81 research outputs found

    A Wireless, High-Voltage Compliant, and Energy-Efficient Visual Intracortical Microstimulator

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    RÉSUMÉ L’objectif général de ce projet de recherche est la conception, la mise en oeuvre et la validation d’une interface sans fil intracorticale implantable en technologie CMOS avancée pour aider les personnes ayant une déficience visuelle. Les défis majeurs de cette recherche sont de répondre à la conformité à haute tension nécessaire à travers l’interface d’électrode-tissu (IET), augmenter la flexibilité dans la microstimulation et la surveillance multicanale, minimiser le budget de puissance pour un dispositif biomédical implantable, réduire la taille de l’implant et améliorer le taux de transmission sans fil des données. Par conséquent, nous présentons dans cette thèse un système de microstimulation intracorticale multi-puce basée sur une nouvelle architecture pour la transmission des données sans fil et le transfert de l’énergie se servant de couplages inductifs et capacitifs. Une première puce, un générateur de stimuli (SG) éconergétique, et une autre qui est un amplificateur de haute impédance se connectant au réseau de microélectrodes de l’étage de sortie. Les 4 canaux de générateurs de stimuli produisent des impulsions rectangulaires, demi-sinus (DS), plateau-sinus (PS) et autres types d’impulsions de courant à haut rendement énergétique. Le SG comporte un contrôleur de faible puissance, des convertisseurs numérique-analogiques (DAC) opérant en mode courant, générateurs multi-forme d’ondes et miroirs de courants alimentés sous 1.2 et 3.3V se servant pour l’interface entre les deux technologies utilisées. Le courant de stimulation du SG varie entre 2.32 et 220μA pour chaque canal. La deuxième puce (pilote de microélectrodes (MED)), une interface entre le SG et de l’arrangement de microélectrodes (MEA), fournit quatre niveaux différents de courant avec la valeur maximale de 400μA par entrée et 100μA par canal de sortie simultanément pour 8 à 16 sites de stimulation à travers les microélectrodes, connectés soit en configuration bipolaire ou monopolaire. Cette étage de sortie est hautement configurable et capable de délivrer une tension élevée pour satisfaire les conditions de l’interface à travers l’impédance de IET par rapport aux systèmes précédemment rapportés. Les valeurs nominales de plus grandes tensions d’alimentation sont de ±10V. La sortie de tension mesurée est conformément 10V/phase (anodique ou cathodique) pour les tensions d’alimentation spécifiées. L’incrémentation de tensions d’alimentation à ±13V permet de produire un courant de stimulation de 220μA par canal de sortie permettant d’élever la tension de sortie jusqu’au 20V par phase. Cet étage de sortie regroupe un commutateur haute tension pour interfacer une matrice des miroirs de courant (3.3V /20V), un registre à décalage de 32-bits à entrée sérielle, sortie parallèle, et un circuit dédié pour bloquer des états interdits.----------ABSTRACT The general objective of this research project is the design, implementation and validation of an implantable wireless intracortical interface in advanced CMOS technology to aid the visually impaired people. The major challenges in this research are to meet the required highvoltage compliance across electrode-tissue interface (ETI), increase lexibility in multichannel microstimulation and monitoring, minimize power budget for an implantable biomedical device, reduce the implant size, and enhance the data rate in wireless transmission. Therefore, we present in this thesis a multi-chip intracortical microstimulation system based on a novel architecture for wireless data and power transmission comprising inductive and capacitive couplings. The first chip is an energy-efficient stimuli generator (SG) and the second one is a highimpedance microelectrode array driver output-stage. The 4-channel stimuli-generator produces rectangular, half-sine (HS), plateau-sine (PS), and other types of energy-efficient current pulse. The SG is featured with low-power controller, current mode source- and sinkdigital- to-analog converters (DACs), multi-waveform generators, and 1.2V/3.3V interface current mirrors. The stimulation current per channel of the SG ranges from 2.32 to 220μA per channel. The second chip (microelectrode driver (MED)), an interface between the SG and the microelectrode array (MEA), supplies four different current levels with the maximum value of 400μA per input and 100μA per output channel. These currents can be delivered simultaneously to 8 to 16 stimulation sites through microelectrodes, connected either in bipolar or monopolar configuration. This output stage is highly-configurable and able to deliver higher compliance voltage across ETI impedance compared to previously reported designs. The nominal values of largest supply voltages are ±10V. The measured output compliance voltage is 10V/phase (anodic or cathodic) for the specified supply voltages. Increment of supply voltages to ±13V allows 220μA stimulation current per output channel enhancing the output compliance voltage up to 20V per phase. This output-stage is featured with a high-voltage switch-matrix, 3.3V/20V current mirrors, an on-chip 32-bit serial-in parallel-out shift register, and the forbidden state logic building blocks. The SG and MED chips have been designed and fabricated in IBM 0.13μm CMOS and Teledyne DALSA 0.8μm 5V/20V CMOS/DMOS technologies with silicon areas occupied by them 1.75 x 1.75mm2 and 4 x 4mm2 respectively. The measured DC power budgets consumed by low-and mid-voltage microchips are 2.56 and 2.1mW consecutively

