Development of a miniaturized, reconnectable, and implantable multichannel connector.

Objective. Connectors for implantable neural prosthetic systems provide several advantages such as simplification of surgery, safe replacement of implanted devices, and modular design of the implant systems. With the rapid advancement of technologies for neural implants, miniaturized multichannel implantable connectors are also required. In this study, we propose a reconnectable and area-efficient multichannel implantable connector.Approach. A female-to-female adapter was fabricated using the thermal-press bonding of micropatterned liquid crystal polymer films. A bump inside the adapter enabled a reliable electrical connection by increasing the contact pressure between the contact pads of the adapter and the inserted cable. After connection, the adapter is enclosed in a metal case sealed with silicone elastomer packing. With different sizes of the packings, leakage current tests were performed under accelerated conditions to determine the optimal design for long-term reliability. Repeated connection tests were performed to verify the durability and reconnectability of the fabricated connector. The connector was implanted in rats, and the leakage currents were monitored to evaluate the stability of the connectorin vivo. Main results. The fabricated four- and eight-channel implantable connectors, assembled with the metal cases, had a diameter and length of 6 and 17 mm, respectively. Further, the contact resistances of the four- and eight-channel connectors were 53.2 and 75.2 mΩ, respectively. The electrical contact remained stable during repeated connection tests (50 times). The fabricated connectors with packings having 125%, 137%, and 150% volume ratios to the internal space of the metal case failed after 14, 88, and 14 d, respectively, in a 75 °C saline environment. In animal tests with rats, the connector maintained low leakage current levels for up to 92 d.Significance. An implantable and reconnectable multichannel connector was developed and evaluated. The feasibility of the proposed connector was evaluated in terms of electrical and mechanical characteristics as well as sealing performance. The proposed connector is expected to have potential applications in implantable neural prosthetic systems.

A Fully Implantable Miniaturized Liquid Crystal Polymer (LCP)-Based Spinal Cord Stimulator for Pain Control.

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.

Current Stimulation of the Midbrain Nucleus in Pigeons for Avian Flight Control.

A number of research attempts to understand and modulate sensory and motor skills that are beyond the capability of humans have been underway. They have mainly been expounded in rodent models, where numerous reports of controlling movement to reach target locations by brain stimulation have been achieved. However, in the case of birds, although basic research on movement control has been conducted, the brain nuclei that are triggering these movements have yet to be established. In order to fully control flight navigation in birds, the basic central nervous system involved in flight behavior should be understood comprehensively, and functional maps of the birds' brains to study the possibility of flight control need to be clarified. Here, we established a stable stereotactic surgery to implant multi-wire electrode arrays and electrically stimulated several nuclei of the pigeon's brain. A multi-channel electrode array and a wireless stimulation system were implanted in thirteen pigeons. The pigeons' flight trajectories on electrical stimulation of the cerebral nuclei were monitored and analyzed by a 3D motion tracking program to evaluate the behavioral change, and the exact stimulation site in the brain was confirmed by the postmortem histological examination. Among them, five pigeons were able to induce right and left body turns by stimulating the nuclei of the tractus occipito-mesencephalicus (OM), nucleus taeniae (TN), or nucleus rotundus (RT); the nuclei of tractus septo-mesencephalicus (TSM) or archistriatum ventrale (AV) were stimulated to induce flight aviation for flapping and take-off with five pigeons.

Preclinical study to improve microbubble-mediated drug delivery in cancer using an ultrasonic probe with an interchangeable acoustic lens.

