Boron Nitride Nanotubes in Nanomedicine

Boron Nitride Nanotubes in Nanomedicine compiles, for the first time in a single volume, all the information needed by researchers interested in this promising type of smart nanoparticles and their applications in biomedicine. Boron nitride nanotubes (BNNTs) represent an innovative and extremely intriguing class of nanomaterials.

After introducing BNNTs and explaining their preparation and evaluation, the book shows how the physical, chemical, piezoelectric and biocompatibility properties of these nanotubes give rise to their potential uses in biomedicine. Evidence is offered (from both in vitro and in vivo investigations) for how BNNTs can be useful in biomedical and nanomedicine applications such as therapeutic applications, tissue regeneration, nanovectors for drug delivery, and intracellular nanotransducers.

• Covers a range of promising biomedical BNNT applications
• Provides great value not just to academics but also industry researchers in fields such as materials science, molecular biology, pharmacology, biomedical engineering, and biophysical sciences
• Offers evidence for how BNNTs can be useful in biomedical and nanomedicine applications such as therapy, tissue regeneration, nanovectors for drug delivery, and intracellular nanotransducers
• Incorporates, for the first time in a single volume, all the information needed by researchers interested in this promising type of smart nanoparticles and their applications in biomedicine

• Language: English
• Publisher: Elsevier Science
• Release date: Apr 26, 2016
• ISBN: 9780323389600

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Boron Nitride Nanotubes in Nanomedicine

Edited by

Gianni Ciofani

Virgilio Mattoli

Table of Contents

Cover

Title page

Copyright

List of Contributors

Biographies

Foreword

Chapter 1: Introduction to boron nitride nanotubes: synthesis, properties, functionalization, and cutting

Abstract

1.1. Introduction

1.2. Properties of BNNTs for potential biomedical applications

1.3. Synthesis of BNNTs

1.4. Comparison of production rate, purity, and dispersibility of BNNTs

1.5. Functionalization and cutting of BNNTs for biomedical applications

1.6. Summary

Acknowledgments

Chapter 2: Functionalization of boron nitride nanotubes for applications in nanobiomedicine

Abstract

2.1. Introduction

2.2. Covalent functionalization

2.3. Noncovalent functionalization

2.4. Defect reaction approach

2.5. Filling BNNTs approach

2.6. Conclusions and perspectives

Chapter 3: Biocompatibility evaluation of boron nitride nanotubes

Abstract

3.1. Introduction

3.2. Common methods for evaluating in vitro biocompatibility

3.3. In vitro biocompatibility assessment

3.4. In vivo biocompatibility assessment

3.5. Future studies and perspectives

3.6. Conclusions

Chapter 4: Theoretical investigations of interactions between boron nitride nanotubes and drugs

Abstract

4.1. Introduction

4.2. Density functional theory methods

4.3. BNNTs/biomolecules interactions

4.4. Conclusions

Chapter 5: Boron nitride nanotubes as drug carriers

Abstract

5.1. Introduction

5.2. Improving the dispersibility of BNNT-BASED drug carriers

5.3. Various drug molecules loaded onto BNNT-based drug carriers

5.4. Interactions between BNNTs and drug molecules

5.5. Integration of multifunctional properties in BNNT-BASED drug carriers

5.6. Biocompatibility, distribution, and excretion of BNNTs as drug carriers

5.7. Future of BNNTs as drug carriers

Chapter 6: Applications and perspectives of boron nitride nanotubes in cancer therapy

Abstract

6.1. Cancer: aspects of diagnosis and treatment

6.2. Boron nitride nanotubes and nanomedicine

6.3. Drug delivery

6.4. Active targeting and uptake

6.5. Gene transfection

6.6. Magnetohyperthermia

6.7. Boron neutron capture therapy

6.8. Perspectives

Chapter 7: Boron nitride nanotubes as magnetic resonance imaging contrast agents

Abstract

7.1. Nanomaterials: the way to higher magnetic resonance contrast

7.2. Superparamagnetic BNNTs as T2-weighted contrast agents

7.3. Gd-doped BNNTs: promising contrast properties at high and low fields

7.4. Conclusions and perspectives

7.5. Appendix. MRI contrast enhancement: the basics

Chapter 8: Boron nitride nanotubes as nanotransducers

Abstract

8.1. Introduction

8.2. BNNT nanotransducers

8.3. BNNT bionanotransducers

8.4. Conclusions and future perspectives

Acknowledgement

Chapter 9: Optical properties of boron nitride nanotubes: potential exploitation in nanomedicine

