Silicon Carbide Biotechnology: A Biocompatible Semiconductor for Advanced Biomedical Devices and Applications

Silicon Carbide (SiC) is a wide-band-gap semiconductor biocompatible material that has the potential to advance advanced biomedical applications. SiC devices offer higher power densities and lower energy losses, enabling lighter, more compact and higher efficiency products for biocompatible and long-term in vivo applications ranging from heart stent coatings and bone implant scaffolds to neurological implants and sensors.

The main problem facing the medical community today is the lack of biocompatible materials that are also capable of electronic operation. Such devices are currently implemented using silicon technology, which either has to be hermetically sealed so it cannot interact with the body or the material is only stable in vivo for short periods of time.

For long term use (permanent implanted devices such as glucose sensors, brain-machine-interface devices, smart bone and organ implants) a more robust material that the body does not recognize and reject as a foreign (i.e., not organic) material is needed. Silicon Carbide has been proven to be just such a material and will open up a whole new host of fields by allowing the development of advanced biomedical devices never before possible for long-term use in vivo.

This book not only provides the materials and biomedical engineering communities with a seminal reference book on SiC that they can use to further develop the technology, it also provides a technology resource for medical doctors and practitioners who are hungry to identify and implement advanced engineering solutions to their everyday medical problems that currently lack long term, cost effective solutions.

• Discusses Silicon Carbide biomedical materials and technology in terms of their properties, processing, characterization, and application, in one book, from leading professionals and scientists
• Critical assesses existing literature, patents and FDA approvals for clinical trials, enabling the rapid assimilation of important data from the current disparate sources and promoting the transition from technology research and development to clinical trials
• Explores long-term use and applications in vivo in devices and applications with advanced sensing and semiconducting properties, pointing to new product devekipment particularly within brain trauma, bone implants, sub-cutaneous sensors and advanced kidney dialysis devices

• Language: English
• Publisher: Elsevier Science
• Release date: Nov 14, 2011
• ISBN: 9780123859075

Book preview

Table of Contents

Cover image

Front-matter

Copyright

Dedication

Preface

Acknowledgments

Chapter 1. Silicon Carbide Materials for Biomedical Applications

1.1. Introduction

1.2. Silicon Carbide—Materials Overview

1.3. Silicon Carbide Material Growth and Processing

1.4. Silicon Carbide as a Biomedical Material

1.5. Summary

Chapter 2. SiC Films and Coatings

2.1. Introduction

2.2. SiC CVD Introduction

2.3. Amorphous Silicon Carbide, a Sic

2.4. Polycrystalline SiC Films

2.5. Single-Crystalline SiC Films

2.6. 3C-SiC Heteroepitaxial Growth on Novel Substrates

2.7. Summary

Chapter 3. Multifunctional SiC Surfaces

3.1. Introduction

3.2. Surface Terminations

3.3. Organic Surface Modification via Self-Assembly Techniques

3.4. Polymer Brushes

3.5. Increased Cell Proliferation on SiC-Modified Surfaces

3.6. Conclusion

Chapter 4. SiC In Vitro Biocompatibility

4.1. Introduction

4.2. Cell Cultures on Single-Crystal SiC Surfaces

4.3. Influence of Surface Properties on Cell Adhesion and Proliferation

4.4. Cleaning of SiC Surfaces for Bioapplications: RCA versus Piranha

4.5. Summary

Chapter 5. Hemocompatibility Assessment of 3C-SiC for Cardiovascular Applications

5.1. Introduction

5.2. Biocompatibility of Materials

5.3. Platelet Adhesion and Activation

5.4. Protein Adsorption to Surfaces

5.5. Microvascular Endothelial Cell Proliferation on Semiconductor Substrates

5.6. Conclusion

Chapter 6. Biocompatibility of SiC for Neurological Applications

6.1. Introduction

6.2. The Basic Central Nervous System

6.3. In Vitro Foreign Material and Living Cell Surface Interaction

6.4. Mouse Primary Cortical Neurons on 3C-SiC

6.5. In Vivo Neuronal Tissue Reaction to Cubic Silicon Carbide

6.6. Michigan Probe Style 3C-SiC Biocompatibility Investigation Device

6.7. Conclusion

Chapter 7. SiC for Brain–Machine Interface (BMI)

7.1. Introduction

7.2. Theory of Bioelectricity

7.3. The Brain–Machine Interface

7.4. Implantable Neural Prosthetics and the Immune System Interaction

7.5. Silicon Carbide Neural Activation Device (SiC-NAD)

7.6. Neural Interface Signal Production, Reception and Processing

7.7. Conclusion

Chapter 8. Porous SiC Microdialysis Technology

8.1. Introduction to Microdialysis Principles

8.2. Membrane Types

8.3. Summary

Chapter 9. Biocompatible Sol–Gel Based Nanostructured Hydroxyapatite Coatings on Nano-porous SiC

