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.

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.

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.

Electrical Properties of Thiol-ene-based Shape Memory Polymers Intended for Flexible Electronics.

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 °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.

High-Performance Graphene-Fiber-Based Neural Recording Microelectrodes.

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.

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 [...].

Amorphous Silicon Carbide Platform for Next Generation Penetrating Neural Interface Designs.

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 µm or below are thought to minimize the inflammatory response; however, the reduction of implant thickness also decreases buckling thresholds for materials with low Young'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'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 µm or 6 µm. The 6 µm 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 µm.

Chronic Intracortical Recording and Electrochemical Stability of Thiol-ene/Acrylate Shape Memory Polymer Electrode Arrays.

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.

Thinking Small: Progress on Microscale Neurostimulation Technology.

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.

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.