Abstract

9.1. Introduction

9.2. Optical properties of boron nitride nanotubes

9.3. Boron nitride nanotubes in nanomedicine

9.4. BNNT nonlinear optical properties: exploitation in nanomedicine

9.5. Conclusions

Chapter 10: Boron nitride nanotubes as bionanosensors

Abstract

10.1. Introduction

10.2. Vibration analysis of BNNTs with attached mass

10.3. Mass detection and sensitivity calculation

10.4. Vibrational analysis of BNNTs using molecular mechanics

10.5. Results and discussions

10.6. Conclusions

Chapter 11: Boron nitride nanotube films: preparation, properties, and implications for biology applications

Abstract

11.1. Introduction

11.2. Growth of BNNT films

11.3. Wettability properties of BNNT films

11.4. Wettability modification of BNNT films

11.5. Biocompatibility of BNNT films

11.6. Conclusion

Chapter 12: Structural and physical properties of boron nitride nanotubes and their applications in nanocomposites

Abstract

12.1. Introduction

12.2. Structure and Synthesis of BNNTs

12.3. Physical properties of BNNTs

12.4. BNNT-based nanocomposites

12.5. Conclusions and outlook

Acknowledgments

Chapter 13: Boron nitride nanotubes in nanomedicine: historical and future perspectives

Abstract

13.1. A brief history of boron nitride nanotubes: from the theoretical hypothesis to the market

13.2. Main research groups involved in BNNT research

13.3. BNNT availability on the market

13.4. Patent analysis and economical implications

13.5. Toward the future: regulatory aspects and translational research

Subject Index

Copyright

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Notices

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Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

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A catalogue record for this book is available from the British Library

ISBN: 978-0-323-38945-7

For information on all William Andrew publications visit our website at https://www.elsevier.com/

List of Contributors

Sondipon Adhikari,     College of Engineering, Swansea University, Swansea, United Kingdom

Yoshio Bando,     International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, Japan

Shiva Bhandari,     Department of Physics, Michigan Technological University, Houghton, MI, United States of America

Lucia Calucci,     Institute of Chemistry of Organometallic Compounds, National Research Council, Pisa, Italy

Ying Chen,     Institute for Frontier Materials, Deakin University, Waurn Ponds, Victoria, Australia

Xiaoming Chen,     Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY, United States of America

Gianni Ciofani

Center for Micro-BioRobotics @SSSA, Italian Institute of Technology, Pontedera, Pisa, Italy;

Department of Aerospace and Mechanical Engineering, Polytechnic University of Torino, Torino, Italy

Mustafa Çulha,     Department of Genetics and Bioengineering, Yeditepe University, Ataşehir, Istanbul, Turkey

Serena Danti,     Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, Pisa, Italy

Edesia M.B. de Sousa,     Nuclear Technology Development Center, CDTN, Belo Horizonte, MG, Brazil

Melis Emanet,     Department of Genetics and Bioengineering, Yeditepe University, Ataşehir, Istanbul, Turkey

Claudia Forte,     Institute of Chemistry of Organometallic Compounds, National Research Council, Pisa, Italy

Zhenghong Gao,     Digital Laboratory Photonics and Nanoscience (LP2N), Institute of Optics, CNRS, University of Bordeaux, Bordeaux, France

Mauro Gemmi,     Center for Nanotechnology Innovation @NEST, Italian Institute of Technology, Pisa, Italy

Dmitri Golberg,     International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, Japan

Giada Graziana Genchi,     Center for Micro-BioRobotics @SSSA, Italian Institute of Technology, Pontedera, Pisa, Italy

Agostina Grillone

Center for Micro-BioRobotics @SSSA, Italian Institute of Technology, Pontedera, Pisa, Italy;

The BioRobotics Institute, Scuola Superiore Sant’Anna, Pontedera, Pisa, Italy

Tiago Hilario Ferreira,     Nuclear Technology Development Center, CDTN, Belo Horizonte, MG, Brazil

Lu Hua Li,     Institute for Frontier Materials, Deakin University, Waurn Ponds, Victoria, Australia

Changhong Ke,     Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY, United States of America

Yoke Khin Yap,     Department of Physics, Michigan Technological University, Houghton, MI, United States of America

Xia Li,     International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, Japan