9.1. Introduction

9.2. Porous SiC

9.3. Results and Discussion

9.4. Conclusion

Chapter 10. Silicon Carbide BioMEMS

10.1. Introduction

10.2. 6H-SiC-Based BioMEMS

10.3. 3C-SiC-Based BioMEMS

10.4. Amorphous-SiC-Based BioMEMS

10.5. Conclusions

Chapter 11. SiC as a Biocompatible Marker for Cell Labeling

11.1. Introduction

11.2. Synthesis

11.3. Structural and Chemical Properties of SiC Nanoparticles

11.4. Optical Properties

11.5. Biocompatible Cell Labeling

11.6. Cancer Therapy

11.7. Chapter Summary

Chapter 12. Carbon Based Materials on SiC for Advanced Biomedical Applications

12.1. Introduction

12.2. Graphene

12.3. Pyrolyzed Photoresist Films (PPF)

12.4. Graphene and Pyrolyzed Photoresist Films for Biomedical Devices

12.5. Biocompatibility of Epitaxial Graphene on SiC and PPF

12.6. Conclusions

Index

Front-matter

Silicon Carbide Biotechnology

FIRST EDITION

SILICON CARBIDE BIOTECHNOLOGY

A BIOCOMPATIBLE SEMICONDUCTOR FOR ADVANCED BIOMEDICAL DEVICES AND APPLICATIONS

FIRST EDITION

S tephen E. S addow

AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD • PARIS • SAN DIEGO • SAN FRANCISCO • SYDNEY • TOKYO

Copyright

Elsevier

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First edition 2012

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Library of Congress Cataloging-in-Publication Data

Saddow, Stephen E.

Silicon carbide biotechnology : biocompatible semiconductor for advanced biomedical devices and applications/Stephen Saddow. – 1st ed.

p.; cm.

Includes bibliographical references and index.

ISBN 978-0-12-385906-8 (alk. paper)

I.Title.

[DNLM: 1. Biocompatible Materials. 2. Carbon Compounds, Inorganic. 3. Semiconductors. 4. Silicon Compounds. QT 37]

LC classification not assigned

577′.144–dc23

2011031601

British Library Cataloguing-in-Publication Data

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

ISBN: 978-0-12-385906-8

For information on all Elsevier publications visit our web site at elsevierdirect.com

Printed and bound in USA

12 13 14 10 9 8 7 6 5 4 3 2 1

Dedication

This book is dedicated to Luca Edward Saddow—may you always respect those around you, question conventional wisdom, seek to make this world a better place, and, above all, live a happy, healthy, long, and productive life under the eyes of God.

Preface

Prof. Stephen E. Saddow

Editor, University of South Florida, Tampa, FL, USA

The twenty-first century has long been hailed as the century of biology, since the extremely complex nature of the biological system is only now beginning to be more fully understood through the use of technology and the scientific tools that allow mankind to observe biological processes at the nano-scale. This has resulted in the ever pressing need to develop advanced smart materials for biomedical applications, and this important field of research has taken center stage worldwide as the new frontier of advanced scientific research. Although biocompatible materials have been in use for decades, the quest to merge smart materials, such as those used in modern computer integrated circuits, with the biological system, has proven to be much more difficult than originally imagined. If we take the brain–machine interface, or BMI, as an example, which was first reported in the early 1970s and was based on silicon probes, we learn that mankind is not much closer to the prospect of long-term (multiple years or even decades) implantation of these devices. Why? Simply put most smart materials such as semiconductors are typically poisonous to the biological system, and silicon is no exception. What is needed is therefore a material with the smart propertiesof silicon and the biocompatible properties of polymers. In this book such a candidate material, silicon carbide, is presented and the evidence that has been amassed, mostly over the last decade, indicates that this material system may prove to be the dream material for biomedical devices that must do more than simply provide structural support.

Silicon carbide has a long history as a robust and hard material, first used as a cutting material in the nineteenth century and later as a high-temperature semiconductor for advanced applications in the twentieth century. Indeed, the first solid-state blue light emission was observed from SiC in 1907, and this material has been under study ever since that time. It is best to consult the literature to fully understand all of the many aspects of SiC, from how it is formed to its myriad crystal properties, and finally to the large number and types of applications it is being used in. Fortunately it is sufficient here to provide a brief overview of SiC so that the reader can understand why this material is so compelling for biomedical applications and may become one of the most used biomaterials in the future. Indeed, the purpose of this book is to lay the foundation for exactly this—to introduce silicon carbide to biomedical engineers, medical professionals, and scientists, thus bringing together technologists from across many disciplines to help develop SiC as one of the next generation of smart biomaterials to realize advanced biomedical devices.

