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Continuous glucose monitoring system (CGMS) is growing popular and preferred by diabetes over conventional methods of self-blood glucose monitoring (SBGM) systems. However, currently available commercial CGMS in the market is useful for few days to few months. This paper presents a durable, highly sensitive and minimally invasive implant type electromagnetic sensor for continuous glucose monitoring that is capable of tracking minute changes in blood glucose level (BGL).The proposed sensor utilizes strong oscillating nearfield to detect minute changes in dielectric permittivity of interstitial fluid (ISF) and blood due to changes in BGL. A biocompatible packaging material is used to cover the sensor. It helps in minimizing foreign body reactions (FBR) and improves stability of the sensor.The performance of the proposed sensor was evaluated on live rodent models (C57BL/6J mouse and Sprague Dawley rat) through intravenous glucose and insulin tolerance tests. Biocompatible polyolefin was used as the sensor packaging material, and the effect of packaging thickness on the sensitivity of sensor was examined in in-vivo test. Proposed sensor could track real-time BGL change measured with a commercial blood glucose meter. High linear correlation (RThe experimental results demonstrate that the proposed sensor is suitable for long term CGMS applications with a high accuracy.Present work offers a new perspective towards development of long term CGM system using electromagnetic based implant sensor. The in vivo evaluation of the sensor shows excellent tracking of BGL changes.

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.

Objective. Neurostimulator is one of the most important part in artificial retina design. In this paper, we discuss the main challenges in the design of application-specific integrated circuit for high-resolution artificial retina and suggest corresponding solutions. Approach. Problems in the design of the neurostimulator for the existing artificial retina have not been solved yet are analyzed and solutions are presented. For verification of the solutions, mathematical proof, MATLAB and Ansys simulations are used. Main results. The drawbacks of resorting to a high-voltage complementary metal oxide semiconductor (CMOS) process to deal with the large voltage compliance demanded by the stimulator output stage are pointed out, and an alternative approach based on a circuit that switches the voltage of the common reference electrode is proposed to overcome. The necessity of an active discharge circuit to remove the residual charge of electrodes caused by an unbalanced stimulus is investigated. We present a circuit analysis showing that the use of a passive discharge circuit is sufficient to suppress problematic direct current in most situations. Finally, possible restrictions on input and output (I/O) count are investigated by estimating the resistive-capacitive delay caused by the interconnection between the I/O pad and the microelectrode array. Significance. The results of this paper clarified the problems currently faced by neurostimulator design for the artificial retina. Through the solutions presented in this study, circuits with more competitiveness in power and area consumption can be designed.

OBJECTIVEThe 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.METHODSAn 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.RESULTSUsing 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.CONCLUSIONSThe 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.

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.

Blood pressure (BP) is a physiological parameter reflecting hemodynamic factors and is crucial in evaluating cardiovascular disease and its prognosis. In the present study, the reliability of a non-invasive and continuous BP measurement using a three-axis tactile force sensor was verified. All the data were collected every 2 min for the short-term experiment, and every 10 min for the long-term experiment. In addition, the effects on the BP measurement of external physical factors such as the tension to the radial artery on applying the device and wrist circumference were evaluated. A high correlation between the measured BP with the proposed system and with the cuff-based non-invasive blood pressure, and reproducibility, were demonstrated. All data satisfied the Association for the Advancement of Medical Instrumentation criteria. The external physical factors did not affect the measurement results. In addition to previous research indicating the high reliability of the arterial pulse waveforms, the present results have demonstrated the reliability of numerical BP values, and this implies that the three-axis force sensor can be used as a patient monitoring device.

