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Carbon containing materials, such as graphene, carbon-nanotubes (CNT), and graphene oxide, have gained prominence as possible electrodes in implantable neural interfaces due to their excellent conductive properties. While carbon is a promising electrochemical interface, many fabrication processes are difficult to perform, leading to issues with large scale device production and overall repeatability. Here we demonstrate that carbon electrodes and traces constructed from pyrolyzed-photoresist-film (PPF) when combined with amorphous silicon carbide (a-SiC) insulation could be fabricated with repeatable processes which use tools easily available in most semiconductor facilities. Directly forming PPF on a-SiC simplified the fabrication process which eliminates noble metal evaporation/sputtering and lift-off processes on small features. PPF electrodes in oxygenated phosphate buffered solution at pH 7.4 demonstrated excellent electrochemical charge storage capacity (CSC) of 14.16 C/cm2, an impedance of 24.8 ± 0.4 kΩ, and phase angle of −35.9 ± 0.6° at 1 kHz with a 1.9 kµm2 recording site area.

Carbon containing materials, such as graphene, carbon-nanotubes (CNT), and graphene oxide, have gained prominence as possible electrodes in implantable neural interfaces due to their excellent conductive properties. While carbon is a promising electrochemical interface, many fabrication processes are difficult to perform, leading to issues with large scale device production and overall repeatability. Here we demonstrate that carbon electrodes and traces constructed from pyrolyzed-photoresist-film (PPF) when combined with amorphous silicon carbide (a-SiC) insulation could be fabricated with repeatable processes which use tools easily available in most semiconductor facilities. Directly forming PPF on a-SiC simplified the fabrication process which eliminates noble metal evaporation/sputtering and lift-off processes on small features. PPF electrodes in oxygenated phosphate buffered solution at pH 7.4 demonstrated excellent electrochemical charge storage capacity (CSC) of 14.16 C/cm2, an impedance of 24.8 ± 0.4 kΩ, and phase angle of −35.9 ± 0.6° at 1 kHz with a 1.9 kµm2 recording site area.

Implantable neural interfaces (INI) have gained significant interest since the 1970s. However, the materials currently utilized for neural interfaces suffer from limitations such as degradation, induce a foreign body response, and experience a loss of target neurons in close proximity. Therefore, the development of new implantable device materials for biomedical applications continues to be an important direction of research and development. Carbon-based nanomaterials are promising candidates and also interesting since carbon has many allotropes with different structures and properties, many of which have also been developed for biomedical devices. Moreover, many carbon allotropes have excellent electrical conductivity and mechanical properties. In this framework, the biocompatibility of graphene, carbon nanotubes, and pyrolyzed-photoresist films, which are three very promising carbon-based nanomaterials (CBN), will be discussed. The neural probe fabricated solely using amorphous silicon carbide as support and pyrolyzed photoresist film (PPF) will be presented as this system represents a highly robust, thin, and flexible neural interface using well-known neurocompatible materials.

An essential method to investigate neuromodulation effects of an invasive neural interface (INI) is magnetic resonance imaging (MRI). Presently, MRI imaging of patients with neural implants is highly restricted in high field MRI (e.g., 3 T and higher) due to patient safety concerns. This results in lower resolution MRI images and, consequently, degrades the efficacy of MRI imaging for diagnostic purposes in these patients. Cubic silicon carbide (3C-SiC) is a biocompatible wide-band-gap semiconductor with a high thermal conductivity and magnetic susceptibility compatible with brain tissue. It also has modifiable electrical conductivity through doping level control. These properties can improve the MRI compliance of 3C-SiC INIs, specifically in high field MRI scanning. In this work, the MRI compliance of epitaxial SiC films grown on various Si wafers, used to implement a monolithic neural implant (all-SiC), was studied. Via finite element method (FEM) and Fourier-based simulations, the specific absorption rate (SAR), induced heating, and image artifacts caused by the portion of the implant within a brain tissue phantom located in a 7 T small animal MRI machine were estimated and measured. The specific goal was to compare implant materials, thus, the effect of leads outside the tissue was not considered. The results of the simulations were validated via phantom experiments in the same 7 T MRI system. The simulation and experimental results revealed that free-standing 3C-SiC films had little to no image artifacts compared to silicon and platinum reference materials inside the MRI at 7 T. In addition, FEM simulations predicted an ~30% SAR reduction for 3C-SiC compared to Pt. These initial simulations and experiments indicate an all-SiC INI may effectively reduce MRI induced heating and image artifacts in high field MRI. In order to evaluate the MRI safety of a closed-loop, fully functional all-SiC INI as per ISO/TS 10974:2018 standard, additional research and development is being conducted and will be reported at a later date.

