Preface ................................................... XV
List of Authors .......................................... XIX
1 Biosensing using Carbon Nanotube Field-effect Transistors .. 1
Padmakar D. Kichambare and Alexander Star
1.1 Overview ................................................... 1
1.2 Introduction ............................................... 1
1.3 Carbon Nanotube Field-effect Transistors (NTFETs) .......... 3
1.3.1 Carbon Nanotubes .................................... 3
1.3.2 Nanotube Synthesis .................................. 4
1.3.3 Fabrication of NTFETs ............................... 6
1.4 Sensor Applications of NTFETs .............................. 9
1.4.1 Sensitivity of NTFETs to Chemical Environment ....... 9
1.4.2 Bioconjugates of Carbon Nanotubes .................. 12
1.4.3 Protein Detection .................................. 14
1.4.4 Detection of Antibody-Antigen Interactions ......... 15
1.4.5 DNA Detection ...................................... 17
1.4.6 Enzymatic Reactions ................................ 19
1.4.7 Glucose Detection .................................. 20
1.5 Conclusion and Outlook .................................... 21
References ................................................ 21
2 Carbon Nanotube-based Sensor .............................. 27
Jian-Shan Ye and Fwu-Shan Sheu
2.1 Overview .................................................. 27
2.2 Introduction of Carbon Nanotubes .......................... 27
2.3 Growth of Carbon Nanotubes ................................ 29
2.4 Methods to Prepare CNTs-based Sensors and Biosensors ...... 29
2.4.1 Individual MWCNTs as Nanoelectrodes ................ 29
2.4.2 Randomly Distributed CNT Electrodes ................ 30
2.4.3 Well-aligned Carbon Nanotube Electrodes ............ 30
2.4.4 Carbon Nanotube Paste Electrodes ................... 31
2.4.5 Screen-printing Carbon Nanotubes ................... 32
2.4.6 Self-assembly of Carbon Nanotubes .................. 33
2.4.7 Carbon Nanotube-packaged Microelectrodes ........... 34
2.5 Application of CNTs-based Electrochemical Sensors and
Biosensors ................................................ 34
2.5.1 Electrochemical and Electrocatalytical Properties
of Carbon Nanotubes ................................ 34
2.5.2 CNTs-based Electrochemical Biosensors .............. 37
2.6 Functionalization of CNTs ................................. 39
2.6.1 Biological Functionalization of CNTs ............... 39
2.6.2 Self-assembly of Surfactant and Lipid Molecules
at CNTs ............................................ 39
2.6.3 Electrochemical Functionalization of CNTs .......... 42
2.6.4 Electrochemical Application of Functionalized
CNTs ............................................... 43
2.6.4.1 Application of Lipid-CNT Nanomaterials in
Electrochemical Sensors ........................ 43
2.6.4.2 Achieving direct Electron Transfer to Redox
Proteins by Functional CNTs .................... 44
2.6.4.3 Biomolecule-functionalized CNTs for
Electrochemical Sensors and Biosensors ......... 45
2.7 Conclusions and Future Prospects .......................... 48
Acknowledgments ........................................... 49
References ................................................ 49
3 Nanotubes, Nanowires, and Nanocantilevers in Biosensor
Development ............................................... 56
Jun Wang, Cuodong Liu, and Yuehe Lin
3.1 Introduction .............................................. 56
3.2 Carbon Nanotubes in Biosensor Development ................. 57
3.2.1 Preparation and Purification of CNTs ............... 58
3.2.2 Construction of CNT-based Biosensors ............... 60
3.2.2.1 Dispersion and Stabilization by Oxidative
Acids .......................................... 60
3.2.2.2 Dispersion by Surfactant Interaction ........... 61
3.2.2.3 Polymer-assisted Solubilization ................ 61
3.2.2.4 CNT Adsorption on the Transducer Substrate ..... 61
3.2.2.5 Surface Functionalization of CNTs .............. 62
3.2.2.6 Composite Entrapment and CNTs Bulky Electrode
Material ....................................... 63
3.2.2.7 More Sophisticated Surface Tailoring Based on
Combination of Co-adsorption, Integration,
Prohibition, Spacing, Linkage, Sandwich,
Tagging, and other Anchoring Approaches ........ 66
3.2.3 CNT-based Electrochemical Biosensors ............... 69
3.2.3.1 Direct Electrochemistry of Biomolecules on
Carbon Nanotubes ............................... 69
3.2.3.2 Enzyme/CNTs Biosensors ......................... 72
3.2.3.3 DNA and Protein Biosensors ..................... 73
3.2.3.4 Immunosensors .................................. 74
3.2.4 Flow-injection Analysis ............................ 75
