Assessing the manufacturable 32-channel cochlear electrode array: evaluation results for clinical trials.

Reliability evaluation results of a manufacturable 32-channel cochlear electrode array are reported in this paper. Applying automated laser micro-machining process and a layer-by-layer silicone deposition scheme, authors developed the manufacturing methods of the electrode array for fine patterning and mass production. The developed electrode array has been verified through the requirements specified by the ISO Standard 14708-7. And the insertion trauma of the electrode array has been evaluated based on human temporal bone studies. According to the specified requirements, the electrode array was assessed through elongation & insulation, flexural, and fatigue tests. In addition, Temporal bone study was performed using eight fresh-frozen cadaver temporal bones with the electrode arrays inserted via the round window. Following soaking in saline condition, the impedances between conducting wires of the electrode array were measured over 100 kΩ (the pass/fail criterion). After each required test, it was shown that the electrode array maintained the electrical continuity and insulation condition. The average insertion angle of the electrode array inside the scala tympani was 399.7°. The human temporal bone studies exhibited atraumatic insertion rate of 60.3% (grade 0 or 1). The reliability of the manufacturable electrode array is successfully verified in mechanical, electrical, and histological aspects. Following the completion of a 32-channel cochlear implant system, the performance and stability of the 32-channel electrode array will be evaluated in clinical trials.

Fabrication and evaluation of an improved polymer-based cochlear electrode array for atraumatic insertion.

An atraumatic cochlear electrode array has become indispensable to high-performance cochlear implants such as electric acoustic stimulation (EAS), wherein the preservation of residual hearing is significant. For an atraumatic implantation, we propose and demonstrate a new improved design of a cochlear electrode array based on liquid crystal polymer (LCP), which can be fabricated by precise batch processes and a thermal lamination process, in contrast to conventional wire-based cochlear electrode arrays. Using a thin-film process of LCP-film-mounted silicon wafer and thermal press lamination, we devise a multi-layered structure with variable layers of LCP films to achieve a sufficient degree of basal rigidity and a flexible tip. A peripheral blind via and self-aligned silicone elastomer molding process can reduce the width of the array. Measuring the insertion and extraction forces in a human scala tympani model, we investigate five human temporal bone insertion trials and record electrically evoked auditory brainstem responses (EABR) acutely in a guinea pig model. The diameters of the finalized electrode arrays are 0.3 mm (tip) and 0.75 mm (base). The insertion force with a displacement of 8 mm from a round window and the maximum extraction force are 2.4 mN and 34.0 mN, respectively. The electrode arrays can be inserted from 360° to 630° without trauma at the basal turn. The EABR data confirm the efficacy of the array. A new design of LCP-based cochlear electrode array for atraumatic implantation is fabricated. Verification indicates that foretells the development of an atraumatic cochlear electrode array and clinical implant.

A liquid crystal polymer-based neuromodulation system: an application on animal model of neuropathic pain.

OBJECTIVE: We developed a custom-made miniaturized neural stimulation system with a liquid crystal polymer (LCP)-based electrode array for animal experiments. In order to verify the feasibility of the system, motor cortex stimulation (MCS) was applied on the rat pain model induced by sciatic nerve injury. MATERIALS AND METHODS: LCP is mechanically stable and chemically inert and has a much lower water absorption rate than other biocompatible polymers such as polyimide or parylene. In the present study, a film-type LCP substrate is used to microfabricate the cortical stimulation electrode array. A miniaturized electrical neuromodulation system is implemented using an application-specific integrated chip for generation of electrical stimulation current. In vivo experiment was performed using a rat neuropathic pain model induced by sciatic nerve injury. The electrodes were attached to the contralateral primary motor cortex, which processes the hind limb movement. Mechanical allodynia was measured before, during, and after electrical stimulation to determine the effects on pain threshold. RESULTS: Electrical stimulation into the brain structure processing pain perception was effective in alleviating neuropathic pain. The pain threshold of the rats increased more than fivefold during the electrical stimulation. CONCLUSION: We developed a miniaturized electrical stimulation system with a novel flexible LCP electrode array for MCS in rats. This system is expected to be used in studying various neurological diseases and examining in vivo brain function.

VPL-DBS on neuropathic pain rat model is effective in mechanical allodynia than cold allodynia.

