Introductory Bioelectronics For Engineers and Physical Scientists

by Pethig, Ronald R.; Smith, Stewart

• ISBN13: 9781119970873
• ISBN10: 1119970873
• Edition: 1st
• Format: Hardcover
• Copyright: 2012-11-05
• Publisher: Wiley

Summary

The first book to bring together the various topics within a concise and introductory overview with basic theory and practical applications With emphasis on the fundamentals of the biochemical, biophysical, electrical and physiological concepts relevant to bioelectronics, this is the only book available on the topic that is suitable for students. It uses an interdisciplinary approach to present basic theory with practical examples and clinical applications, and delivers the necessary biological knowledge from an electrical engineer's perspective. Each chapter contains a problem section that readers can use for self-assessment, and model answers are given at the end of the book (with references to key scientific publications). It also contains many new developments in the bioelectronics and biosensors fields, such as microfluidic devices and nanotechnology.

Author Biography

Professor Ronald Pethig, Bioelectronics, School of Engineering, University of Edinburgh He has PhD degrees in electrical engineering and physical chemistry, and a D.Sc degree for work in the field of biomolecular electronics. He is author of one book (Dielectric and Electronic Properties of Biological Materials, Wiley) and more than 200 scientific papers in the field of biomolecular electronics and dielectrophoresis. He has received several awards, including in 2001 being the first recipient of the Herman P Schwan Award for work in biodielectrics. He serves on the editorial boards of several scientific journals, including acting as editor-in-chief of the IET journal Nanobiotechnology.

Stewart Smith, RCUK Academic Fellow, School of Engineering, University of Edinburgh He has a PhD in microelectronics and has authored over 60 scientific papers on subjects ranging from implantable drug delivery systems to test structures for the characterisation of MEMS processes. He is based at the Scottish Microelectronics Centre in Edinburgh where he works on the development of biomedical microsystems. He is a member of the technical committee for the IEEE International Conference on Microelectronic Test Structures.