Objectives Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational, and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume which may improve selectivity of therapeutic stimuli. Current microelectrode technology is associated with chronic tissue response which limits utility of these devices for neural recording and stimulation. One approach for addressing the tissue response problem may be to reduce physical dimensions of the device. "Thinking small" is a trend for the electronics industry, and for implantable neural interfaces, the result may be a device that can evade the foreign body response. Materials and methods This review paper surveys our current understanding pertaining to the relationship between implant size and tissue response and the state-of-the-art in ultrasmall microelectrodes. A comprehensive literature search was performed using PubMed, Web of Science (Clarivate Analytics), and Google Scholar. Results The literature review shows recent efforts to create microelectrodes that are extremely thin appear to reduce or even eliminate the chronic tissue response. With high charge capacity coatings, ultramicroelectrodes fabricated from emerging polymers, and amorphous silicon carbide appear promising for neurostimulation applications. Conclusion We envision the emergence of robust and manufacturable ultramicroelectrodes that leverage advanced materials where the small cross-sectional geometry enables compliance within tissue. Nevertheless, future testing under in vivo conditions is particularly important for assessing the stability of thin film devices under chronic stimulation.

Thiol-ene/acrylate-based shape memory polymers (SMPs) with tunable mechanical and thermomechanical properties are promising substrate materials for flexible electronics applications. These UV-curable polymer compositions can easily be polymerized onto pre-fabricated electronic components and can be molded into desired geometries to provide a shape-changing behavior or a tunable softness. Alternatively, SMPs may be prepared as a flat substrate, and electronic circuitry may be built directly on top by thin film processing technologies. Whichever way the final structure is produced, the operation of electronic circuits will be influenced by the electrical and mechanical properties of the underlying (and sometimes also encapsulating) SMP substrate. Here, we present electronic properties, such as permittivity and resistivity of a typical SMP composition that has a low glass transition temperature (between 40 and 60 &deg, C dependent on the curing process) in different thermomechanical states of polymer. We fabricated parallel plate capacitors from a previously reported SMP composition (fully softening (FS)-SMP) using two different curing processes, and then we determined the electrical properties of relative permittivity and resistivity below and above the glass transition temperature. Our data shows that the curing process influenced the electrical permittivity, but not the electrical resistivity. Corona-Kelvin metrology evaluated the quality of the surface of FS-SMP spun on the wafer. Overall, FS-SMP demonstrates resistivity appropriate for use as an insulating material.

The intracortical neural interface (INI) could be a key component of brain machine interfaces (BMI), devices which offer the possibility of restored physiological neurological functionality for patients suffering from severe trauma to the central or peripheral nervous system. Unfortunately the main components of the INI, microelectrodes, have not shown appropriate long-term reliability due to multiple biological, material, and mechanical issues. Silicon carbide (SiC) is a semiconductor that is completely chemically inert within the physiological environment and can be micromachined using the same methods as with Si microdevices. We are proposing that a SiC material system may provide the improved longevity and reliability for INI devices. The design, fabrication, and preliminary electrical and electrochemical testing of an all-SiC prototype microelectrode array based on 4H-SiC, with an amorphous silicon carbide (a-SiC) insulator, is described. The fabrication of the planar microelectrode was performed utilizing a series of conventional micromachining steps. Preliminary electrochemical data are presented which show that these prototype electrodes display suitable performance.