Focused ultrasound with microbubbles (FUS-MBs) has shown that it can lead to an efficient drug delivery system (DDS) involving the oscillation and destruction of the MB but is limited in drug delivery due to its narrow pressure field. However, unfocused ultrasound with MBs (UUS-MBs) and an interchangeable acoustic lens can tune and enhance the pressure field for MB destruction to overcome the disadvantages of FUS-MB DDSs. We designed a lens suitable for an ultrasound-phased array probe and studied the optimal treatment conditions for MB destruction in vitro through an optical imaging setup. The DDS effects were evaluated in a rat hepatoma model using doxorubicin (DOX) treatment. A concave lens with a radius of curvature of 2.6 mm and a thickness of 4 mm was selected and fabricated. UUS-MBs with the acoustic lens at 60 Vpp for 32 cycles and a PRF of 1 kHz could induce MB destruction, promoting the DDS even under fluidic conditions. In the animal experiment, the UUS-MBs in the acoustic lens treatment group had a higher concentration of DOX in the tumor than the control group. Our system suggests uses an acoustic lens to increase DDS effectiveness by providing sufficient ultrasound irradiation to the MBs.

Versatile Low-Cost Volumetric 3D Ultrasound Imaging Using Gimbal-Assisted Distance Sensors and an Inertial Measurement Unit.

This study aims at creating low-cost, three-dimensional (3D), freehand ultrasound image reconstructions from commercial two-dimensional (2D) probes. The low-cost system that can be attached to a commercial 2D ultrasound probe consists of commercial ultrasonic distance sensors, a gimbal, and an inertial measurement unit (IMU). To calibrate irregular movements of the probe during scanning, relative position data were collected from the ultrasonic sensors that were attached to a gimbal. The directional information was provided from the IMU. All the data and 2D ultrasound images were combined using a personal computer to reconstruct 3D ultrasound image. The relative position error of the proposed system was less than 0.5%. The overall shape of the cystic mass in the breast phantom was similar to those from 2D and sections of 3D ultrasound images. Additionally, the pressure and deformations of lesions could be obtained and compensated by contacting the probe to the surface of the soft tissue using the acquired position data. The proposed method did not require any initial marks or receivers for the reconstruction of a 3D ultrasound image using a 2D ultrasound probe. Even though our system is less than $500, a valuable volumetric ultrasound image could be provided to the users.

Investigation of stereotactic surgery for avian brain stimulation by a fully implanted wireless system.

OBJECTIVE: The authors' goal was to study avian motor brain mapping via wireless stimulation to induce certain behaviors. In this paper, the authors propose an electrode design that is suitable for avian brain stimulation as well as a stereotactic implant procedure for the proposed electrode. METHODS: An appropriate breed for avian brain study was chosen. A fully implantable remote-controlled electrical stimulation system was inserted to minimize discomfort. A suitable electrode design and stereotactic surgery method based on the electrode design were investigated. RESULTS: Using a wireless stimulation system, flapping and rotation behaviors were induced by stimulating the ventral part of the nucleus intercollicularis and formatio reticularis medialis mesencephali both on the ground and during flight. CONCLUSIONS: The authors were able to implant the entire brain stimulation system inside the avian body without any surgical complications. Postoperative observations suggested that the bird did not find the implant uncomfortable.

Retinal Prosthetic Approaches to Enhance Visual Perception for Blind Patients.

Retinal prostheses are implantable devices that aim to restore the vision of blind patients suffering from retinal degeneration, mainly by artificially stimulating the remaining retinal neurons. Some retinal prostheses have successfully reached the stage of clinical trials; however, these devices can only restore vision partially and remain insufficient to enable patients to conduct everyday life independently. The visual acuity of the artificial vision is limited by various factors from both engineering and physiological perspectives. To overcome those issues and further enhance the visual resolution of retinal prostheses, a variety of retinal prosthetic approaches have been proposed, based on optimization of the geometries of electrode arrays and stimulation pulse parameters. Other retinal stimulation modalities such as optics, ultrasound, and magnetics have also been utilized to address the limitations in conventional electrical stimulation. Although none of these approaches have been clinically proven to fully restore the function of a degenerated retina, the extensive efforts made in this field have demonstrated a series of encouraging findings for the next generation of retinal prostheses, and these could potentially enhance the visual acuity of retinal prostheses. In this article, a comprehensive and up-to-date overview of retinal prosthetic strategies is provided, with a specific focus on a quantitative assessment of visual acuity results from various retinal stimulation technologies. The aim is to highlight future directions toward high-resolution retinal prostheses.