Table of Contents

About the Authors xiii

Foreword xv

Preface xvii

Acknowledgements xix

1 Basic Chemical and Biochemical Concepts 1

1.1 Chapter Overview 1

1.2 Energy and Chemical Reactions 1

1.2.1 Energy 1

1.2.2 Covalent Chemical Bonds 2

1.2.3 Chemical Concentrations 4

1.2.4 Nonpolar, Polar and Ionic Bonds 6

1.2.5 Van der Waals Attractions 7

1.2.6 Chemical Reactions 9

1.2.7 Free-Energy Change DG Associated with Chemical Reactions 10

1.3 Water and Hydrogen Bonds 15

1.3.1 Hydrogen Bonds 16

1.4 Acids, Bases and pH 18

1.4.1 The Biological Importance of pH 20

1.4.2 The Henderson-Hasselbalch Equation 21

1.4.3 Buffers 24

1.5 Summary of Key Concepts 25

Problems 26

References 27

Further Readings 27

2 Cells and their Basic Building Blocks 29

2.1 Chapter Overview 29

2.2 Lipids and Biomembranes 29

2.2.1 Fatty Acids 30

2.3 Carbohydrates and Sugars 32

2.4 Amino Acids, Polypeptides and Proteins 34

2.4.1 Amino Acids and Peptide Bonds 35

2.4.2 Polypeptides and Proteins 39

2.5 Nucleotides, Nucleic Acids, DNA, RNA and Genes 43

2.5.1 DNA 43

2.5.2 Ribonucleic Acid (RNA) 47

2.5.3 Chromosomes 50

2.5.4 Central Dogma of Molecular Biology (DNA Makes RNA Makes Protein) 50

2.6 Cells and Pathogenic Bioparticles 51

2.6.1 Prokaryotic and Eukaryotic Cells 52

2.6.2 The Plasma Membrane 53

2.6.3 The Cell Cycle 54

2.6.4 Blood Cells 55

2.6.5 Bacteria 58

2.6.6 Plant, Fungal and Protozoal Cells 60

2.6.7 Viruses 61

2.6.8 Prions 62

2.6.9 Cell Culture 63

2.6.10 Tissue Engineering 64

2.6.11 Cell–Cell Communication 66

2.7 Summary of Key Concepts 70

References 71

Further Readings 71

3 Basic Biophysical Concepts and Methods 73

3.1 Chapter Overview 73

3.2 Electrostatic Interactions 74

3.2.1 Coulomb’s Law 74

3.2.2 Ions in Water 78

3.2.3 The Formation of an Ionic Double Layer 79

3.2.4 Ion–Dipole and Dipole–Dipole Interactions 86

3.2.5 Ions in a Membrane or Protein 88

3.3 Hydrophobic and Hydration Forces 90

3.3.1 Hydrophobic Forces 90

3.3.2 Hydration Forces 91

3.4 Osmolarity, Tonicity and Osmotic Pressure 91

3.4.1 Osmoles 91

3.4.2 Calculating Osmolarity for Complex Solutions 92

3.4.3 Osmolarity Versus Tonicity 92

3.5 Transport of Ions and Molecules across Cell Membranes 94

3.5.1 Diffusion 94

3.5.2 Osmosis 95

3.5.3 Facilitated Diffusion 97

3.5.4 Active Transport 97

3.6 Electrochemical Gradients and Ion Distributions Across Membranes 99

3.6.1 Donnan Equilibrium 100

3.7 Osmotic Properties of Cells 103

3.8 Probing the Electrical Properties of Cells 105

3.8.1 Passive Electrical Response 108

3.8.2 Active Electrical Response 108

3.8.3 Membrane Resistance 108

3.8.4 Membrane Capacitance 109

3.8.5 Extent of Ion Transfer Associated with the Membrane Resting Potential 110

3.9 Membrane Equilibrium Potentials 111

3.10 Nernst Potential and Nernst Equation 112

3.11 The Equilibrium (Resting) Membrane Potential 114

3.12 Membrane Action Potential 116

3.12.1 Nerve (Axon) Membrane 117

3.12.2 Heart Muscle Cell Membrane 118

3.13 Channel Conductance 120

3.14 The Voltage Clamp 121

3.15 Patch-Clamp Recording 122

3.15.1 Application to Drug Discovery 123

3.16 Electrokinetic Effects 124

3.16.1 Electrophoresis 124

3.16.2 Electro-Osmosis 129

3.16.3 Capillary Electrophoresis 132

3.16.4 Dielectrophoresis (DEP) 137

3.16.5 Electrowetting on Dielectric (EWOD) 143

References 145

4 Spectroscopic Techniques 147

4.1 Chapter Overview 147

4.2 Introduction 148

4.2.1 Electronic and Molecular Energy Transitions 148

4.2.2 Luminescence 150

4.2.3 Chemiluminescence 150

4.2.4 Fluorescence and Phosphorescence 150

4.3 Classes of Spectroscopy 151

4.3.1 Electronic Spectroscopy 153

4.3.2 Vibrational Spectroscopy 156

4.3.3 Rotational Spectroscopy 157

4.3.4 Raman Spectroscopy 159

4.3.5 Total Internal Reflection Fluorescence (TIRF) 160

4.3.6 Nuclear Magnetic Resonance (NMR) Spectroscopy 162

4.3.7 Electron Spin Resonance (ESR) Spectroscopy 163

4.3.8 Surface Plasmon Resonance (SPR) 163