The intracortical neural interface (INI) is a key component of brain machine interfaces (BMI) which offer the possibility to restore functions lost by patients due to severe trauma to the central or peripheral nervous system. Unfortunately today’s neural electrodes suffer from a variety of design flaws, mainly the use of non-biocompatible materials based on Si or W with polymer coatings to mask the underlying material. Silicon carbide (SiC) is a semiconductor that has been proven to be highly biocompatible, and this chemically inert, physically robust material system may provide the longevity and reliability needed for the INI community. The design, fabrication, and preliminary testing of a prototype all-SiC planar microelectrode array based on 4H-SiC with an amorphous silicon carbide (a-SiC) insulator is described. The fabrication of the planar microelectrode was performed utilizing a series of conventional micromachining steps. Preliminary data is presented which shows a proof of concept for an all-SiC microelectrode device.

Silicon carbide is a well-known wide-band gap semiconductor traditionally used in power electronics and solid-state lighting due to its extremely low intrinsic carrier concentration and high thermal conductivity. What is only recently being discovered is that it possesses excellent compatibility within the biological world. Since publication of the first edition of Silicon Carbide Biotechnology: A Biocompatible Semiconductor for Advanced Biomedical Devices and Applications five years ago [1], significant progress has been made on numerous research and development fronts. In this paper three very promising developments are briefly highlighted – progress towards the realization of a continuous glucose monitoring system, implantable neural interfaces made from free-standing 3C-SiC, and a custom-made low-power ‘wireless capable’ four channel neural recording chip for brain-machine interface applications.

Microelectrode arrays that consistently and reliably record and stimulate neural activity under conditions of chronic implantation have so far eluded the neural interface community due to failures attributed to both biotic and abiotic mechanisms. Arrays with transverse dimensions of 10 &micro, m or below are thought to minimize the inflammatory response, however, the reduction of implant thickness also decreases buckling thresholds for materials with low Young&rsquo, s modulus. While these issues have been overcome using stiffer, thicker materials as transport shuttles during implantation, the acute damage from the use of shuttles may generate many other biotic complications. Amorphous silicon carbide (a-SiC) provides excellent electrical insulation and a large Young&rsquo, s modulus, allowing the fabrication of ultrasmall arrays with increased resistance to buckling. Prototype a-SiC intracortical implants were fabricated containing 8 - 16 single shanks which had critical thicknesses of either 4 &micro, m or 6 &micro, m. The 6 &micro, m thick a-SiC shanks could penetrate rat cortex without an insertion aid. Single unit recordings from SIROF-coated arrays implanted without any structural support are presented. This work demonstrates that a-SiC can provide an excellent mechanical platform for devices that penetrate cortical tissue while maintaining a critical thickness less than 10 &micro, m.

Current intracortical probe technology is limited in clinical implementation due to the short functional lifetime of implanted devices. Devices often fail several months to years post-implantation, likely due to the chronic immune response characterized by glial scarring and neuronal dieback. It has been demonstrated that this neuroinflammatory response is influenced by the mechanical mismatch between stiff devices and the soft brain tissue, spurring interest in the use of softer polymer materials for probe encapsulation. Here, we demonstrate stable recordings and electrochemical properties obtained from fully encapsulated shape memory polymer (SMP) intracortical electrodes implanted in the rat motor cortex for 13 weeks. SMPs are a class of material that exhibit modulus changes when exposed to specific conditions. The formulation used in these devices softens by an order of magnitude after implantation compared to its dry, room-temperature modulus of ~2 GPa.

Intracortical neural interfaces (INI) have made impressive progress in recent years but still display questionable long-term reliability. Here, we report on the development and characterization of highly resilient monolithic silicon carbide (SiC) neural devices. SiC is a physically robust, biocompatible, and chemically inert semiconductor. The device support was micromachined from p-type SiC with conductors created from n-type SiC, simultaneously providing electrical isolation through the resulting p-n junction. Electrodes possessed geometric surface area (GSA) varying from 496 to 500 K &mu, m2. Electrical characterization showed high-performance p-n diode behavior, with typical turn-on voltages of ~2.3 V and reverse bias leakage below 1 nArms. Current leakage between adjacent electrodes was ~7.5 nArms over a voltage range of &minus, 50 V to 50 V. The devices interacted electrochemically with a purely capacitive relationship at frequencies less than 10 kHz. Electrode impedance ranged from 675 &plusmn, 130 kΩ (GSA = 496 &micro, m2) to 46.5 &plusmn, 4.80 kΩ (GSA = 500 K &micro, m2). Since the all-SiC devices rely on the integration of only robust and highly compatible SiC material, they offer a promising solution to probe delamination and biological rejection associated with the use of multiple materials used in many current INI devices.

