Implantable Neural Prostheses 2 (eBook)

Preface 6
Contents 7
Contributors 9
Acronyms 11
The Biocompatibility and Biostability of New Cardiovascular Materials and Devices 15
1 Introduction 16
2 Background 17
2.1 Learning from the Past 17
2.2 Environmental Stress Cracking (ESC) 18
2.3 Metal Ion Oxidation (MIO) 20
2.4 Subclavian Crush 22
2.5 Why Were These Mechanisms Not Discovered Before Market Release? 23
2.6 Chronic Removability of Transvenous Cardiac Leads 24
3 Risk Assessment 26
4 Material Biocompatibility Testing 26
4.1 Substantially Equivalent Materials 26
4.2 New Materials 26
4.3 Phase 1 Tests (ISO 10993-1) 27
4.3.1 Phase 2 Tests 28
5 Potential for Biodegradation 29
6 New Material Stability Testing In Vitro 29
6.1 Metals 30
6.2 Polymers 30
7 In Vivo Materials Testing 32
8 Device Implants in Animal Models 33
9 Human Clinical Implants 34
10 Market Release and Postmarket Surveillance 34
10.1 Returned Products Analysis 34
10.2 Postmarket Clinical Studies 35
11 Summary and Conclusions 38
References 38
Technology Advances and Challenges in Hermetic Packaging for Implantable Medical Devices 41
1 Introduction 42
1.1 Hermetic Packaging Technology Advances 42
1.2 Significance of Hermetic Packaging for Implantable Medical Devices 45
2 General Packaging Considerations for Implantable Medical Devices 45
2.1 Biocompatibility 45
2.2 Hermeticity Requirement 46
2.3 Outgassing of Internal Materials 46
2.4 Wireless Communication 47
2.5 Package Heating 47
2.6 Coefficient of Thermal Expansion Compatibility 47
3 Types of Hermetic Sealing and Their Applications 48
3.1 Polymer Encapsulation 48
3.2 Glass-to-Metal Seal 48
3.3 Ceramic-to-Metal Feedthrough 49
3.4 Ceramic-to-Metal Seal 51
3.4.1 Active Brazing 51
3.4.2 Nonactive Brazing 52
3.4.3 Diffusion Bonding of Ceramic-to-Metal 52
3.5 Hermetic Seal with Fusion Welding 53
3.6 Conductive Vias on Ceramic Substrate 54
4 Testing Methods for Hermetic Sealing of Implantable Medical Devices 55
4.1 Mechanical and Environmental Tests 55
4.2 Hermeticity Testing Methods and Their Limitations 56
4.3 Biocompatibility Tests 59
4.4 Corrosion Tests 60
4.5 Morphological and Microstructural Characterization 61
4.6 Accelerated Life Test 62
4.7 X-Ray Microscopy 63
4.8 Acoustic Microscopy 65
5 Challenges of Hermetic Packaging for Implantable Medical Devices 65
5.1 Long-Term Stability of Ceramic Materials 65
5.2 Metals and Alloys Corrosion 66
5.3 Challenges in Accelerated Life Test 67
5.4 Hermeticity Test Reliability for Miniature Devices 68
5.5 Design challenges for Miniature Devices 69
5.6 Hermetic Packaging of MEMS for Implantable Medical Devices 69
6 Conclusions 70
References 70
Science and Technology of Bio-Inert Thin Films as Hermetic-Encapsulating Coatings for Implantable Biomedical Devices: Application to Implantable Microchip in the Eye for the Artificial Retina 77
1 Scientific and Technological State-of-the-Art of Bio-inert Coatings for Encapsulation of Implantable Microchips 78
2 Process and Design Considerations for Hermetic Bio-inert Coatings for Implantable Artificial Retina 80
2.1 Materials for Hermetic-Encapsulating Coatings 80
2.2 Carbon-Based Ultrananocrystalline Diamond (UNCD) Coatings and Film 81
2.3 Oxide Films Alone or as Component of Hybrid UNCD/Oxide for Hermetic-Encapsulating Coatings 85
3 Characterization of Bio-inert Hermetic-Encapsulating Coatings 86
3.1 Characterization of Chemical, Microstructural, and Morphological Properties of UNCD Coatings 86
3.2 Characterization of Microstructural and Morphological Properties of Oxide Films for Hybrid Hermetic-Encapsulating Coatings 91
3.3 Characterization of Electrochemical Performance in Saline Solution for Hermetic UNCD Coatings 91
3.4 Characterization of Electrochemical Performance in Saline Solution for Hermetic Oxide Films 92
3.5 Characterization of UNCD/CMOS Integration 93
3.6 In Vivo Animal Tests of Hermetic-Encapsulating Coatings for Artificial Retina 94
4 Challenges for Bio-inert Microchip Encapsulation Hermetic Coatings 95
