Fabrication and validation of flexible neural electrodes based on polyimide tape and gold sheet.

This research was conducted to apply polyimide tape, which has the advantages of low price ans strong adhesive strength, to the neural electrode process. In addition, to maximize the low-cost characteristics, a fabrication process based on UV laser patterning rather than a photolithography process was introduced. The fabrication process started by attaching the gold sheet on the conductive double-sided tape without being torn or crushed. Then, the gold sheet and the double-sided tape were patterned together using UV laser. The patterned layer was transferred to the single-side polyimide tape. For insulation layer, electrode site opened single-sided polyimide tape was prepared. Polydimethylsiloxane was used as an adhesion layer, and alignment between electrode sites and opening sites was processed manually. The minimum line width achieved through the proposed fabrication process was approximately 100 µm, and the sheet resistance of the conductive layer was 0.635 Ω/sq. Measured cathodal charge storage capacity was 0.72 mC/cm2 and impedance at 1 kHz was 4.07 kΩ/cm2. Validation of fabricated electrode was confirmed by conducting 30 days accelerated soak test, flexibility test, adhesion test and ex vivo stimulation test. The novel flexible neural electrodes based on single-sided polyimide tape and UV laser patterned gold sheet was fabricated successfully. Conventional neural electrode fabrication processes based on polyimide substrate has a disadvantages such as long fabrication time, expensive costs, and probability of delamination between layers. However, the novel fabrication process which we introduced can overcome many shortcomings of existing processes, and offers great advantages such as simplicity of fabrication, inexpensiveness, flexibility and long-term reliability.

Implantable Neural Electrodes Fabrication Based on Perfluoroalkoxyalkane Film.

OBJECTIVE: In this paper, the fabrication of perfluoro-alkoxy alkane (PFA) film-based planar neural electrodes was proposed. METHODS: The fabrication of PFA-based electrodes started with cleaning of PFA film. The argon plasma pretreatment was performed on the PFA film surface and attached to a dummy silicon wafer. Metal layers were deposited and patterned using the standard Micro Electro Mechanical Systems (MEMS) process. Electrode-sites and pads were opened using reactive ion etching (RIE). Lastly, the electrode patterned PFA substrate film was thermally laminated with the other bare PFA film. Electrical-physical evaluation tests were conducted along with in vitro tests, ex vivo tests and soak tests to evaluate the electrode performance and biocompatibility. RESULTS: The electrical and physical performance of PFA-based electrodes had better performances compared to other biocompatible polymer-based electrodes. Also, the biocompatibility and longevity were verified by cytotoxicity test, elution test, and accelerated life test. CONCLUSION: The PFA film-based planar neural electrode fabrication was established and evaluated. The PFA based electrodes showed excellent benefits such as long-term reliability, low water absorption rate, and flexibility using the neural electrode. SIGNIFICANCE: For implantable neural electrodes, hermetic sealing is required for in vivo durability. PFA fulfilled a low water absorption rate with relatively low Young's modulus to increase the longevity and biocompatibility of the devices.

Investigation of toxicity and performance deterioration of parylene-C packaged copper coils using accelerated test.

OBJECTIVES: In this paper, to figure out the reliability of copper wire wound coil in an in vitro environment, performance deterioration and copper ion elution of coil was investigated using accelerated tests. METHODS: Bare coils with enamel coating and parylene-C coated coils were immersed into the 75-degree Celsius phosphate-buffered saline for accelerated tests. Performance and elution of the copper ion were investigated using proper equipment. RESULTS: The parylene-C coating with a thickness of several um effectively depress the performance degradation and the elution of the copper ion. However, it has not reached a perfect level and research on additional packaging methods is needed. SIGNIFICANCE: Coil for wireless power and data transfer is an important element in the design of implantable devices. Copper is the most widely used material for the design of coils in general. However, because of its cytotoxicity and high reactivity with water, the packaging capabilities should be investigated closely. In this paper, a method for evaluating the packaging performance when the coil is coated with parylene-C and the results are presented.

Fabrication of Implantable Microelectrode Array using Cyclic Olefin Copolymer and SU-8 via Photocrosslinking Lamination.

In this work, a fabrication process for implantable electrodes using a Cyclic Olefin Copolymer (COC) substrate and a SU-8 passivation layer was presented. COC and SU-8 were shown to be suitable for implantable neural electrodes due to their biocompatibility, chemical resistance, and thermal stability. The electrodes were successfully patterned on the COC film, and the SU-8 passivation layer was coated while maintaining site-opened via photolithography. The photocrosslinking lamination of the substrate and passivation layer was used to produce electrodes with fine line widths of 20um without applying heat.