    광 다이오드 기반 인공 망막 시스템을 위한 저전력 설계 및 LCP 패키징에 대한 연구

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    학위논문 (박사)-- 서울대학교 대학원 : 전기·컴퓨터공학부, 2017. 2. 김성준.The retinal prosthesis is an implantable electronic device that delivers electrical stimuli containing visual information to the retina for the visual restoration of the blinds. The currently available retinal prostheses have several problems in the number of pixels. They are limited in the number of pixels, which restricts the amount of visual information they can deliver. Many research groups are trying to improve their device in this aspect. In order to achieve a significant number of pixels, retinal prosthesis needs large stimulus power dissipation. A typical device consumes more than 20 mW of power to drive 1000 channels. Some of this power can lead to temperature rise which is a safety issue. As the power dissipation scales up with the increase in the number of channels, it is desired to minimize the power per channel as much as possible. Another problem is the absence of a suitable packaging material for the long-term reliable optical window. Due to the curved and narrow implant space available for this kind of device, as well as the transparency required for the incoming wavelengths of lights, it is quite difficult to choose a material that satisfies all requirements of long-term hermetic packaging with optically transparent window. Sapphire glass with titanium metal package are too bulky and rigid, and flexible transparent polymers such as polyimide and parylene-C have high moisture absorption for the implant. This dissertation proposes strategies and methods to solve the problems mentioned above. Two stimulation strategies are proposed. One strategy is to confine the stimulus level with a threshold that cell is activated. Thus we coin it as thresholding strategy.' The other strategy is to reduce the number of stimulation channels by using only outlines of images (outline extraction strategy). Prototype ICs were designed and fabricated for the verification of the effects of these strategies. The simulation and the measurement agree to show that retinal implant with the thresholding and outline extraction strategies consumes below one-third of the stimulus power of the conventional photodiode-based devices. Area-efficient designs of the voltage-controlled current source are also adopted to increase the number of channels. The unit pixel area of the fabricated prototype IC was 0.0072 mm2, expanding up to 1200-channels in the macular area. Liquid crystal polymer (LCP) is proposed as the long-term implantable packaging material with an optical window. It is an inert, biocompatible, and flexible polymer material that has a moisture absorption rate similar to Pyrex glass. We showed that an LCP film with a thickness less than 10 μm allows transmission of the lights in the visible wavelengths by more than 10 %, as the rate increases with thinner films. Thus a thinning process was developed. O2 DRIE was shown effective in reducing the roughness of the film, and the corresponding light scattering. The spatial resolution of LCP with 8.28 μm thickness showed a minimum distinguishable pitch of 90 μm, allowing a 1200 channel integration within a macular area.Chapter 1: Introduction 1 1.1. Retinal Prosthesis – State of the Arts 2 1.1.1. Retinal Prosthesis with External Camera 3 1.1.2. Retinal Prosthesis with Internal Photodiode Array 5 1.2. Photodiode-based Retinal Prosthesis 8 1.2.1. Problems 8 1.2.2. Possible Solutions 12 Chapter 2: Methods 17 2.1. Thresholding 17 2.1.1. Concept 17 2.1.2. Circuit Descriptions 19 2.2. Outline Extraction 28 2.2.1. Concept 28 2.2.2. Circuit Descriptions 30 2.3. Average Stimulus Power Estimation 40 2.3.1. Stimulus Patterns Generation of Conventional and Proposed Strategies 40 2.3.2. Minimum Distinguishable Channels to Recognize 41 2.4. Virtual Channel 43 2.4.1. Concept 43 2.4.2. Circuit Descriptions 44 2.5. Polymer Packaging 51 2.5.1. LCP as a Long-term Reliable Packaging Material 51 2.5.2. Test Methods 53 Chapter 3: Results 58 3.1. Thresholding 58 3.1.1. Fabricated IC 58 3.1.2. Test Setup 60 3.1.3. Test Results 61 3.2. Outline Extraction 65 3.2.1. Simulation Results 65 3.2.2. Fabricated IC 67 3.2.3. Test Setup 68 3.2.4. Test Results 72 3.3. Average Stimulus Power Estimation 76 3.4. Virtual Channels 79 3.4.1. Fabricated IC 79 3.4.2. Test Setup 80 3.4.3. Test Results 81 3.4.4. Two-dimensional Virtual Channel Generator– Test setup and Its Result 84 3.5. Polymer Packaging 87 3.5.1. Light Transmittance according to LCP Thickness 87 3.5.2. Thickness Control of LCP 89 3.5.3. Spatial Resolution of LCP 89 Chapter 4: Discussion 92 4.1. Average Stimulus Power 92 4.2. Visual Acuity 95 4.3. Hermeticity of the Thinned LCP Film 97 Chapter 5: Conclusion and Future Directions 99 References 103 Appendix – Generated Stimulus Patterns of Various the Number of Channels 112 국 문 초 록 139Docto

