Sang Beom Jun

Design for a Simplified Cochlear Implant System

A simplified cochlear implant (CI) system would be appropriate for widespread use in developing countries. Here, we describe a CI that we have designed to realize such a concept. The system implements 8 channels of processing and stimulation using the continuous interleaved sampling (CIS) strategy. A generic digital signal processing (DSP) chip is used for the processing, and the filtering functions are performed with a fast Fourier transform (FFT) of a microphone or other input. Data derived from the processing are transmitted through an inductive link using pulse width modulation (PWM) encoding and amplitude shift keying (ASK) modulation. The same link is used in the reverse direction for backward telemetry of electrode and system information. A custom receiver-stimulator chip has been developed that demodulates incoming data using pulse counting and produces charge balanced biphasic pulses at 1000 pulses/s/electrode. This chip is encased in a titanium package that is hermetically sealed using a simple but effective method. A low cost metal-silicon hybrid mold has been developed for fabricating an intracochlear electrode array with 16 ball-shaped stimulating contacts

Enhanced infrared neural stimulation using localized surface plasmon resonance of gold nanorods.

An advanced optical activation of neural tissues is demonstrated using pulsed infrared light and plasmonic gold nanorods. Photothermal effect localized in plasma membrane triggers action potentials of in vivo neural tissues. Compared with conventional infrared stimulation, the suggested method can increase a neural responsivity and lower a threshold stimulation level significantly, thereby reducing a requisite radiant exposure and the concern of tissue damage.

A Flexible Depth Probe Using Liquid Crystal Polymer

We proposed a method of making a flexible depth-type neural probe using liquid crystal polymer. Conventional depth neural probes made of metal or silicon have the limitations of a single recording site per shank or the brittleness of the silicon substrate. To avoid these drawbacks, polymer-based depth neural probes have been developed with biocompatible polymers such as polyimides or parylenes. However, those have suffered from the difficulty of inserting the probes into brain tissues due to their high flexibility, requiring mechanical reinforcements. Herein, we report the first attempt to use a flexible material, liquid crystal polymer (LCP), as a substrate for a depth-type neural probe. The LCP-based probe offers a controllable stiffness vs. flexibility and compatibility with thin-film processes in addition to its inherent characteristics such as high reliability and biocompatibility. In the present study, an LCP neural probe was fabricated to have enough stiffness to penetrate the dura mater of rodent brains without a guide tool or additional reinforcement structures. A simultaneous multichannel neural recording was successfully achieved from the somatosensory motor cortex of the rodents. Immunohistochemistry showed that the electrodes could be inserted into the desired regions in the brain.

Synergistic combination of near-infrared irradiation and targeted gold nanoheaters for enhanced photothermal neural stimulation

Despite a potential of infrared neural stimulation (INS) for modulating neural activities, INS suffers from limited light confinement and bulk tissue heating. Here, a novel methodology for an advanced optical stimulation is proposed by combining near-infrared (NIR) stimulation with gold nanorods (GNRs) targeted to neuronal cell membrane. We confirmed experimentally that in vitro and in vivo neural activation is associated with a local heat generation based on NIR stimulation and GNRs. Compared with the case of NIR stimulation without an aid of GNRs, combination with cell-targeted GNRs allows photothermal stimulation with faster neural response, lower delivered energy, higher stimulation efficiency and stronger behavior change. Since the suggested method can reduce a requisite radiant exposure level and alleviate a concern of tissue damage, it is expected to open up new possibilities for applications to optical neuromodulations for diverse excitable tissues and treatments of neurological disorders.

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.

A Liquid Crystal Polymer-Based Neuromodulation System: An Application on Animal Model of Neuropathic Pain

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.

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.

Multi-color fluorescence imaging based on plasmonic wavelength selection and double illumination by white light

We demonstrate the proof-of-concept for developing a multi-color fluorescence imaging system based on plasmonic wavelength selection and double illumination by white light source. This technique is associated with fluorescence excitation by transmitted light via a diffraction of propagating surface plasmons. Since double illumination through both sides of isosceles triangle prism in the Kretschmann configuration enables multiple transmission beams of different wavelengths to interact with the specimen, our approach can be an alternative to conventional fluorescence detection owing to alignment stability and functional expandability. After fabricating a plasmonic wavelength splitter and integrating it with microscopic imaging system, we successfully confirm the performance by visualizing in vitro neuron cells labeled with green and red fluorescence dyes. The suggested method has a potential that it could be combined with plasmonic biosensor scheme to realize a multi-functional platform which allows imaging and sensing of biological samples at the same time.

Photothermal activation of astrocyte cells using localized surface plasmon resonance of gold nanorods

Although it has been revealed that astrocytes, generally known as star-shaped glial cells, play critical roles in the functions of central nervous system, there have been few efforts to directly modulate their activities and responses. In this study, an optical stimulation strategy for producing intracellular Ca2+ transients of astrocytes is demonstrated using near-infrared (NIR) light and localized surface plasmon resonance. It is presented that NIR stimulation of micro-second duration combined with gold nanorods (GNRs) efficiently produces stronger Ca2+ transients of astrocytes, which seems to be associated with a local heat generation by photothermal effects of GNRs. Since the proposed scheme can directly activate astrocytes with a high reliability, it is expected that GNR-mediated NIR stimulation could be utilized to facilitate minimally invasive physiological studies on the astrocyte functions. Photos of intracellular Ca2+ transient of astrocytes with membrane-bound GNRs after optical stimulation at 30 s.

Low-Affinity Zinc Sensor Showing Fluorescence Responses with Minimal Artifacts

The study of the zinc biology requires molecular probes with proper zinc affinity. We developed a low-affinity zinc probe (HBO-ACR) based on an azacrown ether (ACR) and an 2-(2-hydroxyphenyl)benzoxazole (HBO) fluorophore. This probe design imposed positive charge in the vicinity of a zinc coordination center, which enabled fluorescence turn-on responses to high levels of zinc without being affected by the pH and the presence of other transition-metal ions. Steady-state and transient photophysical investigations suggested that such a high tolerance benefits from orchestrated actions of proton-induced nonradiative and zinc-induced radiative control. The zinc bioimaging utility of HBO-ACR has been fully demonstrated with the use of human pancreas epidermoid carcinoma, PANC-1 cells, and rodent hippocampal neurons from cultures and acute brain slices. The results obtained through our studies established the validity of incorporating positively charged ionophores for the creation of low-affinity probes for the visualization of biometals.