Low dead space encapsulation and integration of circuits for retinal prosthesis based on cyclic olefin copolymer.

A retinal prosthesis is a device that can provide artificial vision to people who have lost their sight from certain retinal disorder. Because the device needs to be inserted into the body, high flexibility and reliability is required. Recently, devices using thermoplastic polymers such as LCP and COC as substrates have been studied. Being a highly functional integrated device, retinal prosthesis poses many design challenges. Among them, the stimulation chip embedding can be a particularly important task. Although it is common to use a wire bonding method for chip embedding, there are several limitations that are difficult to apply to implantable device. In this investigation, a novel approach is developed for high spaceefficient electrical connections and perform reliable encapsulation of integrated circuits to replace wire bonding. Since designing and manufacturing the stimulator chip used in retinal prosthesis requires non-negligible cost, a silicon die with the identical shape was selected as a substitute for testing purposes.

Feasibility, credence, and usefulness of out-of-office cuffless blood pressure monitoring using smartwatch: a population survey.

BACKGROUND: Cuffless blood pressure (BP) measurement, enabled by recent advances in wearable devices, allows for BP monitoring in daily life. This study aims to evaluate the feasibility, cresdence, and usefulness of cuffless BP monitoring through a population survey. METHODS: During the "Daily BP Measurement with Your Galaxy Watch" campaign held by the Korean Society of Hypertension, participants were asked to share their experiences with cuffless BP measurement using a smartwatch application through an online survey. The questionnaire included questions about age, underlying medical conditions, smartwatch utilization, experience with BP calibration, the reliability of BP values measured by a smartwatch, and willingness to use the BP monitoring function in the future. RESULTS: A total of 1071 participants responded to the survey. The largest age group (decile) was 50-59 years old (33.3%), followed by 40-49 years old (29.9%). Although nearly half of the participants (47.5%) had no chronic diseases, 40.1% reported having hypertension. BP monitoring was the most frequently utilized smartwatch function (95.8%), followed by heart rate measurement (87.1%). 31.8% of participants reported that BP values measured by the smartphone application were "very accurate and helpful," while 63.5% rated them as "slightly lower (44.4%)" or "higher (19.1%)" compared to the standard home BP monitoring device. 93% of the participants reported utilizing the BP monitoring function at least once a week. Regarding the BP calibration process, most participants (93.9%) calibrated the BP measurement application themselves, and 50.8% rated the difficulty level as "very easy." CONCLUSION: Cuffless BP measurement using a smartwatch application was feasible in the general population, including the self-calibration process. However, the satisfaction level in terms of accuracy is still modest, indicating a need for further development.

Automatic Lung Cancer Segmentation in [18F]FDG PET/CT Using a Two-Stage Deep Learning Approach.

Purpose: Since accurate lung cancer segmentation is required to determine the functional volume of a tumor in [18F]FDG PET/CT, we propose a two-stage U-Net architecture to enhance the performance of lung cancer segmentation using [18F]FDG PET/CT. Methods: The whole-body [18F]FDG PET/CT scan data of 887 patients with lung cancer were retrospectively used for network training and evaluation. The ground-truth tumor volume of interest was drawn using the LifeX software. The dataset was randomly partitioned into training, validation, and test sets. Among the 887 PET/CT and VOI datasets, 730 were used to train the proposed models, 81 were used as the validation set, and the remaining 76 were used to evaluate the model. In Stage 1, the global U-net receives 3D PET/CT volume as input and extracts the preliminary tumor area, generating a 3D binary volume as output. In Stage 2, the regional U-net receives eight consecutive PET/CT slices around the slice selected by the Global U-net in Stage 1 and generates a 2D binary image as the output. Results: The proposed two-stage U-Net architecture outperformed the conventional one-stage 3D U-Net in primary lung cancer segmentation. The two-stage U-Net model successfully predicted the detailed margin of the tumors, which was determined by manually drawing spherical VOIs and applying an adaptive threshold. Quantitative analysis using the Dice similarity coefficient confirmed the advantages of the two-stage U-Net. Conclusion: The proposed method will be useful for reducing the time and effort required for accurate lung cancer segmentation in [18F]FDG PET/CT.

Feasibility and measurement stability of smartwatch-based cuffless blood pressure monitoring: A real-world prospective observational study.

