Technical advance in silico and in vitro development of a new bipolar radiofrequency ablation device for renal denervation.

BACKGROUND: Renal denervation with radiofrequency ablation has become an accepted treatment for drug-resistant hypertension. However, there is a continuing need to develop new catheters for high-accuracy, targeted ablation. We therefore developed a radiofrequency bipolar electrode for controlled, targeted ablation through Joule heating induction between 60 and 100 °C. The bipolar design can easily be assembled into a basket catheter for deployment inside the renal artery. METHODS: Finite element modeling was used to determine the optimum catheter design to deliver a minimum ablation zone of 4 mm (W) × 10 mm (L) × 4 mm (H) within 60 s with a 500 kHz, 60 Vp-p signal, and 3 W maximum. The in silico model was validated with in vitro experiments using a thermochromic phantom tissue prepared with polyacrylamide gel and a thermochromic ink additive that permanently changes from pink to magenta when heated over 60 °C. RESULTS: The in vitro ablation zone closely matched the size and shape of the simulated area. The new electrode design directs the current density towards the artery walls and tissue, reducing unwanted blood temperature increases by focusing energy on the ablation zone. In contrast, the basket catheter design does not block renal flow during renal denervation. CONCLUSIONS: This computational model of radiofrequency ablation can be used to estimate renal artery ablation zones for highly targeted renal denervation in patients with resistant hypertension. Furthermore, this innovative catheter has short ablation times and is one of the lowest power requirements of existing designs to perform the ablation.

Electronic Nose With Detection Method for Alcohol, Acetone, and Carbon Monoxide in Coronavirus Disease 2019 Breath Simulation Model.

Electronic nose technology may have the potential to substantially slow the spread of contagious diseases with rapid signal indication. As our understanding of infectious diseases such as Corona Virus Disease 2019 improves, we expect electronic nose technology to detect changes associated with pathogenesis of the disease such as biomarkers of immune response for respiratory symptoms, central nervous system injury, and/or peripheral nervous system injury in the breath and/or odor of an individual. In this paper, a design of an electronic nose was configured to detect the concentration of a COVID-19 breath simulation sample of alcohol, acetone, and carbon monoxide mixture. After preheating for 24 hours, the sample was carried into an internal bladder of the collection vessel for analysis and data was collected from three sensors to determine suitability of these sensors for the application of exhaled breath analysis. Test results show a detection range in parts-per-million within the sensor detection range of at least 10-300 ppm. The output response of an MQ-2 and an MQ-135 sensor to a diverse environment of target gasses show the MQ-2 taking a greater length of time to normalize baseline drift compared to an MQ-135 sensor due to cross interferences with other gasses. The COVID-19 breath simulation sample was established and validated based on preliminary data obtained from parallel COVID-19 breath studies based in Edinburgh and Dortmund. This detection method provides a non-invasive, rapid, and selective detection of gasses in a variety of applications in virus detection as well as agricultural and homeland security.

A thin film approach for SiC-derived graphene as an on-chip electrode for supercapacitors.

We designed a nickel-assisted process to obtain graphene with sheet resistance as low as 80 Ω square(-1) from silicon carbide films on Si wafers with highly enhanced surface area. The silicon carbide film acts as both a template and source of graphitic carbon, while, simultaneously, the nickel induces porosity on the surface of the film by forming silicides during the annealing process which are subsequently removed. As stand-alone electrodes in supercapacitors, these transfer-free graphene-on-chip samples show a typical double-layer supercapacitive behaviour with gravimetric capacitance of up to 65 F g(-1). This work is the first attempt to produce graphene with high surface area from silicon carbide thin films for energy storage at the wafer-level and may open numerous opportunities for on-chip integrated energy storage applications.

Silicon carbide: a versatile material for biosensor applications.