Silicon has been used as one of the primary substrates for micro-machined intra-cortical neural implants (INI). The presence of various ions in the extracellular environment combined with cellular biological activity establishes a harsh, corrosive environment in the brain for INI, and as such, a long-term implant’s construction materials must be able to resist these environments. We have examined if environmental components could contribute to changes in the material, which in turn may be a contributing factor to the decreased long-term reliability in INI optimal neural recordings, which have prevented clinical use these devices for the last 4 decades. We tested silicon in artificial cerebrospinal fluid (ACSF), Dulbecco's modified eagle medium (DMEM), and H4 cells cultured within DMEM for 96 hours at 37°C as three various physiological environments to investigate the material degradation. We have observed that Si samples immersed in only DMEM and ACSF showed very minor surface alterations. However, Si samples cultured with H4 cells exhibited a large change in surface roughness from 0.24±0.04 nm to 4.85 nm. The scanning electron microscope (SEM) micrographs showed the presence of pyramid shaped pits. Further characterization with atomic force microscope (AFM) verified this result and quantified the severe changes in the surface roughness of these samples. At this initial stage of the investigation, we are endeavoring to identify the cause of these changes to the Si surface, but based on our observations, we believe that the increased corrosion could be result of chemical products released into the surrounding environment by the cells.

One of the main issues with micron-sized intracortical neural interfaces (INIs) is their long-term reliability, with one major factor stemming from the material failure caused by the heterogeneous integration of multiple materials used to realize the implant. Single crystalline cubic silicon carbide (3C-SiC) is a semiconductor material that has been long recognized for its mechanical robustness and chemical inertness. It has the benefit of demonstrated biocompatibility, which makes it a promising candidate for chronically-stable, implantable INIs. Here, we report on the fabrication and initial electrochemical characterization of a nearly monolithic, Michigan-style 3C-SiC microelectrode array (MEA) probe. The probe consists of a single 5 mm-long shank with 16 electrode sites. An ~8 µm-thick p-type 3C-SiC epilayer was grown on a silicon-on-insulator (SOI) wafer, which was followed by a ~2 µm-thick epilayer of heavily n-type (n+) 3C-SiC in order to form conductive traces and the electrode sites. Diodes formed between the p and n+ layers provided substrate isolation between the channels. A thin layer of amorphous silicon carbide (a-SiC) was deposited via plasma-enhanced chemical vapor deposition (PECVD) to insulate the surface of the probe from the external environment. Forming the probes on a SOI wafer supported the ease of probe removal from the handle wafer by simple immersion in HF, thus aiding in the manufacturability of the probes. Free-standing probes and planar single-ended test microelectrodes were fabricated from the same 3C-SiC epiwafers. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were performed on test microelectrodes with an area of 491 µm2 in phosphate buffered saline (PBS) solution. The measurements showed an impedance magnitude of 165 kΩ ± 14.7 kΩ (mean ± standard deviation) at 1 kHz, anodic charge storage capacity (CSC) of 15.4 ± 1.46 mC/cm2, and a cathodic CSC of 15.2 ± 1.03 mC/cm2. Current-voltage tests were conducted to characterize the p-n diode, n-p-n junction isolation, and leakage currents. The turn-on voltage was determined to be on the order of ~1.4 V and the leakage current was less than 8 μArms. This all-SiC neural probe realizes nearly monolithic integration of device components to provide a likely neurocompatible INI that should mitigate long-term reliability issues associated with chronic implantation.

