About the Authors ............................................ xiii
Preface ........................................................ xv
Acknowledgement ............................................... xix
Chapter 1 Introduction to Molecular Sensors .................... 1
1.1 Introduction ............................................... 1
1.2 Principles of Molecular Sensors ............................ 3
1.2.1 Definition of Molecular Sensors ..................... 3
1.2.2 Applications of Molecular Sensors ................... 4
1.2.3 Model of a Molecular Sensor ......................... 5
1.2.4 Example of Molecular Sensor 1: Immunosensor Based
on Field Effect Transistor .......................... 6
1.2.5 Example of Molecular Sensor 2: Animal Olfactory
System .............................................. 8
1.3 Capture and Recognition Elements in Molecular Sensors ..... 11
1.3.1 Antibody—Antigen Binding ........................... 11
1.3.2 DNA as a Recognition Element ....................... 14
1.3.3 Aptamers ........................................... 19
1.4 Transduction Mechanisms ................................... 21
1.4.1 Electrical Transduction ............................ 21
1.4.2 Sensitivity of a Transducer ........................ 22
1.5 Performance of Molecular Sensors .......................... 25
1.6 Animals as Molecular Sensors .............................. 26
1.6.1 Sensitivity of Animal Olfactory Systems ............ 28
1.6.2 Applications of Animal Molecular Sensors ........... 29
1.6.3 Discussion on Animals as Molecular Sensors ......... 36
1.7 Conclusion ................................................ 36
Problems .................................................. 37
References ................................................ 39
Further Reading ........................................... 42
Chapter 2 Fundamentals of Nano/Microfabrication and Effect
of Scaling ..................................................... 43
2.1 Introduction .............................................. 43
2.2 Scaling in Molecular Sensors .............................. 45
2.3 Microfabrication Basics ................................... 47
2.1 Silicon as a Material for Microfabrication ................ 48
2.3.2 Photolithography ................................... 49
2.3.3 Deposition ......................................... 54
2.3.4 Etching ............................................ 62
2.3.5 Lift Off ........................................... 67
2.3.6 Doping ............................................. 68
2.4 Micro-electro-mechanical Systems (MEMS) ................... 70
2.4.1 Bulk Micromachining ................................ 71
2.4.2 Surface Micromachining ............................. 73
2.5 Soft Lithography .......................................... 81
2.5.1 Microcontact Printing .............................. 82
2.5.2 Soft Lithography-Based Microfabrication ............ 83
2.5.3 Immobilization and Patterning Techniques for
Biomolecules ....................................... 86
2.6 "Top Down" and "Bottom Up" Approaches ..................... 91
2.7 Conclusion ................................................ 93
Problems .................................................. 93
References ................................................ 97
Further Reading .......................................... 101
Chapter 3 Microfluidics and Micro Total Analytical Systems ... 103
3.1 Introduction ............................................. 103
3.2 Microfluidics Fundamentals ............................... 104
3.2.1 Diffusion ......................................... 104
3.2.2 Laminar Flow and the Hдgen - Poiseuille Equation .. 107
3.2.3 Reynolds Number and Scaling Law ................... 111
3.3 Microfluidics for Molecular Sensors ...................... 114
3.3.1 Microfluidic Device Basics ........................ 115
3.3.2 Microfluidic Cell Separation and Detection ........ 120
3.3.3 Microfluidic Devices for DNA Analysis ............. 138
Problems ................................................. 155
References ............................................... 162
Further Reading .......................................... 168
Chapter 4 Electrical Transducers ............................. 169
4.1 Introduction ............................................. 169
4.2 Electrochemical Sensors .................................. 170
4.2.1 Principles of Electrochemical Measurements ........ 170
4.2.2 Applications of Electrochemical Sensors ........... 178
4.3 FET-Based Molecular Sensors .............................. 186
4.3.1 Semiconductor Basics .............................. 186
4.3.2 Silicon FET-Based Molecular Sensors ............... 203
4.3.3 Organic Transistor-Based Sensors .................. 207
4.3.4 Nanowire Based FET Sensors ........................ 208
4.4 Carbon Nanotubes and Graphene-Based Sensors .............. 214
4.4.1 CNT-Based Molecular Sensors ....................... 214
4.4.2 Graphene-Based Molecular Sensors .................. 218
4.5 Conclusion ............................................... 225
Problems ................................................. 225
References ............................................... 229
Further Reading .......................................... 232
Chapter 5 Optical Transducers ................................ 233
5.1 Introduction ............................................. 234
5.2 Basic EM Theory .......................................... 234
5.2.1 Maxwell's Equations ............................... 235
5.2.2 Wave Equation ..................................... 236
5.2.3 Phasor Notation ................................... 238
5.2.4 Interference ...................................... 239
5.2.5 Polarization, Incidence and Reflection of light ... 240
5.2.6 Evanescent Field .................................. 244
5.3 Waveguide-Based Molecular Sensors ........................ 246
5.3.1 Introduction ...................................... 247
5.3.2 Principles of Wave Propagation in Waveguide ....... 248
5.3.3 Slab Waveguide .................................... 251
5.3.4 Rectangular Waveguide (Channel Waveguides) ........ 254
5.3.5 Circular Waveguide (Optical Fibers) ............... 258