Brain is complex organ composed of numerous glial cells and neurons to convey information using chemical and electrical signals. Neural interface technology using the electrical brain signals has attracted great attention for the clinical and experimental applications. Electrode as the neural interface is the most important part in stimulating neural cells or recording neural activities. In this paper, we provide an overview of electrodes for recording the electrical brain signal. The noninvasive electrodes are primarily used to capture electroencephalogram (EEG) from outside the skull while the implantable electrodes are employed to measure electrocorticogram (ECoG), local field potential (LFP) or spike activity. Recent progress in microfabrication technology enables the development of on-board electrode that combines the entire signal processing including amplification, filtering, and digitization. This will contribute to diagnostic and therapeutic application of the neural interface for restoring physical, psychological and social functions by improving motor, sensory or cognitive abilities.

In order to provide high-quality visual information to patients who have implanted retinal prosthetic devices, the number of microelectrodes should be large. As the number of microelectrodes is increased, the dimensions of each microelectrode must be decreased, which in turn results in an increased microelectrode interface impedance and decreased injection current dynamic range. In order to improve the trade-off envelope between the number of microelectrodes and the current injection characteristics, a 3D microelectrode structure can be used as an alternative. In this paper, the electrical characteristics of 2D and 3D Au microelectrodes were investigated. In order to examine the effects of the structural difference, 2D and 3D Au microelectrodes with different base areas but similar effective surface areas were fabricated and evaluated. Interface impedances were measured and similar dynamic ranges were obtained for both 2D and 3D Au microelectrodes. These results indicate that more electrodes can be implemented in the same area if 3D designs are used. Furthermore, the 3D Au microelectrodes showed substantially enhanced electrical durability characteristics against over-injected stimulation currents, withstanding electrical currents that are much larger than the limit measured for 2D microelectrodes of similar area. This enhanced electrical durability property of 3D Au microelectrodes is a new finding in microelectrode research, and makes 3D microelectrodes very desirable devices.

Retinal prosthetic devices stimulate retinal nerve cells with electrical signals proportional to the incident light intensities. For a high-resolution retinal prosthesis, it is necessary to reduce the size of the stimulator pixels as much as possible, because the retinal nerve cells are concentrated in a small area of approximately 5 mm × 5 mm. In this paper, a miniaturized biphasic current stimulator integrated circuit is developed for subretinal stimulation and tested in vitro. The stimulator pixel is miniaturized by using a complementary metal-oxide-semiconductor (CMOS) image sensor composed of three transistors. Compared to a pixel that uses a four-transistor CMOS image sensor, this new design reduces the pixel size by 8.3%. The pixel size is further reduced by simplifying the stimulation-current generating circuit, which provides a 43.9% size reduction when compared to the design reported to be the most advanced version to date for subretinal stimulation. The proposed design is fabricated using a 0.35 μm bipolar-CMOS-DMOS process. Each pixel is designed to fit in a 50 μ m × 55 μm area, which theoretically allows implementing more than 5000 pixels in the 5 mm × 5 mm area. Experimental results show that a biphasic current in the range of 0 to 300 μA at 12 V can be generated as a function of incident light intensities. Results from in vitro experiments with rd1 mice indicate that the proposed method can be effectively used for retinal prosthesis with a high resolution.

Long-term electrode implant is a challenge for successful brain-computer interfaces (BCIs). It is well known that electrocorticography (ECoG) using flexible planar electrodes is more suitable for long-term implants than intracortical neural recordings using penetrative electrodes. In this study, we propose a convex-shaped, PDMS-parylene hybrid multi-electrode array for long-term stable ECoG recording on the brain or the spinal cord. The electrode array consists of 10 gold recording sites which show impedance values between 50 and 70 kOhm at 1 kHz with a diameter of 100 µm. It is designed like octopus's leg to tightly adhere to the ellipsoidal brain. To assess its performance, epidural ECoG recordings were performed from the main olfactory bulb (MOB) of an anesthetized rat during odor stimulation. The odor-evoked response was shown with an increase of the power in the beta band.

In this paper, brain-machine interface (BMI) was adopted to investigate the motor area in the animal brain. Stainless steel wire electrodes were implanted to search the brain area for rotation, forward movement, and flapping. In continuation of our search for optimized coordinates for stimulation, we designed electrode case for safer transport and for a more accurate fabrication of the electrode array. The cases are customized for each set of coordinates, and quickly built using a 3D printer. The case reduced the surgery time and increased accuracy in electrode placement. Stimulation of various sites in the brain derived the pigeon to move as we have anticipated.