Silicon carbide (SiC) has been around for more than 100 years as an industrial material and has found wide and varied applications because of its unique electrical and thermal properties. In recent years there has been increased attention to SiC as a viable material for biomedical applications. Of particular interest in this review is its potential for application as a biotransducer in biosensors. Among these applications are those where SiC is used as a substrate material, taking advantage of its surface chemical, tribological and electrical properties. In addition, its potential for integration as system on a chip and those applications where SiC is used as an active material make it a suitable substrate for micro-device fabrication. This review highlights the critical properties of SiC for application as a biosensor and reviews recent work reported on using SiC as an active or passive material in biotransducers and biosensors.

Emerging SiC Applications beyond Power Electronic Devices.

In recent years, several new applications of SiC (both 4H and 3C polytypes) have been proposed in different papers. In this review, several of these emerging applications have been reported to show the development status, the main problems to be solved and the outlooks for these new devices. The use of SiC for high temperature applications in space, high temperature CMOS, high radiation hard detectors, new optical devices, high frequency MEMS, new devices with integrated 2D materials and biosensors have been extensively reviewed in this paper. The development of these new applications, at least for the 4H-SiC ones, has been favored by the strong improvement in SiC technology and in the material quality and price, due to the increasing market for power devices. However, at the same time, these new applications need the development of new processes and the improvement of material properties (high temperature packages, channel mobility and threshold voltage instability improvement, thick epitaxial layers, low defects, long carrier lifetime, low epitaxial doping). Instead, in the case of 3C-SiC applications, several new projects have developed material processes to obtain more performing MEMS, photonics and biomedical devices. Despite the good performance of these devices and the potential market, the further development of the material and of the specific processes and the lack of several SiC foundries for these applications are limiting further development in these fields.

SiC Electrochemical Sensor Validation for Alzheimer Aß42 Antigen Detection.

Alzheimer's disease (AD) is a neurodegenerative disease with only late-stage detection; thus, diagnosis is made when it is no longer possible to treat the disease, only its symptoms. Consequently, this often leads to caregivers who are the patient's relatives, which adversely impacts the workforce along with severely diminishing the quality of life for all involved. It is, therefore, highly desirable to develop a fast, effective and reliable sensor to enable early-stage detection in an attempt to reverse disease progression. This research validates the detection of amyloid-beta 42 (Aß42) using a Silicon Carbide (SiC) electrode, a fact that is unprecedented in the literature. Aß42 is considered a reliable biomarker for AD detection, as reported in previous studies. To validate the detection with a SiC-based electrochemical sensor, a gold (Au) electrode-based electrochemical sensor was used as a control. The same cleaning, functionalization and Aß1-28 antibody immobilization steps were used on both electrodes. Sensor validation was carried out by means of Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS) aiming to detect an 0.5 µg·mL-1 Aß42 concentration in 0.1 M buffer solution as a proof of concept. A repeatable peak directly related to the presence of Aß42 was observed, indicating that a fast SiC-based electrochemical sensor was constructed and may prove to be a useful approach for the early detection of AD.

Silicon Carbide Technology for Advanced Human Healthcare Applications.

Silicon carbide (SiC) is a highly robust semiconductor material that has the potential to revolutionize implantable medical devices for human healthcare, such as biosensors and neuro-implants, to enable advanced biomedical therapeutic applications for humans. SiC is both bio and hemocompatible, and is already commercially used for long-term human in vivo applications ranging from heart stent coatings and dental implants to short-term diagnostic applications involving neural implants and sensors. One challenge facing the medical community today is the lack of biocompatible materials which are inherently smart or, in other words, capable of electronic functionality. Such devices are currently implemented using silicon technology, which either has to be hermetically sealed so it does not directly interact with biological tissue or has a short lifetime due to instabilities in vivo. Long-term, permanently implanted devices such as glucose sensors, neural interfaces, smart bone and organ implants, etc., require a more robust material that does not degrade over time and is not recognized and rejected as a foreign object by the inflammatory response. SiC has displayed these exceptional material properties, which opens up a whole new host of applications and allows for the development of many advanced biomedical devices never before possible for long-term use in vivo. This paper is a review of the state-of-the art and discusses cutting-edge device applications where SiC medical devices are poised to translate to the commercial marketplace.

Silicon Carbide and MRI: Towards Developing a MRI Safe Neural Interface.

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.