The organization of this book follows a logical sequence from an introduction of SiC, with a particular emphasis on biomedical applications, to the growth of thin SiC films and coatings (Chapter 2). Since the actual interface between any material and the biological system involves the atomic-scale interface between atoms in the material and the biomolecules (proteins at the microscopic scale to cells and then tissue), an overview of the SiC surface properties is given, so that the reader can understand how biocompatible SiC surfaces are prepared. Chapter 3 discusses the biofunctionalization of SiC surfaces that is the key to control the chemical properties of the material and optimize the SiC bio-interface for implants, sensors, and so on. This concludes the first section of the book which serves the purpose of introducing SiC as a biomedical material, touching upon some basic technology that applies to many biomedical devices and systems. The next section of the book focuses on establishing SiC as a biocompatible material: skin and connective tissue (Chapter 4), cardiovascular (Chapter 5), and the central nervous system (Chapter 6). The last section of the book is dedicated to biomedical devices that are enabled by the use of SiC materials. Chapter 7 discusses the potential of SiC for brain–machine interfaces (BMIs) that are one of the important chronic applications for semiconductor-based materials that will be implanted for not just years but decades in patients. Chapter 8 discusses novel work using porous SiC as a filtering media for such critical applications as micro-dialysis, followed by the use of porous SiC for bone implants (Chapter 9). A review of SiC for bio-microelectromechanical systems (bioMEMs), which is the basis for sensors and advanced implants in SiC, is discussed in Chapter 10. One of the areas where SiC can greatly assist in disease detection and diagnosis is in the area of photoluminescent dye markers as discussed in Chapter 11. Finally we come full circle, back to the biocompatibility of materials and discuss a very new and exciting topic—the biocompatibility of carbon-based materials for electrodes in Chapter 12. The discussion focuses on pyrolyzed photoresist films (PPF) and graphene. Graphene is a carbon-based thin film that has extremely high electron conductivity and could serve as an ideal conductive layer for numerous biomedical devices that require an electrical interface to the biological applications. Photoresist, when pyrolyzed at high temperatures in an inert atmosphere, results in a durable carbon film that is easily patterned. In both cases the obvious benefit is to remove any possibility of metal contamination from the biomedical device, thus enhancing the biocompatibility while improving device performance. Hence this chapter ties it all together leaving only the bibliographical section where all of the references cited in the book are provided.

The authors listed at the beginning of each chapter provided the content, including figures and text that comprise the majority of this book. The Editor both solicited these chapters and edited the content in an effort to achieve a uniform and consistent text. This was done so that the reader could both focus on the very interesting subject matter contained within and see the connection that many of the chapters have with each other. The editor hopes that this endeavor was successful and that you, the reader of this book, will find this work both informative and enjoyable to read. Indeed, it was an extremely rewarding experience putting together this book and the editor hopes that this will be similarly felt by you, the reader.

At Academic Press/Elsevier Science, the project was coordinated by Louisa Hutchins and the editor is grateful to her for all of her support and kind assistance throughout the project. In addition, Parvathy Bala very capably coordinated the production of the book and is gratefully acknowledged for all of her hard work in making sure galley proof corrections were made, copyright approvals completed, and for her overall help in pulling this book together. The editor of Silicon Carbide Biotechnology hopes that users of this book, and especially the students who will become the next generation of biomedical practitioners and technologists, will find the subject matter of Silicon Carbide Biotechnology as interesting and exciting as the editor does.

Acknowledgments

Prof. Stephen E. Saddow

Editor, Tampa, FL

This project was made possible by so many people that it is difficult to thank everyone sufficiently and completely, and if I forget to include anyone in this acknowledgment, it is truly inadvertent. I am first grateful to my family who raised me to have real values—those of honest work and to always respect and appreciate others. To them I remain ever grateful. None of this would not have been possible had it not been for all of the teachers and professors in my life, most notably my Ph.D. advisor, Prof. Chi Lee at the University of Maryland, who taught me that no matter how successful one is, or how famous one becomes, the true measure of a colleague is kindness and respect. Naturally none of this would have been possible without the dedicated students that I have had the good fortune to work with and advise over the past 15 years. It is upon the shoulders of many of these fine students that this work rests upon. A few deserve a special note of recognition since they were the SiC biomaterials pioneers who laid the foundation for this book. They are Dr. C. Coletti for her pioneering work on the in-vitro biocompatibility of SiC and upon whose work Dr. N. Schettini (hemacompatibility) and Dr. C. Frewin (neuronal biocompatibility) directly followed. In addition Ms. A. Oliveros, my current Ph.D. student, has continued this tradition and has begun to develop SiC biosensors along with exploring the biocompatibility of graphene and carbon-based conductors. This core cadre of students made this work possible and I am eternally indebted to them. I wish to also thank Dr. C. Locke for his nonwavering support of all of the research in my group, mostly notably by growing and processing the needed SiC films. In addition, I wish to thank all of the present and former students of the USF SiC Group, as well as my close colleagues Dr. A. Hoff and Dr. S. Thomas of the Department of Electrical Engineering at USF. Dr. Hoff was my inspiration to enter the biomedical engineering field and introduced me to Dr. M. Jaroszeski of the Chemical and Biomedical Engineering Department who opened his laboratory to my students thus making the work of the Bio-SiC group possible. Dr. Thomas provides consistent encouragement and new ideas that continue to move the group forward into new areas of Bio-SiC research, currently with our joint student Ms. S. Afroz who is pioneering SiC in-vivo glucose sensors. I wish to thank the USF NREC staff for their support and kind assistance to my students as well as my department chairman Dr. S. Morgera who has always been extremely supportive of my research activity and group. I especially want to thank Dr. E. Weeber of the Byrd Alzheimer Center for our very fruitful collaboration in neuroscience and neuroengineering that has led to many of the recent breakthroughs in my group. None of this would have been possible without the support of Dr. C. Wood, formerly of the Office of Naval Research, who had the vision to encourage me to devote some resources to start the biomaterials research of Dr. Coletti. Finally, and most dear to my heart, is the ever present love and support of my wife Vaine Angelo, with whom we just had a son, little Luca Edward, who provides all of the incentive that anyone needs to continue to strive for scientific and technological excellence—in some small way I hope that all of this work will allow for his quality of life to be the best that man on earth can provide.

