MEDICAL INSTRUMENT DESIGN AND DEVELOPMENT FROM REQUIREMENTS TO MARKET PLACEMENTS

Includes a case study in ECG implementation

Claudio Becchetti

Alessandro Neri

©WILEY A John Wiley & Sons, Ltd., Publication

Contents

Foreword xv

Preface xvii

Acknowledgment xxi

1 SYSTEM ENGINEERING 1 Chapter Organization 1 Part I: Theory 4

1.1 Introduction 4 1.2 Problem Formulation in Product Design 4 1.3 The Business Context for Design 6 1.4 The Engineering Product Design Process 10 1.5 System-subsystem Decomposition 15 1.6 The Product Development Life Cycle 21 1.7 Project Management in Product Design 24 1.8 Intellectual Property Rights and Reuse 30

Part II: Implementation 32

1.11 The ECG: Introduction 32 1.11.1 The ECG's diagnostic relevance 32 1.11.2 ECG Types 33

1.12 The ECG Design Problem Formulation 34 1.13 The ECG Business Plan 36

1.13.1 Market Size and Trend 37 1.13.2 Core and Distinctive Features 38

1.14 The ECG Design Process 40 1.14.1 Transverse Activities of the ECG Design Process 43 1.14.2 Core Activities of the ECG Design Process 44

1.15 ECG System-subsystem Decomposition 44 1.15.1 Hardware Platform Decomposition 45 1.15.2 Software Application Decomposition 45

Vlll Contents

1.16 ECG Product Life Cycle 46 1.16.1 Overcoming Risk of Inadequate Visualization of ECG Signal 47 1.16.2 Overcoming Risk of Error Fixing in System Integration 50 1.16.3 Overcoming Risks for Non-stable/Unfeasible Requirements 50

1.17 The ECG Development Plan and Project Management 51 1.18 IPR and Reuse Strategy for the ECG 55 References 57

CONCEPTS AND REQUIREMENTS 59 Chapter Organization 59 Part I: Theory 61 2.1 Introduction 61 2.2 The Medical Instrumentation Approach 62 2.3 Extraction of Physiological Parameters 67 2.4 Pressure and Flow 70

2.4.1 Blood Pressure 72 2.4.2 Blood Flow and Hemodynamics 74

2.5 Biopotential Recording 79 2.6 Electroencephalography 81 2.7 Electromyography 85

Part II: Implementation 88 2.8 Introduction 88 2.9 Requirements Management 89 2.10 Medical Instruments Requirements and Standards 91 2.11 ECG Requirements 94 2.12 The Patient Component 96

2.12.1 The Heart's Pumping Function and the Circulatory System 96 2.12.2 Heart Conduction 'Control' System 97

2.13 The ECG Method for Observation 99 2.13.1 Recording the Heart's Electrical Signals 99 2.13.2 ECG Definition and History 103 2.13.3 ECG Standard Method of Observation 103

2.14 Features of the Observations 108 2.14.1 ECG Signal 108 2.14.2 Clinically Significant Signal 110 2.14.3 Power Line Noise 117 2.14.4 Isoelectric Line Instability 118 2.14.5 Muscle Artifacts 119

2.15 Requirements Related to Measurements 119 2.16 Safety Requirements 126

2.16.1 EMC Performance 128

2.17 Usability and Marketing Requirements 2.18 Environment Issues 2.19 Economic Requirements References

3 BIOMEDICAL ENGINEERING DESIGN Chapter Organization Part I: Theory

3.1 Design Principles and Regulations 3.2 General Design System Model 3.3 Pressure and Flow Instruments

3.3.1 Blood Pressure Instruments 3.3.2 Flow Measurements 3.3.3 Measuring Oxygen Concentration

3.4 Biopotential Instruments 3.4.1 Electroencephalographs 3.4.2 Electromyo graphs

3.5 The Design Process 3.5.1 The Conceptual Design 3.5.2 System-wide Design Decisions 3.5.3 System Architectural Design 3.5.4 Risk Management

Part II: Implementation

3.6 ECG-wide Decisions 3.6.1 The Gamma Cardio CG Use Case 3.6.2 Human Factors and the User Interface Design 3.6.3 Patient Interface: the Biopotential Electrodes

3.7 The ECG System Architectural Design 3.7.1 Subsystem Identification 3.7.2 The Communication Interfaces 3.7.3 Acquisition Hardware Requirements 3.7.4 Firmware Requirements 3.7.5 Software Application Requirements 3.7.6 Concept of Execution among Subsystems