Cuffless wearable devices are currently being developed for long-term monitoring of blood pressure (BP) in patients with hypertension and in apparently healthy people. This study evaluated the feasibility and measurement stability of smartwatch-based cuffless BP monitoring in real-world conditions. Users of the first smartwatch-based cuffless BP monitor approved in Korea (Samsung Galaxy Watch) were invited to upload their data from using the device for 4 weeks post calibration. A total of 760 participants (mean age 43.7 ± 11.9, 80.3% men) provided 35,797 BP readings (average monitoring 22 ± 4 days [SD]; average readings 47 ± 42 per participant [median 36]). Each participant obtained 1.5 ± 1.3 readings/day and 19.7% of the participants obtained measurements every day. BP showed considerable variability, mainly depending on the day and time of the measurement. There was a trend towards higher BP levels on Mondays than on other days of the week and on workdays than in weekends. BP readings taken between 00:00 and 04:00 tended to be the lowest, whereas those between 12:00 and 16:00 the highest. The average pre-post calibration error for systolic BP (difference in 7-day BP before and after calibration), was 6.8 ± 5.6 mmHg, and was increased with higher systolic BP levels before calibration. Smartwatch-based cuffless BP monitoring is feasible for out-of-office monitoring in the real-world setting. The stability of BP measurement post calibration and the standardization and optimal time interval for recalibration need further investigation.

Minimally Invasive Implant Type Electromagnetic Biosensor for Continuous Glucose Monitoring System: In Vivo Evaluation.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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 (R2 > 0.9) with measured BGL was observed during in vivo experiments. CONCLUSION: The experimental results demonstrate that the proposed sensor is suitable for long term CGMS applications with a high accuracy. SIGNIFICANCE: 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.

Neurostimulators for high-resolution artificial retina: ASIC design challenges and solutions.

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.

Subcutaneously implantable electromagnetic biosensor system for continuous glucose monitoring.

Continuous glucose monitoring systems (CGMS) are becoming increasingly popular in diabetes management compared to conventional methods of self-blood glucose monitoring systems. They help understanding physiological responses towards nutrition intake, physical activities in everyday life and glucose control. CGMS available in market are of two types based on their working principle. Needle type systems with few weeks lifespan (e.g., enzyme-based Freestyle Libre) and implant type system (e.g., fluorescence-based Senseonics) with few months of lifespan are commercially available. An alternate to both working methods, herein, we propose electromagnetic-based sensor that can be subcutaneously implanted and capable of tracking minute changes in dielectric permittivity owing to changes in blood glucose level (BGL). Proof-of-concept of proposed electromagnetic-based implant sensor has been validated in intravenous glucose tolerance test (IVGTT) conducted on swine and beagle in a controlled environment. Sensor interface modules, mobile applications, and glucose mapping algorithms are also developed for continuous measurement in a freely moving beagle during oral glucose tolerance test (OGTT). The results of the short-term (1 h, IVGTT) and long-term (52 h, OGTT) test are summarized in this work. A close trend is observed between sensor frequency and BGL during GTT experiments on both animal species.

The Design and Analysing Heating Effect of Spiral Planar Coil in COMSOL Multiphysics for Implantable Artificial Retina.

In this paper, simulation data and heat generation due to electromagnetic from spiral planar pair of coils for arti-ficial retinal implant were analyzed by COMSOL Multiphysics. Planar spiral outer and inner coils for an implantable artificial retina were designed and analyzed. The whole geometry was designed in a transplant situation. The parameters of the coil were set within the design limits due to the limitations of im-plant space. The inductance for the coil and the thermal change due to the electromagnetic force generated in the inductively coupled coil were calculated. Analysis of heat transfer in a biological model showed that the maximum heat did not exceed the internal tissue damage temperature. The results showed that a pair of coils designed for artificial retinas can be implanted in vivo without destruction of body tissues.

Manually wound coil fabrication process based on cyclic olefin copolymer substrate.

Neural prostheses are systems that interact with the human nervous system to recover function lost as a result of disease by recording or stimulating neural signals. Neural implants have a variety of components, but among them, designing highly efficient wireless power transmission systems is particularly important. However, there is a problem that it is difficult to design a wireless power transmission system with high transmission efficiency because power transmission efficiency is affected by various coil parameters. In addition, nerve implants are mainly designed based on polymer substrates, but studies have not been conducted on the process of manufacturing coils based on polymer substrates. In this study, to overcome the mentioned problems, an easy and fast manufacturing process was proposed before designing a precise coil on a polymer substrate. Coil was made by manually winding the 200um copper wire, and the coil was packaged using COC. The coil feasibility test was conducted after fabrication to evaluate the performance of fabrication process. It did not fit the expected frequency because the wire was manually wound to make a small size coil. However, the wire wound coil is expected to be more efficient than the coil made through the PCB process, and if the sophistication is supplemented, it can be used as a highly efficient coil for wireless power transmission.

Selective Edge Rounding of Cyclic Olefin Copolymer Film Using UV Laser for Implantable Electrode Package.

