In vitro feasibility testing of floating light-activated minroelectrical stimulators

One of the major challenges of neural stimulation is the mechanical stress and resulting trauma induced on the implanted electrodes by the constant movement of the interconnects. A potential way of eliminating interconnects is to use floating micro-stimulators that can be activated through optical means. As a method of energy transfer to the micro-stimulator, we propose to use a laser beam at near infrared (NIR) wavelengths. There are two main objectives in this project to test the feasibility of the main approach; investigate the charge injection capacity of titanium nitride (TiN) and iridium oxide (IrOx) as potential contact materials, and measure the transmitted light power through the neural tissue for various implantation depths. The charge injection capacity of TiN electrodes for an extended range of cathodic voltages was also investigated. Because the microstimulator will be implanted into the neural tissue, the laser beam must penetrate a few millimeters before reaching the device. The transmitted light power was measured for various types of neural tissue. The transmitted light power through rat brain gray matter was much higher than that of the white matter and the sciatic nerve. Penetration depth and reflectance were calculated according to Lambert-Beer’s law from measurements of transmission for various tissue thicknesses. The results suggest that FLAMES approach is feasible for implantation depths of a few millimeters in the peripheral and central nervous system. Both IrOx and TiN allow sufficient charge injection for this application. TiN is preferred for future experimentation since TiN does not require a bias voltage to achieve useful charge injection rates, and thus is a good choice as an electrode material in this application

Metal Ir coatings on endocardial electrode tips, obtained by MOCVD

The present work demonstrates the application of the Metal-Organic Chemical Vapor Deposition technique to fabricate metal iridium coatings onto the pole tips of endocardial electrodes. Using iridium (III) acetylacetonate as volatile precursor, the target coatings were successfully applied to the working surface of cathodes and anodes of pacemaker electrodes in the flow type reactor in hydrogen atmosphere at deposition temperature of 550°C. The coating samples were characterized by means of XRD, SEM, Raman- and XPS-spectroscopies. The formation of non-textured coatings with fractal-like morphology and 7-24 nm crystallite size has been realized. The electrochemical properties of the coatings were investigated by cyclic voltammetry and electrochemical impedance spectroscopy. The charge storage capacity values of the electrochemically activated samples were 17.0-115 mC·cm–2 and 14.4-76.5 mC·cm–2 for measurements carried out in 0.1M sulfuric acid and in phosphate buffer saline solutions, respectively. A comparison of some characteristics of the samples obtained with commercially available cathode of pacemaker electrodes is also presented

Poly(3,4-ethylenedioxythiophene) as a Micro-Neural Interface Material for Electrostimulation

Chronic microstimulation-based devices are being investigated to treat conditions such as blindness, deafness, pain, paralysis, and epilepsy. Small-area electrodes are desired to achieve high selectivity. However, a major trade-off with electrode miniaturization is an increase in impedance and charge density requirements. Thus, the development of novel materials with lower interfacial impedance and enhanced charge storage capacity is essential for the development of micro-neural interface-based neuroprostheses. In this report, we study the use of conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) as a neural interface material for microstimulation of small-area iridium electrodes on silicon-substrate arrays. Characterized by electrochemical impedance spectroscopy, electrodeposition of PEDOT results in lower interfacial impedance at physiologically relevant frequencies, with the 1 kHz impedance magnitude being 23.3 ± 0.7 kΩ, compared to 113.6 ± 3.5 kΩ for iridium oxide (IrOx) on 177 μm2 sites. Further, PEDOT exhibits enhanced charge storage capacity at 75.6 ± 5.4 mC/cm2 compared to 28.8 ± 0.3 mC/cm2 for IrOx, characterized by cyclic voltammetry (50 mV/s). These improvements at the electrode interface were corroborated by observation of the voltage excursions that result from constant current pulsing. The PEDOT coatings provide both a lower amplitude voltage and a more ohmic representation of the applied current compared to IrOx. During repetitive pulsing, PEDOT-coated electrodes show stable performance and little change in electrical properties, even at relatively high current densities which cause IrOx instability. These findings support the potential of PEDOT coatings as a micro-neural interface material for electrostimulation

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

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

Electrochemical Safety Studies of Cochlear Implant Electrodes Using the Finite Element Method

Cochlear implants, amongst other neural prostheses, utilise platinum electrodes as an interface between the synthetic implant and the biological tissue environment. If excessive electrical charge is injected via these electrodes, injury to the tissue may result. Empirically derived stimulation limits have been defined to prevent tissue damage, however the injurious mechanisms are still unclear. Evidence suggests that the non-uniform distribution of charge on electrodes influences the electrochemical generation of toxic by-products. However, in vivo and in vitro techniques are limited in their ability to systematically explore the factors and mechanisms that contribute to stimulation-induced tissue injury. To this end, an in silico approach was used to develop a time-domain model of cochlear implant stimulation electrodes. A constant phase angle impedance was used to model the reversible processes on the electrode surface, and Butler-Volmer reaction kinetics were used to define the behaviour of the water window irreversible electrochemical reactions. The resulting model provided time-domain responses of the current density distributions, and net charge consumed by the hydrolysis reactions. This model was then used to perform systematic evaluations of various electrode geometries and stimulation parameters. The modelling results showed the current associated with irreversible reactions was non-uniform and tended towards the periphery of the electrode. A comparison of electrode geometries revealed interactions between electrode size, shape and recess depth. Stimulation mode, electrode position, and electrolyte conductivity were found to impact the shape of the electric field and the extent of irreversible reactions. This emphasised the influence of the physiological environment on the stimulation safety. In vitro experiments were conducted to validate the model. The implications of the results described in this thesis can be used to inform the design of safer electrodes

