Biomedical devices that function in vivo offer a tremendous promise to improve the quality of life for many who suffer from disease and trauma. The most important consideration for these devices is that they interact with the physiological environment as designed without initiating a deleterious inflammatory response. ISO 10993 outlines the current international guideline for investigating the biocompatibility and hemocompatibility of such devices. We evaluated cubic (3C–SiC) and amorphous silicon carbide (a-SiC) since they comprise a very promising candidate material system for neuroprosthetics. Not only have we confirmed the outstanding in vitro response of 3C–SiC and a-SiC, we have added hemocompatibility data, which indicates that these materials are also hemocompatible. The latter was accomplished using platelet-rich plasma in a flow cell and confirms earlier work in our group using the same methodology but in static mode.

Approved continuous glucose monitoring (CGM) systems require the insertion of a needle-like device inside the body that lasts up to 7 days and also requires several finger prick calibrations per day. This chapter describes an alternative for CGM systems based on the remote sensing of glucose-related changes in an implanted SiC-based antenna sensor. Earlier we demonstrated that a 4H–SiC-based antenna operating at 10 GHz will experience a shift in resonant frequency as a function of change in glucose levels. A shift of 97 and 67 kHz per 1 mg/dL change in blood glucose was observed in blood-mimicking liquid and pig blood, respectively. The antenna has now been redesigned for the industrial, scientific, and medical radio band, suitable for medical applications, and tested in a platform design composed of two additional antennas to enable remote sensing. This radio frequency identification approach does not require contact with patient interstitial fluid, thus solving the short time of use issue with present day implantable CGM sensors. The correlation between the external reflected signals with the variations of shift of the parameters of the implanted antenna are recorded and analyzed to determine patient glucose level in real time.

Since the pioneering work by Coletti et al. in 2006–07, there has been growing evidence that the cubic form of silicon carbide (SiC), 3C–SiC, is both bio- and hemocompatible. In this previous work performed by our group, we relied on protocols reported in journals to establish our in vitro assay methods. Unfortunately, we have reviewed our method and found that it has since proven to have difficulties accurately examining some materials as well as it has shown issues with repeatability. In short, our methods evaluated cellular viability by examining the ability of adherent cells to attach, grow, and proliferate on a device or material’s surface. The International Organization for Standardization (ISO) has created a standard for the testing of biomedical devices incorporating successful methods developed through research. In this chapter, we outline our recent work presenting a strict adherence to ISO 10993-5 cytotoxicity methodologies, namely, the extract and direct contact methods, as well as our own protocol developed combining the two methods. We also examine the use of a colorimetric assay mentioned in ISO 10993, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide), alongside a very powerful, fluorescent assay called LIVE/DEAD®. The MTT assay was found to produce false positives due to chemical reactions between the MTT and many of the tested materials, in particular metallic surfaces. Finally, we reexamine 3C–SiC using the new ISO 10993-based in vitro cytotoxicity methodology and verify that this interesting material is indeed a potentially biocompatible surface, displaying a cellular viability and proliferation nearly equivalent to culture-treated polycarbonate, supported by ISO 10993-verified reaction controls and statistical analysis. This chapter details work which sets the stage for further ISO 10993 in vitro examinations presented in chapter: Study of the Hemocompatibility of 3C–SiC and a-SiC Films Using ISO 10993-4 on amorphous SiC (a-SiC) as well as the hemocompatibility experiments performed using platelet-rich plasma.

This chapter reviews the growth, chemical functionalization, and sensing applications of graphene. Techniques used to modify graphene in order to attach “bioreceptor” molecules, capable of specific and selective detection of target biomarkers, are reviewed. A range of different chemistries are discussed including methods used for exfoliated and solution-based graphene, as well as chemical vapor deposition (CVD) and epitaxial graphene. The suitability of different types of graphene for sensing applications will be discussed. Direct and indirect (using a modification of an adsorbed layer or polymer film on top of the graphene) functionalization techniques will be reviewed. Emphasis is placed on techniques suitable for fabricating devices on a wafer scale, using CVD and epitaxial graphene grown on SiC. Sensor device design and fabrication will be discussed. The effect of functionalization on the electrical transport properties, including carrier type and mobility, will be examined. Issues including characterization of sensor operation, reproducibility, and reliability will all be addressed. There are several advantages of graphene sensors over alternative sensor platforms such as carbon nanotubes or silicon nanowires. The main benefits of graphene for sensing applications will be highlighted in a comparison with other materials. Finally, the range of potential applications from DNA sensors to immunoassays to detection of food toxins will be reviewed.

Implantable neural interfaces offer promise as prosthetic devices that enable communication and control of artificial limbs for individuals suffering from paralysis and amputation. While proof-of-concept recordings from microelectrode arrays (MEAs) have been promising, work in animal models demonstrates that the obtained signals degrade over time until device failure. Amorphous silicon carbide (a-SiC), a robust material that is corrosion resistant, has emerged as an alternative encapsulation layer for biomedical devices. The purpose of this chapter is to discuss mechanisms involved in the degradation of MEA performance, the role of material choice in the tissue response, the biological response of neural tissue to a-SiC both in vitro and in vivo, and the utility of a-SiC as an encapsulant for implantable neural interfaces.

