Label-Free Biosensing (eBook)

Michael J. Schöning Aachen University of Applied Sciences Institute of Nano- and Biotechnologies Heinrich-Mußmann-Str. 1 52428 Jülich, Germany e-mail: schoening@fh-aachen.de   Arshak Poghossian Aachen University of Applied Sciences Institute of Nano- and Biotechnologies Heinrich-Mußmann-Str. 1 52428 Jülich, Germany e-mail: a.poghossian@fz-juelich.de

Series Editor 6
Aims and Scope 6
Preface 7
Contents 10
Nanomaterial-Modified Capacitive Field-Effect Biosensors 12
1 Introduction 13
2 Capacitive EIS Sensors Modified with AuNP/Molecule Hybrids 14
2.1 Preparation of AuNP-Modified EIS Sensors and Measurement Setup 15
2.2 Functioning of EIS Sensors Modified with AuNP/Molecule Hybrids 17
2.3 Detection of Cytochrome c 19
2.4 Detection of Poly-d-lysine 20
2.5 Detection of LbL Adsorption of Oppositely Charged PE Macromolecules and Multilayer Formation 20
2.6 Enzyme Logic Gates Based on an AuNP-Modified EIS Sensor 22
3 Polyelectrolyte-Modified EIS Sensors 25
3.1 Label-Free Detection of DNA with PAH-Modified EIS Sensor 25
3.2 Biosensors Based on an EIS Sensor Modified with a PAH/Enzyme Multilayer 28
4 Summary and Outlook 30
References 31
Silicon Nanowire Field-Effect Biosensors 37
1 Introduction: Ion-Sensitive Field-Effect Transistors 38
2 Sensor Operation and Readout Strategies 45
2.1 Surface-Charge Sensing 46
2.2 Beyond Surface-Charge Sensing 49
3 Silicon Nanowire Ion-Sensitive Field-Effect Transistors 51
3.1 Fabrication of SiNW ISFETs 57
3.2 Limitations of SiNW-based ISFETs 58
3.2.1 Downscaling of ISFETs 58
3.2.2 Surface Functionalization 59
3.2.3 Gate Oxide and Sensor Configuration 59
3.2.4 Sensing in Physiological Solutions 60
4 Competing Platforms and New Concepts 60
4.1 New Materials and Nanowire Hybrids 60
4.2 Microfluidic Integration 61
5 Conclusions 61
References 62
Label-Free Biosensors Based on III-Nitride Semiconductors 68
1 Introduction 69
2 Group III-Nitrides 71
2.1 Basic Properties 71
2.2 Polarization in Group III-Nitrides 72
2.3 Indium Nitride 73
2.4 Summary of Features Relevant for Biosensors 73
2.5 Overview on Nitride-Based Biosensors 75
3 High-Electron-Mobility Transistor Sensors 76
3.1 Sensor Structure and Technology 76
3.2 pH Sensors 76
3.3 Monitoring Biochemical Reactions 79
4 Surface Treatment and Stability 80
4.1 Oxidation 80
4.2 Stability in Water 81
4.3 Cleaning of GaN Surfaces 82
4.4 Wetting Behavior 83
4.5 Impact of Device Processing 84
5 Biofunctionalization of the Surfaces 85
6 BioFETs (Detection of Biomarkers) 88
6.1 Enzyme-Modified Sensor: EnFET 88
6.2 Immunologically Based Sensor: ImmunoFET 88
6.3 DNA-Modified Sensor: DNA-FET 90
6.4 Advanced Measurement Schemes 90
6.4.1 Subthreshold Operation 91
6.4.2 Impedance Spectroscopy 91
6.4.3 Dynamic Measurements 92
7 Cell Proliferation 92
8 Cell-FETs (Monitoring Living Cells) 96
9 Further Biosensors 98
9.1 Electrical Biosensors: Nanowires 98
9.2 Mechanical Biosensors: Electroacoustic Resonators 99
9.3 Optical Biosensors 99
10 Multiparameter Systems 100
11 Conclusions 101
References 101
(Bio-)chemical Sensing and Imaging by LAPS and SPIM 112
1 Introduction 113
2 Principles of LAPS and SPIM 114
2.1 Measurement Set-Up 114
2.2 Generation of Photocurrent Dependent on Analyte Concentration 115
2.3 Photocurrent-Voltage and Phase-Voltage Characteristics 117
2.4 Equivalent Circuit of the LAPS 118
2.5 Operation Modes 120
2.5.1 Constant-Bias Mode 120
2.5.2 Constant-Current Mode 121
2.5.3 Potential-Tracking Mode 121
2.5.4 Phase Mode 121
2.5.5 SPIM Mode 121
3 LAPS-Based Sensing and Imaging 123
3.1 Detection of Various Ions 123
3.2 Utilisation of Enzymes and Antibodies 124
3.3 Detection of DNA 127
3.4 LAPS-Based Chemical Imaging 128
3.4.1 Spatial Resolution 129
3.4.2 Temporal Resolution 129
3.4.3 Applications 130
