To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing.

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Progress towards biocompatible intracortical microelectrodes for neural interfacing applications

Retinal prosthesis has been translated from the laboratory to the clinic over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa. These devices provide partial sight restoration and patients use this improved vision in their everyday lives. Improved mobility and object detection are some of the more notable findings from the clinical trials. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. This paper reviews the recent clinical trials and highlights technology breakthroughs that will contribute to next generation of retinal prostheses.

Retinal Prosthesis

Engineered systems that can serve as chronically stable, high-performance electronic recording and stimulation interfaces to the brain and other parts of the nervous system, with cellular-level resolution across macroscopic areas, are of broad interest to the neuroscience and biomedical communities. Challenges remain in the development of biocompatible materials and the design of flexible implants for these purposes, where ulimate goals are for performance attributes approaching those of conventional wafer-based technologies and for operational timescales reaching the human lifespan. This Review summarizes recent advances in this field, with emphasis on active and passive constituent materials, design architectures and integration methods that support necessary levels of biocompatibility, electronic functionality, long-term stable operation in biofluids and reliability for use in vivo. Bioelectronic systems that enable multiplexed electrophysiological mapping across large areas at high spatiotemporal resolution are surveyed, with a particular focus on those with proven chronic stability in live animal models and scalability to thousands of channels over human-brain-scale dimensions. Research in materials science will continue to underpin progress in this field of study. This Review provides an overview of the advances in materials and device design that are enabling the realization of implantable electronic interfaces for long-term, multiplexed recording and stimulation of the brain and nervous system.

Materials for flexible bioelectronic systems as chronic neural interfaces.

Electronic neural interfaces have been developed to restore function to the nervous system for patients with neural disorders. A conformal and chronically stable dielectric encapsulation is required to protect the neural interface device from the harsh physiological environment and localize the active electrode tips. Chemical vapor deposited Parylene-C films were studied as a potential implantable dielectric encapsulation material using impedance spectroscopy and leakage current measurements. Both tests were performed in 37degC saline solution, and showed that the films provided an electrically insulating encapsulation for more than one year. Isotropic and anisotropic oxygen plasma etching processes were compared for removing the Parylene-C insulation to expose the active electrode tips. Also, the relationship between tip exposure and electrode impedance was determined. The conformity and the uniformity of the Parylene-C coating were assessed using optical microscopy, and small thickness variations on the complex 3-D electrode arrays were observed. Parylene C was found to provide encapsulation and electrical insulation required for such neural interface devices for more than one year. Also, oxygen plasma etching was found to be an effective method to etch and pattern Parylene-C films.

Encapsulation of an Integrated Neural Interface Device With Parylene C

The search for materials and systems, capable of operating long term under physiological conditions, has been a strategy for many research groups during the past years. Silicon carbide (SiC) is a material, which can meet the demands due to its high biocompatibility, high inertness to biological tissues and to aggressive environment, and the possibility to make all types of electronic devices.This paper reviews progress in biomedical and biosensor related research on SiC. For example, less biofouling and platelet aggregation when exposed to blood is taken advantage of in a variety of medical implantable materials while the robust semiconducting properties can be explored in surface functionalized bioelectronic devices.

https://iopscience.iop.org/article/10.1088/0022-3727/40/20/S20/pdf

Surface functionalization and biomedical applications based on SiC

Amorphous silicon carbide (a-SiC) films, deposited by plasma-enhanced chemical vapor deposition (PECVD), have been evaluated as insulating coatings for implantable microelectrodes. The a-SiC was deposited on platinum or iridium wire for measurement of electrical leakage through the coating in phosphate-buffered saline (PBS, pH 7.4). Low leakage currents of <10(-11) A were observed over a +/-5-V bias. The electronic resistivity of a-SiC was 3 x 10(13) Omega-cm. Dissolution rates of a-SiC in PBS at 37 and 90 degrees C were determined from changes in infrared absorption band intensities and compared with those of silicon nitride formed by low-pressure chemical vapor deposition (LPCVD). Dissolution rates of LPCVD silicon nitride were 2 nm/h and 0.4 nm/day at 90 and 37 degrees C, respectively, while a-SiC had a dissolution rate of 0.1 nm/h at 90 degrees C and no measurable dissolution at 37 degrees C. Biocompatibility was assessed by implanting a-SiC-coated quartz discs in the subcutaneous space of the New Zealand White rabbit. Histological evaluation showed no chronic inflammatory response and capsule thickness was comparable to silicone or uncoated quartz controls. Amorphous SiC-coated microelectrodes were implanted in the parietal cortex for periods up to 150 days and the cortical response evaluated by histological evaluation of neuronal viability at the implant site. The a-SiC was more stable in physiological saline than LPCVD Si(3)N(4) and well tolerated in the cortex.

Ying Ping Liu

Papers

Plasma-enhanced chemical vapor deposited silicon carbide as an implantable dielectric coating.