Fluorescent Nanodiamonds

The most comprehensive reference on fluorescent nanodiamond physical and chemical properties and contemporary applications

Fluorescent nanodiamonds (FNDs) have drawn a great deal of attention over the past several years, and their applications and development potential are proving to be manifold and vast. The first and only book of its kind, Fluorescent Nanodiamonds is a comprehensive guide to the basic science and technical information needed to fully understand the fundamentals of FNDs and their potential applications across an array of domains. In demonstrating the importance of FNDs in biological applications, the authors bring together all relevant chemistry, physics, materials science and biology.

Nanodiamonds are produced by powerful cataclysmic events such as explosions, volcanic eruptions and meteorite impacts. They also can be created in the lab by high-pressure high-temperature treatment of graphite or detonating an explosive in a reactor vessel. A single imperfection can give a nanodiamond a specific, isolated color center which allows it to function as a single, trapped atom. Much smaller than the thickness of a human hair, a nanodiamond can have a huge surface area that allows it to bond with a variety of other materials. Because of their non-toxicity, nanodiamonds may be useful in biomedical applications, such as drug delivery and gene therapy. 

• The most comprehensive reference on a topic of rapidly increasing interest among academic and industrial researchers across an array of fields
• Includes numerous case studies and practical examples from many areas of research and industrial applications, as well as fascinating and instructive historical perspectives
• Each chapter addresses, in-depth, a single integral topic including the fundamental properties, synthesis, mechanisms and functionalisation of FNDs
• The first book published by the key patent holder with his research group in the field of FNDs

Fluorescent Nanodiamonds is an important working resource for a broad range of scientists and engineers in industry and academia. It will also be a welcome reference for instructors in chemistry, physics, materials science, biology and related fields.

Huan-Cheng Chang, PhD, Distinguished Research Fellow, Institute of Atomic and Molecular Sciences (IAMS), Academia Sinica, Taipei, Taiwan, Republic of China. Academia Sinica is the national academy of the Republic of China.

Wesley Wei-Wen Hsiao, PhD, LLM is CEO of FND Biotech, Inc., Taipei, Taiwan, Republic of China.

Meng-Chih Su, PhD, Professor in Chemistry, Sonoma State University (SSU), Rohnert Park, California, USA. Dr. Su has served as Department Chair for the Chemistry Department and later the Engineering Science Department at SSU.

