The a-SiC MEAs provide a significant advancement in the development of microelectrodes that over the years has relied on silicon platforms for device manufacture. These flexible a-SiC MEAs have the potential for decreased tissue damage and reduced foreign body response. The technique is promising and has potential for clinical translation and large scale manufacturing.

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 ultra-small 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, ultra-microelectrodes fabricated from emerging polymers and amorphous silicon carbide appear promising for neurostimulation applications. Conclusion We envision the emergence of robust and manufacturable ultra-microelectrodes 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.

Our innovations in fabrication technique pave the way for further miniaturization of carbon fiber ultra-microelectrode arrays. We believe these advances to be key steps to enable a shift from labor intensive, manual assembly to a more automated manufacturing process.

Most preparations for making neural recordings degrade over time and eventually fail due to insertion trauma and reactive tissue response. The magnitudes of these responses are thought to be related to the electrode size (specifically, the cross-sectional area) and the relative stiffness of the electrode material. Carbon fiber ultramicroelectrodes have a much smaller cross-section than traditional electrodes and thus may enable improved longevity of neural recordings in the central and peripheral nervous systems. Only two carbon fiber array designs have been described previously, each with limited channel densities due to limitations of the fabrication processes or interconnect strategies. Here, we describe a method for assembling carbon fiber electrodes on a flexible polyimide substrate that will facilitate the construction of high-density recording and stimulating arrays for acute use in peripheral nerves. Fibers were aligned using an alignment tool that was 3D-printed with sub-micron resolution using direct laser writing. Indium deposition on the carbon fibers provided a robust and reliable method of electrical connection to the polyimide traces. Spontaneous action potentials and stimulation-evoked compound responses with SNR > 10 and > 120, respectively, were recorded from a small (125 µm) peripheral nerve. We also improved the typically poor charge injection capacity of small diameter carbon fibers can be improved by electrodepositing 100 nm thick iridium oxide films, making the carbon fiber arrays suitable for electrical stimulation as well as recording.

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.

Host encapsulation decreases the ability of chronically implanted microelectrodes to record or stimulate neural activity. The degree of foreign body response is thought to depend strongly on the cross-sectional dimensions of the electrode shaft penetrating neural tissue. Microelectrodes with cellular or sub-cellular scale shaft cross-sectional dimensions, such as carbon fiber ultramicroelectrodes have been previously demonstrated to elicit minimal tissue response, but their small geometric surface area results in high electrode impedances for neural recording, and reduced charge injection capacity during current pulsing for neural stimulation. We investigated electrodeposited iridium oxide films (EIROF) on carbon fiber ultramicroelectrodes as a means of enhancing the charge injection capacity and reducing electrode impedance. EIROF coatings reduced the electrode impedance measured at 1 kHz by a factor of 10 and improved charge storage and charge injection capacities. The maximum charge injection capacity was also strongly dependent on the interpulse bias and pulse width, and reflected a potential-dependent EIROF impedance. The charge injection capacity of the EIROF-coated carbon fiber ultramicroelectrodes measured in an inorganic buffered saline model of interstitial fluid exceeded 17 mC/cm 2 with appropriate biasing, allowing charge-injection at levels well above reported charge/phase thresholds for intraneural microstimulation.

Here, we report on chronic in-vivo testing of a 16-channel wireless floating microelectrode array (WFMA) in a rat sciatic nerve model. Muscle threshold currents, charge injection levels, and charge density were monitored for electrodes of two WFMA devices implanted into animal subjects over a five month period. This type of wireless stimulation device could eliminate problems associated with percutaneous connectors for a variety of neural prostheses and other medical devices.

Size and material considerations are important in the development of next-generation chronically reliable neural interface devices. In this review, we discuss the use of amorphous silicon carbide (a-SiC) for the fabrication of indwelling electrode arrays with ultrathin penetrating shanks for neural stimulation and recording. The a-SiC film is stable in saline environments and has a high intrinsic stiffness that allows fabrication of tissue-penetrating arrays with extremely small cross-sectional areas (<60 μm2). Present literature on arrays with extremely small shanks and/or ultramicroelectrode (UME) sites are reviewed. Properties of a-SiC films and their current biomedical applications are summarized. Reduced shank dimensions increase the flexibility of high Young's modulus a-SiC arrays. Iridium oxide-coated UMEs had electrochemical properties suitable for neural recording and stimulation, and recorded neural signals with high amplitudes and high signal-to-noise ratios. UMEs and a-SiC may provide a platform for next-generation high-density chronic neural interface devices.