3.2.5 Carbon Nanotube Array-based Biosensors ............. 76
3.2.6 Chemiluminescence .................................. 80
3.2.7 Field-effect Transistor and Bioelectronics ......... 82
3.3 Nanowires in Biosensor Development ........................ 84
3.3.1 Silicon Nanowire-based Biosensors .................. 84
3.3.2 Conducting Polymer Nanowire-based Biosensors ....... 86
3.3.3 Metal Oxide Nanowire-based Biosensors .............. 89
3.4 Nanocantilevers for Biosensors ............................ 89
3.5 Summary ................................................... 90
Acknowledgments ........................................... 91
Glossary .................................................. 91
Abbreviations ............................................. 92
References ................................................ 93
4 Fullerene-based Electrochemical Detection Methods for
Biosensing ............................................... 101
Nikos Chaniotakis
4.1 Introduction ............................................. 101
4.2 Aims of the Chapter ...................................... 101
4.3 Electrochemical Biosensing ............................... 103
4.3.1 Making a Biosensor ................................ 205
4.4 Evolution of Biosensors .................................. 105
4.5 Mediation Process in Biosensors .......................... 206
4.5.1 Case A: Non-mediated Biosensor .................... 107
4.5.2 Case B: Mediated Biosensor ........................ 108
4.6 Fullerenes ............................................... 109
4.6.1 Synthesis of Fullerenes ........................... 109
4.6.2 Biofunctionalization of Fullerenes ................ 109
4.6.3 Electrochemistry of Fullerenes .................... 113
4.7 Fullerene-mediated Biosensing ............................ 114
4.8 Conclusions .............................................. 118
References ............................................... 118
5 Optical Biosensing Based on Metal and Semiconductor
Colloidal Nanocrystals ................................... 123
Roberto Comparelli, Maria Lucia Curri, Pantaleo Davide
Cozzoli, and Marinella Striccoli
5.1 Overview ................................................. 123
5.2 Introduction ............................................. 123
5.3 Colloidal Nanocrystals ................................... 127
5.3.1 Size-dependent Optical Properties ................. 127
5.3.2 Chemical Synthesis ................................ 131
5.4 Nanocrystal Functionalization for Biosensing ...... 134
5.4.1 Surface Capping Exchange .......................... 135
5.4.2 Coating with a Silica Shell ....................... 237
5.4.3 Surface Modification through Hydrophobic
Interactions ...................................... 237
5.5 Optical Techniques ................................ 239
5.5.1 Colorimetric Tests ................................ 239
5.5.2 Fluorescence ...................................... 239
5.5.3 Fluorescence Resonance Energy Transfer ............ 141
5.5.4 Fluorescence Lifetime ............................. 142
5.5.5 Multiphoton Techniques ............................ 145
5.5.6 Metal-enhanced Fluorescence ....................... 245
5.5.7 Surface Plasmon Resonance ......................... 246
5.5.8 Surface-enhanced Resonance Spectroscopy ........... 249
5.6 Advantages and Disadvantages of Nanocrystals in Optical
Detection ................................................ 252
5.7 Applications ............................................. 253
5.7.1 Biosensing with Semiconductor Nanocrystals ........ 253
5.7.2 Biosensing with Metallic Nanoparticles ............ 257
5.8 Towards Marketing ........................................ 262
5.9 Conclusions .............................................. 264
References ............................................... 264
6 Quantum Dot-based Nanobiohybrids for Fluorescent
Detection of Molecular and Cellular Biological Targets ... 275
Zhivko Zhelev, Rumiana Bakalova, Hideki Ohba, and
Yoshinobu Baba
6.1 Introduction ............................................. 275
6.2 Quantum Dots - Basic Principles of Design and
Synthesis, Optical Properties, and Advantages over
Classical Fluorophores ................................... 276
6.2.1 Basic Principles of Design and Synthesis of
Quantum Dots ...................................... 276
6.2.2 Optical and Chemical Properties - Advantages
Compared with Classical Fluorophores .............. 278
6.3 Quantum Dots for Fluorescent Labeling and Imaging ........ 282
6.3.1 Structure of Quantum Dot Nanobiohybrids for
Fluorescent Microscopic Imaging ................... 282
6.3.2 Quantum Dots for Fluorescent Cell Imaging ......... 282
6.3.3 Quantum Dots for Fluorescent Deep-tissue Imaging