Preface xi

Acknowledgements xv

Part I Basics 1

1 Introduction to Nanotechnology 3

1.1 Nanotechnology: From Large to Small 3

1.1.1 Feynman: Plenty of Room at the Bottom 3

1.1.2 Nanotechnology Today 6

1.1.3 The Bottom‐Up Approach 7

1.2 Nanocarbons: Now and Then 8

1.2.1 Classification 9

1.2.2 Fullerenes 9

1.2.3 Carbon Nanotubes 11

1.2.4 Graphenes 13

References 15

2 Nanodiamonds 19

2.1 Ah, Diamonds, Eternal Beautiful 19

2.2 Diamonds: From Structure to Classification 22

2.2.1 Structure 22

2.2.2 Classification 24

2.3 Diamond Synthesis 26

2.3.1 HPHT 27

2.3.2 CVD 29

2.3.3 Detonation 30

2.4 Nanodiamonds: A Scientist’s Best Friend 30

References 33

3 Color Centers in Diamond 37

3.1 Nitrogen Impurities 37

3.2 Crystal Defects 40

3.3 Vacancy‐Related Color Centers 41

3.3.1 GR1 and ND1 41

3.3.2 NV⁰ and NV⁻ 44

3.3.3 H3 and N3 46

3.3.4 SiV⁻ 46

3.4 The NV⁻ Center 47

References 50

4 Surface Chemistry of Nanodiamonds 55

4.1 Functionalization 56

4.2 Bioconjugation 61

4.2.1 Noncovalent Conjugation 61

4.2.2 Covalent Conjugation 64

4.3 Encapsulation 66

4.3.1 Lipid Layers 66

4.3.2 Silica Shells 67

References 69

5 Biocompatibility of Nanodiamonds 73

5.1 Biocompatibility Testing 73

5.1.1 Cytotoxicity 74

5.1.2 Genotoxicity 76

5.1.3 Hemocompatibility 76

5.2 In Vitro Studies 77

5.2.1 HPHT‐ND 77

5.2.2 DND 80

5.3 Ex Vivo Studies 82

5.4 In Vivo Studies 83

References 86

Part II Specific Topics 91

6 Producing Fluorescent Nanodiamonds 93

6.1 Production 93

6.1.1 Theoretical Simulations 93

6.1.2 Electron/Ion Irradiation 96

6.1.3 Size Reduction 99

6.2 Characterization 101

6.2.1 Fluorescence Intensity 101

6.2.2 Electron Spin Resonance 104

6.2.3 Fluorescence Lifetime 105

6.2.4 Magnetically Modulated Fluorescence 107

References 110

7 Single Particle Detection and Tracking 113

7.1 Single Particle Detection 113

7.1.1 Photostability 113

7.1.2 Spectroscopic Properties 117

7.1.3 Color Center Numbers 118

7.2 Single Particle Tracking 120

7.2.1 Tracking in Solution 120

7.2.2 Tracking in Cells 122

7.2.3 Tracking in Organisms 127

References 130

8 Cell Labeling and Fluorescence Imaging 135

8.1 Cell Labeling 135

8.1.1 Nonspecific Labeling 136

8.1.2 Specific Labeling 139

8.2 Fluorescence Imaging 142

8.2.1 Epifluorescence and Confocal Fluorescence 142

8.2.2 Total Internal Reflection Fluorescence 144

8.2.3 Two‐Photon Excitation Fluorescence 146

8.2.4 Time‐Gated Fluorescence 147

References 150

9 Cell Tracking and Deep Tissue Imaging 155

9.1 Cellular Uptake 155

9.1.1 Uptake Mechanism 155

9.1.2 Entrapment 158

9.1.3 Quantification 159

9.2 Cell Tracking 161

9.2.1 Tracking In Vitro 161

9.2.2 Tracking In Vivo 163

9.3 Deep Tissue Imaging 165

9.3.1 Wide‐Field Fluorescence Imaging 165

9.3.2 Optically Detected Magnetic Resonance Imaging 169

9.3.3 Time‐Gated Fluorescence Imaging 170

9.3.4 Magnetically Modulated Fluorescence Imaging 170

References 171

10 Nanoscopic Imaging 175

10.1 Diffraction Barrier 176

10.2 Superresolution Fluorescence Imaging 177

10.2.1 Stimulated Emission Depletion Microscopy 177

10.2.2 Saturated Excitation Fluorescence Microscopy 181

10.2.3 Deterministic Emitter Switch Microscopy 182

10.2.4 Tip‐Enhanced Fluorescence Microscopy 183

10.3 Cathodoluminescence Imaging 184

10.4 Correlative Light‐Electron Microscopy 188

References 191

11 Nanoscale Quantum Sensing 195

11.1 The Spin Hamiltonian 196

11.2 Temperature Sensing 197

11.2.1 Ultrahigh Precision Temperature Measurement 197

11.2.2 Time‐Resolved Nanothermometry 200

11.2.3 All‐Optical Luminescence Nanothermometry 203

11.2.4 Scanning Thermal Imaging 205

11.3 Magnetic Sensing 207

11.3.1 Continuous‐Wave Detection 207

11.3.2 Relaxometry 210

References 211

12 Hybrid Fluorescent Nanodiamonds 215

12.1 Silica/Diamond Nanohybrids 215

12.2 Gold/Diamond Nanohybrids 217

12.2.1 Photoluminescence Enhancement 217

12.2.2 Dual‐Modality Imaging 218

12.2.3 Hyperlocalized Hyperthermia 220

12.2.4 NV‐Based Nanothermometry 224

12.3 Silver/Diamond Nanohybrids 226

12.4 Iron Oxide/Diamond Nanohybrids 228

12.4.1 Single‐Domain Magnetization 228

12.4.2 Magnetic Resonance Imaging 229

References 232

13 Nanodiamond‐Enabled Medicine 235

13.1 NDs as Therapeutic Carriers 236

13.2 Drug Delivery 237

13.2.1 Small Molecules 237

13.2.2 Proteins 241

13.3 Gene Therapy 244

13.3.1 RNA 244

13.3.2 DNA 245

13.4 Animal Experiments 247

References 249

14 Diamonds in the Sky 253

14.1 Unidentified Infrared Emission 253

14.2 Extended Red Emission 258

14.3 Cosmic Events at Home on Earth 264

References 267

Further Reading 271

Index 273

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