5.3.6 Discussion on Waveguide Sensors ................... 260
5.4 Surface Plasmon Resonance (SPR) Sensors .................. 261
5.4.1 Introduction ...................................... 261
5.4.2 Principles of Surface Plasmons .................... 261
5.4.3 Experimental Configuration ........................ 265
5.4.4 SPR Sensor for Molecular Sensing .................. 266
5.4.5 Discussion on SPR Sensors ......................... 272
5.5 Absorption Spectroscopy .................................. 273
5.5.1 Optical Density Measurement ....................... 273
5.5.2 Beer-Lambert Law .................................. 274
5.5.3 Sensors Based on Absorption Spectroscopy .......... 275
5.6 Fluorescence Spectroscopy ................................ 277
5.6.1 Basics of Fluorescence ............................ 277
5.6.2 Fluorescence Spectroscopy and Imaging ............. 280
5.6.3 Quantum Dots ...................................... 283
5.7 Light Scattering ......................................... 285
5.7.1 Forms of Light Scattering ......................... 286
5.7.2 Methods Based on Light Scattering Measurements .... 287
5.7.3 Metal Nanoparticles ............................... 297
5.8 Near-Field Scanning Optical Microscopy ................... 302
5.8.1 Aperture-Based NSOM Tip ........................... 304
5.8.2 Metal Plasmonic Tip ............................... 304
5.8.3 Functional NSOM Tip ............................... 306
Problems ................................................. 307
References ............................................... 316
Further Reading .......................................... 320
Chapter 6 Mechanical Transducers ............................. 321
6.1 Introduction ............................................. 322
6.2 Cantilever-Based Molecular Sensors ....................... 323
6.2.1 Introduction ...................................... 323
6.2.2 Mechanics of Cantilevers .......................... 325
6.2.3 Fabrication of Microcantilevers: Materials and
Design Features ................................... 339
6.2.4 Principles of Sensing ............................. 344
6.2.5 Principles of Transduction ........................ 349
6.2.6 Molecular Sensing with Cantilever-Based Sensors ... 360
6.2.7 Discussion on Silicon Cantilever Sensors .......... 361
6.2.8 Nanomaterial-Based Cantilever Sensors ............. 363
6.3 Acoustic Molecular Sensors: TSM, SAW, FPW, АРМ,
and Tuning Forks ......................................... 367
6.3.1 Introduction ...................................... 367
6.3.2 Principles of Piezoelectric materials ............. 368
6.3.3 Thickness-Shear-Mode (TSM) Sensors ................ 371
6.3.4 Surface Acoustic Wave Sensors ..................... 375
6.3.5 Flexural Plate Wave Sensors ....................... 383
6.3.6 Acoustic Plate Mode Sensors ....................... 385
6.3.7 Quartz Tuning Fork Resonators ..................... 386
6.3.8 Conclusion ........................................ 388
6.4 Thermal Sensors .......................................... 389
6.4.1 Introduction ...................................... 389
6.4.2 Thermocouples ..................................... 390
6.4.3 Thermistors ....................................... 393
6.4.4 CMOS Temperature Sensors .......................... 397
6.4.5 Bilayer Cantilever Sensors ........................ 397
6.4.6 IR Imaging ........................................ 399
6.4.7 Discussions on Thermal Sensors .................... 403
6.5 Conclusions .............................................. 404
Problems ................................................. 404
References ............................................... 409
Further Reading .......................................... 414
Chapter 7 Implantable Sensors ................................ 415
7.1 Introduction ............................................. 416
7.2 Sensing in Cardiac Pacemakers ............................ 416
7.2.1 Components of Pacemakers .......................... 417
7.2.2 Types of Pacemakers ............................... 420
7.2.3 Recent Developments and Future Research ........... 421
7.3 Implantable Electrodes ................................... 423
7.3.1 Microelectrode .................................... 423
7.3.2 Neural Implants ................................... 425
7.3.3 Cochlear Implants ................................. 426
7.3.4 Retinal Implants .................................. 428
7.3.5 Heart Blood Volume Sensor ......................... 429
7.3.6 Subcutaneous Electrodes for Continuous Glucose
Monitoring ........................................ 432
7.4 Implantable Mechanical Sensors ........................... 433
7.4.1 Implantable Pressure Sensors ...................... 433
7.4.2 Implantable Piezoresistive Pressure Sensors ....... 434
7.4.3 Capacitive Sensors for Implantable Pressure
Sensors ........................................... 437
7.4.4 Optical Transduction-Based Pressure Sensors ....... 441
7.4.5 Piezoelectric Pressure Sensors .................... 442
7.5 Drug Delivery Devices .................................... 445
7.5.1 Working Principle ................................. 446
7.5.2 Implementation Method ............................. 448
7.6 Energy Harvesting Implantable Devices .................... 449
7.7 FDA Regulation of Medical Devices ........................ 453
7.7.1 Definition of Medical Device ...................... 454
7.7.2 Classification of Medical Devices ................. 454
7.7.3 Regulatory Procedures for Medical Devices ......... 455
7.7.4 FDA Regulation of Devices Based on Silicon Nano/
Microfabrication .................................. 456
7.8 Conclusion ............................................... 457
Problems ................................................. 458
References ............................................... 460
Appendix 5A: Fresnel Diffraction and Fraunhofer Diffraction ... 467
Appendix 5B: Coupling Between the Evanescent Wave and the
Surface Plasmon .......................................... 475
Appendix 6A: Analysis of Beam Bending ......................... 479
Index ......................................................... 481
|