A Flexible a-SiC-Based Neural Interface Utilizing Pyrolyzed-Photoresist Film (C) Active Sites.

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.

Enhancement of X-ray-Excited Red Luminescence of Chromium-Doped Zinc Gallate via Ultrasmall Silicon Carbide Nanocrystals.

X-ray-activated near-infrared luminescent nanoparticles are considered as new alternative optical probes due to being free of autofluorescence, while both their excitation and emission possess a high penetration efficacy in vivo. Herein, we report silicon carbide quantum dot sensitization of trivalent chromium-doped zinc gallate nanoparticles with enhanced near-infrared emission upon X-ray and UV-vis light excitation. We have found that a ZnGa2O4 shell is formed around the SiC nanoparticles during seeded hydrothermal growth, and SiC increases the emission efficiency up to 1 order of magnitude due to band alignment that channels the excited electrons to the chromium ion.

Editorial for the Special Issue on SiC Based Miniaturized Devices.

The MEMS devices are found in many of today's electronic devices and systems, from air-bag sensors in cars to smart phones, embedded systems, etc [...].

Fabrication of a Monolithic Implantable Neural Interface from Cubic Silicon Carbide.

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.

Demonstration of a Robust All-Silicon-Carbide Intracortical Neural Interface.

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 µm². 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 -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 ± 130 kΩ (GSA = 496 µm²) to 46.5 ± 4.80 kΩ (GSA = 500 K µm²). 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.

Correction: Bernardin E.K.; et al. Demonstration of a Robust All-Silicon-Carbide Intracortical Neural Interface. Micromachines, 2018, 9, 412.

The authors would like to indicate the following financial support they received to the Acknowledgement Section of their published paper [...].

GABAa excitation and synaptogenesis after Status Epilepticus - A computational study.

The role of GABAergic neurotransmission on epileptogenesis has been the subject of speculation according to different approaches. However, it is a very complex task to specifically consider the action of the GABAa neurotransmitter, which, in its dependence on the intracellular level of Cl-, can change its effect from inhibitory to excitatory. We have developed a computational model that represents the dentate gyrus and is composed of three different populations of neurons (granule cells, interneurons and mossy cells) that are mutually interconnected. The interconnections of the neurons were based on compensation theory with Hebbian and anti-Hebbian rules. The model also incorporates non-synaptic mechanisms to control the ionic homeostasis and was able to reproduce ictal discharges. The goal of the work was to investigate the hypothesis that the observed aberrant sprouting is promoted by GABAa excitatory action. Conjointly with the abnormal sprouting of the mossy fibres, the simulations show a reduction of the mossy cells connections in the network and an increased inhibition of the interneurons as a response of the neuronal network to control the activity. This finding contributes to increasing the changes in the connectivity of the neuronal circuitry and to increasing the epileptiform activity occurrences.

Use of cortical neuronal networks for in vitro material biocompatibility testing.

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.

Organic functionalization of 3C-SiC surfaces.

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.

Single-crystal cubic silicon carbide: an in vivo biocompatible semiconductor for brain machine interface devices.

Single crystal silicon carbide (SiC) is a wide band-gap semiconductor which has shown both bio- and hemo-compatibility [1-5]. Although single crystalline SiC has appealing bio-sensing potential, the material has not been extensively characterized. Cubic silicon carbide (3C-SiC) has superior in vitro biocompatibility compared to its hexagonal counterparts [3, 5]. Brain machine interface (BMI) systems using implantable neuronal prosthetics offer the possibility of bi-directional signaling, which allow sensory feedback and closed loop control. Existing implantable neural interfaces have limited long-term reliability, and 3C-SiC may be a material that may improve that reliability. In the present study, we investigated in vivo 3C-SiC biocompatibility in the CNS of C56BL/6 mice. 3C-SiC was compared against the known immunoreactive response of silicon (Si) at 5, 10, and 35 days. The material was examined to detect CD45, a protein tyrosine phosphatase (PTP) expressed by activated microglia and macrophages. The 3C-SiC surface revealed limited immunoresponse and significantly reduced microglia compared to Si substrate.