Chapter 1. Silicon Carbide Materials for Biomedical Applications

Stephen E. Saddow

Department of Electrical Engineering, College of Engineering and Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, FL 33620, USA

Silicon carbide (SiC) is a wide bandgap semiconductor that is also a well-known ceramic. It has been used for more than 100 years as an industrial material because of its extreme hardness and robust chemical performance. Recently, it has been investigated as a hard coating for numerous biomedical applications, with the more well known being nonfouling coatings on coronary heart stents and as a passivation layer for prosthetic bone implants. While there is much information in the literature about SiC, there are contradictions that mainly originate from the complex solid-state form of this material. Indeed, SiC can be formed in numerous crystalline forms, called polytypes, each with its own unique physical, optical, electrical, and chemical properties. Until recently, it was thought that SiC was biologically invariant, meaning that the biological interface between SiC and various tissues, cells, etc., was not influenced by the various forms of SiC. In this book, we will see that this cannot be farther from the case. A comprehensive study of single-crystal SiC biocompatibility has been undertaken at the University of South Florida, and we have shown surprising and dramatic differences between the biointerface of SiC and the cardiovascular and nervous systems. Indeed, it is not possible to simply state that SiC is biocompatible or that SiC is hemacompatible, as one must ask the question differently: Is SiC compatible with blood platelets? or Is SiC compatible with neurons? As we will see in this introductory chapter and later on in the book, the answers to these questions are somewhat known now, and one simply needs to tailor the specific SiC polytype to the application at hand. One of the most dramatic discoveries was that, for the nervous system, cubic-SiC, more commonly referred to as 3C-SiC, outperforms by a significant amount of nanocrystalline diamond, which was a very surprising discovery. Indeed, SiC is a very interesting and useful material and, now that its biocompatibility has been fully determined, it is poised to enable the next generation of smart biomedical devices. The reader will find numerous chapters in this book that literally cover the entire mammalian system, from skin and connective tissue, to blood, bone, microdialysis, and finally the nervous system.

Keywords

Biomaterials, silicon carbide, biocompatibility, hemacompatibility, single-crystal SiC, skin, bone, microdialysis, central nervous system, in vitro, in vivo, cells, platelets, MTT assay, fluorescence microscopy

1.1. Introduction

Silicon carbide (SiC) has a long history as a robust and hard material, first used as a cutting material in the nineteenth century and later as a high-temperature semiconductor for advanced applications in the twentieth century. The history of SiC is quite interesting and the reader is referred to the first chapter in a book dedicated to this subject [1]. It is best to consult the literature to fully understand all of the many aspects of SiC, from how it is formed, to its myriad crystal properties, and finally to the large number and types of applications it is being used in. Fortunately, it is sufficient here to provide a brief overview of SiC so that the reader can understand why this material is so compelling for biomedical applications and may become one of the most used biomaterials in the twenty-first century. Indeed, the purpose of this book is to lay the foundation for this—to introduce SiC to biomedical engineers, medical professionals, and scientists, thus bringing together technologists from across many disciplines to help realize the ultimate use of SiC as one of the next generation of smart biomaterials for advanced biomedical devices.