4.3.9 F€orster Resonance Energy Transfer (FRET) 164

4.4 The Beer-Lambert Law 165

4.4.1 Limitations of the Beer-Lambert Law 168

4.5 Impedance Spectroscopy 170

Problems 173

References 175

Further Readings 175

5 Electrochemical Principles and Electrode Reactions 177

5.1 Chapter Overview 177

5.2 Introduction 178

5.3 Electrochemical Cells and Electrode Reactions 180

5.3.1 Anodes and Cathodes 181

5.3.2 Electrode Reactions 182

5.3.3 Electrode Potential 184

5.3.4 Standard Reduction Potential and the Standard Hydrogen Electrode 187

5.3.5 The Relative Reactivities of Metal Electrodes 189

5.3.6 The Nernst Equation 192

5.4 Electrical Control of Electron Transfer Reactions 194

5.4.1 Cyclic Voltammetry 197

5.4.2 Amperometry 200

5.4.3 The Ideal Polarised Electrode 201

5.4.4 Three-Electrode System 201

5.5 Reference Electrodes 203

5.5.1 The Silver-Silver Chloride Reference Electrode 204

5.5.2 The Saturated-Calomel Electrode 205

5.5.3 Liquid Junction Potentials 207

5.6 Electrochemical Impedance Spectroscopy (EIS) 208

Problems 212

References 213

Further Readings 213

6 Biosensors 215

6.1 Chapter Overview 215

6.2 Introduction 215

6.3 Immobilisation of the Biosensing Agent 217

6.3.1 Physical Methods 217

6.3.2 Chemical Methods 218

6.4 Biosensor Parameters 218

6.4.1 Format 218

6.4.2 Transfer Function 220

6.4.3 Sensitivity 220

6.4.4 Selectivity 221

6.4.5 Noise 221

6.4.6 Drift 222

6.4.7 Precision and Accuracy 222

6.4.8 Detection Limit and Decision Limit 224

6.4.9 Dynamic Range 226

6.4.10 Response Time 226

6.4.11 Resolution 227

6.4.12 Bandwidth 227

6.4.13 Hysteresis 227

6.4.14 Effects of pH and Temperature 228

6.4.15 Testing of Anti-Interference 228

6.5 Amperometric Biosensors 228

6.5.1 Mediated Amperometric Biosensors 231

6.6 Potentiometric Biosensors 233

6.6.1 Ion Selective Electrodes (ISEs) 235

6.7 Conductometric and Impedimetric Biosensors 237

6.8 Sensors Based on Antibody–Antigen Interaction 240

6.9 Photometric Biosensors 242

6.10 Biomimetic Sensors 245

6.11 Glucose Sensors 247

6.12 Biocompatibility of Implantable Sensors 252

6.12.1 Progression of Wound Healing 252

6.12.2 Impact of Wound Healing on Implanted Sensors 254

6.12.3 Controlling the Tissue Response to Sensor Implantation 254

6.12.4 Regulations for and Testing of Implantable Medical Devices 255

References 255

Further Readings 256

7 Basic Sensor Instrumentation and Electrochemical Sensor Interfaces 259

7.1 Chapter Overview 259

7.2 Transducer Basics 260

7.2.1 Transducers 260

7.2.2 Sensors 260

7.2.3 Actuators 260

7.2.4 Transduction in Biosensors 260

7.2.5 Smart Sensors 261

7.2.6 Passive vs. Active Sensors 262

7.3 Sensor Amplification 262

7.3.1 Equivalent Circuits 262

7.4 The Operational Amplifier 264

7.4.1 Op-Amp Basics 264

7.4.2 Non-inverting Op-Amp Circuit 265

7.4.3 Buffer Amplifier Circuit 266

7.4.4 Inverting Op-Amp Circuit 267

7.4.5 Differential Amplifier Circuit 267

7.4.6 Current Follower Amplifier 268

7.5 Limitations of Operational Amplifiers 269

7.5.1 Resistor Values 269

7.5.2 Input Offset Voltage 269

7.5.3 Input Bias Current 269

7.5.4 Power Supply 270

7.5.5 Op-Amp Noise 270

7.5.6 Frequency Response 270

7.6 Instrumentation for Electrochemical Sensors 271

7.6.1 The Electrochemical Cell (Revision) 271

7.6.2 Equivalent Circuit of an Electrochemical Cell 271

7.6.3 Potentiostat Circuits 272

7.6.4 Instrumentation Amplifier 274

7.6.5 Potentiostat Performance and Design Considerations 275

7.6.6 Microelectrodes 277

7.6.7 Low Current Measurement 277

7.7 Impedance Based Biosensors 278

7.7.1 Conductometric Biosensors 278

7.7.2 Electrochemical Impedance Spectroscopy 280

7.7.3 Complex Impedance Plane Plots and Equivalent Circuits 281

7.7.4 Biosensing Applications of EIS 283

7.8 FET Based Biosensors 284

7.8.1 MOSFET Revision 284

7.8.2 The Ion Sensitive Field Effect Transistor 287

7.8.3 ISFET Fabrication 290