    Biomedical Engineering

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    Biomedical engineering is currently relatively wide scientific area which has been constantly bringing innovations with an objective to support and improve all areas of medicine such as therapy, diagnostics and rehabilitation. It holds a strong position also in natural and biological sciences. In the terms of application, biomedical engineering is present at almost all technical universities where some of them are targeted for the research and development in this area. The presented book brings chosen outputs and results of research and development tasks, often supported by important world or European framework programs or grant agencies. The knowledge and findings from the area of biomaterials, bioelectronics, bioinformatics, biomedical devices and tools or computer support in the processes of diagnostics and therapy are defined in a way that they bring both basic information to a reader and also specific outputs with a possible further use in research and development

    Doctor of Philosophy

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    dissertationThis dissertation provides an in-depth evaluation of microstimulation of the primary visual cortex (V1) using chronically implanted Utah Electrode Arrays (UEAs) in macaque monkeys for use as a visual prosthesis. Within the scope of this dissertation are several significant contributions. First, a minimally invasive and robust device for head fixation was developed. In comparison to other available designs, this device improved long-term outcomes by providing a stronger, less invasive interface that reduced the risk of infection. This device made it possible to acquire chronic microstimulation data in macaque monkeys. It has been tested on three animals and has provided a stable interface for over two years. Second, this dissertation is the first to describe the factors influencing the performance and safety of microstimulation of V1 with the UEA. Two UEAs were implanted in V1 of two macaque monkeys, and experiments were performed several months following implantation. The electrical and recording properties of the electrodes and the high-resolution visuotopic organization of V1 were measured. In addition, threshold stimulation levels that evoked behavioural responses using single electrodes were determined. Periodic microstimulation at currents up to 96 pA did not impair the ability to record neural signals and did not affect the animal's vision where the UEAs were implanted. It was discovered, however, that microstimulation at these levels evoked behavioural responses on only 8 of 82 systematically stimulated electrodes. It was suggested that the ability to evoke behavioral responses may depend on the location of the electrode tips within the cortical layers of V1, the distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts. Finally, this dissertation is the first to describe the spatial and temporal characteristics of microstimulation of V1 with the UEA over chronic time periods. Two years after implantation, it was found that consistent behavioural responses could be evoked during simultaneous stimulation of multiple contiguous electrodes. Saccades to electrically-evoked targets using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with a resolution comparable to the current epiretinal prostheses. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a UEA-based visual prosthesis for the blind

    Towards clinical trials of a novel Bionic Eye: Building evidence of safety and efficacy