Cyclic Olefin Copolymer is emerging as a packaging material for implantable electrodes due to its physical properties such as low water absorption rate and low water vapor permeability. The electrode-tissue interface is often regarded as a major focus of implantable electrodes, but its packaging should also be considered thoroughly since it directly contacts the adjoining body cells. Therefore, eliminating any sharp boundaries or edges around the package would be beneficial to minimize potential inflammatory responses caused by physical/mechanical stresses. To smooth both inner/outer edges of a cyclic olefin copolymer packaging, an optimal UV laser condition was investigated by varying its marking speed and iterations. Clinical relevance - This establishes a method that can selectively smooth the edges around a cyclic olefin copolymer pack-aged implantable electrodes for reduced mechanical mismatch after insertion.

Investigation of neural electrode fabrication process on Polycarbonate substrate.

Polycarbonate is a polymer that has been widely used including medical application due to its useful properties. It has high temperature resistance, biocompatibility, transparency and low water absorption rate, which are needful characteristics for packaging material of implantable neural prosthetic devices. In this study, we investigated fabrication of neural electrode with polycarbonate film using standard photolithography process and heated hydraulic press for thermal lamination. First, oxygen plasma surface treatment was performed to increase the adhesion between metal and polycarbonate film. Then thin layer of titanium and gold layer were deposited. Metal layer is patterned through standard photolithography techniques. After completing the metal patterning, thermal lamination was performed with site opened polycarbonate film.

Low-cost, thermoplastic micro-lens array with a carbon black light screen for bio-mimetic vision.

Micro-lens array is a great example of bio-mimetic technology which was inspired by compound eyes found in insects and is used in lasers, optical communication, and 3D imaging. In this study, a micro-lens array was fabricated from cyclic olefin copolymer using a cost-effective method: compression molding and thermal reflow. Also, a light screen was installed between lenses to reduce the optical interference for clearer individual images. Cyclic olefin copolymer-based micro-lens array showed good optical results under a standard optical microscope. By placing the fabricated micro-lens array directly on an image sensor, it was observed that the light screen shows significant improvement in image quality. Also, the point spread function was analyzed to confirm the optical performance and the effectiveness of the micro-lens array with the light screen installed.

Vision-correcting holographic display: evaluation of aberration correcting hologram.

Vision-correcting displays are key to achieving physical and physiological comforts to the users with refractive errors. Among such displays are holographic displays, which can provide a high-resolution vision-adaptive solution with complex wavefront modulation. However, none of the existing hologram rendering techniques have considered the optical properties of the human eye nor evaluated the significance of vision correction. Here, we introduce vision-correcting holographic display and hologram acquisition that integrates user-dependent prescriptions and a physical model of the optics, enabling the correction of on-axis and off-axis aberrations. Experimental and empirical evaluations of the vision-correcting holographic displays show the competence of holographic corrections over the conventional vision correction solutions.

Artificial Compound Eye Systems and Their Application: A Review.

The natural compound eye system has many outstanding properties, such as a more compact size, wider-angle view, better capacity to detect moving objects, and higher sensitivity to light intensity, compared to that of a single-aperture vision system. Thanks to the development of micro- and nano-fabrication techniques, many artificial compound eye imaging systems have been studied and fabricated to inherit fascinating optical features of the natural compound eye. This paper provides a review of artificial compound eye imaging systems. This review begins by introducing the principle of the natural compound eye, and then, the analysis of two types of artificial compound eye systems. We equally present the applications of the artificial compound eye imaging systems. Finally, we suggest our outlooks about the artificial compound eye imaging system.

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.

Change in the eye position under general anesthesia in children with intermittent exotropia.

PURPOSE: To evaluate the eye position in subjects with intermittent exotropia and normal subjects under general anesthesia (GA) using the strabismus photo analyzer. METHODS: This retrospective case-control study included 78 subjects with intermittent exotropia and 25 normal control subjects who underwent epiblepharon surgery. Eye position under GA was assessed using the strabismus photo analyzer, based on eye models generated from corneal lights and limbus in pre- and post-anesthesia images. Eye positions under GA in the control and intermittent exotropia groups were compared. Preoperative angle of deviation was also compared with amount of change in eye position under GA in the intermittent exotropia group. RESULTS: Eye position under GA was more divergent in subjects with intermittent exotropia than in controls (P = 0.008). The amount of change in eye position under GA was correlated with the preoperative angle of deviation (r2 = 0.47; P < 0.001). In small preoperative exodeviations, the change in eye position was primarily more divergent, whereas in large exodeviations, a convergent tendency-less exotropic compared with the preoperative angle of exodeviation-was observed. CONCLUSIONS: In subjects with small preoperative exodeviations, there was a tendency for eye position to become more divergent after GA; in those with large exodeviations, there was less exotropia after GA.