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<p>Preface xv</p> <p><b>1 Fundamentals of Acoustic Wave Generation and Propagation 1<br /> </b><i>Mehmet A. Sahin, Mushtaq Ali, Jinsoo Park, and Ghulam Destgeer</i></p> <p>1.1 Introduction 1</p> <p>1.1.1 Acoustic or Sound Waves 1</p> <p>1.1.2 Dominos Effect 1</p> <p>1.1.3 Elastic vs Inelastic Waves 2</p> <p>1.1.4 Scope of Acoustics 4</p> <p>1.2 Brief History of Acoustic Waves 4</p> <p>1.2.1 Early History 4</p> <p>1.2.2 History of Acoustic Streaming 4</p> <p>1.2.3 History of Acoustic Radiation Force 5</p> <p>1.3 What Is an Acoustic Wave? 6</p> <p>1.3.1 Acoustic Parameters 6</p> <p>1.3.2 Displacement, Velocity, and Pressure Fields 6</p> <p>1.3.3 Wave Propagation 7</p> <p>1.3.4 Wave Dissipation 7</p> <p>1.3.5 Wave Dispersion 8</p> <p>1.4 Modes of Acoustic Waves 8</p> <p>1.4.1 Categorization Based on Frequency Range 9</p> <p>1.4.2 Categorization Based on Propagation Mode 9</p> <p>1.4.2.1 Longitudinal Waves 9</p> <p>1.4.2.2 Shear Waves 10</p> <p>1.4.2.3 Rayleigh Waves 11</p> <p>1.4.2.4 Love Waves 12</p> <p>1.4.2.5 Lamb Waves 12</p> <p>1.4.3 Categorization Based on Wave Configuration 12</p> <p>1.4.3.1 Traveling Waves 12</p> <p>1.4.3.2 Standing Waves 13</p> <p>1.5 Acoustic Wave Propagation and Interaction 13</p> <p>1.5.1 Transmission and Reflection of Acoustic Waves 13</p> <p>1.5.2 Acoustic Scattering 14</p> <p>1.5.3 Acoustic Radiation 16</p> <p>1.6 Acoustic Wave Attenuation 18</p> <p>1.6.1 Viscoelastic Attenuation 18</p> <p>1.6.2 Acousto-Thermal Heating 19</p> <p>1.6.3 Acoustic Streaming Flow 19</p> <p>1.6.3.1 Eckart Streaming 20</p> <p>1.6.3.2 Rayleigh Streaming 20</p> <p>1.6.3.3 Bubble-Driven Microstreaming 21</p> <p>1.6.3.4 Applications of Acoustic Streaming Flow 21</p> <p>1.7 Generation and Propagation of Acoustic Waves 22</p> <p>1.7.1 Acoustic Waves Generation in Nature 22</p> <p>1.7.2 Generation of Acoustic Waves in Lab 22</p> <p>1.7.2.1 Lower-Frequency Acoustic Waves 22</p> <p>1.7.2.2 Piezoelectricity and High-Frequency Wave Generation 23</p> <p>1.8 Acoustic Waves Effects in Fluidic Media 24</p> <p>1.8.1 Vibrating Membranes and Sharp-Edge Structures 25</p> <p>1.8.2 Oscillating Bubbles 25</p> <p>1.8.2.1 Cavitation 26</p> <p>1.8.3 Optoacoustic Imaging 27</p> <p>1.8.4 Manifestations of Acoustic Radiation Force and Acoustic Streaming Flow 28</p> <p>List of Abbreviations and Symbols 28</p> <p>References 29</p> <p><b>2 Basic Theories and Physics of Acoustic Technologies 37<br /> </b><i>Khemraj G. Kshetri and Nitesh Nama</i></p> <p>2.1 Introduction 37</p> <p>2.2 Acoustic Waves in Solids 38</p> <p>2.2.1 Governing Equation 39</p> <p>2.2.2 Acoustic Waves in Non-piezoelectric Solids 39</p> <p>2.2.3 Acoustic Waves in Piezoelectric Solids 40</p> <p>2.3 Acoustic Waves in Fluids 