4 High-Resolution SPIM and LAPS Imaging Based on SOS Substrates 131
4.1 Surface Functionalisation of SOS Substrates 132
4.2 SPIM and LAPS Imaging 133
5 Summary 135
References 136
Biosensorial Application of Impedance Spectroscopy with Focus on DNA Detection 142
1 Impedance Spectroscopy and Biosensors 142
1.1 General Principles Used in Impedimetric Analyte Detection 143
1.1.1 Capacitance and Resistance Measurements 143
1.1.2 Sensor and Sensor Preparation 145
1.1.3 Impedimetric Enzyme- and Cell-Based Sensors 146
1.1.4 Impedimetric Immunosensing 148
1.1.5 Impedimetric Nucleic Acid Sensing 150
1.2 Amplification Strategies to Enhance the Signal of Impedimetric Analysis 154
2 Impedimetric DNA Detection 160
2.1 Sensor Concept 160
2.2 Sensor Properties 162
2.2.1 Reusability 162
2.2.2 Signal Stability 163
2.2.3 Sensitivity and Selectivity 164
2.2.4 Mismatch Detection 165
2.3 Factors Influencing the Sensing Performance 166
2.3.1 Buffer Concentration 166
2.3.2 DNA Probe Concentration and Length 166
2.3.3 Size of the Target DNA 168
2.4 Detection of DNA-Binding Molecules 170
2.4.1 Low-Molecular-Weight Compounds 170
2.4.2 Protein Binding 172
2.4.3 Sequence-Specific DNA Cleavage 173
3 Conclusions 174
References 174
Label-Free Impedimetric Biosensing Using 3D Interdigitated Electrodes 188
1 Introduction 189
2 Impedance of Interdigitated Electrode Arrays 190
3 Three-Dimensional Sensor Design, Fabrication and Characterization 195
4 Direct Label-Free Analyte Detection 197
5 Conclusions 204
References 205
Electrochemical Nanocavity Devices 208
1 Introduction 209
2 Single-Electrode Nanocavity Devices 211
2.1 Fabrication 213
3 Multi-Electrode Devices (Electrochemical Sensors) 215
3.1 Nanocavity Redox Cycling Sensors 215
3.2 Applications in Electrochemical Biosensing 217
3.3 Next-Generation Fabrication Approaches 219
4 Summary and Outlook 220
References 221
Computational Modeling of Biomolecule Sensing with a Solid-State Membrane 224
1 Introduction 225
2 Model and Methods 226
2.1 Nanopore-Membrane System 226
2.2 Computational Model of Surface Modified Nanopore 227
2.3 Computational Model of a Polymer Chain Attached to a Molecular Stop 229
3 Results 233
3.1 Surface Modified Nanopore 233
3.2 Molecular Stop 241
4 Conclusion 243
References 245
Amperometric Sensors Based on Carbon Nanotubes in Layer-by-Layer Films 248
1 Introduction 249
2 Carbon Nanotubes as Materials for Electrochemical Sensors 249
3 Layer-by-Layer Technique for Incorporation of CNTs in Sensors 251
4 Carbon Nanotubes in Layer-by-Layer Films for Sensing Applications 253
4.1 Sensors for Clinical Diagnostics 253
4.2 DNA Sensors 259
4.3 Glucose Sensors 261
5 Conclusions 263
References 263
Graphene-Based Biosensors and Their Applications in Biomedical and Environmental Monitoring 269
1 Introduction 270
2 Functionalization of Graphene and GO 272
2.1 Covalent Functionalization 272
2.2 Non-covalent Functionalization 274
3 Applications of Graphene and Graphene Oxide-Based Biosensors 275
3.1 Biomedical Applications 275
3.1.1 Detection of Glucose 275
3.1.2 Detection of Hydrogen Peroxide (H2O2) 277
3.1.3 Detection of Cholesterol 279
3.1.4 Detection of Urea 279
3.1.5 Detection of DNA 282
3.1.6 Detection of Protein Biomarkers for Disease Diagnosis and Therapy 282
3.2 Environmental Monitoring Applications 285
3.2.1 Detection of Heavy Metal Ions 285
3.2.2 Detection of Pesticides 286
3.2.3 Detection of Other Organic Molecules 289
4 Conclusion and Outlook 291
References 294
Label-Free MIP Sensors for Protein Biomarkers 299
1 Introduction 300
1.1 MIPs for Proteins 301
1.2 MIP-Sensor Configurations 305
2 MIPs for Biomarkers 307
2.1 Cancer Markers 307
2.1.1 Prostate Cancer Markers 307
2.1.2 Ovarian and Breast Cancer Antigens 308
2.1.3 Human Papillomavirus-Derived E7 Protein 309
2.1.4 Cancerogenic Embryonic Antigen 309
