Vladimir M. Mirsky

Ultrathin Electrochemical Chemo- and Biosensors

Technology and Performance

Springer

Contents

Parti: Receptors

Chapter 1 Antibodies for Biosensors 3

K. KRAMER, B. HOCK

1 Introduction 4 2 Structure and Function of Antibodies 4 3 Productionof Antibodies 6 3.1 Antibodies Obtained from Sera and Hybridoma Cell Cultures. . . . 6 3.2 Recombinant Antibodies 6 3.3 Antibody Library Derived from a Set of B Cells 7 4 Diversification by Chain Shuffling 11 5 Antibody Optimization as a Special Case of Genetic Algorithms . . 14 6 Biosensors asa Tool in Evolutionary Antibody Synthesis 15

6.1 Antibodies as Receptors in Biosensor Designs 15

6.2 Limitationsof Antibody-Based Biosensor Designs 17

7 Conclusions and Outlook 20 References 21

Chapter 2 Molecularly Imprinted Polymers as Recognition Elements in Sensors 23

KARSTEN HAUPT

1 Molecularly Imprinted Polymers 24 1.1 General Principleof Molecular Imprinting 24 1.2 The Imprinting Matrix 26 1.2.1 Acrylic and Vinyl Polymers 26 1.2.2 Other Organic Polymers . 27 1.2.3 Other Imprinting Matrices . . . 28

1.3 Target Molecules 28

1.4 Physical Forms and Preparation Methods of MIPs 29

X Contents

1.4.1 Imprinted Particles: Making MIPs Smaller 29 1.4.2 Imprinting at Surfaces 30 1.4.3 Thin Imprinted Polymer Films 31 2 Applications of Imprinted Polymers in Sensors 31 2.1 General Considerations 31 2.2 General Transducer Types 32 2.3 The Analyte Generates the Signal 34 2.4 The Polymer Generates the Signal 35 3 Outlook 37 References 37

Part II: Impedometric and amperometric chemical and biological sensors

Chapter3 Capacitance Affinity Biosensors 43

HELEN BERNEY

1 Introduction 44 2 Capacitance-Based Transduction 45 2.1 The Electrode/Electrolyte Interface 47 2.1.1 Metal Electrodes 47 2.1.2 Semiconductor Electrodes 49 2.2 Modelling the Electrode/Electrolyte Interface 50 3 Capacitance Sensors 53 3.1 Capacitance Sensing with Interdigitated Electrodes 53 3.2 Capacitance Sensing at the Metal/Solution Interface 55 3.3 Capacitance Sensing at the Semiconductor/Solution Interface.. . . 60 4 Conclusions 64 References 64

Chapter4 Immunosensors and DNA Sensors Basedon Impedance Spectroscopy 67

EUGENII KATZ, ITAMAR WILLNER

1 Introduction 69 2 Impedance Spectroscopy: Theoretical Background 70 3 Immunosensors Based on Impedance Spectroscopy 74 3.1 Immunosensors Based on In-Plane Impedance Measurements

between Conductive Electrodes 74

Contents X I

3.2 Immunosensors Based on Interfacial Impedance Measurements at Conductive Electrodes 79

4 DNA Sensors Based on Impedance Spectroscopy 96 4.1 Impedimetric Sensing of DNA Hybridization 99 4.2 Impedimetric Sensing of Single-Base Mismatches

in DNA Sequences 104 4.3 Impedimetric Sensing of DNA and RNA Replication 108 5 Conclusions and Perspectives 112 References 113

Chapter5 "Voltohmmetry"-a New Transducer Principle for Electrochemical Sensors. . . . 117

MICHAEL J. SCHÖNING

1 Introduction 118 2 Theory and Experiment 120 2.1 Theory of Surface Resistance Change 120 2.2 FabricationofThin-Film Electrodes 121 2.3 Instrumentation and Chemicals 123 2.4 Measurement Procedure 124 3 Characterisation and Applications ofVoltohmmetric Sensors . . . 126 3.1 Physical Characterisation of Thin-Film Electrodes 126 3.2 Analytical Approach 128 3.2.1 Resistance/Voltage Curve and Evaluation Procedure 128 3.2.2 Sensitivity and Selectivity 131 3.2.3 Reproducibility 134 3.2.4 Heavy Metal Determination in Complex Analytes 135 4 Conclusion and Perspectives 137 References 139