40</p> <p>2.3.1 Governing Equations 40</p> <p>2.3.2 Acoustic Streaming 41</p> <p>2.3.2.1 Modeling Approach for Slow Streaming 44</p> <p>2.3.2.2 Modeling Approach for Fast Streaming 45</p> <p>2.3.3 Distinction Between Lagrangian and Eulerian Fluid Velocity and Stokes’ Drift 46</p> <p>2.3.4 Acoustic Streaming Near Solid Particles 47</p> <p>2.3.5 Acoustic Streaming Near Fluid–Fluid Interfaces 47</p> <p>2.4 Forces in Acoustofluidic Systems 49</p> <p>2.4.1 Primary Acoustic Radiation Force 49</p> <p>2.4.2 Secondary Acoustic Radiation Force 52</p> <p>2.4.2.1 Forces Between Two Rigid Spheres 53</p> <p>2.4.2.2 Forces Between Two Bubbles 53</p> <p>2.4.2.3 Forces Between a Solid Particle and a Bubble 54</p> <p>2.4.2.4 Forces Between a Liquid Drop and a Bubble 55</p> <p>2.4.3 Hydrodynamic Drag Force 55</p> <p>2.5 Conclusions and Perspectives 57</p> <p>References 58</p> <p><b>3 Materials for Acoustic Wave Generation and Modulation 67<br /> </b><i>Noé Jiménez</i></p> <p>3.1 Introduction 67</p> <p>3.1.1 Generation and Detection of Ultrasound 67</p> <p>3.1.2 Technologies for Ultrasound Transducers 68</p> <p>3.2 Piezoelectricity 68</p> <p>3.2.1 Model Equations 68</p> <p>3.2.1.1 Stress-Charge Formulation 69</p> <p>3.2.1.2 Strain-Charge Formulation 70</p> <p>3.2.1.3 Stress-Field Formulation 70</p> <p>3.2.1.4 Strain-Field Formulation 70</p> <p>3.2.2 The Piezoelectric Constants 70</p> <p>3.2.3 Longitudinal Motion in a Piezoelectric Material 71</p> <p>3.2.3.1 A Simple Piezoelectric Model 71</p> <p>3.2.3.2 Waves in the Piezoelectric Material 72</p> <p>3.3 Piezoelectric Materials 73</p> <p>3.3.1 Piezoelectric Crystals 73</p> <p>3.3.2 Piezoelectric Ceramics 74</p> <p>3.3.3 Piezoelectric Polymers 74</p> <p>3.3.4 Piezoelectric Composites 74</p> <p>3.4 Ultrasound Transducers 75</p> <p>3.4.1 Elements of a Transducer 75</p> <p>3.4.2 The Piezoelectric Slab 75</p> <p>3.4.3 Matching Layers 76</p> <p>3.4.3.1 Classical Matching Layer Design 76</p> <p>3.4.3.2 Multiple Matching Layer Design 77</p> <p>3.4.3.3 Broadband Matching Layer Design 77</p> <p>3.4.4 Backing Layer 77</p> <p>3.4.5 Electrical Impedance Matching Network 78</p> <p>3.5 Ultrasound Beams 78</p> <p>3.5.1 Circular Aperture Transducers 78</p> <p>3.5.2 Focused Transducers 80</p> <p>3.5.3 Phased-Array Transducers 83</p> <p>3.6 Acoustic Lenses 83</p> <p>3.6.1 Refraction by Bulky Lenses 84</p> <p>3.6.1.1 Spherical Lenses 84</p> <p>3.6.1.2 Ellipsoidal Lenses 85</p> <p>3.6.1.3 Axicon Lenses 85</p> <p>3.6.1.4 Frensel and Fraxicon Lenses 86</p> <p>3.6.1.5 Lenses for Vortex Generation 86</p> <p>3.6.2 Diffraction by Gratings 87</p> <p>3.6.2.1 Cartesian Diffraction Grating 87</p> <p>3.6.2.2 Asymmetric Diffraction Grating 87</p> <p>3.6.2.3 Fresnel Zone Plates 88</p> <p>3.6.2.4 Archimedean Spiral Gratings 89</p> <p>3.6.2.5 