The organization of this book follows a logical sequence from an introduction of SiC, with a particular emphasis on biomedical applications, to the growth of thin SiC films and coatings (Chapter 2). Since the actual interface between any material and the biological system involves the atomic-scale interface between atoms in the material and the neighboring biomolecules (proteins at the microscopic scale to cells and then, ultimately, tissue), an overview of the SiC surface properties is given, so that the reader can understand how biocompatible SiC surfaces are prepared. Chapter 3 discusses the biofunctionalization of SiC surfaces that is the key to controlling the chemical properties of the material and optimizing the SiC biointerface for implants, sensors, and so on. This concludes the first section of the book that serves the purpose of introducing SiC as a biomedical material, touching upon some basic technology that applies to many biomedical devices and systems. The next section of the book focuses on establishing SiC as a biocompatible material: skin and connective tissue (Chapter 4), cardiovascular system (Chapter 5), and the central nervous system (Chapter 6). The last section of the book is dedicated to biomedical devices that are enabled by the use of SiC materials. Chapter 7 discusses the potential of SiC for brain–machine interfaces (BMIs). The BMI is one of the most important chronic applications for semiconductor-based materials as they will be implanted for not only years but for decades in patients. Chapter 8 discusses novel work using porous SiC as a filtering media for critical applications such as microdialysis, followed by the use of porous SiC for bone implants (Chapter 9). SiC for biomicroelectromechanical systems (bioMEMS), which is the basis for sensors and advanced implants in SiC, is reviewed in Chapter 10. One of the areas where SiC can greatly assist in disease detection and diagnosis is the area of photoluminescent dye markers as discussed in Chapter 11. Finally, we come full circle, back to the biocompatibility of materials and discuss a very new and exciting topic—the biocompatibility of carbon-based materials for advanced electrodes in Chapter 12. The discussion focuses on pyrolyzed photoresist films (PPFs) and graphene. Graphene is a carbon-based thin film that has extremely high electron conductivity and serves as an ideal conductive layer for numerous biomedical devices that require an electrical interface to the biological system. Photoresist, when pyrolyzed at high temperatures in an inert atmosphere, results in a durable carbon film that is easily patterned. In both cases, the obvious benefit is to remove any possibility of metal contamination from the biomedical device, thus enhancing the biocompatibility while improving device performance. Hence, this chapter ties it all together leaving only the bibliography section where all of the references cited in the book are provided.

1.2. Silicon Carbide—Materials Overview

SiC is first and foremost a material that consists of the covalent bonding of Si and C atoms, typically in biatomic layers as shown in Figure 1.1. These form tetrahedrally oriented molecules of Si–C, with a very short bond length and, hence, a very high bond strength. This is the origin of the extremely high chemical and mechanical stability of SiC [2] and [3]. SiC can be formed in amorphous, polycrystalline, and monocrystalline solid forms, and because of the high bond strength and high-temperature operating capabilities of SiC, synthesis of SiC materials normally requires high temperatures (>1,000 °C). The material can be grown in bulk (boule) crystal form, currently with diameters up to 150 mm (6 in.), and can be heteroepitaxially grown on Si substrates (details of how this is accomplished are provided in the next chapter).

One of the important characteristics of SiC is that the bilayers of Si and C (Figure 1.1) can be stacked one upon the other in different crystal orientations: cubic, hexagonal, and rhombohedral. With more than 200 known polytypes reported in the literature, the three technologically relevant forms are one purely cubic form (β-SiC) and two hexagonal forms that actually have some cubic symmetry (α-SiC). These three polytypes are shown in Figure 1.2. The cubic form has the designation 3C-SiC, where the 3 delineates that 3 bilayers of Si–C are needed to form the basic structure and the C indicates that the crystal form is cubic. The hexagonal forms are 4H-SiC and 6H-SiC, where the 4 and 6 delineate that 4 and 6 bilayers are needed, while the H indicates that the crystal form is hexagonal. While interesting in their own right, these various forms of SiC actually have varying application, where the dominant power electronic device crystal of choice is 4H-SiC because of it having the highest bandgap (3.2 eV), while 6H-SiC is ideally suited for solid-state lighting (LEDs), as its lattice constant is close to the GaN family of alloys used in advanced LEDs that have enabled DVD and blue ray technology, not to mention the solid-state lighting revolution that is currently leading to dramatic reductions in power consumption worldwide. ¹ A comparison of the properties of SiC relative to Si is shown in Table 1.1 for reference.

¹< http://www.forbes.com/2008/02/27/incandescent-led-cfl-pf-guru_in_mm_0227energy_inl.html> (accessed 08.05.11)

1.3. Silicon Carbide Material Growth and Processing

There is a long history of how to grow, process, and characterize SiC materials—the reader is referred to several of the excellent references if further details are desired [13] and [14]. For the purpose of this book, it is sufficient to provide an overview of the technology as it pertains to future biomedical devices; hence, a simple discussion follows with sufficient references to fill in the details. We will first review how bulk hexagonal crystals of SiC are grown and, more importantly, what the state-of-the-art is and what the key characteristics of these commercially available substrates are. Next the growth and synthesis of thin films, starting with homoepitaxy on hexagonal substrates, followed by heteroepitaxy on Si substrates, and finally polycrystalline growth on various surfaces will be presented. One of the great benefits of SiC is that it can be deposited in amorphous SiC ( a-Sic) form at lower temperatures than for single-crystal film growth. This technology will be reviewed in this chapter and the final section will be an introduction to how SiC can be micromachined, and how this points to the potential of SiC as an excellent bioMEMS material.