Chapter6 Electrochemical Sensors for the Detection of Superoxide and Nitric Oxide -Two Biologically Important Radicals 141

F. LlSDAT

1 Introduction 141 2 Superoxide and Nitric Oxide: Short-Lived Reactive Species 142 3 Sensors for Superoxide 145 3.1 Sensors Based on Enzymatic Product Detection 146 3.2 Sensors Based on Direct Protein-Electrode Contacts 147 3.3 Sensors for Antioxidants 148

X I I Contents

4 Nitric Oxide Sensors 149

5 Conclusion 152 References 152

Part III: Non-invasive electrical monitoring of living cells

Chapter7 Living Cells on Chip: Bioanalytical Applications 159

MARTIN BRISCHWEIN, HELMUT GROTHE, ANGELA M. OTTO,

CHRISTOPH STEPPER, THOMAS WEYH, BERNHARD WOLF

1 Introduction 160

2 Chip Design and Fabrication 163

3 Cell Culture on Chips and Accessory Devices for Biohybrid Systems 167

4 Transducers for Cellular Output Signals 169 4.1 pH Sensors 170 4.2 Oxygen Sensors 170 4.3 Sensors Directed to Biomembranes and Morphological Patterns . . 172 4.4 Sensors for Electrophysiological Activity 175 5 Conclusions, Applications and Future Prospects 175 References 179

Chapter8 Bioanalytical Application of Impedance Analysis:Transducing in Polymer-Based Biosensors and Probes for Living Tissues 181

G. FARACE, P. VADGAMA

1 Introduction 181

2 Impedance for Transduction in Biosensors 184

3 Impedance as a Basis for Probing Bacteria and Cells 190

4 Future Directions 195

References 196

Chapter9 Noninvasive Electrical Sensor Devices to Monitor Living Cells Online 199

ANDREAS JANSHOFF, CLAUDIA STEINEM, JOACHIM WEGENER

1 Introduction 200 2 Electrochemical Impedance Measurements

to Monitor Living Cells 201

2.1 Experimental Background of ECIS 202

2.2 Biomedical Applications 204

Contents X I I I

2.2.1 Attachment and Spreading of Mammalian Cells to Adhesive Proteins 204

2.2.2 ß-Adrenergic Stimulation of Cells Forming the Blood Vessels . . . . 209 3 Piezoelectric Approaches to Monitor Living Cells 213 3.1 Physical Background of the QCM Technique 214 3.1.1 Thickness Shear Mode Resonators 214 3.1.2 Electromechanical Coupling in TSM Resonators 216 3.1.3 Devices, Setups, and Measuring Principles 220 3.1.3.1 Active Mode 220 3.1.3.2 Passive Mode 221 3.2 Cell Adhesion Monitoring 223

3.2.1 Cell Adhesion Monitored in the Active Mode 223 3.2.2 Cell Adhesion Monitored in the Passive Mode 227 3.3 Manipulating the Actin Cytoskeleton 230

3.4 Double-Mode Impedance Analysis of Cell-Substrate and Cell-Cell Contacts 230

References 234

Part IV: Lipid membranes as biosensors

ChapterlO Functional Tethered Bilayer Lipid Membranes 239

WOLFGANG KNOLL, KENICHI MORIGAKI, RENATE NAUMANN,

BARBARA SACCÄ, STEFAN SCHILLER, EVA-KATHRIN SINNER

1 Introduction 240

2 Designing Tethered Bilayer Lipid Membranes 241

2.1 A novel Archaea Analog Lipid as Seif-Assembling Telechelic 241

2.2 Sequential Deposition of Structural Elements 243

3 Patterningof Tethered Bilayer Lipid Membranes 244

3.1 Micropatterning by Photopolymerization 244

3.2 Back-Filling the EmptyCorralsbyVesicle Fusion 247

4 Electrical Properties of Tethered Membranes 247

4.1 Impedance Spectroscopy 247

4.2 FunctionalizationbyValinomycin 248

5 Binding Studies with Tethered Membranes 248

References 252

X I V Contents

Chapterll Electrostatk Potentials of Bilayer Lipid Membranes: Basic Principles and Analytical Applications 255