Attilio Marino

Center for Micro-BioRobotics @SSSA, Italian Institute of Technology, Pontedera, Pisa, Italy;

The BioRobotics Institute, Scuola Superiore Sant’Anna, Pontedera, Pisa, Italy

Vincenzo Piazza,     Center for Nanotechnology Innovation @NEST, Italian Institute of Technology, Pisa, Italy

Antonella Rocca

Center for Micro-BioRobotics @SSSA, Italian Institute of Technology, Pontedera, Pisa, Italy;

The BioRobotics Institute, Scuola Superiore Sant’Anna, Pontedera, Pisa, Italy

Özlem Şen,     Department of Genetics and Bioengineering, Yeditepe University, Ataşehir, Istanbul, Turkey

Takeshi Serizawa,     Department of Organic and Polymeric Materials, Tokyo Institute of Technology, Tokyo, Japan

Ehsan Shakerzadeh,     Department of Chemistry, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Bishnu Tiwari,     Department of Physics, Michigan Technological University, Houghton, MI, United States of America

Nazmiye Yapici,     Department of Physics, Michigan Technological University, Houghton, MI, United States of America

Dongyan Zhang,     Department of Physics, Michigan Technological University, Houghton, MI, United States of America

Chunyi Zhi,     Department of Physics and Materials Science, City University of Hong Kong, Hong Kong, China

Biographies

Gianni Ciofani (born on Aug. 14th, 1982) is an Associate Professor at the Polytechnic University of Torino, Department of Mechanical and Aerospace Engineering (Torino, Italy) and Affiliated Researcher at the Italian Institute of Technology (IIT), Center for Micro-BioRobotics @SSSA (Pontedera, Pisa, Italy).

He received his Master’s Degree in Biomedical Engineering (with honors) from the University of Pisa, Italy, in Jul. 2006, with an experimental thesis on a polymeric microparticle system for drug delivery of neurotrophic factors. In the same year, he obtained his Diploma in Engineering (with honors) from the Scuola Superiore Sant’Anna (Sant’Anna School of Advanced Studies) of Pisa, Italy, with an experimental thesis on carbon nanotube-mediated cell electroporation.

From Jul. 2006 to Jan. 2010, he collaborated with the CRIM Lab of the Scuola Superiore Sant’Anna, formerly as a Research Assistant and then as a PhD student, working on micro- and nanosystems for drug delivery and cell surgery. He also spent research periods as visiting PhD student at the Waseda University (Tokyo, Japan) and at the Center of Investigation Principe Felipe (Valencia, Spain). In Jan. 2010, he obtained his PhD in Innovative Technologies (with honors) from the Scuola Superiore Sant’Anna. From Jan. 2010 to Aug. 2013, he was Post-Doc at the IIT, Center for Micro-BioRobotics @SSSA (Pontedera, Pisa, Italy), where, from Sep. 2013 to Oct. 2015, he was a Researcher in the framework of the Smart Materials Platform. In Oct. 2015, he was appointed as an Associate Professor at the Polytechnic University of Torino (Torino, Italy), maintaining his research activity in IIT as an Affiliated Researcher.

His main research interests are in the field of innovative materials for nanomedicine, bio/nonbio interactions, regenerative medicine, and biohybrid devices. For his research activity, he has been awarded by several national and international prizes. In collaboration with the European Space Agency, he is also carrying out researches on human physiology and cell biology in altered gravity conditions.

Gianni Ciofani is the author or coauthor of about 80 ISI papers (H-index 18, excluding self-citations), 2 edited books, 12 book chapters, 2 applications of international patents and several communications to international conferences. He serves as a Reviewer for about 90 international journals and is an Editorial Board Member of the International Journal of Biological Engineering, of Advances in Nano Research, and Senior Editor of Nanomaterials & Nanosciences.