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    In the quest for therapeutic solutions for the visually impaired, electrical stimulation of the retina is, and has been, the focus of intense research. Some of these efforts have led to the development of the Phoenix99 Bionic Eye, a device which combines promising technological features with novel stimulation strategies. For medical devices, considerable challenges must be overcome before they’re allowed to be trialled in their target population. The requirements for a study to be performed include the demonstration of a positive risk-benefit ratio of the research. The present dissertation is an attempt to address how pre-clinical trials in animals can be used to understand and minimise risks. A positive risk-benefit ratio means that the potential benefits of the research outweigh the risks of the intervention. In the case of retinal prostheses, the risks include the surgical intervention, the immune response to the device, the safety of the electrical stimuli, and the effects of device ageing. In this work, successful demonstration of the surgical safety and biocompatibility of passive Phoenix99 devices during long-term implantation in sheep called for the evaluation of the chronic effects of the novel stimulation paradigms it can deliver. As preparation for this study, the techniques used to evaluate the safety and efficacy of the stimuli in animals were refined. A systematic approach to minimise the impact of anaesthesia on the experimental results is presented, as well as a novel in vivo retinal recording technique. To maximise the clinical relevance of all animal trials, a computer model for the prediction of thresholds was developed. Finally, in vitro device ageing was performed to deepen our understanding of the design’s potential for long-term implantation. Protocols for a long-term device safety study in sheep and for an acute human trial are also presented, thus taking concrete and sensible steps towards the first clinical use of the Phoenix99 Bionic Eye

    Design and implementation of compact dual-band conformal antenna for leadless cardiac pacemaker system

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    The leadless cardiac pacemaker is a pioneering device for heart patients. Its rising success requires the design of compact implantable antennas. In this paper, we describe a circularly polarized Hilbert curve inspired loop antenna. The proposed antenna works in the WMTS (Wireless Medical Telemetry Services) 1.4 GHz and ISM (Industrial, Scientific, and Medical) 2.45 GHz bands. High dielectric constant material Rogers RT/Duroid 6010 LM ([Formula: see text]=10) and fractal geometry helps to design the antenna with a small footprint of 9.1 mm3 (6 mm × 6 mm × 0.254 mm). The designed antenna has a conformal shape that fits inside a leadless pacemaker's capsule is surrounded by IC models and battery, which are tightly packed in the device enclosure. Subsequently, the integrated prototype is simulated deep inside at the center of the multi-layer canonical heart model. To verify experimentally, we have put dummy electronics (IC and battery) inside the 3D printed pacemaker's capsule and surfaced the fabricated conformal antenna around the inner curved body of the TCP (Transcatheter Pacing) capsule. Furthermore, we have tested the TCP capsule by inserting it in a ballistic gel phantom and minced pork. The measured impedance bandwidths at 1.4 GHz and 2.45 GHz are 250 MHz and 430 MHz, whereas measured gains are - 33.2 dBi, and - 28.5 dBi, respectively

    Novel flexible multielectrode arrays for neuronal stimulation and recording

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    This thesis will focus on developments in coupling the multidisciplinary research interests of Physics, Micro-engineering and neurobiology towards the development of a proof of concept retinal prosthetic device. With recent developments in low-power electronics and semiconductor fabrication techniques many applications in the life sciences have emerged. One such application is in the development of a retinal prosthetic device which relies on the ability to record information from and feed information directly to small retinal neuronal cells which are approximately 5mum diameter. Where successful, we achieve the possibility of restoring sight to people affected by degenerative visual diseases such as Age Related Macular Degeneration and Retinitis Pigmentosa. Both these conditions affect the photosensitive elements of the eye yet leave the remaining pathways to the visual cortex, the area of the brain responsible for our visual precept, intact. High-density electrode arrays axe becoming well established as tools for the measurement of neuronal signals. The fabrication of arrays on flexible materials allows for 2D position sensitive recording of cellular activity in vivo and for the possibility of direct in vivo stimulus. Using flexible polymer materials (Pryalin PI2545), compliant with semiconductor fabrication techniques, a process allowing the fabrication of flexible multi-site microelectrode neuronal recording and stimulating arrays is presented. The development of both 8 and 74 electrode arrays on polyimide substrates with 50mum and 5mum minimum linewidths respectively is described. Implementing low noise amplification, 8muV rms (bandpass typically 80-2000 Hz), the polyimide 8-electrode arrays have been used to stimulate and record electroretinogram and ganglion cell action potentials in vivo from the frog retina (Rana lemporaria). Such arrays coupled to our application specific pixellated CMOS sensors, the IPIX, incorporating an ability to apply neural network algorithms should allow for the recovery of basic functionality in the human retina. The IPIX detector is an Active Pixel Sensor which responds to incident light in the visible region. It responds to the varying intensity of light over 3 log units and outputs varying frequency voltage pulses of similar form to that of a healthy retina. Stimulation studies for electro-deposited platinum electrodes of 4 nA/mum2 indicate upper breakdown limits for charge density approaching 100 muCm-2. Investigations of lifetime stimulation of a 50 mum diameter electrode, of typical impedance less than 20 kO at 1 kHz, suggest operational limits over lifetime in the order of 10 muCm-2. These charge densities are adequate for neuronal cell stimulation. It is believed that the system described in this thesis can form the basis on which to deploy a retinal prosthetic device. Moreover, in the short term, the information provided by this system will allow for investigations into deciphering the 'wiring diagram' of the retina