Fabrication of flexible and free-standing graphene-fiber- (GF-) based microelectrode arrays with a thin platinum coating, acting as a current collector, results in a structure with low impedance, high surface area, and excellent electrochemical properties. This modification results in a strong synergistic effect between these two constituents leading to a robust and superior hybrid material with better performance than either graphene electrodes or Pt electrodes. The low impedance and porous structure of the GF results in an unrivalled charge injection capacity of 10.34 mC cm-2 with the ability to record and detect neuronal activity. Furthermore, the thin Pt layer transfers the collected signals along the microelectrode efficiently. In vivo studies show that microelectrodes implanted in the rat cerebral cortex can detect neuronal activity with remarkably high signal-to-noise ratio (SNR) of 9.2 dB in an area as small as an individual neuron.

We demonstrate the functionalization of n-type (100) and (111) 3C-SiC surfaces with organosilanes. Self-assembled monolayers (SAMs) of amino-propyldiethoxymethylsilane (APDEMS) and octadecyltrimethoxysilane (ODTMS) are formed via wet chemical processing techniques. Their structural, chemical, and electrical properties are investigated using static water contact angle measurements, atomic force microscopy, and X-ray photoelectron spectroscopy, revealing that the organic layers are smooth and densely packed. Furthermore, combined contact potential difference and surface photovoltage measurements demonstrate that the heterostructure functionality and surface potential can be tuned by utilizing different organosilane precursor molecules. Molecular dipoles are observed to significantly affect the work functions of the modified surfaces. Furthermore, the magnitude of the surface band bending is reduced following reaction of the hydroxylated surfaces with organosilanes, indicating that partial passivation of electrically active surface states is achieved. Micropatterning of organic layers is demonstrated by lithographically defined oxidation of organosilane-derived monolayers in an oxygen plasma, followed by visualization of resulting changes of the local wettability, as well as fluorescence microscopy following immobilization of fluorescently labeled BSA protein.

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.

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.

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.

Crystalline silicon carbide (SiC) and silicon (Si) biocompatibility was evaluated in vitro by directly culturing three skin and connective tissue cell lines, two immortalized neural cell lines, and platelet-rich plasma (PRP) on these semiconducting substrates. The in vivo biocompatibility was then evaluated via implantation of 3C-SiC and Si shanks into a C57/BL6 wild type mouse. The in vivo results, while preliminary, were outstanding with Si being almost completely enveloped with activated microglia and astrocytes, indicating a severe immune system response, while the 3C-SiC film was virtually untouched. The in vitro experiments were performed specifically for the three adopted SiC polytypes, namely 3C-, 4H- and 6H-SiC, and the results were compared to those obtained for Si crystals. Cell proliferation and adhesion quality were studied using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays and fluorescent microscopy. The neural cells were studied via atomic force microscopy (AFM) which was used to quantify filopodia and lamellipodia extensions on the surface of the tested materials. Fluorescent microscopy was used to assess platelet adhesion to the semiconductor surfaces where significantly lower values of platelet adhesion to 3C-SiC was observed compared to Si. The reported results show good indicators that SiC is indeed a more biocompatible substrate than Si. While there were some differences among the degree of biocompatibility of the various SiC polytypes tested, SiC appears to be a highly biocompatible material in vitro that is also somewhat hemocompatible. This extremely intriguing result appears to put SiC into a unique class of materials that is both bio- and hemo-compatible and is, to the best of our knowledge, the only semiconductor with this property.

An ever-increasing demand for biocompatible materials provides motivation for the development of advanced materials for challenging applications ranging from disease detection to organ function restoration. Carbon-based materials are considered promising candidates because they combine good biocompatibility with high chemical resistance. In this work we present an initial assessment of the biocompatibility of epitaxial graphene on 6H-SiC(0001). We have analyzed the interaction of HaCaT (human keratinocyte) cells on epitaxial graphene and compared it with that on bare 6H-SiC(0001). We have found that for both graphene and 6H-SiC there is evidence of cell-cell and cell substrate interaction which is normally an indication of the biocompatibility of the material.