Virgilio Mattoli received his Laurea degree in chemistry (with honors) from the University of Pisa and the diploma in chemistry from the Scuola Normale Superiore of Pisa in 2000. In 2005 he received his PhD in bioengineering (with honors) from Scuola Superiore Sant’Anna, with a thesis focused on the control and integration of miniaturized devices for environmental application. In 2004 he was visiting researcher at the University of Stanford, Center for Design Research, where he focused his activity on sensors and controls modules for biomimetic robotics applications. In 2005 and 2008 he was a short-term visiting researcher at Waseda University (Tokyo, Japan) working on a bioinspired minirobot and on development of ultraconformable polymeric films. From Jun. 2008 to Oct. 2009 he obtained a temporary position of assistant professor of bioengineer engineering at the Scuola Superiore Sant’Anna (SSSA). Since Nov. 2009, he has been a team leader of the Smart Materials Platform in the Center for Micro-BioRobotics of the Istituto Italiano di Tecnologia. His main research interests include: smart and bioinspired materials, nanomaterials, ultrathin polymeric films, thin film sensors, sensor conditioning, miniaturized acquisition system and biorobotics. He is currently involved in several research projects on these topics. He is author or coauthor of more than 70 articles on ISI journals, of more than 40 full papers published in peer-reviewed international conferences proceedings and of several deposited patents.

Foreword

Nanotechnology has recently revolutionized the way scientists approached their research interests in view of several exciting discoveries and improved performance of their miniaturized systems. This is due to the fact that materials produced at the nanoscale might not only show unique mechanical, physical, and chemical properties, but also unpredictable effects that can promote either enthusiastic or distrustful behaviors in research scientists worldwide.

Boron nitride nanotubes (BNNTs) have recently emerged as an intriguing source of excitement, because they enable the realization of advanced, integrated, and compact nanocomposites to be fabricated. What renders these nanomaterials so special is the similarity of boron nitride atoms to carbon in terms of electronic structure (they hold the same number of electrons between adjacent atoms). Nonetheless, boron nitride shows huge versatility in shapes, including squares, pentagons, hexagons, and octagons, as well as tubular structures. These last ones are responsible for a widespread number of applications, ranging from water purification systems to biosensors and transducers, and stretched all the way into the field of biology and medicine.

This volume covers all these aspects, offering a general overview on the preparation and properties of these BNNTs, as well as suggesting the main factors that render them unique for current and further promising applications. A special focus is given to the field of nanomedicine, whereby the reader is educated on how physical, chemical, and piezoelectric properties can be precisely tuned to offer potential advantages over current approaches in medicine. The most relevant aspect is that this book is not meant exclusively for chemists or medical scientists. On the contrary, the strategies reported for the functionalization of these tubes can be used for several applications, thus targeting a very broad audience.

Notwithstanding the previously stated exciting properties, the extensive use of BNNTs in biomedicine is not exempted from concerns on their safety, their quality and their impact on the environment. The reason behind such uncertainty is the evidence that structures and materials that are normally inert can elicit biological irregularities and chemical variances as nanospecies. An in-depth evaluation on the biocompatibility of BNNTs is therefore a crucial asset to this book. Besides that, the reader is gradually introduced to advanced in vitro and in vivo studies performed by the most established research groups, showing the possibility to use BNNTs as drug carriers, contrast agents, nanotransducers, nanosensors, and even as scaffolds for tissue engineering and repair.

This unique book comes at the right moment, when the scientific community and numerous laboratories are exploring the potential broad applicability of BNNTs. The authors offer additional perspectives and dynamic visions on the current state of the art of BNNTs. Hence this volume represents an excellent reference for inspiring scientists and students in their research endeavors.

Giorgia Pastorin

Pharmacy Department, National University of Singapore, Singapore

Chapter 1

Introduction to boron nitride nanotubes: synthesis, properties, functionalization, and cutting

Shiva Bhandari

Bishnu Tiwari

Nazmiye Yapici

Dongyan Zhang

Yoke Khin Yap    Department of Physics, Michigan Technological University, Houghton, MI, United States of America

Abstract

This chapter presents an introductory review on properties, synthesis, functionalization, and cutting of boron nitride nanotubes (BNNTs). First, the intriguing properties of BNNTs are highlighted in the perspective of their application in the biomedical field. Then, the developments on the synthesis of BNNTs are summarized. In particular, recent advancements in mass production of BNNTs are described. The quality, purity, and dispersion issues of BNNTs synthesized by various techniques are then analyzed and compared for their potential use in biomedical applications. Later section of the chapter is devoted to review the covalent and noncovalent functionalization of BNNTs with various biocompatible polymers. Their dispersibility and cutting in aqueous media are then finally discussed.