Recently, deep brain stimulation (DBS) is widely used in various types of neurodegenerative disorders for minimal invasiveness and safety of the procedure. Deep brain stimulation is consistently applied for the treatment of patients with neuropathic pain even though the success rate is not as high as other neurodegenerative disorders. Furthermore, it is also unclear how DBS improves neuropathic pain. In this study, we investigated the role of DBS following the stimulation parameter for analgesic effect on mechanical allodynia and cold allodynia in neuropathic pain rats. We used a sciatic nerve injury model to induce neuropathic pain, and observed responses to mechanical and cold stimulation by the von Frey test and acetone test, respectively. We classified the rats into four groups: naïve (naïve, n = 10), naïve + DBS (N + DBS, n = 10), neuropathic pain (NP, n = 10), and neuropathic pain + DBS (NP + DBS, n = 10). We inserted the DBS electrode into the ventral posterolateral nucleus (VPL) into the rats (VPL-DBS). The score for mechanical allodynia was significantly decreased in NP + DBS group (p < 0.01). However, the score for cold allodynia did not significantly drop in any groups including NP + DBS group (p > 0.05). In this study, we found that the electrical stimulation of the VPL works more effectively with mechanical allodynia than cold one, and pain signal induced by mechanical stimulus and cold stimulus may be processed through different pathways in the brain.

Fabrication of Planar Microelectrode Array Using Laser-Patterned ITO and SU-8.

For several decades, microelectrode array (MEA) has been a powerful tool for in vitro neural electrophysiology because it provides a unique approach for monitoring the activity of a number of neurons over time. Due to the various applications of MEAs with different types of cells and tissues, there is an increasing need to customize the electrode designs. However, the fabrication of conventional MEAs requires several microfabrication procedures of deposition, etching, and photolithography. In this study, we proposed a simple fabrication method with a laser-patterned indium tin oxide (ITO) conductor and SU-8 photoresist insulation. Unlike in a conventional metal patterning process, only the outlines of ITO conductors are ablated by laser without removing background ITO. Insulation is achieved simply via SU-8 photolithography. The electrode sites are electroplated with iridium oxide (IrOX) to improve the electrochemical properties. The fabricated MEAs are electrochemically characterized and the stability of insulation is also confirmed by impedance monitoring for three weeks. Dissociated neurons of rat hippocampi are cultured on MEAs to verify the biocompatibility and the capacity for extracellular neural recording. The electrochemical and electrophysiological results with the fabricated MEAs are similar to those from conventional SiNX-insulated MEAs. Therefore, the proposed MEA with laser-patterned ITO and SU-8 is cost-effective and equivalently feasible compared with the conventional MEAs fabricated using thin-film microfabrication techniques.

Manufacturable 32-Channel Cochlear Electrode Array and Preliminary Assessment of Its Feasibility for Clinical Use.

(1) Background: In this study, we introduce a manufacturable 32-channel cochlear electrode array. In contrast to conventional cochlear electrode arrays manufactured by manual processes that consist of electrode-wire welding, the placement of each electrode, and silicone molding over wired structures, the proposed cochlear electrode array is manufactured by semi-automated laser micro-structuring and a mass-produced layer-by-layer silicone deposition scheme similar to the semiconductor fabrication process. (2) Methods: The proposed 32-channel electrode array has 32 electrode contacts with a length of 24 mm and 0.75 mm spacing between contacts. The width of the electrode array is 0.45 mm at its apex and 0.8 mm at its base, and it has a three-layered arrangement consisting of a 32-channel electrode layer and two 16-lead wire layers. To assess its feasibility, we conducted an electrochemical evaluation, stiffness measurements, and insertion force measurements. (3) Results: The electrochemical impedance and charge storage capacity are 3.11 ± 0.89 kOhm at 1 kHz and 5.09 mC/cm2, respectively. The V/H ratio, which indicates how large the vertical stiffness is compared to the horizontal stiffness, is 1.26. The insertion force is 17.4 mN at 8 mm from the round window, and the maximum extraction force is 61.4 mN. (4) Conclusions: The results of the preliminary feasibility assessment of the proposed 32-channel cochlear electrode array are presented. After further assessments are performed, a 32-channel cochlear implant system consisting of the proposed 32-channel electrode array, 32-channel neural stimulation and recording IC, titanium-based hermetic package, and sound processor with wireless power and signal transmission coil will be completed.

A miniaturized, eye-conformable, and long-term reliable retinal prosthesis using monolithic fabrication of liquid crystal polymer (LCP).

A novel retinal prosthetic device was developed using biocompatible liquid crystal polymer (LCP) to address the problems associated with conventional metal- and polymer-based devices: the hermetic metal package is bulky, heavy, and labor-intensive, whereas a thin, flexible, and MEMS-compatible polymer-based system is not durable enough for chronic implantation. Exploiting the advantageous properties of LCP such as a low moisture absorption rate, thermobonding, and thermoforming, we fabricate a small, light-weight, long-term reliable retinal prosthesis that can be conformally attached on the eye-surface. A LCP fabrication process using monolithic integration and conformal deformation was established enabling miniaturization and a batch manufacturing process as well as eliminating the need for feed-through technology. The functionality of the fabricated device was tested through wireless operation in saline solution. Its efficacy and implantation stability were verified through in vivo animal tests by measuring the cortical potential and monitoring implanted dummy devices for more than a year, respectively.