Fresnel-Spiral Zone Plate 90</p> <p>3.6.3 Reflection by Curved Surfaces 90</p> <p>3.6.3.1 Parabolic Reflectors 91</p> <p>3.6.3.2 Ellipsoidal Reflectors 91</p> <p>3.6.4 Holograms 91</p> <p>3.6.4.1 Field Projections 91</p> <p>3.6.4.2 Synthesis of Acoustic Images 93</p> <p>3.6.4.3 Biomedical Applications of Holograms 94</p> <p>References 95</p> <p><b>4 Ultrasound and Ultrasonic Imaging in Medicine: Recent Advances 99<br /> </b><i>Tuğba Ö. Onur</i></p> <p>4.1 Introduction 99</p> <p>4.2 Ultrasound Waves 99</p> <p>4.2.1 Types of Ultrasonic Waves 100</p> <p>4.2.2 Behavior of Ultrasound Waves at Interfaces 100</p> <p>4.2.3 Ultrasound Power and Intensity 101</p> <p>4.2.4 Ultrasound Applications 102</p> <p>4.3 Ultrasonic Imaging 103</p> <p>4.3.1 Ultrasonic Imaging System 106</p> <p>4.3.1.1 Transducer 106</p> <p>4.3.1.2 Probes 107</p> <p>4.3.1.3 Central Processing Unit 109</p> <p>4.3.1.4 Output Display 109</p> <p>4.3.2 Focus 109</p> <p>4.3.3 Resolution 109</p> <p>4.3.4 Beamforming 110</p> <p>4.4 Sound-Tissue Interactions in Ultrasonography 110</p> <p>4.4.1 Reflection 110</p> <p>4.4.2 Refraction 111</p> <p>4.4.3 Absorption 112</p> <p>4.4.4 Attenuation 112</p> <p>4.4.4.1 Attenuation by Reflection, Refraction, and Deflection 112</p> <p>4.4.4.2 Attenuation by Scattering 113</p> <p>4.4.4.3 Attenuation by Absorption 113</p> <p>4.4.4.4 Time Gain Reduction (TGR) and Depth Gain Reduction (DGR) 114</p> <p>4.5 Ultrasonic Imaging Methods 114</p> <p>4.5.1 Real-Time Imaging 114</p> <p>4.5.1.1 A-Mode 115</p> <p>4.5.1.2 M-Mode 116</p> <p>4.5.1.3 B-Mode 117</p> <p>4.5.2 Doppler Ultrasonography 118</p> <p>4.5.2.1 Continuous Wave Doppler 119</p> <p>4.5.2.2 Duplex Doppler 119</p> <p>4.5.2.3 Color Doppler 119</p> <p>4.5.3 Real-Time Artifacts in Imaging 119</p> <p>4.5.4 Factors Affecting Image Quality 120</p> <p>4.6 Tissue Harmonic Imaging (THI) 121</p> <p>4.6.1 The Occurrence of Harmonic Signals 121</p> <p>4.6.2 The Separation of Harmonic Signals from the Main Signal 122</p> <p>4.6.3 The Advantages of Harmonic Signals 122</p> <p>4.7 Recent Advances in Ultrasound Imaging for Medicine 122</p> <p>References 123</p> <p><b>5 Photoacoustic Imaging and Sensing for Biomedical Applications 127<br /> </b><i>Amalina B. E. Attia, Ruochong Zhang, Mohesh Moothanchery, and Malini Olivo</i></p> <p>5.1 Introduction 127</p> <p>5.2 Photoacoustic Imaging Applications 130</p> <p>5.2.1 PAI of Breast Cancer 130</p> <p>5.2.1.1 In Vivo Imaging 130</p> <p>5.2.1.2 Ex Vivo Imaging 132</p> <p>5.2.2 PAI for Skin Imaging 133</p> <p>5.2.2.1 PAI of Skin Cancer 135</p> <p>5.2.2.2 PAI of Inflammatory Skin Diseases 137</p> <p>5.2.2.3 PAI of Wounds 137</p> <p>5.3 Photoacoustic Sensing for Biomedical Applications 139</p> <p>5.3.1 Noninvasive Temperature Monitoring in Deep Tissue 