A polymer-based implantable stimulator for wirelessly navigating pigeons was conceptually suggested and a pilot study using depth electrodes was conducted. In this study, depth electrodes based on liquid crystal polymer (LCP) with eight channels were designed and fabricated. Electrochemical impedance spectrum (EIS) assessments were performed to measure impedances of the electrodes. The average value of the measured impedances was 16.8∠15.8 ° kμ. The electrodes were then advanced to a target nucleus (formatio reticularis medialis mesencephalic, FRM) of a pigeon to prove their in vivo feasibilities. Biphasic current pulses were generated by a custom-made stimulator and delivered to the electrodes to stimulate the FRM electrically. Pulses with an amplitude level of 0.567 μA, a rate of 58.0 Hz, and a duration of 1.00 ms were applied with inter-stimulus intervals of three minutes. Turning and circling behaviors were consistently shown when the FRM was stimulated. The feasibilities of the electrodes were proved in both in vitro and in vivo tests, as a pilot study for the suggested scheme. Finally, several discussions of the assessments and extensions for a fully implantable stimulator were described.

Sacral nerve stimulation (SNS) is a therapeutic medical procedure that stimulates the sacral nerve using an electrode inserted near the sacral nerve to treat the conditions of overactive bladder and fecal incontinence. The primary challenge in the SNS procedure is that the physician inserts a needle to place an electrode through the narrow structure of the sacrum while relying on fluoroscopic images. We developed a navigation system which relies on an off-the-shelf electromagnetic tracking device, preoperative CT images, and a graphical user interface for needle insertion. Subjects inserted the needle into targets in a free metallic environment and in a surgical environment with a sacral phantom model. The mean registration error in four trials was 0.90±0.081 mm in the free metallic environment and 1.16±0.49 mm in the surgical environment. The mean user error (UE) between the needle tip position and a target was 5.08±1.27 mm in the free metallic environment and 4.26±2.87 mm in the surgical environment. We believe that our navigation system has potential to improve clinical sacral nerve stimulation treatment considerably. To support clinical application of this method, several remaining issues pertaining to the developed navigation system in an in vivo environment must be resolved.

The concepts of microrobots has been drawn significant attentions recently since its unprecedented applicability in nanotechnology and biomedical field. Bacteria attached microparticles presented in this work are one of pioneering microrobot technology for self-propulsion or producing kinetic energy from ambient for their motions. Microfluidic device, especially utilizing laminar flow characteristics, were employed for anisotropic attachment of Salmonella typhimurium flagellated chemotactic bacteria to 30 um × 30 um and 50 um × 50 um microparticles that made of biodegradable polymer. Any toxic chemicals or harmful treatments were excluded during the attachment process and it finished within 100 s for the anisotropic attachment. The attachments were directly confirmed by fluorescent intensity changes and SEM visualization. Chemotaxis motions were tracked using aspartate and the maximum velocity of the bacteria-attached microrobot was measured to be ~5 um/s which is comparable to prior state of art technologies. This reusable and scalable method could play a key role in chemotaxis delivery of functional microparticles such as drug delivery system.