Growth of 3C-SiC on (100) Si has been performed via chemical vapor deposition under two pressure regimes (low and atmospheric pressure) in the early stage of growth. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) have been conducted to study the initial stage of growth while X-ray diffractometry (XRD) and TEM have been used to analyze thicker films and to detect and quantify defects, resulting in a comprehensive and detailed investigation of 3C-SiC structural defects. We have found out that the secondary nucleation of 3C-SiC island growth leads to a higher defect generation rate and, at the same time, to a more effective defect elimination rate. Hillocks found on the surface of thin samples grown under reduced pressure conditions are more pronounced as they seem to be a consequence of twins created in the early stage of growth. Finally, a different initial nucleation density (in the two pressure regimes considered) does not strongly influence stacking fault and microtwin density when growth of thick 3C-SiC films is performed. A very strong influence is indeed observed when 3C-SiC thickness is limited to hundreds of nanometers.

The growth of highly oriented 3C–SiC directly on an oxide release layer, composed of a 20-nm-thick poly-Si seed layer and a 550-nm-thick thermally deposited oxide on a (1 1 1)Si substrate, was investigated as an alternative to using silicon-on-insulator (SOI) substrates for freestanding SiC films for MEMS applications. The resulting SiC film was characterized by X-ray diffraction (XRD) with the X-ray rocking curve of the (1 1 1) diffraction peak displaying a FWHM of 0.115° (414″), which was better than that for 3C–SiC films grown directly on (1 1 1)Si during the same deposition process. However, the XRD peak amplitude for the 3C–SiC film on the poly-Si seed layer was much less than for the (1 1 1)Si control substrate, due to slight in-plane misorientations in the film. Surprisingly, the film was solely composed of (1 1 1) 3C–SiC grains and possessed no 3C–SiC grains oriented along the 〈3 1 1〉 and 〈1 1 0〉 directions which were the original directions of the poly-Si seed layer. With this new process, MEMS structures such as cantilevers and membranes can be easily released leaving behind high-quality 3C–SiC structures.

Brain machine interface (BMI) devices offer a platform that can be used to assist people with extreme disabilities, such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease. Silicon (Si) has been the material of choice used for the manufacture of BMI devices due to its mechanical strength, its electrical properties and multiple fabrication techniques; however, chronically implanted BMI devices have usually failed within months of implantation due to biocompatibility issues and the fact that Si does not withstand the harsh environment of the body. Single crystal cubic silicon carbide (3C-SiC) and nanocrystalline diamond (NCD) are semiconductor materials that have previously shown good biocompatibility with skin and bone cells. Like Si, these materials have excellent physical characteristics, good electrical properties, but unlike Si, they are chemically inert. We have performed a study to evaluate the general biocompatibility levels of all of these materials through the use of in vitro techniques. H4 human neuroglioma and PC12 rat pheochromocytoma cell lines were used for the study, and polystyrene (PSt) and amorphous glass were used as controls or for morphological comparison. MTT [3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide] assays were performed to determine general cell viability with each substrate and atomic force microscopy (AFM) was used to quantify the general cell morphology on the substrate surface along with the substrate permissiveness to lamellipodia extension. 3C-SiC was the only substrate tested to have good viability and superior lamellipodia permissiveness with both cell lines, while NCD showed a good level of viability with the neural H4 line but a poor viability with the PC12 line and lower permissiveness than 3C-SiC. Explanations pertaining to the performance of each substrate with both cell lines are presented and discussed along with future work that must be performed to further evaluate specific cell reactions on these substrates. Copyright © 2009 John Wiley & Sons, Ltd.

Electron channeling contrast imaging (ECCI) has been utilized to evaluate the surface morphology and crystalline quality of 3C-SiC films grown by chemical vapor deposition (CVD) on (100) and (111) Si substrates. ECCI in this study was performed using an electron backscatter diffraction (EBSD) system equipped with forescatter diode detectors and mounted inside a commercial scanning electron microscope (SEM). This nondestructive method permits direct dislocation imaging through local fluctuations in forescattered electron yield attributable to lattice strain. Coordinated ECCI, SEM, and EBSD analysis of film surfaces allowed correlations between film orientation, surface morphology, and dislocation behavior. Evidence of lateral dislocations parallel to directions and atomic step pinning by dislocations was observed.