Keywords

boron nitride nanotubes

synthesis

functionalization

purity

dispersibility

1.1. Introduction

The advancement of nanoscale science and technology has led to the discovery of several interesting boron nitride (BN) nanostructures, including boron nitride nanotubes (BNNTs), boron nitride nanosheets (BNNSs) and boron nitride nanoribbons (BNNRs). Interestingly, all these BN nanostructures are based on hexagonal phase BN (h-BN), with BN bonds that are isoelectronic (having same number of valence electrons) with CC bonds. Therefore, BNNTs, BNNSs, and BNNRs are structurally similar to carbon nanotubes (CNTs), graphene, and graphene nanoribbons (GNRs), respectively.

BNNTs are relatively well studied among all BN nanostructures and can be understood as seamless cylindrical rolls of h-BN as shown in Fig. 1.1 [1]. They were theoretically predicted in 1994 [2,3], and experimentally produced in the following year [4]. As shown in Fig. 1.1a, single-walled (SW) BNNTs can be classified by vectors (n,m), according to the rolling/chiral angles. SW-BNNTs in the (n,0) configuration represent the zigzag nanotube structures, SW-BNNTs in the (n,n) configuration are known as armchair nanotubes, and all other (n,m) configurations are chiral nanotubes. The atomic arrangements of a BNNS, a zigzag (10,0), armchair (6,6), and chiral (7,5) SW-BNNTs are illustrated in Fig. 1.1b–e, respectively. Multiwalled (MW) BNNTs are seamless roll of stacked h-BN sheets, which are relatively easier to produce than SW-BNNTs.

Figure 1.1   (a) Vector (n,m) of SW-BNNTs on a h-BN sheet. Atomic arrangements of (b) BNNSs and (c) zigzag (10,0), (d) armchair (6,6), and (e) chiral (7,5) BNNTs. Part a: adapted with permission from [1]; copyright (2010) The Royal Society of Chemistry. Part c,d and e: adapted with permission from [5]; copyright (2009) Springer.

BNNTs possess extraordinary mechanical properties like CNTs [6–8], while offering higher resistance to oxidation [9–11]. BNNTs have merely uniform bandgap (∼6 eV) regardless of their chirality and SW or MW structures [2,3]. Despite some discrepancies [12], BNNTs are well accepted to be biologically compatible [13] for various biomedical applications [14]. Due to these intriguing properties, research interest in exploring application of BNNTs is increasing in recent years. However, synthesis of high quality and high purity BNNTs is still challenging to sufficiently meet the demand of the application.

In this Chapter, the properties of BNNTs and their production techniques will be first discussed. Then, functionalization and cutting of BNNTs in water will be approached, focusing on their biomedical applications.

1.2. Properties of BNNTs for potential biomedical applications

BNNTs have exceptionally high Young’s modulus of ∼1.2 TPa [15] comparable to that of CNTs [16]. Hence, they are suitable filler materials for reinforcing polymer composites [17] and ceramic composites [18]. These composites would potentially be applicable for biomedical implants, but have not being extensively explored yet. On the other hand, the difference in electronegativity between B and N atoms [19] affects the physical and chemical properties of BNNTs. For example, the polarized BN bonds [20] have enabled covalent functionalization of BNNTs with several kinds of molecules [21].

The polarized BN bonds also lead to localized states in BNNTs and create the uniform wide energy bandgap. Therefore, pure BNNTs are electrical insulators [22]. Theory predicted that their bandgap is tunable by applying transverse electric field [23,24], carbon substitution [25], and surface modification/functionalization [26,27]. Although brief bandgap modification were experimentally observed, even if speculative [28,29], BNNTs are still not applicable for electronic devices. More recently, Lee et al. demonstrated a novel approach enabling the creation of tunneling field effect transistors (TFETs) using gold quantum dots functionalized BNNTs (QDs-BNNTs) [30]. These TFETs could potentially lead to biological and chemical sensors.

MW-BNNTs (outer diameter 30–40 nm) are known for their high thermal conductivity (350 W/mK) [31] on par with CNTs of same diameter [32]. Noteworthy, thermal transfer in CNTs is due to electron and phonon, whereas the latter is responsible for the case of BNNTs [33]. In addition, BNNTs offer high resistance to oxidation and can survive in air up to ∼900°C while CNTs are oxidized at ∼500°C. Creative future work is needed to explore potential biomedical applications of BNNTs which uses these unusual properties.