Using 18F- fluorodeoxyglucose positron emission tomography (FDG PET), we aimed to assess the cortical areas activated by light and electrical stimuli in rabbits and to determine the nature of the electrically evoked visual perception by comparing the 2 activated cortical images. Three adult white rabbits were used, and 5 18F-FDG PET scans were performed on 5 different days for each rabbit: a resting image, 2 light stimulation images, and 2 electrical retinal stimulation images by suprachoroidal electrodes of the right and left eyes. A small-animal PET scanner (resolution: 1.18 to 1.45 mm) was used for image acquisition. Activated cortical areas were determined by voxel-wise statistical analysis of the difference between the stimulation and resting PET images, and three-dimensional brain imaging of functional activation was constructed. After visual and electrical stimulation of the rabbit retina, increased metabolism was found in 2 distinct cerebral cortical areas: (1) the ipsilateral frontal cortex (frontal eye field) and (2) the contralateral occipito-parietal cortex (visual cortex). Cortical areas activated after electrical retinal stimulation were nearly identical to the visually activated cortical areas. Electrical stimulation of the rabbit retina using suprachoroidal electrodes induced a similar cortical activation response as that induced by light stimulation. Brain PET images obtained from stimulation of the retina with light and electric current increase our understanding of cortical perceptions by both stimuli and can be a useful methodology for retinal prosthesis research.

In this paper, a novel microelectrode array (MEA), with varying arrowhead shapes, is fabricated and evaluated for retinal prostheses. The proposed MEA has a total of 199 arrowhead-shaped microelectrodes, with heights ranging from 42 to 123.5 μm. This height variation allows each microelectrode to contact the spherical eyeball conformably and to approach the stimulation target retinal cells very closely. The fabricated MEAs are implanted in rabbit eyes. The physical contact of the MEA is evaluated using optical coherent tomography (OCT) images, which show that the implanted MEA makes an excellent conformal contact with the spherically shaped retinal layers. These OCT images also exhibit good biocompatibility of the implanted MEA. The evaluation results show that the proposed MEA has a high potential for clinical applications. Our ongoing project is aimed at clinical application in three years. [2010-0037].

Purpose To investigate reproducible surgical techniques to optimize the long-term safety of liquid crystal polymer (LCP)-based retinal prosthesis implantation. Methods An LCP-based retinal prosthesis is fabricated monolithically on a single-body LCP substrate with all components, including the package and electrode array. We implanted the electrode array into the suprachoroidal space and anchored the package and transition part to the sclera in rabbits (n = 11). The safety profile was assessed upon the completion of the surgery and postoperatively. Results The surgical procedures for implantation of the entire system were easily performed in nine eyes (81.8%) without any intraoperative complications. In the other two eyes (18.2%), surgical complications related to electrode insertion, including optic nerve damage and retinal tear, arose. In 10 eyes (90.9%), the devices were well tolerated for at least 3 months. However, in most eyes (nine; 81.8%), two complications began to appear after 3 months, postoperatively, including conjunctival erosion or dehiscence over the package or transition part. The electrode arrays were maintained safely in the suprachoroidal space after surgery without any complications, regardless of the status of the extraocular components in all cases except two intraoperative complications. Conclusions We established safe and reproducible surgical techniques for implantation of our LCP-based retinal prosthesis into the suprachoroidal space. Although issues related to surgical technique or device configuration were identified, further technical solutions would improve the long-term safety of device implantation. Translational Relevance This study presents successful implantation of LCP-based retinal prosthesis. The technical solutions will permit an optimization of surgical techniques.

To establish a Korean normative database of retinal nerve fiber layer (RNFL) thickness.Data was collected from 103 healthy volunteers. Total ophthalmologic examinations, including fast RNFL thickness analysis by time domain optical coherence tomography (STRATUS OCT) were performed. The RNFL thickness of 64 glaucoma patients with localized RNFL defects and 48 independent healthy subjects were collected. The RNFL thickness of both the glaucoma patients and the healthy subjects was evaluated using both normative databases.The average RNFL thickness of Koreans was 108.3 +/- 10.3 microm. The sensitivity rates recorded in the Korean normative database with 5% and 1% significance were 0.984 and 0.984, with specificity values of 0.938 and 1.000. By comparison, the sensitivity rates in the conventional normative database with 5% and 1% significance are 0.984 and 0.953, and the specificity values are 1.000 and 1.000.In detecting localized RNFL defects, the Korean database showed higher sensitivity than the conventional database.