139</p> <p>5.3.2 Noninvasive Glucose Sensing 142</p> <p>References 148</p> <p><b>6 Therapeutic Ultrasound 159<br /> </b><i>Bar Glickstein, Hila Shinar, and Tali Ilovitsh</i></p> <p>6.1 Introduction 159</p> <p>6.2 Ultrasound-Induced Bioeffects 160</p> <p>6.2.1 Introduction 160</p> <p>6.2.2 Thermal Effects 160</p> <p>6.2.3 Mechanical Effects 161</p> <p>6.2.3.1 Cavitation 161</p> <p>6.2.4 Contrast-Enhanced Effects 161</p> <p>6.2.4.1 Microbubbles 161</p> <p>6.2.4.2 Nanobubbles 162</p> <p>6.2.4.3 Nanodroplets 162</p> <p>6.2.5 Safety and Regulations 163</p> <p>6.3 Therapeutic Ultrasound Applications 164</p> <p>6.3.1 High-Intensity Focused Ultrasound 164</p> <p>6.3.2 Histotripsy 166</p> <p>6.3.3 Shock Wave Lithotripsy 169</p> <p>6.3.4 Drug Delivery and Gene Therapy 170</p> <p>6.3.5 Blood–Brain Barrier Opening 171</p> <p>6.3.6 Low-Intensity Ultrasound for Neuromodulation 172</p> <p>6.3.7 Bone Healing 172</p> <p>6.3.8 Sonothrombolysis 172</p> <p>6.3.9 Other Applications 173</p> <p>6.4 Conclusions 173</p> <p>References 174</p> <p><b>7 Application of Ultrasound-Responsive Reagents for Drug Delivery Systems 181<br /> </b><i>Hiroshi Kida and Katsuro Tachibana</i></p> <p>7.1 Historical Background of Research on Bubble Reagents for Medicine 181</p> <p>7.2 Use of Bubble Reagents as Drug Delivery Systems 182</p> <p>7.2.1 Acoustic Cavitation 182</p> <p>7.2.2 Importance of Inertial and Non-inertial Cavitation in Improving Drug Permeability 184</p> <p>7.2.3 Targeting and Focusing Using Acoustic Means 186</p> <p>7.3 Variation of Ultrasound-Responsive Reagents for DDS 186</p> <p>7.3.1 Shell Composition 186</p> <p>7.3.2 Improved Stability by Polyethylene Glycol (PEG) Modification 187</p> <p>7.3.3 Modification with Targeting Ligands 188</p> <p>7.3.4 Drug and Gene Loading 188</p> <p>7.3.5 Extended Adaptation of Ultrasound-Responsive Reagents 190</p> <p>7.4 Research on Treatment of Diseases Using Ultrasonic Drug Delivery 192</p> <p>7.4.1 Cancer 192</p> <p>7.4.2 Central Nervous System Diseases 195</p> <p>7.5 Conclusion 197</p> <p>References 198</p> <p><b>8 Acoustic Levitation and Acoustic Holograms 217<br /> </b><i>Tatsuki Fushimi and Yoichi Ochiai</i></p> <p>8.1 Introduction 217</p> <p>8.1.1 History of Acoustic Levitation 217</p> <p>8.1.1.1 Classical Acoustic Levitator 218</p> <p>8.1.1.2 Phased Array Levitator (PAL) 221</p> <p>8.2 Acoustic Holograms 224</p> <p>8.3 Numerical Simulation of Acoustic Levitator 227</p> <p>8.3.1 Pressure Field Calculation 227</p> <p>8.3.1.1 Huygens’ Approach 227</p> <p>8.3.1.2 Spherical Harmonics Expansion 228</p> <p>8.3.1.3 Angular Spectrum Method 229</p> <p>8.3.2 Acoustic Radiation Force 230</p> <p>8.3.2.1 Gor’kov 230</p> <p>8.3.2.2 Spherical Harmonic Approach 231</p> <p>8.4 Acoustic Hologram Optimization 231</p> <p>8.4.1 