1.3.1. Bulk Growth

Single-crystal substrates of SiC have been in commercial production for more than two decades, starting with Cree, Inc.’s first commercial 6H-SiC wafers, which were 25 mm in diameter in 1990. ² Much progress has been made worldwide since then, with both the quality and diameter of the wafers improving over the years; the current commercially available wafers are 100 mm (4 in.) and are available in n-, p-, and intrinsic (very high semi-insulating) forms (Figure 1.3). Several manufacturers around the world sell SiC wafers and the crystal specifications are readily available [15]. In the research laboratory, 150-mm-diameter (6-in.-diameter) wafers of quite high quality have been produced, ³ which bodes well for the economic viability of SiC as an electronics technology.

²< http://www.cree.com/about/milestones.asp> (accessed 24.05.10).

³< http://compoundsemiconductor.net/csc/news-details.php?cat=news&id=19732335> (accessed 08.05.11).

All SiC bulk wafers are grown in a high-temperature (>2,000 °C) furnace that is either gas fed (silicon- and carbon-containing precursors transported in a carrier gas) or solid fed with SiC powder that is sublimated (evaporated) and condenses on a single-crystal SiC seed [4] and [16]. Growth rates are typically 0.1–0.3 mm/h and a typical boule thickness is roughly 25–30 mm. ⁴ Resistivities range from 1×10 ⁵ to 1×10 ⁷Ω cm for semi-insulating (SI) crystals, and with high-temperature CVD (HTVCD) bulk growth resistivities as high as 1×10 ¹¹Ω cm have been reported [5]. The wafers are either cut parallel to the basal plane (i.e. perpendicular to the growth direction) or cut at a slight miscut angle, typically 3.5° and 4.0° for 6H-SiC and 4H-SiC, respectively. This is done to ensure that the epitaxy replicates the proper polytype.

⁴Olle Kordina, Private communication.

1.3.2. Thin Films Growth

Single-crystal SiC films can be grown epitaxially using a number of methods. The preferred method is chemical vapor deposition (CVD) [6], but liquid-phase epitaxy (LPE) [7] and molecular beam epitaxy (MBE) [8] have been also used for some time. The application of high-temperature CVD (HT-CVD), which is used to also grow bulk crystals, has been used to achieve high growth rates [8]. The current state-of-the-art CVD reactors employ what is referred to as a hot-wall design, whereas the growth substrate is surrounded by an actively heated graphite susceptor that allows for very high growth rates (as high at 100 µm/h with good crystal quality typically) [9]. The epitaxy of SiC is an active field of research, with numerous improvements in growth rate, crystal quality, doping control, etc., being made, which is critical for advanced device development. In addition, SiC crystals can be hydrogen polished via a hydrogen etching process that is somewhat dependent on both polytype and surface orientation (on-axis and off-axis) [10]. In addition, hydrogen surface passivation using the same approach has been demonstrated, which has an important role to play in the control of the SiC crystal surface chemical state, particularly when performing surface functionalization [11].

The growth of SiC thin films via homoepitaxy is a relatively straightforward process that involves the use of silicon- and carbon-containing precursor molecules transported to the growth surface via a carrier gas, typically hydrogen. The silicon and carbon precursors have traditionally been silane and propane [12] and more recently chlorine-based silane precursors such as trichlorosilane have been used since the addition of Cl allows for higher growth rates with low Si-cluster defect levels [17]. When growing 3C-SiC, the only cubic polytype, on Si, this heteroepitaxy process typically involves three steps: first hydrogen surface etching is performed to remove any native oxide that may be present, then a buffer layer is formed with the so-called carbonization step, which seeks to bind C to Si dangling bonds to create a first SiC layer, and finally the growth step that involves Si and C atoms delivered in the same way as described above for homoepitaxy [18]. Recently, this process was adapted by several groups to allow for the use of the hot-wall CVD reactor and it was discovered that the removal of the hydrogen etching step and the inclusion of a small amount of silane between the carbonization and growth steps resulted in very high-quality films [19]. The use of this method has resulted in growth rates on the order of 10–30 µm/h, and the addition of chlorine has allowed for nearly double the growth rate in a large-diameter reactor [20] (Figure 1.4).

A new process that has been demonstrated uses a polycrystalline silicon film as a seed layer for poly-SiC growth [21]. While other groups have reported poly-SiC film growth, this work involves the use of an oxide layer whereby the eventual release of poly-SiC MEMS structures can be easily facilitated [22], which will be discussed further in the next chapter. A study of the mechanical properties of both monocrystalline and polycrystalline 3C-SiC films grown on Si substrates was performed by Volinsky and coworkers [23]. The results demonstrate the mechanical durability of SiC, as expected, but also point out a very important property—3C-SiC films are relatively flexible with a Young’s modulus of nearly three times that of Si.