5 Conclusions and a Future Outlook 96
References 97
The Electrochemistry of Charge Injection at the Electrode/Tissue Interface 99
1 Physical Basis of the Electrode/Electrolyte Interface 100
1.1 Capacitive/Non-Faradaic Charge Transfer 101
1.2 Faradaic Charge Transfer and the Electrical Model of the Electrode/Electrolyte Interface 102
1.3 Reversible and Irreversible Faradaic Reactions 104
1.4 The Origin of Electrode Potentials and the Three-Electrode Electrical Model 106
1.5 Faradaic Processes: Quantitative Description 110
1.6 Ideally Polarizable Electrodes and Ideally Nonpolarizable Electrodes 115
2 Charge Injection Across the Electrode/Electrolyte Interface During Electrical Stimulation 117
2.1 Charge Injection During Pulsing: Interaction of Capacitive and Faradaic Mechanisms 117
2.2 Methods of Controlling Charge Delivery During Pulsing 119
2.3 Charge Delivery by Current Control 120
2.4 Pulse train response during current control 121
2.5 Electrochemical reversal 124
2.6 Charge delivery by a voltage source between the working electrode and counter electrode 126
3 Materials Used as Electrodes for Charge Injection and Reversible Charge Storage Capacity 128
4 Charge Injection for Extracellular Stimulation of Excitable Tissue 133
5 Mechanisms of Damage 137
6 Design Compromises for Efficacious and Safe Electrical Stimulation 141
References 145
In Situ Characterization of Stimulating Microelectrode Arrays: Study of an Idealized Structure Based on Argus II Retinal implants 153
1 Introduction 154
2 Physical Analysis of Argus II Electrode Array and Representative Analogs 154
2.1 The Argus II Electrode Array 154
2.2 Electrical Properties of the Vitreous 155
2.2.1 Stimulation Waveforms 156
2.2.2 AC and DC Impedance 156
2.2.3 Retinal Tissues 156
2.3 Electrical Stimulation, Electrodes, and Systems 157
2.3.1 Electrode Configuration 157
2.3.2 Electrode Size and Spacing 157
2.3.3 Materials and Stability 157
2.4 Return Electrode 158
2.4.1 Functions 158
2.4.2 Design 158
3 Characterization of Simplified Argus II Analogs 159
3.1 Single Electrode 159
3.1.1 Design and Material 159
3.2 9-Electrode Array Structure 159
4 Numerical Simulation of Argus II Simplified Model 166
4.1 Numerical Simulation 166
4.2 Single Electrode 166
4.3 60-Electrode Array Cross-Talk Modeling 168
5 Conclusions 169
References 169
Thin-Film Microelectrode Arrays for Biomedical Applications 171
1 Introduction 172
2 Microfabrication Methods and Materials 173
2.1 Micromachining 173
2.2 Microfabricated Microelectrodes 174
2.3 Silicon-Based Thin-Film Electrodes 175
2.3.1 Planar Silicon-Based Electrodes 176
2.3.2 Three-Dimensional Silicon-Based Electrodes 178
2.3.3 Sieve Electrodes 179
2.4 Metal-Based Thin-Film Electrodes 180
2.5 Ceramic-Based Thin-Film Electrodes 181
2.6 Polymer-Based Thin-Film Electrodes 182
2.6.1 Polyimide 182
2.6.2 Other Polymer-Based Microelectrodes 185
2.7 Nanostructured Electrodes 188
2.7.1 Carbon Nanotube Coatings 189
2.7.2 Conductive Polymer Nanotubes 190
3 Central Nervous System Response to Implanted Devices 191
3.1 Reactive Gliosis 192
3.2 Histology 192
3.3 Glial Scar and Tissue Impedance 193
4 Implant Biocompatibility 194
4.1 Microelectrode Structure 195
4.2 Pharmacology 195
4.3 Hybrid Structures 196
5 Conclusion 197
References 197
Stimulation Electrode Materials and Electrochemical TestingMethods 205
1 Introduction 206
2 Electrode Reactions 207
2.1 Electrode Interface 207
2.2 Electrical Double Layer 208
2.3 Reversible Metal Oxidation/Reduction 208
2.4 Irreversible Chemical Reaction 209
2.5 Electrolyte Resistance 210
3 Common Electrochemical Tests and Electrode Materials 210
3.1 Cyclic Voltammetry 210
3.2 Platinum 212
3.3 Titanium 213
3.4 Iridium 213
3.5 Effect of Protein 215
3.6 Impedance Measurement 215
4 Neural Stimulation Settings Which Affect Charge Injections 216
4.1 Basis of Neural Stimulation 216
4.2 Components of a Neural Stimulation System 217
4.3 Monophasic Voltage Stimulation 217
4.4 Constant Voltage vs. Constant Current 217