A polymer-based multichannel cochlear electrode array.

OBJECTIVE: Compared with conventional cochlear electrode arrays, which are hand assembled and wire-based, polymer-based implants have several advantages. They are very precise, and their fabrication is inexpensive because of the use of thin-film processes. In the present study, a cochlear electrode array based on a high-performance liquid crystal polymer material is devised. Furthermore, the device is encapsulated in silicone elastomer. METHODS: The fabrication steps introduced here include thin-film processes with liquid crystal polymer (LCP) films and customized self-aligning molding processes for the electrode array. To assess the feasibility of the proposed electrode array, the charge storage capacitance and impedance were measured using a potentiostat. Vertical and horizontal deflection forces were measured using a customized fixture and a force sensor. Insertion and extraction forces were also measured using a transparent human cochlear plastic model, and five cases involving human temporal insertion trials were undertaken to assess the level of safety during the insertion process. RESULTS: The charge storage capacity and impedance at 1 kHz were 33.26 mC/cm and 1.02 kΩ, respectively. Likewise, the vertical force and horizontal force of the electrode array were 3.15 g and 1.07 g. The insertion force into a transparent plastic cochlear model with displacement of 8 mm from a round window was 8.2 mN, and the maximum extraction force was 110.4 mN. Two cases of human temporal bone insertion showed no observable trauma, whereas 3 cases showed a rupture of the basilar membrane. CONCLUSION: An LCP-based intracochlear electrode array was fabricated, and its electrical and mechanical properties were found to be suitable for clinical use.

Modiolus-hugging intracochlear electrode array with shape memory alloy.

In the cochlear implant system, the distance between spiral ganglia and the electrodes within the volume of the scala tympani cavity significantly affects the efficiency of the electrical stimulation in terms of the threshold current level and spatial selectivity. Because the spiral ganglia are situated inside the modiolus, the central axis of the cochlea, it is desirable that the electrode array hugs the modiolus to minimize the distance between the electrodes and the ganglia. In the present study, we propose a shape-memory-alloy-(SMA-) embedded intracochlear electrode which gives a straight electrode a curved modiolus-hugging shape using the restoration force of the SMA as triggered by resistive heating after insertion into the cochlea. An eight-channel ball-type electrode array is fabricated with an embedded titanium-nickel SMA backbone wire. It is demonstrated that the electrode array changes its shape in a transparent plastic human cochlear model. To verify the safe insertion of the electrode array into the human cochlea, the contact pressures during insertion at the electrode tip and the contact pressures over the electrode length after insertion were calculated using a 3D finite element analysis. The results indicate that the SMA-embedded electrode is functionally and mechanically feasible for clinical applications.

Magnetic Resonance Imaging Compatibility of the Polymer-based Cochlear Implant.

OBJECTIVES: In this study, we compared the magnetic resonance (MR) image artifacts caused by a conventional metal-based cochlear implant and a newly developed liquid crystal polymer (LCP)-based device. METHODS: The metal-based cochlear implant system (Nurobiosys Co.) was attached to side of the head of a subject and the LCP-based device was attached to opposite side. In both devices, alignment magnets were removed for safety. Magnetic resonance imaging (MRI) was performed on a widely used 3.0 T and an ultra-high 7.0 T MRI machine. 3.0 and 7.0 T MR images were acquired using T1- and T2(*)-weighted gradient echo sequences, respectively. RESULTS: In the 3.0 T images, the metal-based device on the left side generated the significant amount of artifacts. The MR images in the proximity of the metal package were obscured by the artifacts in both axial and sagittal views. On the other hand, the MR images near the LCP-based device were relatively free from the artifacts and clearly showed the brain structures. 7.0 T MR images showed the more severe distortion in the both sides but the metal-based cochlear implant system caused a much larger obscure area than the LCP-based system. CONCLUSION: The novel LCP-based cochlear implant provides a good MRI compatibility beyond present-day cochlear implants. Thus, MR images can be obtained from the subjects even with the implanted LCP-based neural prosthetic systems providing useful diagnostic information. Furthermore, it will be also useful for functional MRI studies of the auditory perception mechanism after cochlear implantations as well as for positron emission tomography-MRI hybrid imaging.