Using a Berkovich indenter, the mechanical properties of thin (~1-µm-thick) 3C-SiC films on Si(100) substrates were studied in our laboratory. Table 1.2 reports the average values of the measured hardness and modulus of elasticity of single-crystal 3C-SiC, polycrystalline 3C-SiC, a 15R-SiC Lely platelet, and Si(100) substrate. At least five indents were performed at each maximum load. A 15R-SiC Lely platelet was used as a comparison since this material is known to have a minimum amount of dislocations (typically dislocation free in the center of the platelet). There is a relatively large absolute variation in measured elastic modulus (±50 GPa), not typically observed in the indentation of softer materials. One must consider the relative variation, which is typically on the order of 10%. The reported mechanical properties are for a maximum indentation depth range between 60 and 250 nm, where quartz calibration is reasonable.

Wear tests on the single-crystal 3C-SiC film were also performed in a 3×3-µm area using the low-load transducer at 2 µN normal load and 1 Hz frequency. The objective of this procedure was to determine the wear resistance of the sample by repeated scanning of the poly-3C-SiC surface. After a certain number of wear cycles, the scan area was zoomed out to 5×5 µm to determine the material wear. The film topography of the monocrystalline and polycrystalline 3C-SiC film surface was measured before and after tip-induced wear test, which was performed for 1,045 scans. During this scanning, there was very little or negligible wear, as only 1–2 nm of material depth was removed. This result confirms the high wear resistance of 3C-SiC films necessary for MEMS applications [14].

1.3.3. Amorphous SiC coatings

Amorphous SiC has long been studied and applied as a biomaterial. The amorphous form of SiC can be deposited using different techniques, most of which are familiar to the materials community such as sputtering, pulsed laser deposition, evaporation, among others [23, Chapter 2]. The advantage of a-Sic is that it can be deposited at low temperatures, which allows the coatings of plastics and other low-temperature materials such as polymers [24]. Another important advantage of a-Sic is that it can be electrically insulating, a property that many seek to exploit for numerous bioelectric devices [14]. One of the additional benefits, which is at the same time a challenge, is that line-of-sight coating of surfaces is usually the deposition mode, meaning that coating both sides of a material requires a rotation of the material during a-Sic coating. Issues that impact a-Sic functionality are the morphology of the film (smooth, rough, etc.) and the presence of any pinholes or cracks. In fact, one of the recent uses of a-Sic was in the coating of polyimide-based BMI devices to overcome the problem of polymer swelling inside the brain [25] (Fig. 1.5). Perhaps one of the best-known biomedical uses of a-Sic coatings was the very successful coating of coronary heart stents to reduce the serious problem of clotting in the cardiovascular system [25]. Rzany and Schladach at the University of Erlangen studied a-Sic:H (i.e., hydrogenated a-Sic [26]) as a candidate coating for stainless steel stents, and reported that SiC appears to be an ideal biomaterial due to its electronic properties in a physiological environment. They compared the performance of a-Sic:H-coated and bare stainless steel in vitro and saw significantly improved performance for the SiC-coated steel [25].

1.3.4. SiC Micromachining

The realization of mechanical devices based on microelectronic circuit processing techniques is known as microelectromechanical systems or MEMS. While a full treatment of MEMS is not practical here, a brief summary of the salient features of this technology will allow the reader to have an adequate understanding of the technology. The thermal, mechanical, and chemical strength of the Si–C bond manifests itself in a very high material hardness and Young’s modulus. These values, as measured by Volinsky and coworkers [23], were ~31 and 433 GPa, respectively, for 1-µm-thick monocrystalline 3C-SiC films grown on Si(100) substrates. Similar measurements made on polycrystalline 3C-SiC (i.e., poly-SiC) films of the same thickness and grown on the same substrate were comparable with measured values of ~33 and 457 GPa, respectively. For comparison purposes, the corresponding values for Si(100) in bulk substrate (700-µm-thick) form were only ~12 and ~172 GPa, respectively, or roughly two-thirds of the value for these 3C-SiC films.

In Chapter 10 a more comprehensive discussion of bioMEMS technology based on SiC will be presented. Basically SiC MEMS are fabricated using the same micromachining technology of Si MEMS, so there is not the need to reinvent the processing required to make highly robust SiC MEMS. The basic process flow for SiC MEMS depends on whether one is using bulk SiC or 3C-SiC on Si as the MEMS material. One advantage of using the first option (all-SiC materials) is that there is no problem with differing thermal expansion coefficients during processing, but the cost and difficulty in forming mechanical structures in this highly robust material is an issue [28]. Amorphous, polycrystalline and monocrystalline 3C-SiC on Si MEMS can be fabricated using standard Si MEMS techniques, as shown in Figure 1.6 and allows for a much more simple MEMS process technology, in particular when poly-SiC on oxide release layers are utilized as described in the following chapter. In this instance, the resulting MEMS structures were very straight and displayed a high durability during processing [29]. Subsequent 3C-SiC on Si MEMS devices did, however, display wafer bow issues resulting from the coefficient of thermal expansion mismatch between 3C-SiC and Si (approximately 8%) as well as the lattice mismatch (approximately 20%) between the two materials [30].