    Multimodal Investigation of the Efficiency and Stability of Microstimulation using Electrodes Coated with PEDOT/CNT and Iridium Oxide

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    Electrical microstimulation is an invaluable tool in neuroscience research to dissect neural circuits, relate brain areas, and identify relationships between brain structure and behavior. In the clinic, electrical microstimulation has enabled partial restoration of vision, movement, sensation and autonomic functions. Recently, novel materials and new fabrication techniques of traditional metals have emerged such as iridium oxide and the conducting polymer PEDOT/CNT. These materials have demonstrated particular promise in the improvement in electrical efficiency. However, the in vivo stimulation efficiency and the in vivo stability of these materials have not been thoroughly characterized. In this dissertation, we use a multimodal approach to study the efficiency and stability of electrode-tissue interface using novel materials in microstimulation

    Closed-loop approaches for innovative neuroprostheses

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    The goal of this thesis is to study new ways to interact with the nervous system in case of damage or pathology. In particular, I focused my effort towards the development of innovative, closed-loop stimulation protocols in various scenarios: in vitro, ex vivo, in vivo

    Designing sensory feedback approaches for restoring touch and position feedback in upper limb amputees

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    Upper limb amputation disrupts most daily activities and reduces the quality of life of affected individuals. Building a suitable prosthetic limb, which can restore at least some of the lost capabilities, is a goal which has been pursued for centuries. In the last few decades, our rapidly expanding understanding of the human nervous system has unlocked impressive advances in artificial limbs. Today, commercial prosthetic hands can be controlled intuitively through voluntary muscle contractions. Nevertheless, despite leaps in the quality of modern prostheses, sensory feedback remains one of the major omissions, forcing users to rely on vision to accomplish basic tasks, such as holding a plastic cup without crushing it. Several sensory feedback strategies have recently been developed to restore tactile and proprioceptive feedback to amputees, demonstrating benefits in important areas, such as higher functional performance and increases in the sense of prosthesis ownership. Sensory feedback strategies can be distinguished based on whether the sensation they restore matches the quality (homologous feedback) or the location (somatotopic feedback) of the original sensation. Despite promising results, somatotopic tactile feedback strategies often result in unnatural sensations (e.g. electricity). Furthermore, restoration of more than a single sensory modality is rarely reported, despite being necessary to create artificial limbs capable of delivering realistic sensorimotor experiences during use. In this work, I proposed three novel and complementary strategies to improve sensory feedback restoration in upper limb prostheses. I begin by describing a non-invasive transcutaneous electrical nerve stimulation (TENS) approach aimed at restoring somatotopic tactile sensations, which is potentially applicable to all trans-radial amputees. This stimulation strategy was shown to lead to high performance during functional tasks, and compared favorably to more invasive approaches, despite a few key differences. Considering that there is no such thing as a one-size-fits-all solution for amputees, I concluded that TENS represents a viable alternative to invasive systems, especially in cases where an implant is not possible or desirable. In the second part, I proposed a sensory substitution approach to multimodal feedback, which delivered somatotopic tactile and remapped proprioceptive feedback simultaneously. This stimulation strategy relied entirely on implantable electrodes, simplifying the overall system by delivering two streams of sensory information with the same device. Using this feedback system, two amputees were able to perform interesting functional tasks, such as understanding the size and compliance of various objects, with high accuracy. Finally, I proposed a novel stimulation technique for sensory feedback designed to desynchronize induced neural activity during electrical stimulation, leading to more biomimetic patterns of activity. I discussed how this strategy could be combined with the results obtained in a recent study which I contributed to, in which we demonstrated that a model based encoding strategy resulted in more natural sensations of touch. This thesis provides evidence that advances in electrical stimulation protocols can lead to more capable prosthetic limbs. These new methods enable the delivery of multimodal, biomimetic sensory feedback and will help bridge the gap between scientific discovery and clinical translation
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