In Vivo ........................................... 184
6.3.4 Potential of Quantum Dots for Positron Emission
Tomography (PET) and functional Magnetic
Resonance Imaging (fMRI) .......................... 292
6.4 Quantum Dots for Immunoblot Analysis with Fluorescent
Detection ................................................ 292
6.4.1 Basic Principles of Classical and QD-based
Immunoblot Analyses ............................... 292
6.4.2 QD-based Immunoblot Analysis of "tracer"
Proteins - Privileges over Classical Immunoblot
Analysis .......................................... 294
6.5 Quantum Dots for FRET Analyses, Time-resolved
Fluorimetry, and Development of Optical Recognition-
based Biosensors ......................................... 296
6.5.1 Quantum Dots for FRET-based Bioanalyses ........... 296
6.5.2 Quantum Dots for Time-resolved Fluorimetry ........ 297
6.5.3 Quantum Dots for development of New Generation
Optical Recognition-based Biosensors .............. 297
6.6 Quantum Dots as New Fluorescent Standards for the Thin
Calibration of Fluorescent Instrumentation ............... 202
References ............................................... 202
7 Detection of Biological Materials by Cold Nano-
biosensor-based Electrochemical Method ................... 208
Juan Jiang, Manju Basu, Sara Seggerson, Albert Miller,
Michael Pugia, and Subhash Basu
7.1 Introduction ............................................. 208
7.2 Template Synthesis of Gold Nano-wire Arrays for
Biosensor Applications ................................... 209
7.2.1 General Template Synthesis ........................ 209
7.2.2 Template Formation ................................ 212
7.2.3 Fabrication of Gold Nano-wire Arrays (GNW) ........ 214
7.3 Synthesis of a Linker and its Attachment to Gold Posts
of GNW followed by Binding to Specific Antibodies ........ 220
7.4 Development of Electrochemical Nano-biosensor for
Bacteria Detection ....................................... 224
7.4.1 General Detections for Biosensors ................. 224
7.4.2 Experimental Conditions ........................... 226
7.4.3 Electrochemical Impedance (EIS) Detection of
E. coli ........................................... 227
7.4.3.1 EIS on Flat Gold Surfaces ..................... 228
7.4.3.2 EIS on GNW .................................... 230
7.4.3.3 EIS on GNW with A12O3 ......................... 230
7.4.4 Summary of EIS Detection of E. coli Bacteria....... 233
7.5 Conclusions .............................................. 235
Acknowledgments .......................................... 235
References ............................................... 236
8 Dendrimer-based Electrochemical Detection Methods ........ 240
Hak-Sung Kim and Hyun C. Yoon
8.1 Overview ................................................. 240
8.2 Introduction ............................................. 240
8.2.1 Background ........................................ 240
8.2.2 Dendrimers as a new Constituent of Biocomposite
Structures ........................................ 241
8.3 Applications for Biosensors .............................. 242
8.3.1 Bioelectrocatalytic Enzyme Electrodes based on
LBL (layer-by-layer) Assembly with Dendrimers ..... 243
8.3.2 Bioelectrocatalytic Immunosensors based on the
Dendrimer-associated SAMs ......................... 244
8.3.2.1 Affinity Recognition Surface based on the
Dendrimer-associated SAMs ..................... 244
8.3.2.2 Electrochemical Signaling from Affinity
Recognition Reactions ......................... 248
8.3.3 Protein Micropatterning on Sensor Surfaces for
Multiplexed Analysis .............................. 253
8.4 Conclusions .............................................. 256
Acknowledgments .......................................... 256
References ............................................... 256
9 Coordinated Biosensors: Integrated Systems for
Ultrasensitive Detection of Biomarkers ................... 259
Joanne I. Yeh
9.1 Overview ................................................. 259
9.2 Introduction ............................................. 260
9.3 Elements of a Nanobiosensor .............................. 262
9.3.1 Biomolecular Components ........................... 262
9.3.2 Nanoparticles ..................................... 263
9.3.3 Nanoelectrodes .................................... 264
9.4 Coordinated Biosensors ................................... 265
9.4.1 Biomolecular Conduits: Signal Transducing
Mediators ......................................... 265
9.4.2 NADH Peroxidase: the Biocatalytic Element ......... 267
9.4.3 Undecagold Nanoparticle: Role in Alignment and
Directing Electron Flow ........................... 270
9.4.4 Integrated Signals ................................ 270