2.2 Markers for Myocardial Infarction 309
2.2.1 Cardiac Troponin T 309
2.2.2 Myoglobin 310
2.2.3 Trypsin 311
2.3 Further MIPs for Biomarkers 312
2.3.1 Glycated Haemoglobin: A Long-Term Diabetes Marker 312
2.3.2 C-Reactive Protein: A Marker for Infections 312
2.3.3 Acetylcholine Esterase: A Potential Biomarker in Alzheimer´s Disease 313
2.3.4 Ferritin: A Marker for Iron Storage and Inflammation 315
2.3.5 Transferrin: A Marker for Alcohol Abuse 316
2.3.6 HIV-1-Related Glycoprotein 41 317
2.3.7 Procalcitonin: A Sepsis Marker 317
2.3.8 Immunoglobulin G: Indicator of the Immune Status 318
3 Conclusions 319
References 321
Biomimetic Recognition for Acoustic Sensing in Liquids 330
1 Introduction 331
1.1 Biomimetics 331
1.2 Biosensors and Biomimetic Sensors 332
2 Acoustic Signal Transduction 333
2.1 Quartz Crystal Microbalance 334
2.2 Surface Acoustic Wave Devices 335
2.3 Cantilevers 336
3 Biomimetic Receptors 337
3.1 Aptamers 338
3.1.1 Sensor Applications 339
3.2 Molecularly Imprinted Polymers 340
3.2.1 Sensor Applications 342
3.3 Self-Assembled Monolayers 346
3.3.1 Sensor Applications 347
4 Conclusion 348
References 348
Enzyme Logic Systems: Biomedical and Forensic Biosensor Applications 352
1 Introduction: Bioanalytical Applications of Enzyme Logic Systems 353
2 Biocomputing Approach to the Analysis of Injury Biomarkers 355
3 Biocomputing Applications in Forensic Science 362
3.1 Biocatalytic Logic Analysis of Biomarkers for Forensic Identification of Ethnicity Between Caucasian and African American 364
3.2 Biocatalytic Logic Analysis of Biomarkers for Forensic Identification of Gender 372
3.3 Biocatalytic Logic Assay to Determine Age of Blood Sample 378
4 Conclusions and Perspectives 383
References 385
Heat Transfer as a New Sensing Technique for the Label-Free Detection of Biomolecules 389
1 Introduction 390
2 General Sensing Concept 392
3 Detection of Single-Nucleotide Polymorphisms in DNA 393
4 Detection of Small Organic Molecules with Molecularly Imprinted Polymers 396
5 Cell and Pathogen Detection 398
6 Phase Transition Study on Supported Lipid Vesicle Layers 403
7 Protein Detection 405
8 Thermal Wave Transport Analysis 408
9 Conclusions 408
References 410
Toward Ultrasensitive Surface Plasmon Resonance Sensors 414
1 Introduction 415
2 Basic Measurement Configuration 416
3 Main Factors Limiting the Performance of SPR-Based Sensors 420
4 Increase of the Signal Magnitude and Signal-to-Noise Ratio 421
4.1 Optimization of the Receptor Layer 421
4.2 Optimization of the Resonant Layer 423
4.3 Optimization of the Incidence Angle 425
4.4 Instrumental Improvement of SPR Sensitivity 426
5 Self-Referencing in SPR Measurements 428
5.1 Macroscopic Spatially Separated Referencing 428
5.2 Self-Referencing Based on Micro-patterning 429
5.3 In-Place Self-Referencing 430
5.3.1 Dual-Wavelength SPR 430
5.3.2 Referencing by Using Simultaneous Excitation of Long- and Short-Range SPR 432
5.4 Spatiotemporal Referencing 433
5.5 Electrochemically Assisted Referencing 437
5.5.1 Ionic Referencing 437
5.5.2 Electrochemically Assisted Spatiotemporal Referencing 439
6 Evaluation of Affinity Properties from SPR Measurements 440
6.1 Measurements in Quasi-equilibrium Conditions 441
6.2 Kinetic Measurements 443
6.3 Analysis of Temperature Dependencies 445
7 Conclusion 446
References 447
Biomagnetic Sensing 454
1 Introduction 455
2 Superconducting Quantum Interference Devices 456
3 Biomagnetism 459
3.1 Magnetocardiography 459
3.2 Fetal Magnetocardiography 461
3.3 Magnetoencephalography 461
4 Magnetic Resonance Imaging 464
4.1 High-Field MRI 465
4.2 Low-Field MRI 466
5 Hybrid Biomagnetism and Magnetic Resonance Imaging 470
6 Magnetic Resonance Imaging of Neural Activity 470
7 Magnetic Immunoassays 471
8 Conclusion and Perspectives 474
References 474
Index 480