There are several other properties of BNNTs that are merely unexplored for biomedical applications. For example, piezoelectric properties [34,35], hydrogen storage capability [36], and superhydrophobicity of BNNTs [37] (Fig. 1.2a and b) are interesting and not yet fully exploited for nanomedicine applications. The major reason for such unexplored scenario is the lack of high purity BNNTs for experiments [38,39], although many potential biomedical applications have been proposed [40]. In the following sections, methods of BNNTs synthesis will be discussed, and the products of these methods will then be compared.

Figure 1.2   (a) Photograph of water droplet on the surface of BNNT film showing superhydrophobicity. (b) Zoom-in cross-sectional view of BNNTs on silicon substrate showing that these BNNTs are grown vertically aligned on the substrate surface. Adapted with permission from [37]; copyright (2009) American Chemical Society.

1.3. Synthesis of BNNTs

As inspired by the synthesis of CNTs, the production of BNNTs were initially attempted by modified arc discharge [4,41], laser evaporation [42,43], laser ablation [44] and chemical vapor deposition (CVD) [45] techniques.

1.3.1. Chemical vapor deposition

CVD is widely used for the synthesis of materials in high chemical purity [46]. Various types of boron sources have been used for the synthesis of BNNTs by CVD technique, including the corrosive and/or toxic borazines [45,47], diborane (B2H6) [48,49], and boron trichloride (BCl3) [50]. The safest CVD approach has been the boron oxide CVD (BOCVD) method [51,52]. In this method, B, MgO, and/or various other metal oxide precursor powders are mixed and heated (∼1300–1500°C) to generate BxOy vapors, which are then carried by Ar gas to a lower temperature to react with anhydrous NH3 to form BNNTs. Unfortunately, BOCVD requires a reaction chamber that is specially designed to control the flow and reaction of BxOy and NH3, which is still difficult to achieve for reproducible growth of BNNTs. Huang et al. replaced MgO with Li2O to yield BNNTs with sub-10 nm diameter [53], but the technique involves the use of highly corrosive agents.

Using the BOCVD chemistry, Lee et al. have demonstrated a simpler CVD approach to synthesize BNNTs in a conventional horizontal resistive tube furnace [54] commonly used for the synthesis of CNTs [55,56], ZnO nanostructures [57], and graphene. As shown in Fig. 1.3a, the key feature of this catalytic CVD (CCVD) technique is the use of a quartz test tube to trap and confine the vapors for the formation of BNNTs (GVT, growth vapor trapping approach) at relatively lower temperature (∼1100–1200°C). The GVT growth of BNNTs can also be controlled by catalysts (MgO, Fe, Ni) coated on Si substrates, significantly different from the original BOCVD, where BNNTs are merely formed by spontaneous nucleation/condensation. As shown in Fig. 1.3b and c, the CCVD/GVT approach led to the growth of high quality BNNTs at desired locations predefined by catalyst coatings [22]. These BNNTs are vertically aligned as those shown in Fig. 1.2b, with a bandgap of 6 eV without any subband features.

Figure 1.3   (a) Experimental setup for the growth of BNNTs in a horizontal tube furnace. (b) Well-defined patterned growth of BNNTs on a substrate and (c) TEM image showing tubular structure of BNNTs with amorphous free sidewalls. Part a: adapted with permission from [54]; copyright (2008) IOP. Part b and c: adapted with permission from [22]; copyright (2010) American Chemical Society.

Alternative CVD approach was also demonstrated by Ferreira et al. [58]. Boron powder was heated at 1300°C along with mixture of NH4NO3 and Fe2O3 in NH3 ambient. Unfortunately, these BNNTs are filled with Fe nanoparticles. The biocompatibility test of these as-grown (nonpurified) product and the purified BNNTs (etched with HCl) were also investigated.

1.3.2. Ball milling

Ball milling is one of the earliest approach for BNNTs synthesis [59]. The process involves extensive ball milling of boron powder for a long period of time (up to 150 h) in NH3 gas followed by annealing at high temperature (up to 1300°C) in N2 environment. It was suggested that a nitriding reaction was induced between boron powder and NH3 gas due to high energy milling, resulting in metastable disordered BN nanostructures and boron nanoparticles. BNNTs were grown from these reactive phase during a subsequent high-temperature annealing of the powder in ammonia ambient. It is proposed that BN nanoparticles formed during the milling process act as nucleation sites for growth during annealing process. Apart from them, contaminant Fe nanoparticles introduced during the milling process also served as catalyst for the growth. However, the quality and purity of BNNTs grown by ball milling was not satisfactory.