Optimization Example with Diff-PAT 233</p> <p>8.5 Applications in Biology and Medicine 234</p> <p>8.5.1 Specimen Holding 234</p> <p>8.5.2 Experiment Automation 234</p> <p>8.5.3 3D Display 235</p> <p>8.6 Conclusion and Future Remarks 236</p> <p>Acknowledgments 237</p> <p>References 237</p> <p><b>9 Application of Ultrasonic Waves in Bioparticle Manipulation and Separation 243<br /> </b><i>M. Bülent Özer and Barbaros Çetin</i></p> <p>9.1 Introduction 243</p> <p>9.2 Bioparticle Manipulation 244</p> <p>9.2.1 Hydrodynamic Bioparticle Manipulation 244</p> <p>9.2.2 Immunological (Antigen–Antibody Reaction) Bioparticle Manipulation 245</p> <p>9.2.3 Electrokinetic Bioparticle Manipulation 245</p> <p>9.2.4 Magnetophoretic Bioparticle Manipulation 245</p> <p>9.2.5 Acoustophoretic Bioparticle Manipulation 246</p> <p>9.2.6 Unification of Field Manipulation Methods 246</p> <p>9.2.7 Comparison of Bioparticle Manipulation Methods 248</p> <p>9.3 General Architecture of Acoustofluidic Devices 249</p> <p>9.3.1 BAW Device Architecture 249</p> <p>9.3.1.1 Piezoelectric Actuator 249</p> <p>9.3.1.2 Chip Material 250</p> <p>9.3.1.3 Lid Material 251</p> <p>9.3.1.4 Device Assembly and Critical Dimensions 251</p> <p>9.3.2 SAW Device Architecture 252</p> <p>9.3.2.1 Piezoelectric Actuator 252</p> <p>9.3.2.2 Interdigital Electrodes (IDT) 253</p> <p>9.3.2.3 Microfluidic Chamber 254</p> <p>9.3.2.4 Device Assembly and Critical Dimensions 254</p> <p>9.3.3 Comparison of BAW and SAW Devices 254</p> <p>9.4 Governing Equations in Acoustic Bioparticle Manipulation 255</p> <p>9.4.1 First-Order Acoustic Field Variables 255</p> <p>9.4.2 Second-Order Acoustic Field Variables 257</p> <p>9.4.3 Acoustic Radiation Force on a Particle 258</p> <p>9.4.4 Acoustic Radiation Force on a Particle Considering the Effect of Chip Material 260</p> <p>9.5 Simulation of Acoustophoretic Bio-Particle Manipulation 264</p> <p>9.5.1 Simulation of Piezoelectric Actuators 264</p> <p>9.5.2 Numerical Simulations of the Elastic Material Surrounding the Channel 265</p> <p>9.5.3 Simulation of Fluid Flow 266</p> <p>9.5.4 Simulation of Particle Motion 267</p> <p>9.6 Acoustofluidic Devices in Biological and Medical Applications 269</p> <p>9.6.1 Applications Regarding Lipid Particles 269</p> <p>9.6.2 Applications Regarding Cell Wash 278</p> <p>9.6.3 Applications Regarding Separation of Blood Components 279</p> <p>9.6.3.1 Plasma Separation 279</p> <p>9.6.3.2 Platelet Separation 279</p> <p>9.6.3.3 Separation of WBCs 280</p> <p>9.6.4 Applications Regarding Cancer Cells 281</p> <p>9.6.5 Applications Regarding Miscellaneous Cells 282</p> <p>9.6.6 Application Regarding Bacteria 284</p> <p>9.6.7 Applications Regarding Nanoscale (Bio)Particles 287</p> <p>9.6.8 Miscellaneous Applications 289</p> <p>9.7 Commercial and