Single crystal 3C-SiC films were grown on (100) and (111) Si substrate orientations in order to study the resulting mechanical properties of this material. In addition, poly-crystalline 3C-SiC was also grown on (100)Si so that a comparison with monocrystaline 3C-SiC, also grown on (100)Si, could be made. The mechanical properties of single crystal and polycrystalline 3C-SiC films grown on Si substrates were measured by means of nanoindentation using a Berkovich diamond tip. These results indicate that polycrystalline SiC thin films are attractive for MEMS applications when compared with the single crystal 3C-SiC, which is promising since growing single crystal 3C-SiC films is more challenging. MEMS cantilevers and membranes fabricated from a 2 µm thick single crystal 3C-SiC grown on (100)Si under similar conditions resulted in a small degree of bow with only 9 µm of deflection for a cantilever of 700 µm length with an estimated tensile film stress of 300 MPa. Single crystal 3C-SiC films on (111)Si substrates have the highest elastic and plastic properties, although due to high residual stress they tend to crack and delaminate.

A comprehensive study on the hydrogen etching of numerous SiC polytype surfaces and orientations has been performed in a hot wall CVD reactor under both atmospheric and low pressure conditions. The polytypes studied were 4H and 6H-SiC as well as 3C-SiC grown on Si substrates. For the hexagonal polytypes the wafer surface orientation was both on- and off-axis, i.e. C and Si face. The investigation includes the influence of the prior surface polishing method on the required etching process parameters. 3C-SiC was also studied grown in both the (100) and (111) orientations. After etching, the samples were analyzed via atomic force microscopy (AFM) to determine the surface morphology and the height of the steps formed. For all cases the process conditions necessary to realize a well-ordered surface consisting of unit cell and sub-unit cell height steps were determined. The results of these experiments are summarized and samples of the corresponding AFM analysis presented.

A novel method for growing highly-crystalline 3C-SiC on an oxide release layer via a poly-Si seed layer is reported. Silicon carbide’s potential role as a ubiquitous material for MEMS fabrication lies in its dual role as an electronic and mechanical material. Unfortunately, due to residual stresses and crystal defects stemming from the large lattice constant mismatch and the thermal expansion coefficient difference between SiC and Si, the use of SiC in Si-based MEMS fabrication techniques has been very limited. The growth of 3C-SiC on a poly-Si seed layer deposited on oxide on (111)Si substrates (i.e., p-Si/ SiO2/(111)Si) provides an alternative fabrication method to expensive, traditional SOI bonding techniques for producing free-standing 3C-SiC MEMS structures. 3C-SiC grown with a poly-Si seed layer on SiO2 should experience reduced residual stress and far fewer defects due to the compliance of the SiO2 layer. Although poly-Si is utilized as a seed layer in this process, a well-ordered monocrystalline 3C-SiC layer was achieved and the process and film properties reported.

In this work a comparison between atmospheric pressure (AP) and low pressure (LP) carbonization as the first step in the growth process of 3C-SiC on Si substrates is presented. Three different Si substrate orientations have been studied and compared. Characterization analysis has been performed by Atomic Force Microscopy (AFM), X-ray Diffraction Spectroscopy (XRD) and Transmission Electron Microscopy (TEM). XRD and AFM analysis show a lower roughness and a better quality for LPCVD carbonized samples. Substrate orientation plays an important role both in the generation as well as in the effect of such defects in the subsequent growth process, leading to a rougher SiC surface for growth on (110) Si while micro-twin effects are limited for growth on (111) Si, resulting in an extremely flat film.