7.8.4 ISFET Instrumentation 291

7.8.5 The REFET 292

7.8.6 ISFET Problems 293

7.8.7 Other FET Based Sensors 293

Problems 294

References 296

Further Readings 296

8 Instrumentation for Other Sensor Technologies 297

8.1 Chapter Overview 297

8.2 Temperature Sensors and Instrumentation 298

8.2.1 Temperature Calibration 298

8.2.2 Resistance Temperature Detectors 298

8.2.3 p-n Junction Diode as a Temperature Sensor 301

8.3 Mechanical Sensor Interfaces 304

8.3.1 Piezoresistive Effect 304

8.3.2 Applications of Piezoresistive Sensing 306

8.3.3 Piezoelectric Effect 311

8.3.4 Quartz Crystal Microbalance 311

8.3.5 Surface Acoustic Wave Devices 315

8.3.6 Capacitive Sensors 317

8.3.7 Capacitance Measurement 319

8.3.8 Capacitive Bridge 320

8.3.9 Switched Capacitor Circuits 322

8.4 Optical Biosensor Technology 325

8.4.1 Fluorescence 325

8.4.2 Optical Fibre Sensors 328

8.4.3 Optical Detectors 329

8.4.4 Case Study: Label Free DNA Detection with an Optical Biosensor 332

8.5 Transducer Technology for Neuroscience and Medicine 335

8.5.1 The Structure of a Neuron 335

8.5.2 Measuring and Actuating Neurons 336

8.5.3 Extracellular Measurements of Neurons 339

Problems 340

References 341

Further Readings 342

9 Microfluidics: Basic Physics and Concepts 343

9.1 Chapter Overview 343

9.2 Liquids and Gases 343

9.2.1 Gases 344

9.2.2 Liquids 346

9.3 Fluids Treated as a Continuum 346

9.3.1 Density 346

9.3.2 Temperature 346

9.3.3 Pressure 347

9.3.4 Maxwell Distribution of Molecular Speeds 349

9.3.5 Viscosity 352

9.4 Basic Fluidics 354

9.4.1 Static Fluid Pressure 354

9.4.2 Pascal’s Law 354

9.4.3 Laplace’s Law 355

9.5 Fluid Dynamics 356

9.5.1 Conservation of Mass Principle (Continuity Equation) 356

9.5.2 Bernoulli’s Equation (Conservation of Energy) 358

9.5.3 Poiseuille’s Law (Flow Resistance) 360

9.5.4 Laminar Flow 361

9.5.5 Application of Kirchhoff’s Laws (Electrical Analogue of Fluid Flow) 364

9.6 Navier-Stokes Equations 365

9.6.1 Conservation of Mass Equation 366

9.6.2 Conservation of Momentum Equation (Navier-Stokes Equation) 367

9.6.3 Conservation of Energy Equation 369

9.7 Continuum versus Molecular Model 369

9.7.1 Solving Fluid Conservation Equations 370

9.7.2 Molecular Simulations 372

9.7.3 Mesoscale Physics 375

9.8 Diffusion 378

9.9 Surface Tension 383

9.9.1 Surfactants 384

9.9.2 Soap Bubble 384

9.9.3 Contact Wetting Angle 385

9.9.4 Capillary Action 386

9.9.5 Practical Aspects of Surface Tension for Lab-on-Chip Devices 388

Problems 388

References 389

Further Readings 390

10 Microfluidics: Dimensional Analysis and Scaling 391

10.1 Chapter Overview 391

10.2 Dimensional Analysis 391

10.2.1 Base and Derived Physical Quantities 393

10.2.2 Buckingham’s p-Theorem 394

10.3 Dimensionless Parameters 400

10.3.1 Hydraulic Diameter 401

10.3.2 The Knudsen Number 403

10.3.3 The Peclet Number: Transport by Advection or Diffusion? 406

10.3.4 The Reynolds Number: Laminar or Turbulent Flow? 406

10.3.5 Reynolds Number as a Ratio of Time Scales 408

10.3.6 The Bond Number: How Critical is Surface Tension? 409

10.3.7 Capillary Number: Relative Importance of Viscous and Surface Tension Forces 410

10.3.8 Weber Number: Relative effects of Inertia and Surface Tension 410

10.3.9 Prandtl Number: Relative Thickness of Thermal and Velocity Boundary Layers 411

10.4 Applying Nondimensional Parameters to Practical Flow Problems 411

10.4.1 Channel Filled with Water Vapour 411

10.4.2 Channel Filled with a Dilute Electrolyte at 293 K 411

10.5 Characteristic Time Scales 412

10.5.1 Convective Time Scale 412

10.5.2 Diffusion Time Scale 412

10.5.3 Capillary Time Scale 413

10.5.4 Rayleigh Time Scale 413

10.6 Applying Micro- and Nano-Physics to the Design of Microdevices 413

Problems 415

References 416

Appendix A: SI Prefixes 417

Appendix B: Values of Fundamental Physical Constants 419

Appendix C: Model Answers for Self-study Problems 421

Index 435