Non-Penetrating Microelectrode Interfaces for Cortical Neuroprosthetic Applications with a Focus on Sensory Encoding: Feasibility and Chronic Performance in Striate Cortex

abstract: Growing understanding of the neural code and how to speak it has allowed for notable advancements in neural prosthetics. With commercially-available implantable systems with bi- directional neural communication on the horizon, there is an increasing imperative to develop high resolution interfaces that can survive the environment and be well tolerated by the nervous system under chronic use. The sensory encoding aspect optimally interfaces at a scale sufficient to evoke perception but focal in nature to maximize resolution and evoke more complex and nuanced sensations. Microelectrode arrays can maintain high spatial density, operating on the scale of cortical columns, and can be either penetrating or non-penetrating. The non-penetrating subset sits on the tissue surface without puncturing the parenchyma and is known to engender minimal tissue response and less damage than the penetrating counterpart, improving long term viability in vivo. Provided non-penetrating microelectrodes can consistently evoke perception and maintain a localized region of activation, non-penetrating micro-electrodes may provide an ideal platform for a high performing neural prosthesis; this dissertation explores their functional capacity. The scale at which non-penetrating electrode arrays can interface with cortex is evaluated in the context of extracting useful information. Articulate movements were decoded from surface microelectrode electrodes, and additional spatial analysis revealed unique signal content despite dense electrode spacing. With a basis for data extraction established, the focus shifts towards the information encoding half of neural interfaces. Finite element modeling was used to compare tissue recruitment under surface stimulation across electrode scales. Results indicated charge density-based metrics provide a reasonable approximation for current levels required to evoke a visual sensation and showed tissue recruitment increases exponentially with electrode diameter. Micro-scale electrodes (0.1 – 0.3 mm diameter) could sufficiently activate layers II/III in a model tuned to striate cortex while maintaining focal radii of activated tissue. In vivo testing proceeded in a nonhuman primate model. Stimulation consistently evoked visual percepts at safe current thresholds. Tracking perception thresholds across one year reflected stable values within minimal fluctuation. Modulating waveform parameters was found useful in reducing charge requirements to evoke perception. Pulse frequency and phase asymmetry were each used to reduce thresholds, improve charge efficiency, lower charge per phase – charge density metrics associated with tissue damage. No impairments to photic perception were observed during the course of the study, suggesting limited tissue damage from array implantation or electrically induced neurotoxicity. The subject consistently identified stimulation on closely spaced electrodes (2 mm center-to-center) as separate percepts, indicating sub-visual degree discrete resolution may be feasible with this platform. Although continued testing is necessary, preliminary results supports epicortical microelectrode arrays as a stable platform for interfacing with neural tissue and a viable option for bi-directional BCI applications.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

Infrared light activated floating micro stimulators for neuro-prosthetic applications

The most common failures in neural stimulation implants are due to interconnect complications such as tissue response, lead migration, and lead breakages. The challenge in eliminating interconnects lies in minimizing device size to maintain spatial selectivity required in the CNS. One approach to this problem is a current generating device that can be stimulated by an external signal, such as light or sound. Here, we report the design, construction and testing of rnicrophotodiode devices that can be stimulated remotely with near-infrared (NIR) light to generate current that can be injected locally into the peripheral nervous system. The use of near-infrared (NIR) light to activate microphotodiodes was investigated. The chip size of the prototype device is 300μm by 500μm, and the small stimulation area necessitates a contact material capable of delivering a minimum charge injection rate of 0.5 mC/cm2. The charge transfer properties of iridium oxide, platinum, and titanium nitride were analyzed, and titanium nitride was found to have a stable charge injection rate above 0.5 mC/cm2. The volume conductor response of the diode showed a primarily capacitive transfer of energy into the tissue. Three diode geometries were implanted in a peripheral nerve, and an EMG signal was recorded in response to laser stimulation of two diode types. The diodes with the largest active area achieved successful stimulation despite size differences in contact area; this suggests the importance of active area size for stimulation. Further characterization of diode performance in vivoestablished an optimum pulse width for minimum light energy needed for diode activation. This optimum pulse width increased as implantation depth increased. For an implantation depth of 3.5 mm, the energy threshold was 0.53 mJ/cm2 which is 30 times below the maximum permissible exposure for λ = 830 nm. The total energy required for stimulation at a given pulse width increased as tissue depth increased

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

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