VALERI SOKOLOV, VLADIMIR MIRSKY

1 Introduction 256

1.1 Structure of Lipids and Lipid Bilayers 258

1.2 Electrostatic Boundary Potentials 259

1.3 Distribution of the Electric Field Across the Membrane 260

2 Methodsof Measurementof Boundary Potentials 261

2.1 MobilityofVesicles in the Electric Field 261

2.2 Nonstationary Membrane Potentials onPlanarLipidMembranes. . 262

2.3 Short Circuit Currents During Modification of Electrical Double Layers 262

2.4 Determination of Boundary Potential Changes from Measurements of Membrane Conductance 264

2.5 Methods of Compensation of Intramembrane Field 267

3 Effects of Different Compounds on Electrostatic Potentials of Lipid Bilayers 270

3.1 Effects of Inorganic Ions 270 3.2 Effects of Amphiphilic Ions 272 3.2.1 Theoretical Models for Adsorption of Amphiphilic Ions 272 3.2.2 Potential Distribution 274 3.2.3 Transfer Through the Membrane 277 3.3 Effects of Neutral Molecules 279 3.3.1 Dipole Potentials 279 3.3.2 Potential Distribution and the Depthof Adsorption 281

4 Changeof Boundary Potential dueto Lipid Hydrolysis 282

5 Analytical Applications 284

6 Conclusion 286 References 287

Chapter12 Electrostriction of Supported Lipid Membranes and Their Application in Biosensing 293

TlBOR HlANIK

1 Introduction 295

2 Methods of Preparation of Supported Lipid Membranes and Their Modification by Functional Macromolecules 296

2.1 Supported Lipid Membranes 297

Contents X V

2.2 Immobilization of Functional Macromolecules ontheSurfaceofBLMandsBLM 298

3 Basic Principles of the Electrostriction and Dielectric Relaxation 299

3.1 Electrostriction Method 299 3.2 Dielectric Relaxation 300 3.2.1 Dielectric Constant 300 3.2.2 Membrane Thickness 301 3.2.3 Membrane Area 301 3.2.4 Basic Principles of the Measurement of Dielectric Relaxation . . . . 301 4 Electrical and Mechanical Properties of sBLM 303 4.1 Specific Conductivity, Capacitance, and Stability 303

4.2 Mechanical Properties ofBLM and sBLM 307

4.3 Changes of Electrostriction of sBLM Following Interaction

with Surfactants, Surfactant-DNA Complexes, and DNA 311

4.3.1 Interaction ofHDA with sBLM 312

4.3.2 Interaction ofHDA-DNA Complexes with sBLM 313

4.3.3 Interaction of the DNA Complexes with sBLM: Influence of Mg2+ 316

4.4 sBLM Modified by Short Oligonucleotides as aPossible Genosensor 318

4.5 Changes of Physical Properties of sBLM During Binding of Enzymes and Immunoglobulins 323

4.6 Dielectric Relaxation of Lipid Bilayers upon Binding Processes . . . 326 References 328

Chapter13 Transport Proteins on Solid-Supported Membranes: From Basic Research to Drug Discovery 331

KLAUS FENDLER, MARTIN KLINGENBERG, GERARD LEBLANC, JAN JOEP

H. H. M. DEPONT, BELA KELETY, WOLFGANG DÖRNER, ERNST BAMBERG

1 Introduction 332

2 Rapid Solution-Exchange Technique for the Investigation of Electrogenic Ion Pumps 333

2.1 Sensor Preparation 333 2.2 Measuring Procedure 335 3 ATPases 337 3.1 Na+/K+-ATPase 337 4 Carriers 339 4.1 ATP/ADP Exchanger 339

X V I Contents

4.2 Melibiose Permease 341 5 Application: The SSM as a Tool for Drug Discovery 343 5.1 Electrogenic Proteins: Pharmaceutical Relevance and Screening . . 343

5.2 Assays for the Screening of Electrogenic Membrane Proteins . . . . 344

5.2.1 Conventional Assay Technologies 344

5.2.2 Cell-Based Electrophysiological Methods 345

5.2.3 Sensor-Based Methods 345 5.3 An Integrated System for Drug Discovery 346

5.3.1 The Gastric Proton Pump Revisited 347 5.4 Outlook 348

References 348

Subject Index 351