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.

/pdf/progress-towards-biocompatible-intracortical-microelectrodes-2j1pwbs60a.pdf

Progress towards biocompatible intracortical microelectrodes for neural interfacing applications

This report presents results from research towards a fully integrated, wireless neural interface consisting of a 100-channel microelectrode array, a custom-designed signal processing and telemetry IC, an inductive power receiving coil, and SMD capacitors. An integration concept for such a device was developed, and the materials and methods used to implement this concept were investigated. We developed a multi-level hybrid assembly process that used the Utah Electrode Array (UEA) as a circuit board. The signal processing IC was flip-chip bonded to the UEA using Au/Sn reflow soldering, and included amplifiers for up to 100 channels, signal processing units, an RF transmitter, and a power receiving and clock recovery module. An under bump metallization (UBM) using potentially biocompatible materials was developed and optimized, which consisted of a sputter deposited Ti/Pt/Au thin film stack with layer thicknesses of 50/150/150 nm, respectively. After flip-chip bonding, an underfiller was applied between the IC and the UEA to improve mechanical stability and prevent fluid ingress in in vivo conditions. A planar power receiving coil fabricated by patterning electroplated gold films on polyimide substrates was connected to the IC by using a custom metallized ceramic spacer and SnCu reflow soldering. The SnCu soldering was also used to assemble SMD capacitors on the UEA. The mechanical properties and stability of the optimized interconnections between the UEA and the IC and SMD components were measured. Measurements included the tape tests to evaluate UBM adhesion, shear testing between the Au/Sn solder bumps and the substrate, and accelerated lifetime testing of the long-term stability for the underfiller material coated with a a-SiCx:H by PECVD, which was intended as a device encapsulation layer. The materials and processes used to generate the integrated neural interface device were found to yield a robust and reliable integrated package.

Integrated wireless neural interface based on the Utah electrode array.

Objective. Single carbon fiber electrodes (d = 8.4 μm) insulated with parylene-c and functionalized with PEDOT:pTS have been shown to record single unit activity but manual implantation of these devices with forceps can be difficult. Without an improvement in the insertion method any increase in the channel count by fabricating carbon fiber arrays would be impractical. In this study, we utilize a water soluble coating and structural backbones that allow us to create, implant, and record from fully functionalized arrays of carbon fibers with ~150 μm pitch. Approach. Two approaches were tested for the insertion of carbon fiber arrays. The first method used a poly(ethylene glycol) (PEG) coating that temporarily stiffened the fibers while leaving a small portion at the tip exposed. The small exposed portion (500 μm–1 mm) readily penetrated the brain allowing for an insertion that did not require the handling of each fiber by forceps. The second method involved the fabrication of silicon support structures with individual shanks spaced 150 μm apart. Each shank consisted of a small groove that held an individual carbon fiber. Main results. Our results showed that the PEG coating allowed for the chronic implantation of carbon fiber arrays in five rats with unit activity detected at 31 days post-implant. The silicon support structures recorded single unit activity in three acute rat surgeries. In one of those surgeries a stacked device with three layers of silicon support structures and carbon fibers was built and shown to readily insert into the brain with unit activity on select sites. Significance. From these studies we have found that carbon fibers spaced at ~150 μm readily insert into the brain. This greatly increases the recording density of chronic neural probes and paves the way for even higher density devices that have a minimal scarring response.

/pdf/insertion-of-linear-8-4-mm-diameter-16-channel-carbon-fiber-19azqp9z90.pdf

Insertion of linear 8.4 μm diameter 16 channel carbon fiber electrode arrays for single unit recordings.

Objective. Among the currently available neural interface devices, there has been a need for a penetrating electrode array with a high electrode-count and high electrode-density (the number of electrodes/mm 2 ) that can be used for electrophysiological studies of sub-millimeter neuroanatomical structures. We have developed such a penetrating microelectrode array with both a high electrode-density (25 electrodes/mm 2 ) and high electrode-count (up to 96 electrodes) for small nervous system structures, based on the existing Utah Slanted Electrode Array (USEA). Such high electrode-density arrays are expected to provide greater access to nerve fibers than the conventionally spaced USEA especially in small diameter nerves. Approach. One concern for such high density microelectrode arrays is that they may cause a nerve crush-type injury upon implantation. We evaluated this possibility during acute (<10 h) in vivo experiments with electrode arrays implanted into small diameter peripheral nerves of anesthetized rats (sciatic nerve) and cats (pudendal nerve). Main results. Successful intrafascicular implantation and viable nerve function was demonstrated via microstimulation, single-unit recordings and histological analysis. Measurements of the electrode impedances and quantified electrode dimensions demonstrated fabrication quality. The results of these experiments show that such high density neural interfaces can be implanted acutely into neural tissue without causing a complete nerve crush injury, while mediating intrafascicular access to fibers in small diameter peripheral nerves. Significance. This new penetrating microelectrode array has characteristics un-matched by other neural interface devices currently available for peripheral nervous system neurophysiological research.

http://iopscience.iop.org/article/10.1088/1741-2560/10/4/045003/pdf

A new high-density (25 electrodes/mm2) penetrating microelectrode array for recording and stimulating sub-millimeter neuroanatomical structures

This review intends to present a comprehensive analysis of the mechanical considerations for chronically-implanted neural probes. Failure of neural electrical recordings or stimulation over time has shown to arise from foreign body reaction and device material stability. It seems that devices that match most closely with the mechanical properties of the brain would be more likely to reduce the mechanical stress at the probe/tissue interface, thus improving body acceptance. The use of low Young's modulus polymers instead of hard substrates is one way to enhance this mechanical mimetism, though compliance can be achieved through a variety of means. The reduction of probe width and thickness in comparison to a designated length, the use of soft hydrogel coatings and the release in device tethering to the skull, can also improve device compliance. Paradoxically, the more compliant the device, the more likely it will fail during the insertion process in the brain. Strategies have multiplied this past decade to offer partial or temporary stiffness to the device to overcome this buckling effect. A detailed description of the probe insertion mechanisms is provided to analyze potential sources of implantation failure and the need for a mechanically-enhancing structure. This leads us to present an overview of the strategies that have been put in place over the last ten years to overcome buckling issues. Particularly, great emphasis is put on bioresorbable polymers and their assessment for neural applications. Finally, a discussion is provided on some of the key features for the design of mechanically-reliable, polymer-based next generation of chronic neuroprosthetic devices.

https://iopscience.iop.org/article/10.1088/1741-2552/aa8b4f/pdf

A review on mechanical considerations for chronically-implanted neural probes

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.

Jui-Mei Hsu

Papers

Encapsulation of an Integrated Neural Interface Device With Parylene C