive Noise-Reduction Algorithms 220 7.6.5 Compression 220 7.6.6 Multi-Channel Compression: BILL and TILL 224 7.6.7 Frequency Lowering 224 7.7 Digital-to-Analogue Conversion and the Receiver 225 ix Contents 7.8 Power Requirements and Hearing Aid Batteries 227 7.9 Wireless Hearing Aid Connections 227 7.10 Binaural Hearing Aids 229 7.11 Hearing Aid Characterization Using KEMAR 231 8 Mobile Health, Wearable Health Technology and Wireless Implanted Devices 235 8.1 Mobile and Electronic Health: Mobile Phones and Smartphone Apps 238 8.2 Wearable Health Monitors 239 8.2.1 Technology for Wearable Sensors 240 8.3 Design Considerations for Wireless Implanted Devices 243 8.3.1 Data Transmission Through the Body 243 8.4 Examples of Wireless Implanted Devices 250 8.4.1 Cardiovascular Implantable Electronic Devices 250 8.4.2 Continuous Glucose Monitors 261 8.4.3 Implanted Pressure Sensors for Glaucoma 264 8.5 Packaging for Implanted Devices 265 Appendix: Reference Standards and Information Related to Wireless Implant Technology 266 9 Safety of Biomedical Instruments and Devices 271 9.1 Physiological Effects of Current Flow Through the Human Body 274 9.2 The Hospital Electrical Supply 277 9.2.1 Hospital-Grade Receptacles 279 9.3 Macroshock, Microshock and Leakage Currents: Causes and Prevention 280 9.3.1 Macroshock 280 9.3.2 Protection Against Macroshock 280 9.3.3 Microshock 284 9.3.4 Protection Against Microshock 284 9.4 Classification of Medical Devices 285 9.4.1 Classes of Equipment 286 9.4.2 Types of Equipment 287 9.5 Safety Testing Equipment 288 9.5.1 Leakage Current Measurements 289