4.5 Analysis of Constant-Current Electrode-Voltage Waveform 218
4.6 Current Control with Passive Recharge 219
4.7 Active Recharge 220
4.8 Cathodic Bias 221
4.9 Bipolar vs. Monopolar Stimulation 221
5 Other Measurement Techniques 221
5.1 Electrode-Potential Measurement 222
5.2 Pulse Clamp 223
5.3 Computer Simulation 224
5.4 Dissolution Testing 227
5.5 Inductively Coupled Plasma (ICP) 228
6 Summary 228
References 228
Conducting Polymers in Neural Stimulation Applications 231
1 Introduction 232
2 Neural Stimulation and Electrode Materials 233
2.1 Charge Transfer Processes During Stimulation 233
2.2 Electrodes for Neural Stimulation Implants 234
3 Conducting Polymers 236
3.1 Various Conducting Polymers 236
3.1.1 Polypyrrole 236
3.1.2 Polyaniline 237
3.1.3 PEDOT 237
3.2 Methods of Preparing Conducting Polymers 239
3.3 Biomedical Applications of Conducting Polymers 244
4 Challenges of Conducting Polymers for Chronic Neural Stimulation 246
4.1 Electrode Impedance 246
4.2 Polymer Volume Changes Under Electrical Stimulation 251
4.3 Charge Injection Capability 253
4.4 Biocompatibility 255
4.5 Long-Term Stability 257
5 Conclusions 260
References 261
Microelectronics of Recording, Stimulation, and Wireless Telemetry for Neuroprosthetics: Design and Optimization 267
1 Introduction 268
2 Basic Building Blocks 269
2.1 Amplifier 269
2.1.1 Negative-Feedback Amplifier 271
2.1.2 Chopper Amplifier 275
2.2 Filter 276
2.2.1 Passive R-C Filter 276
2.2.2 Active Filter 277
2.2.3 Switched-Capacitor Filter 278
2.3 ADC 279
3 Subsystem Design 280
3.1 Front-End Blocks for Neural Recording 280
3.1.1 System Architecture and Circuit Modeling 280
3.1.2 System Resolution 285
3.1.3 Trade-Off Between System Power and Chip Area 287
3.2 Neural-Signal Processing Unit 291
3.2.1 Theory 291
3.2.2 Spike Sorting Methods and Results 296
3.3 Neuromuscular Current Stimulator with High-Compliance Voltage 302
3.4 Wireless Telemetry 303
3.4.1 Power Telemetry 305
3.4.2 Data Telemetry 312
4 System Design Examples 321
4.1 Recording: 128-Channel Wireless Neural-Recording System 321
4.1.1 Chip Architecture 323
4.1.2 Front-End Block Design 324
4.1.3 Neural-Signal Processing Engine 327
4.1.4 UWB Telemetry 328
4.1.5 Test Results 330
4.1.6 60-Hz Power Interference Issue 331
4.2 Stimulation: 256-Channel Retinal Prosthesis Chip 333
4.2.1 System Architecture 333
4.2.2 Stimulator Pixel Design 334
4.2.3 Dual-Band Power and Data Telemetry Design 335
5 Summary 335
References 336
Microchip-Embedded Capacitors for Implantable NeuralStimulators 345
1 Introduction 346
2 Design and Process Considerations for Oxide Films for Microchip-Embedded Capacitors 346
2.1 Materials for High-Dielectric Constant (K) Layers 346
2.2 TiAlOx or TiO2/Al2O3Superlattice Oxide Layers 348
2.3 Synthesis and Deposition Techniques of Oxide Films for Embedded Capacitors 350
2.3.1 Sputter-Deposition 350
2.3.2 Atomic Layer Deposition (ALD) 350
3 Characterization of Oxide Films for Microchip Embedded Capacitors 352
3.1 Characterization of Oxide/Silicon Interface and Structure 352
3.2 Electrical Performance of High-K Dielectric Oxide 352
4 Challenges for Oxide Films as High-K Dielectric Films for Microchip-Embedded Capacitors 355
5 Conclusions 356
References 356
An Effective Design Process for the Successful Developmentof Medical Devices 359
1 Introduction 360
2 The Design Control Process for the Development of Medical Devices 360
2.1 Overview of the Design Control Process 360
2.2 Research and Development Phase 361
2.3 General Design Control Philosophy 363
2.4 Design and Development Planning 364
2.5 Design Input 365
2.5.1 Case Studies of Design Input Requirements 367
2.6 Design Output 367
2.7 Design Review 368
2.8 Design Verification 368
2.9 Design Validation 369
2.9.1 Case Studies of Design Verification and Validation 370
2.10 Design Transfer 370
2.11 Design Changes 371
2.11.1 Case Studies of the Design Changes Process 371
2.12 Risk and Hazard Analysis 371
2.13 Design History File 372
3 Conclusion 372
References 373
Subject Index 375