In the following years, various works have been done to increase the throughput and improve quality of BNNTs using ball-milling process. Li et. al. showed that addition of catalyst during the milling process can help to increase the production yield [60]. As an example, boron powder and 10% of Fe(NO3)3 was milled in NH3 atmosphere at 250 KPa pressure. Annealing the milled powder at N2 + 15% H2 gas environment at 1100°C mostly resulted in bamboo-like BNNTs. Heating the same milled powder at 1300°C in NH3 environment resulted in the growth of cylindrical BNNTs with diameters approximately 10 nm. Other metal-based compounds such as nickel boride (NiBx) [61] and Li2O [62] are also reported as catalysts to enhance the yield of BNNTs growth. Though large quantity of BNNTs can be synthesized via this process, shortcoming was that the BNNTs are usually bamboo-like structured and contain B/BN reactants (amorphous boron particles and BN bulky flakes) as impurities.

1.3.3. Laser-based techniques

In 1996 Golberg et al. reported the synthesis of MW-BNNTs by laser evaporation of h-BN target by a continuous CO2 laser in very high nitrogen pressure (5–15 GPa) [42]. The process resulted in the formation of short BNNTs with large quantity of impurities such as amorphous BN particles and flakes. Later on, Zhou et al. reported that using additional metal catalysts such as Co and Ni nanoparticles in the laser ablation process can result in longer nanotubes with smaller diameters [63]. Laude et al. reported the growth of BNNTs of length ∼40 μm in somewhat large scale by laser heating under low pressure [64]. Lee et al. were able to synthesize single-walled BNNTs using similar laser ablation process in large scale (0.6 g/h) [43]. The presence of boron nanoparticles at those nanotube tips, as revealed by TEM, suggested a root-based growth mechanism [65]. Wang et al. reported the growth of BNNTs on substrate for the first time using plasma-enhanced pulsed laser deposition (PE-PLD) at 600°C [66]. High-quality vertically aligned BNNTs were successfully grown on substrates coated with Fe catalyst. However, these BNNTs were relatively short (up to 1 μm).

In 2009, Smith et al. reported a modified laser evaporation method termed as pressurized vapor/condenser method (PVC) [67]. This technique is actually quite similar to that reported by Lee et al., which was conducted at lower laser power without the condenser [43]. A typical continuous run for 30 min can produce up to 60 mg of BNNT fibrils by evaporating a boron target at high temperature (∼4000°C) in pressurized N2 gas (2–20 atm) environment. A cooled metal wire traversed through plume acted as a condenser to from liquid boron droplets, which acted as nucleation sites for the growth of BNNT fibril network. The as-grown BNNTs are tube bundles and entangled network of BNNTs as shown in Fig. 1.4a and b. These BNNTs are often fused and anchored with boron nanoparticles and amorphous BNx particles which makes the product difficult to purify and disperse for applications.

Figure 1.4   Images of (a) BNNT fibrils and (b) the entangled BNNT network produced by the pressurized vapor/condenser method (PVC). An arrow marks a round, solidified boron droplet. (c) Entangled BNNTs within the BNNT fibrils grown from hydrogen-catalyzed inductively coupled plasma. (d) Image of entangled BNNT fibril produced by the EPIC system. Part a and b: adapted with permission from [67]; copyright (2009) IOP. Part c: adapted with permission from [68]; copyright (2014) National Research Council Canada. Part d: adapted with permission from [69]; copyright (2014) American Chemical Society.

1.3.4. Large-scale synthesis by plasma-based techniques

Recently, plasma discharge techniques were employed for large-scale synthesis of BNNTs. Kim et. al. demonstrated the synthesis of BNNTs at a rate of 20 g/h by feeding h-BN powder along with N2 and H2 gases in a high temperature induction plasma (>8000 K) at atmospheric pressure [68]. As the high temperature plasma decomposed all the precursor materials into their constituent elements (B, N, and H), nanosized boron droplets were condensed in the cooler downstream of the reactor due to the large temperature gradient (10⁵ K/s). These boron droplets acted as nucleation site to grow BNNTs. Here, hydrogen gas acted as catalyst so that it hindered the recombination of N radicals generated from N2 feedstock or from dissociation of h-BN by forming an intermediate HBN species. These intermediate species can easily result into h-BN-like phase to nucleate BNNTs from the boron droplets. The product appeared in different macroscopic morphologies: entangled network of