3.8 Gamma Cardio CG Technical File Structure References

4 SIGNAL PROCESSING AND ESTIMATION Chapter Organization Parti: Theory

4.1 Discrete Representations of Analog Systems

X Contents

4.2 Discrete Fourier Transform 189 4.2.1 Discrete Fourier Transform Statistics 194

4.3 Estimation Theory Framework 197 4.3.1 Minimum Mean Square Error Estimate 199 4.3.2 Minimum Mean Absolute Error Estimate (MMAE) 201 4.3.3 Maximum A Posteriori (MAP) Probability Estimate 202 4.3.4 Maximum Likelihood Estimation (MLE) 203

4.4 Performance Indicators 204 4.4.1 Efficient Estimators 208 4.4.2 Fisher's Information Matrix 209 4.4.3 Akaike Information Criterion 212

Part II: Implementation 214 4.5 Analog to Digital Conversion 214

4.5.1 Indirect Sampling versus Direct Sampling 214 4.5.2 Quantizer Design 216

4.6 Signal Denoising 221 4.6.1 White Gaussian Signals in Additive White Gaussian Noise 221 4.6.2 Denoising of'Gaussian Cyclo stationary Signals 222 4.6.3 MMSE Digital Filter 222

4.7 Time of Arrival Estimation 224 References 229

APPLIED ELECTRONICS 231 Chapter Organization 231 Part I: Theory 233

5.0 Architectural Design 235 5.1 Sensors 236 5.2 Circuit Protection Function 243

5.2.1 Johnson Noise 246 5.2.2 Transient Voltage Suppressors 247 5.2.3 RF Filter Circuit Protection 248 5.2.4 Circuit Frequency Response 251

5.3 Buffer Stage 254 5.3.1 Operational Amplifiers 256

5.4 Analog Signal Processing 258 5.4.1 Summing Amplifier Circuit 259 5.4.2 Analog Signal Switching 260

5.5 Interference and Instrumentation Amplifiers 262 5.5.7 Eliminating In-band Interference 262 5.5.2 Patient Model 267 5.5.3 The ECG Model 268 5.5.4 Right Leg Connection 270 5.5.5 Right Leg Driver Circuit 272

Contents XI

5.6 Analog Filtering 273 5.6.1 Frequency Domain 273 5.6.2 Analog versus Digital Filtering 278

5.7 ADC Conversion 279 5.8 Programable Devices 285 5.9 Power Module 289

5.9.1 Power Sources 290 5.9.2 Electrical Safety and Appliance Design 294 5.9.3 Power Module Design 298

5.10 B aseband Digital Communication 301 5.10.1 Data Transmission Elements 302

Part II: Implementation 313

5.20 Gamma Cardio CG Architecture 313 5.20.1 ECG Design Choices 314 5.20.2 Gamma Cardio CG Complete Scheme 317

5.21 ECG Sensors 317 5.22 Gamma Cardio CG Protection 321 5.23 Gamma Cardio CG Buffer Stage 325 5.24 The Lead Selector 327

5.24.1 Calibration 331 5.25 ECG Amplification 332

5.25.1 ECG Circuits 333 5.25.2 Input Dynamic Range: Requirement Demonstrations 337 5.25.3 Gain Error: Requirement Demonstrations 338

5.26 Analog Filtering 339 5.27 The ADC Circuit 342 5.28 Programable Devices 346

5.28.1 Circuit Design 341 5.28.2 The Clock 348

5.29 Power Module 351 5.29.1 Power Module Circuit 353

5.30 Communication Module 353 Conclusion 357 References 358

MEDICAL SOFTWARE 359 Chapter Organization 359 Part I: Theory 361

6.1 Introduction 361 6.1.1 Intrinsic Risks and Software Engineering 362 6.1.2 Main Concepts in Software Development 363 6.1.3 Regulatory Requirements for Software 364

6.2 The Process: a Standard for Medical Software 6.2.1 IEC/EN 62304 Overview 6.2.2 Risk Analysis for Hardware and Software Design 6.2.3 Software Safety Classification 6.2.4 System Decomposition and Risks 6.2.5 Impact of Safety Classification 6.2.6 SOUP

6.3 Risk Management Process 6.3.1 Risk Management in Software 6.3.2 Risk Management for Medical Instrument Software

6.4 Software Development Process 6.4.1 Software Development Planning 6.4.2 Software Requirements Analysis 6.4.3 Software Architectural Design 6.4.4 Detailed Software Design 6.4.5 Software Unit Implementation and Verification 6.4.6 Software Integration and Integration Testing 6.4.7 Software System Testing 6.4.8 Software Release