Novel materials are needed for intracortical neural implants (INI) to extend their reliability and functionality beyond a few years. Cubic silicon carbide (3C-SiC) is a chemically inert, physically robust semiconductor that has shown, through extensive in vitro testing, a high biocompatibility with neural cells. Recently we have shown that 3C-SiC does not attract a negative immune response from microglia in vivo, but the implants size did not allow adequate investigation of tissue response [1]. We produced a passive implant to test the in vivo tissue reaction of C57BL/6J mice to 3C-SiC and compare to our positive control of silicon (Si). Dual, triangular shanks were fabricated from each material and combined into a single device which was then implanted simultaneously into three C57BL/6J mouse brains for 35 days. The mice were perfused with 4% paraformaldehyde and the brains treated using immunohistochemistry. Fluorescence microscopy indicated that Si produced the expected increased inflammatory response from both microglia/ macrophage and astrocyte cells, whereas 3C-SiC shows minimal inflammatory reaction from these glial cells. Si also created tissue voids larger than the implants themselves whereas 3C-SiC showed minimal voids and even still had neuronal processes in contact with the implant. Our conclusion is that 3C-SiC shows great potential for use within the neural environment and should be fashioned into active INI to evaluate signal quality over time.

Neural interfaces aim to restore neurological function lost during disease or injury. Novel implantable neural interfaces increasingly capitalize on novel materials to achieve microscale coupling with the nervous system. Like any biomedical device, neural interfaces should consist of materials that exhibit biocompatibility in accordance with the international standard ISO10993-5, which describes in vitro testing involving fibroblasts where cytotoxicity serves as the main endpoint. In the present study, we examine the utility of living neuronal networks as functional assays for in vitro material biocompatibility, particularly for materials that comprise implantable neural interfaces. Embryonic mouse cortical tissue was cultured to form functional networks where spontaneous action potentials, or spikes, can be monitored non-invasively using a substrate-integrated microelectrode array. Taking advantage of such a platform, we exposed established positive and negative control materials to the neuronal networks in a consistent method with ISO 10993-5 guidance. Exposure to the negative controls, gold and polyethylene, did not significantly change the neuronal activity whereas the positive controls, copper and polyvinyl chloride (PVC), resulted in reduction of network spike rate. We also compared the functional assay with an established cytotoxicity measure using L929 fibroblast cells. Our findings indicate that neuronal networks exhibit enhanced sensitivity to positive control materials. In addition, we assessed functional neurotoxicity of tungsten, a common microelectrode material, and two conducting polymer formulations that have been used to modify microelectrode properties for in vivo recording and stimulation. These data suggest that cultured neuronal networks are a useful platform for evaluating the functional toxicity of materials intended for implantation in the nervous system.

A fundamental study on the sterilization of thiol-ene/acrylate polymers for biomedical applications is presented. These polymer networks belong to the emerging field of shape memory polymers and have the capability to undergo softening after insertion into the body. The impact of various sterilization methods, such as radiation, steam, and ethylene oxide on the thermomechanical properties of these stimuli responsive materials is investigated. Time and temperature dependent thermomechanical properties of sterilized and nonsterilized samples are determined by means of dynamic mechanical analysis in an aqueous environment to allow testing of polymers in phosphate buffered saline. The findings show that ethylene oxide sterilization is appropriate for thiol-ene and thiol-ene/acrylate based shape memory polymers. This method does not adversely affect thermomechanical and self-softening properties and after sterilization, endotoxin levels remain below the thresholds recommended in the FDA Guidance.

Although many current biomedical devices have been able to assist millions of people, there are still many critical needs to be addressed. Many individuals need constant diagnostics, controlled and targeted delivery of drugs, or even the replacement of motor and sensory functions. Many of the current biomedical systems that perform these functions are large, non-transportable, cumbersome or, more importantly, they cannot be in contact with the body for extended amounts of time. One solution is to utilize micro-electromechanical machines, or MEMS. With the same processes used to create computer chips, we can now generate a variety of micron sized machines which are designed to deliver drugs, detect physiological changes, and even electrically interface with cells. These micron to nanometer sized devices can potentially be implanted into the body with minimal invasiveness. There is, however, a very important issue which in turn needs to be addressed before their widespread clinical use can come to realization.

The central nervous system (CNS) does not readily regenerate damage from trauma or disease, but instead a glial scar seals off the damaged area from the rest of the brain. The glial scaring process leaves many people with reduced or even complete loss of motor, sensory, or learning functionality. It has long been established that we can interact with neurons and muscles using electrical signals. This chapter is dedicated to the brain–machine interface (BMI), and how SiC has been used in BMI devices to reconnect failed signal paths in the CNS and PNS (peripheral nervous system).