We proposed a simple microfluidic device that enabled anisotropic absorption of detoxified S.typhimurium bacteria to microcubics so that the particles can swim toward desirable direction by chemotaxis of the bacteria. The speed of the “bacteria-based microrobot” was ∼5um/sec which is faster than any prior demonstrations, leading to an effective drug delivery system.

We proposed a simple microfluidic device that enabled anisotropic absorption of detoxified S. typhimurium bacteria to each microcubic so that the particles can swim toward desirable direction by chemotaxis of the bacteria. The speed of the “bacteria-based microrobot” was ∼5 um/sec which is faster than any prior demonstrations, leading to an effective drug delivery system.

We propose a simple method for forming fibroblast (NIH/3T3)-laden alginate lumen gels using a coaxial laminar flow for artificial vascularization, and was evaluated using confocal microscope As increasing the sodium alginate flow rates, the average outer diameters of the composed micro-tubes determined by the thickness of the injecting material, decreased. We mixed NIH/3T3 to gels and were alive during 4 days of cell culture, and this showed fibroblast cells to be well-organized and cultured maintaining the blood-vessel shape. The proposed technique could further be applied to an endothelial co-culturing system for mimicking the real blood vessel.

Single-crystal silicon planar micro-spikes with protruding barbs are developed for micro-scale biopsy and the feasibility of using the micro-spike as a micro-scale biopsy tool is evaluated for the first time. The fabrication process utilizes a deep silicon etch to define the micro-spike outline, resulting in protruding barbs of various shapes. Shanks of the fabricated micro-spikes are 3 mm long, 100 ?m thick and 250 ?m wide. Barbs protruding from micro-spike shanks facilitate the biopsy procedure by tearing off and retaining samples from target tissues. Micro-spikes with barbs successfully extracted tissue samples from the small intestines of the anesthetized pig, whereas micro-spikes without barbs failed to obtain a biopsy sample. Parylene coating can be applied to improve the biocompatibility of the micro-spike without deteriorating the biopsy function of the micro-spike. In addition, to show that the biopsy with the micro-spike can be applied to tissue analysis, samples obtained by micro-spikes were examined using immunofluorescent staining. Nuclei and F-actin of cells which are extracted by the micro-spike from a transwell were clearly visualized by immunofluorescent staining.

Artificial retina is aimed for the stimulation of remained retinal neurons in the patient with degenerated photoreceptors. Microelectrode arrays have been developed for this as a part of stimulator. To minimize the damage during ophthalmic surgery and to get better contact to retina, flexible polyimide, which can be fabricated based on semiconductor manufacturing, was selected as the substrate material. In vitro biocompatibility of polyimide microelectrode array (MEA) was tested by co-culture with human retinal pigment epithelial cells (RPE). In vivo biocompatibility was tested in the rabbit eyes. The polyimide MEA showed good affinity to human RPE and did no harmful effect. It also showed very good stability and safety in rabbit eyes by 12 weeks.

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.

This paper presents a method of fabricating pulverized drug, Lapatinib (Tykerb®), loaded micro chambers made of a biodegradable polymer, poly (e-caprolactone) (PCL), for bacteria-based microrobots. The PCL is a biodegradable, biocompatible polymer which is approved by the U.S. Food and Drug Administration (FDA) for use in the implantable medical devices. Lapatinib is approved by the U.S. FDA for the treatment of advanced or metastatic breast cancer. In order to realize bacteria-based microrobots, selective bacterial adhesion is necessary which can enhance directional locomotion of the bacteria-based microrobots. The x-ray lithography process can be used for biodegradable polymer micromachining to fabricate structures with various shapes which can be applied for bacteria-based microrobots. A pulverized drug is used because a liquefied drug cannot be used for the x-ray lithography process. To fabricate pulverized Lapatinib loaded micro chambers, the PCL films are prepared by the solvent casting method and lamination process. Lapatinib is encapsulated between the PCL films by the screen printing method. The x-ray lithography process is then used for fabrication of micro chambers. The fabrication results indicate that the proposed method is appropriate for fabrication of biodegradable polymeric micro chambers encapsulated with the pulverized drug for bacteria-based microrobots.