A preliminary implementation of an active intraocular prosthesis as a new image acquisition device for a cortical visual prosthesis.

An active intraocular prosthesis is herein proposed as a new image acquisition device for a cortical visual prosthesis. A conventional intraocular prosthesis is a passive device that helps blind patients underwent eye enucleation to maintain the shape of an eyeball. In contrast, an active intraocular prosthesis, which works as an implantable wireless camera, can capture real-time images and transmit them to a cortical visual prosthesis to restore partial vision of the patients. This active device has distinct advantages in that it can garner a variety of image information while focusing on objects in accordance with natural eye movements, compared with a glasses-mounted camera and implanted micro-photodiodes in typical artificial vision systems. Coated with an epoxy and sealed by an elastomer for biocompatibility as well as durability, the active intraocular prosthesis was fabricated in a spherical form miniaturized enough to be inserted into the eye. Its operation was evaluated by wireless image acquisition displaying a processed gray-scale image. Furthermore, signal-to-noise ratio measurements were conducted to find a reliable communication range of the fabricated prosthesis, while it was covered by an 8-mm-thick biological medium that mimicked in vivo environments. In conclusion, the feasibility of the active intraocular prosthesis to cooperate with a cortical visual prosthesis is discussed.

Palatal implant system can provide effective treatment for obstructive sleep apnea by recovering retropalatal patency.

OBJECTIVE: Obstructive sleep apnea (OSA) is a disorder with a high prevalence rate that may induce serious complications. Recent progress in the area of hypoglossal nerve stimulation has played a role as an alternative to conventional therapies though, some patients having retropalatal collapse still have not benefitted. Therefore, here we propose a new type of upper-airway stimulation, referred to as the palatal implant system, which recovers the upper-airway patency by electrically stimulating the soft palate. APPROACH: The system consists of two major parts: an implant that stimulates the soft palate through electrodes and an intra-oral device that delivers power and data simultaneously to the implant via an inductive link. Evaluations of the system are conducted in bench-top, in vitro, and in vivo tests to evaluate its feasibility as an OSA treatment, and the potential development of the system is addressed in the discussion section. MAIN RESULTS: In the bench-top test, the power efficiency was 12.4% at d = 5 mm and the system could operate up to 8 mm distance in a bio-medium. Data transmission was also successful at distances ranging 2 to 8 mm within an error margin of 10%. The measured CSCc and the impedance magnitude of the electrode were 62.25 mC cm-2 and 390 Ω, respectively, proving a feasibility of the electrode as a stimluator interface. The system was applied to a rabbit and contraction of the soft palate muscle was recorded via a C-arm fluoroscopy. SIGNIFICANCE: As a proof of concept, we suggest and demonstrate the palatal implant system as a new therapy for those undergoing treatment for OSA.

A handheld neural stimulation controller for avian navigation guided by remote control.

BACKGROUND: Animal learning based on brain stimulation is an application in a brain-computer interface. Especially for birds, such a stimulation system should be sufficiently light without interfering with movements of wings. OBJECTIVE: We proposed a fully-implantable system for wirelessly navigating a pigeon. In this paper, we report a handheld neural stimulation controller for this avian navigation guided by remote control. METHODS: The handheld controller employs ZigBee to control pigeon's behaviors through brain stimulation. ZigBee can manipulate brain stimulation remotely while powered by batteries. Additionally, simple switches enable users to customize parameters of stimuli like a gamepad. These handheld and user-friendly interfaces make it easy to use the controller while a pigeon flies in open areas. RESULTS: An electrode was inserted into a nucleus (formatio reticularis medialis mesencephalic) of a pigeon and connected to a stimulator fully-implanted in the pigeon's back. Receiving signals sent from the controller, the stimulator supplied biphasic pulses with a duration of 0.080 ms and an amplitude of 0.400 mA to the nucleus. When the nucleus was stimulated, a 180-degree turning-left behavior of the pigeon was consistently observed. CONCLUSIONS: The feasibility of remote avian navigation using the controller was successfully verified.

A Feasibility Study on Optically Transparent Encapsulation for Implantable Neural Prostheses.