Silicon carbide is a well-known wide-bandgap semiconductor traditionally used in power electronics and solid-state lighting due to its extremely low intrinsic carrier concentration and high thermal conductivity. What is not as well known is its compatibility with the biological world. Since publication of the first edition of Silicon Carbide Biotechnology: A Biocompatible Semiconductor for Advanced Biomedical Devices and Applications 5 years ago, significant progress has been made on numerous research and development fronts. We start this edition by completing the in vitro bio- and hemocompatibility story from the first edition by adding new data on 3C–SiC and adding, for the first time, data on amorphous SiC (a-SiC). This is followed by a chapter devoted to graphene functionalization for biosensor applications. Next, some very interesting works on the use of SiC for biosensors and continuous glucose monitoring are reported. Since the first edition significant progress has been made in the development of SiC for neural implants. a-SiC has been successfully implemented as a robust neural interface coating and 3C–SiC is being advanced as a complete material for implantable neural interfaces. This edition closes with two very comprehensive works on the use of SiC nanowires for use in biotechnology and DNA assays.

This chapter first describes the physical and morphological characteristics of different silicon carbide (SiC) nanostructures, such as SiC nanopillars and Si–SiC core–shell nanowires. These nanostructures are elaborated using two alternative methods: inductively coupled plasma etching and the carburization method. Afterward a technological process to fabricate SiC nanowire field effect transistors (NWFETs) is described. In the second part of the chapter the focus is on the surface modification of the as-grown SiC nanostructures to enable label-free electrical DNA detection. A functionalization process has been developed to covalently graft DNA probes on SiC surfaces. DNA grafting and hybridization have been validated using various characterization techniques: fluorescence microscopy, X-ray photoelectron spectroscopy and atomic force microscopy. Finally, preliminary results on label-free electrical DNA detection using SiC NWFETs are presented. The obtained current evolution showed the specificity, reversibility, stability, and reliability of a SiC NWFET sensor. These results provide the basis for promising sensing devices that fully exploit the excellent SiC properties for advanced sensor applications.

We present an extensive overview of SiC biomedical applications, focusing in particular on SiC-based electrochemical biosensors, a very promising field of recent developments and perspectives. The properties, performance, and potential role of SiC are discussed in comparison with the most successful and popular electrochemically active organic semiconductor, that is, poly(3,4-ethylenedioxythiophene): poly(styrene sulfonic acid) (PEDOT:PSS), the most used in bioelectronics. To this end, the state of the art of SiC-based devices is first outlined, discussing the most advanced applications in medicine, diagnostics, and prosthetics. Then, electrochemical biosensors made of SiC as the active and sensing material are introduced and reviewed in detail. Because of the growing importance of organic electrochemical transistors (OECTs) in the organic bioelectronics arena, a whole section is dedicated to comparing the general features and performance of SiC and OECT sensors based on PEDOT:PSS. Finally, the last section is devoted to the perspective and viability of SiC-based ion-sensitive field effect transistors (ISFET) for the efficient and demanding application of ionic species sensing and offers suggestions on potential sensor architectures.

This chapter presents an overview of the growth and optical properties (Section 10.2) and some in vitro applications of 3C–SiC-based nanowires (NWs). We show the cytocompatibility and the cellular internalization mechanisms of core–shell SiC–SiO2 NWs (Section 10.3), the application of NWs conjugated with an organic photosensitizer for X-ray-excited photodynamic therapy (Section 10.4), and, finally, the characterization of NW substrates in the biological environment following the ISO 10993 standard (Section 10.5). Our results highlight that: (1) such NWs do not elicit cytotoxic activity leading to irreversible cellular damage or death; (2) the hybrid NW–porphyrin nanosystem is validated in view of deep cancer oncotherapy; and (3) NW platforms can be used as a biomimetic biomaterial for cell cultures, providing a biocompatible interface. Experiments with platelet-rich plasma indicate that SiC core–shell NWs induce a higher platelet activation compared to bare SiC NWs, which may be exploited for implantable prosthetic devices.

The potential impact of neurocompatible implantable devices to assist millions who suffer from brain and spinal cord injury or limb loss is tremendous, both in restoring patient health, as well as quality of life. Until now, no known reliable solution to this challenge has been found, with most of the current technology relying on nonneurocompatible materials such as silicon, tungsten, or platinum, and polymer insulators. Silicon carbide (SiC) and, in particular cubic-silicon carbide (3C–SiC), appears to be an ideal material to meet this challenging application: the evidence of bio- and hemocompatibility is increasing; it is a semiconductor that allows for tailored doping profiles and the seamless integration of electronics with the implants; it is highly durable, even within harsh, corrosive environments; and SiC is also an excellent thermal conductor. For the first time, a comprehensive analysis of 3C–SiC for neural device applications has been performed and is reported here. Starting with in vitro data from chapter: Cytotoxicity of 3C–SiC Investigated Through Strict Adherence to ISO 10993 and hemocompatibility data from chapter: Study of the Hemocompatibility of 3C–SiC and a-SiC Films Using ISO 10993-4, we add compelling in vivo biocompatibility data from two animal models to complete the 3C–SiC biological profile. We end by demonstrating advanced probe designs combining 3C–SiC neural probes with fully wireless-capable, application-specific neural recording chips. This chapter encompasses all of the required technology necessary to bring this material system to clinical trial. Additionally, we show that 3C–SiC is compatible within 2T field magnetic resonance imaging (MRI), which, if true for higher field MRI scanners, could revolutionize the way patients can receive diagnosis for advanced neurological disorders.