9.5 Conclusion ............................................... 272
Acknowledgments .......................................... 274
References ............................................... 274
10 Protein-based Biosensors using Nanomaterials ............. 278
Cenxi Li
10.1 Introduction ............................................. 278
10.2 Metal Nanoparticles ...................................... 279
10.2.1 Gold Nanoparticles ................................ 279
10.2.2 Silver Nanoparticles .............................. 284
10.2.3 Other Metal Nanomaterials ......................... 285
10.3 Metallic Oxide Nanoparticles ............................. 285
10.4 Carbon Nanotubes ......................................... 286
10.5 Nanocomposite Materials .................................. 292
10.6 Nanoparticles with Special Functions ..................... 293
10.6.1 Semiconductor Nanoparticles ....................... 293
10.6.2 Magnetic Nanoparticles ............................ 295
10.7 Other Nanomaterials ...................................... 295
10.8 Conclusion ............................................... 297
References ............................................... 297
11 Biomimetic Nanosensors ................................... 311
Raz Jelinek and Sofiya Kolusheva
11.1 Introduction ............................................. 311
11.2 Nanostructures in Biosensor Design ....................... 312
11.3 Nanosensors for Probing Biological and Cellular Systems .. 317
11.4 Biological Components in Nanosensors ..................... 323
11.5 Nano-biotechnology and Biomedical Diagnosis .............. 327
11.6 Conclusions and Future Directions ........................ 329
Abbreviations ............................................ 330
References ............................................... 330
12 Reagentless Biosensors Based on Nanoparticles ............ 337
David E. Benson
12.1 Introduction ............................................. 337
12.2 Surface Dielectric Enhancement ........................... 339
12.2.1 Gold Nanoparticle Enhanced Surface Plasmon
Resonance ......................................... 340
12.2.2 Carbon Nanotube and Silicon Nanowire Enhanced
Conductivity ...................................... 343
12.2.3 Advantages and Caveats ............................ 346
12.3 Catalytic Activation ..................................... 346
12.3.1 Electrocatalytic Detection ........................ 347
12.3.2 Catalytically Enabled Optical and Magnetic
Detection ......................................... 349
12.3.3 Advantages and Caveats ............................ 350
12.4 Biomolecule Conformational Modulated Effects ............. 351
12.4.1 Biosensors Based on DNA Conformation Changes ...... 352
12.4.2 Biosensors Based on Protein Conformation Changes .. 355
12.5 Conclusion ............................................... 361
Acknowledgments .......................................... 362
References ............................................... 362
13 Pico/Nanoliter Chamber Array Chips for Single-cell, DNA
and Protein Analyses ..................................... 368
Shohei Yamamura, Ramachandra Rao Sathuluri, and Eiichi
Tamiya
13.1 Introduction ............................................. 368
13.2 Multiplexed Polymerase Chain Reaction from A Single
Copy DNA using Nanoliter-volume Microchamber Array ....... 369
13.2.1 PCR Microchamber Array Chip System ................ 371
13.2.1.1 Microchamber Array Chip Fabrication .......... 371
13.2.1.2 Sample Loading with a Nanoliter Dispenser .... 372
13.2.2 Multiplexed Detection of Different Target DNA
on a Single Chip .................................. 373
13.2.3 On-chip Quantification of Amplified DNA ........... 376
13.3 On-chip Cell-free Protein Synthesis using A Picoliter
Chamber Array ............................................ 378
13.3.1 Cell-free Protein Synthesis Chip Fabrication ...... 379
13.3.2 Cell-free Protein Synthesis using a Microchamber
Array ............................................. 381
13.4 High-throughput Single-cell Analysis System using
Pico-liter Microarray .................................... 384
13.4.1 Single-cell Microarray Chip Fabrication ........... 386
13.4.2 Pico-liter Microarray for Single-cell Studies ..... 388
13.4.3 Single-cell Microarray System for Analysis of
Antigen-specific Single B-cells ................... 389
13.5 Conclusions .............................................. 392
Acknowledgments .......................................... 393
References ............................................... 393
Index .................................................... 398
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