Regulatory Considerations for Acoustofluidic Devices 290</p> <p>9.7.1 Cost 291</p> <p>9.7.2 High Volume Manufacturing 292</p> <p>9.7.3 Sterilization 292</p> <p>9.7.4 Biocompatibility 294</p> <p>9.7.5 Storage and Transportation Requirements 294</p> <p>9.8 Summary and Outlook 294</p> <p>References 296</p> <p><b>10 Acoustic Biosensors 305<br /> </b><i>Alper Şi¸sman, Paddy French, Ay¸se Ogan, Erdal Korkmaz, Abbas A. Husseini, Ali M. Yazdani, and Johan Meyer</i></p> <p>10.1 Introduction 305</p> <p>10.1.1 Bulk Acoustic Wave (BAW) Mode 305</p> <p>10.1.2 Surface Guided Acoustic Wave (SGAW) Modes 307</p> <p>10.2 Biochemical Fundamentals of Sensing 310</p> <p>10.2.1 Immobilization Strategies of Detection Element 311</p> <p>10.2.1.1 Noncovalent Immobilization 311</p> <p>10.2.1.2 Covalent Immobilization 312</p> <p>10.2.1.3 Bioaffinity Bindings 313</p> <p>10.3 Bulk Acoustic Wave Biosensors 314</p> <p>10.3.1 Quartz Microbalance (QMB) Crystal Biosensors 315</p> <p>10.3.2 Film Bulk Acoustic Wave (FBAR) Biosensors 316</p> <p>10.4 Surface Transverse Wave Biosensors 317</p> <p>10.4.1 SH-Wave and Love Wave Biosensors 317</p> <p>10.4.2 Lamb Waves Biosensors 321</p> <p>10.4.3 Rayleigh Wave Biosensors 324</p> <p>10.4.4 Crystal Cuts and Axis Orientation 325</p> <p>10.5 Commercial Biosensors and Trends 327</p> <p>10.6 Conclusion 331</p> <p>References 332</p> <p><b>11 Acoustic Micro/Nanorobots in Medicine 343<br /> </b><i>Murat Kaynak, Amit Dolev, and Mahmut S. Sakar</i></p> <p>11.1 Introduction 343</p> <p>11.2 Theoretical Background 345</p> <p>11.2.1 Introduction to Acoustics 345</p> <p>11.2.2 Time-Averaged Acoustically Induced Forces 348</p> <p>11.2.2.1 Primary Radiation Forces 348</p> <p>11.2.2.2 Secondary Radiation Forces 351</p> <p>11.2.2.3 Drag and Thrust-Induced Acoustic Streaming 354</p> <p>11.3 Acoustic Micromanipulation Techniques 355</p> <p>11.3.1 Introduction to Acoustic Tweezers 356</p> <p>11.3.2 Acoustic Micromanipulation Using Bulk Acoustic Waves 357</p> <p>11.4 Micro/Nanorobotic Devices Actuated by Acoustic Fields 361</p> <p>11.4.1 Mobile Acoustic Micromachines 361</p> <p>11.4.2 Soft Robotic Microsystems 363</p> <p>11.5 In Vivo Actuation of Micro/Nanorobotic Devices 365</p> <p>11.6 Discussion and Outlook 367</p> <p>Acknowledgment 368</p> <p>References 368</p> <p>Index 375</p>

<p><b>Adem Ozcelik</b> is an Associate Professor of Mechanical Engineering at Aydin Adnan Menderes University, Turkey.</p> <p><b>Ryan Becker</b> is a biomedical engineer, scientist, and entrepreneur completing his PhD in biomedical engineering at Duke University.</p> <p><b>Tony Jun Huang</b> is the William Bevan Distinguished Professor of Mechanical Engineering and Materials Science at Duke University.</p>

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