6.5 Software Configuration Management Process 6.6 Software Problem Resolution Process 6.7 Software Maintenance Process 6.8 Guidelines on Software Design

6.8.1 Definitions 6.8.2 Basic Recommendations 6.8.3 Software Core Services 6.8.4 Defensive Programing

Part II: Implementation 6.9 System Decomposition

6.9.1 Gamma Cardio CG Use Case 6.9.2 System Decomposition

6.10 Risk Management 6.11 Software Application

6.11.1 Software Requiremen ts 6.11.2 Architectural Design 6.11.3 Elaboration Module

6.12 Firmware 6.12.1 Firmware Requirements 6.12.2 Architectural Design 6.12.3 Automatic Test Capability

References

C-HEALTH Chapter Organization Parti: Theory

Contents Xl l l

7.1 Introduction 421 7.1.1 The Assessment Framework 421 7.1.2 Assessment Framework for the Health Sector 422

7.2 The Cloud Computing Model 426 7.2.1 Basics of Cloud Computing 426 7.2.2 Cloud Platforms 428 7.2.3 Services in the Cloud 430 7.2.4 The Cloud Shape 432 7.2.5 Features of the Clouds 434

7.3 e-Health 435 7.3.1 Interoperability in e-Health 437

7.4 Electronic Health Record (EHR) 442 7.5 c-Health 445 Part II: Implementation 449 7.6 Telecardiology 450

7.6.7 Application Scenario 450 7.7 Telecardiology Technology 451 7.8 Workflow in Telecardiology 455

7.8.1 Basic Workflows 455 7.8.2 Alternative Workflows 457 7.8.3 Where and When Telecardiology Can Be Used 460

7.9 Risks of Telecardiology 463 References 465

8 CERTIFICATION PROCESS 467 Chapter Organization 467 Part I: Theory 469 8.1 Certification Objectives and Processes 469

8.1.1 Certification, Standards and Definitions 470 8.2 Regulations, Standards and Organizations 474

8.2.1 Technical Standards for Medical Devices All 8.2.2 European Context 478

8.3 Basic Protection Concepts 480 8.3.1 Protection Against Electric Shock 480 8.3.2 Insulation 484 8.3.3 Degree of Protection Provided by Enclosures 485

8.4 Verification of Constructional Requirements 486 8.4.1 Choice of Safety Critical Materials and Components 486 8.4.2 Creepage Distances and Air Clearances 489 8.4.3 Markings 490 8.4.4 Conductors 492 8.4.5 Connections to the Power Supply 494 8.4.6 Fire Enclosure 495

Contents

8.5 Medical Equipment Safety Tests 495 8.5.1 Leakage Current 497 8.5.2 Heating 499 8.5.3 Dielectric Strength 500 8.5.4 Stability and Mechanical Strength 500 8.5.5 Abnormal Operating and Fault Conditions 501 8.5.6 Continuity of Protective Earthing 502 8.5.7 Residual Voltage 503 8.5.8 Voltage on the Accessible Parts 503 8.5.9 Energy Stored-Pressurized Part 503 8.5.10 Current and Power Consumption 504

8.6 Electromagnetic Compatibility 504 8.6.1 Emissions 506 8.6.2 Immunity 511 8.6.3 The Test Report 513

Part II: Implementation 515

8.11 The Process 515 8.11.1 Device Description 516 8.11.2 Medical Device Classes 516 8.11.3 EU Conformity Assessment 519 8.11.4 Risk Management Deliverable 520 8.11.5 The Technical File 527

8.12 Regulatory Approaches to Medical Device Market Placement 537 8.13 Basic Concepts in Device Implementation 540

8.13.1 Protection Against Electric Shock 541 8.13.2 Insulation 541 8.13.3 Enclosure IP Protection 544

8.14 Verification on Design Performance 544 8.14.1 Safety-critical Materials 544 8.14.2 Creepage and Air Clearance 545 8.14.3 Other Verifications 545

8.15 Safety Tests 546 8.15.1 Leakage Current 546 8.15.2 Heating 546 8.75.3 Other Safety Tests 547

8.16 Electromagnetic Compatibility 548 8.76.7 Emission 549 8.16.2 Immunity 550

References 554 Summary of Regulations and Standards 555

Index 559