Optically transparent encapsulation is presented with results from long-term reliability and light transmission tests. This technology is required in certain implantable neural prostheses that demand the transmission of optical signals through an encapsulating material, such as in retinal implants or in optogenetic applications. In this study, biocompatible film-type cyclic olefin polymers (COPs) with low moisture absorption (<; 0.01 %) and high light transmission (92 %) are utilized as encapsulating materials based on thermal lamination. The reliability of COP encapsulation is characterized through accelerated soak tests in a 75 °C saline solution to measure the leakage currents from encapsulated inter-digitated electrodes. These tests had been done for 211 days with the estimated lifetime of 8.05 years at 37 °C. In addition, the optical properties of a thermally laminated COP film sample in relation to its thickness are evaluated by an experimental setup which uses projected line patterns on an image sensor. The light transmittance of COP film samples thinner than 376 µm exceeded 91.69 %, and the minimum distinguishable line pitch was 47.6 µm at a thickness of 26 µm. These results validate the feasibility of optically transparent encapsulation using COPs and may contribute to its use in future implantable neural prostheses.

A Fully Implantable Wireless Stimulation System for Pigeon Navigation.

Navigation of freely moving animals has been studied for potential application to emergency situations and hazardous environments. A fully implantable stimulation system for remote animal navigation was proposed and applied to living pigeons. The animal navigation system, consisting of an external controller and a neural stimulator, was designed based on the anatomy of the pigeons. Depth electrodes were fabricated based on the anatomy of target pigeon brain regions. The fabricated neural stimulators received data wirelessly from the external controller and generated biphasic current pulses with preset parameters of amplitude, duration, and rate. The average impedance of the fabricated electrodes was 12.0∠-13.05° kΩ at 1 kHz. The neural stimulator was implanted on the dorsal side, and the depth electrodes were inserted into the formatio reticularis medialis mesencephali (FRM). When successive current pulses with an amplitude of 400 µA, a rate of 58 Hz, and a duration of 80 µs were applied to the target regions at 0.85 s intervals, turning/circling behaviors were induced for 6.2 s. The feasibility of the proposed wireless stimulation system was demonstrated in vivo.

Preliminary Study of Palatal Implant for Sleep Apnea Control.

A fully-implantable device for treating obstructive sleep apnea (OSA) is conceptually suggested using soft palate stimulation. In this research, two in vivo studies were conducted to demonstrate electrical and physical feasibilities of the suggested device. First, electrical stimulation was delivered to the soft palate of a rabbit using a stimulator ASIC. The stimulation frequencies were swept from 20 Hz to 200 Hz to find out the appropriate parameter. Also, threshold level of the current pulse was evaluated to be 1.10 mA with an observance of a C-arm fluoroscopy. Second, a mock-up was fabricated with liquid crystal polymer (LCP), reflecting dimensions of the suggested device. The mock-up was inserted toward the soft palate of a rabbit by incising the hard palate in a lateral direction. After the mock-up was inserted, protrusion of the device was not detected and the subject stayed alive for at least a month at the time of this writing. Finally, several discussions on the palatal implant fabrication with LCP are presented.

Locomotion Control of Pigeons using Polymer-based Deep Brain Electrodes.

This paper describes the electrical modulation of locomotion in pigeons using deep brain electrodes. Polymer-based depth electrodes with four channels were fabricated. Based on the location of the nucleus intercollicularis (ICo), the shanks of the depth electrodes were designed to be a length of 11 mm. After the implantation of the depth electrode into the ICo region of the brain, it was connected by wires to a custom-made stimulator, and biphasic current pulses were delivered. Current pulses with an amplitude of 0.5 mA, a rate of 58.0 Hz, and a duration of $320\mu \mathrm{s} $s were applied for 0.5 s. When the ICo region was electrically stimulated, taking-off behavior was successfully induced for 0.4 s. Induction of taking-off behavior by electrical stimulation, when coupled to control of turning and running forward locomotions, may contribute to the development of remote flight-control system of freely moving pigeon.