Objective. The aim of this study is to evaluate the long-term reliability of a recently presented liquid crystal polymer (LCP) -based retinal prosthesis in vitro as well as in vivo. Because an all-polymer implant introduces another intrinsic leak type due to gas permeation, for which the traditional helium leak test for metallic packages was not designed to quantify, a new method to investigate its durability is required. Approach. We designed and carried out a series of reliability tests specifically for all-polymer implants by quantitatively investigating moisture ingress through various pathways of the polymer surface, and the polymer–polymer and polymer–metal adhesions. Moisture permeation through the bulk material was estimated by analytic calculation, while water ingress through the adhesively sealed LCP–LCP and LCP–metal interfaces was investigated using the separate parts of an electrode array and a package in an accelerated aging condition. In vivo tests were done in rabbits to examine the long-term biocompatibility and implantation stability by fundus observation and optical coherence tomography (OCT) imaging. Main results. The analytic calculation estimated good barrier properties of the LCP. Samples of the LCP-based electrode array failed after 114 days in 87 °C saline as a result of water penetration through the LCP–metal interface. An eye-conformable LCP package survived for 87 days in an accelerated condition at 87 °C. The in vivo results confirmed that no adverse effects were observed around the retina 2.5 years after the implantation of the device. Significance. These long-term evaluation results show the potential for the chronic use of LCP-based biomedical implants to provide an alternative to traditional metallic packages.

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes.

This paper presents an integrated neural probe that can be used as a neural signal recorder as well as a chemical stimulator. The single unit integrated probe features in-plane shanks with buried microchannels and low impedance microelectrodes. The fabricated neural probe has three 3 mm-long shanks with a 10 /spl mu/m-diameter microchannel and six 30 /spl mu/m /spl times/ 30 /spl mu/m square gold microelectrodes per shank. The measured impedance magnitude and the phase shift of the microelectrodes are 23.1 k/spl Omega//900 /spl mu/m/sup 2/ and 52.9/spl deg/ at 1 kHz, respectively.

A three-dimensional array of single-crystalline silicon microspikes with protruded barbs is developed for microscale biopsy. The developed microbiopsy tool is designed to replace the conventional endoscopic biopsy tool and to reduce patient discomfort and risk during the endoscopic operation. For fabrication we extend the SBM (Sacrificial Bulk Micromachining) process and apply the SBM process to both sides of the wafer. Shanks of the fabricated 3D microspikes are 1.5 mm long, 150 /spl mu/m thick and 150 /spl mu/m wide. The developed microbiopsy tools are evaluated in-vivo experiment by extracting tissues from live anesthetized rabbits and examining the tissue with the hematoxylin and eosin (H&E) staining protocol. In addition, the clinical test of extracting gastric adenocarcinoma tissue samples is also performed. The 3D microspikes successfully extracted tissue samples from the small intestines of the anesthetized rabbits and gastric adenocarcinoma tissue. The evaluation reveals that the biopsy with the 3D microspike can be applied to the medical examination.

Retinal implant is aimed at electronic stimulation of remaining retinal neurons in patients with degenerated photoreceptors. The Korean group for retina implants started development in year 2000, aiming for the rehabilitation of patients suffering from photoreceptor loss due to diseases such as aged-related macular degeneration (AMD) and retinitis pigmentosa (RP). To minimize the damage during ophthalmic surgery and to get better contact to the retina, flexible polyimide is selected as the substrate material of microelectrode arrays. Both the subretinal and epiretinal approaches are investigated in the group. For stimulation, we have considered both direct optical stimulation using unbiased photodiodes, and ordinary electrical stimulation based on cochlear implant-like electronics. The implanted retina produces EEPs (electrically evoked potentials) with typical peaks present, but with smaller latencies. In this presentation, we will describe the neuron-microelectronics interface, the stimulation methods, and the results of in-vitro and in-vivo animal tests.