Partly to resolve these difficulties, and to achieve a more simple and robust manufacturing process, the development of a poly-SiC on oxide technology has been achieved and preliminary MEMS structures have been realized [22]. These preliminary results will be discussed further in the next chapter following a detailed discussion of how the material system was developed. Perhaps the most interesting aspect of this work will be described in Chapter 10 where SiC bioMEMS technology is discussed in detail by Zorman et al.

1.4. Silicon Carbide as a Biomedical Material

While the durability and physical resilience of SiC are well known and documented, the use of SiC as a biomaterial is less known, thus providing the motivation for this book. While the following chapters will provide a detailed discussion on this important subject, at this stage it is useful to review some of the important biomedical devices that have been reported and that use SiC materials. Indeed, SiC has been used in virtually every part of the human body, from a durable coating for bone prosthetics [32] and in dental applications [33], which cover the mechanical/structural biomedical use of SiC, to coatings for BMI devices [29], myocardial heart probes [34] and finally nonfouling coatings for coronary heart stents [35]. A plethora of sensors have been reported, and at this point it is sufficient to review the literature for a sampling of this important work [36]. In all of these instances, SiC materials were in amorphous, bulk crystal, or thin-film (monocrystalline or polycrystalline) form. Thus, in order for the medical community to make best use of this very impressive material, it is incumbent that we begin our discussion of SiC biotechnology with a review of how the various SiC materials are formed and processed into useful devices (some examples are shown in Figure 1.7).

1.5. Summary

In this chapter, we have introduced SiC as a robust and highly useful material for biomedical devices and applications. A review of the basic material structure was made followed by the various forms of SiC that are in use today, and finally the many ways that SiC materials are grown/synthesized/formed. A fast introduction to SiC bioMEMS was made, followed by a quick review of important SiC biomedical devices that have been reported in the literature. On the basis of this introduction, the reader should be able to continue reading the next chapters in this book with a feeling of the overall SiC biotechnology landscape and thus gain in-depth and comprehensive information on why SiC is ideally poised to lead the way to the development of the next generation of biomedical devices, especially for long-term chronic implantation applications. We hope you will enjoy the following discussion as much as we enjoyed putting it together. In fact, once completed this book has motivated us even more to accelerate the development and incorporation of SiC in advanced next generation biomedical devices—a conclusion that we hope and believe you will share after reading this book.

Acknowledgments

I thank all the former and present members of my research group, the USF SiC Group, for their hard work and dedication that led to the research that forms the underpinning of this chapter and book. Specific members stand out, in particular the bio-SiC team of Dr. Camilla Coletti, Dr. Norelli Schettini, and Dr. Christopher Frewin, without whom this work would not have progressed to this level. I am indebted to them as well as Dr. Christopher Locke for providing most of the SiC materials used during the research disclosed in this book. I also thank all of my research sponsors, in particular Dr. Colin Wood, formerly of the ONR, who had the vision to encourage me to move from SiC electronic materials to SiC biomaterials; Bruce Geil of the Army Research Laboratory for providing initial 3C-SiC on Si MEMS funding; the University of South Florida that has made numerous and critical funding available through the Florida Center of Excellence BiTT (Seed grant), College of Engineering interdisciplinary research grant, which was generously matched by the College of Medicine’s Department of Molecular Pharmacology and Physiology, where I have a joint appointment, and the USF NeuroScience Collaborative for the most recent research grant to develop 3C-SiC BMI devices. Finally, many colleagues have been instrumental to this work, with the most important being Prof. Andrew Hoff who has stood by me during this transition to biotechnology and provided much of my inspiration (and took the time to read this manuscript!), Dr. Mark Jaroszeski for supporting several of my students in their in vitro research, and finally Dr. Edwin Weeber for his support in my joint appointment in his department and for his fruitful and engaging collaboration in neuroscience.

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Chapter 2. SiC Films and Coatings

Amorphous, Polycrystalline, and Single Crystal Forms

C.W. Locke*, A. Severino†, F. La Via†, M. Reyes*, J. Register* and S.E. Saddow*‡

*Department of Electrical Engineering, University of South Florida, Tampa, FL 33620, USA

†CNR-IMM, Stradale Primosole 50, 95121, Catania, Italy

‡Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, USA

Silicon carbide is a semiconductor material with ceramic-like properties and can be formed in amorphous, polycrystalline, and single crystal forms. SiC single crystals form various polytypes with hexagonal forms, 4H-SiC and 6H-SiC, grown in bulk form for wafer production, and the only cubic form, 3C-SiC, grown via thin film deposition. In this chapter, a review of methods to synthesize all three forms of SiC is presented along with their respective properties which impact their use in biological systems. Several challenges exist that make the growth of high quality, single-crystal silicon carbide films difficult. Fortunately, SiC’s superior material properties, which make it beneficial for use as a material in biological systems, also appear to be present in the easier-to-deposit amorphous and polycrystalline forms. Chemical vapor deposition and sputtering