Fully-Implantable Self-Contained Dual-Channel Electrical Recording and Directivity-Enhanced Optical Stimulation System on a Chip

This thesis presents an integrated system-on-a-chip (SoC), designed, fabricated, and characterized for conducting simultaneous dual-channel optogenetic stimulation and electrophysiological recording. An inductive coil as well as power management circuits are also integrated on the chip, enabling wireless power reception, hence, allowing full implantation. The optical stimulation channels host a novel LED driver circuit that can generate currents up to 10mA with a minimum required headroom voltage reported in the literature, resulting in a superior power efficiency compared to the state of the art. The output current in each channel can be programmed to have an arbitrary waveform with digitally-controlled magnitude and timing. The final design is fabricated as a 34 mm2 microchip using a CMOS 130nm technology and characterized both in terms of electrical and optical performance. A pair of custom-designed inkjet-printed micro-lenses are also fabricated and placed on top of the LEDs. The lenses are optimized to enhance the light directivity of optical stimulation, resulting in significant improvements in terms of spatial resolution, power consumption (30.5x reduction), and safety aspects (temperature increase of <0.1c) of the device

Integrated circuit design for implantable neural interfaces

Progress in microfabrication technology has opened the way for new possibilities in neuroscience and medicine. Chronic, biocompatible brain implants with recording and stimulation capabilities provided by embedded electronics have been successfully demonstrated. However, more ambitious applications call for improvements in every aspect of existing implementations. This thesis proposes two prototypes that advance the field in significant ways. The first prototype is a neural recording front-end with spectral selectivity capabilities that implements a design strategy that leads to the lowest reported power consumption as compared to the state of the art. The second one is a bidirectional front-end for closed-loop neuromodulation that accounts for self-interference and impedance mismatch thus enabling simultaneous recording and stimulation. The design process and experimental verification of both prototypes is presented herein

Design of a Quasi-Adiabatic Current-Mode Neurostimulator Integrated Circuit for Deep Brain Stimulation

Electrical stimulation of neural tissues is a valuable tool in the retinal prosthesis, cardiac pacemakers, and Deep Brain Stimulation (DBS). DBS is being to treat a growing number of neurological disorders, such as movement disorder, epilepsy, and Parkinson’s disease. The role of the electronic stimulator is paramount in such application, and significant design challenges are to be met to enhance safety and reliability. A current-source based stimulator can accurately deliver a charge-balanced stimulus maintaining patient safety. In this thesis, a general-purpose current-mode neurostimulator (CMS) based upon a new quasi-adiabatic driving technique is proposed which can theoretically achieve more than 80% efficiency with the help of a dynamic high voltage supply (DHVS) as opposed to most conventional general-purpose CMS having less than 25% efficiency. The high-voltage supply is required to withstand the voltage seen across the electrodes (>10V) due to the time-varying impedance presented by the electrode-tissue interface. The overall efficiency of the designed CMS is limited by the efficiency of the DHVS. A HVDD of 15V is created by the DHVS from an input voltage (VDD) of 3V. The DHVS circuit is made by cascading five charge pump circuits using the AMI 0.5µm CMOS process. It can maintain more than 60% efficiency for a wide range of load current from 25µA to 1.4mA, with peak efficiency at 67% and this is comparable with existing specific-purpose state-of-the-art high-voltage supplies used in a current stimulator. The stimulator designed in this thesis employs a new efficient charge recycling mechanism to enhance the overall efficiency, compared to the existing state-of-the-art CMSs. Thus, the overall CMS efficiency is improved by 20% to 25%. A current source, programmable by 8-bit digital input, is also designed which has an output impedance greater than 2MΩ with a dropout voltage of only 120mV. Measurements show voltage compliance exceeding +/-15V when driving a biphasic current stimulus of 10µA to 2.5mA through a simplified R-C model of the electrode-tissue interface. The voltage compliance is defined as the maximum voltage a stimulator can apply across the electrodes to achieve neural stimulation

An implantable micro-system for neural prosthesis control and sensory feedback restoration in amputees

In this work, the prototype of an electronic bi-directional interface between the Peripheral Nervous System (PNS) and a neuro-controlled hand prosthesis is presented. The system is composed of two Integrated Circuits (ICs): a standard CMOS device for neural recording and a High Voltage (HV) CMOS device for neural stimulation. The integrated circuits have been realized in two different 0.35μm CMOS processes available fromAustriaMicroSystem(AMS). The recoding IC incorporates 8 channels each including the analog front-end and the A/D conversion based on a sigma delta architecture. It has a total area of 16.8mm2 and exhibits an overall power consumption of 27.2mW. The neural stimulation IC is able to provide biphasic current pulses to stimulate 8 electrodes independently. A voltage booster generates a 17V voltage supply in order to guarantee the programmed stimulation current even in case of high impedances at the electrode-tissue interface in the order of tens of k­. The stimulation patterns, generated by a 5-bit current DAC, are programmable in terms of amplitude, frequency and pulse width. Due to the huge capacitors of the implemented voltage boosters, the stimulation IC has a wider area of 18.6mm2. In addition, a maximum power consumption of 29mW was measured. Successful in-vivo experiments with rats having a TIME electrode implanted in the sciatic nerve were carried out, showing the capability of recording neural signals in the tens of microvolts, with a global noise of 7μVrms , and to selectively elicit the tibial and plantarmuscles using different active sites of the electrode. In order to get a completely implantable interface, a biocompatible and biostable package was designed. It hosts the developed ICs with the minimal electronics required for their proper operation. The package consists of an alumina tube closed at both extremities by two ceramic caps hermetically sealed on it. Moreover, the two caps serve as substrate for the hermetic feedthroughs to enable the device powering and data exchange with the external digital controller implemented on a Field-Programmable Gate Array (FPGA) board. The package has an outer diameter of 7mm and a total length of 26mm. In addition, a humidity and temperature sensor was also included inside the package to allow future hermeticity and life-time estimation tests. Moreover, a wireless, wearable and non-invasive EEG recording system is proposed in order to improve the control over the artificial limb,by integrating the neural signals recorded from the PNS with those directly acquired from the brain. To first investigate the system requirements, a Component-Off-The-Shelf (COTS) device was designed. It includes a low-power 8- channel acquisition module and a Bluetooth (BT) transceiver to transmit the acquired data to a remote platform. It was designed with the aimof creating a cheap and user-friendly system that can be easily interfaced with the nowadays widely spread smartphones or tablets by means of a mobile-based application. The presented system, validated through in-vivo experiments, allows EEG signals recording at different sample rates and with a maximum bandwidth of 524Hz. It was realized on a 19cm2 custom PCB with a maximum power consumption of 270mW

Neurostimulateur hautement intégré et nouvelle stratégie de stimulation pour améliorer la miction chez les paraplégiques

RÉSUMÉ Une lésion de la moelle épinière est un problème dévastateur médicalement et socialement. Pour la population des États-Unis seulement, il y a près de 10 000 nouveaux cas chaque année. A cause des nombreux types de lésions possibles, divers degrés de dysfonctionnement du bas appareil urinaire peuvent en découler. Une lésion est dite complète lors d’une perte totale des fonctions sensorielles et motrices volontaires en dessous du niveau de la lésion. Une lésion incomplète implique que certaines activités sensorielles et/ou motrices soient encore présentes. Si la lésion se produit au dessus du cône médullaire, la vessie développera une hyperréflexie qui se manifeste par des contractions réflexes non-inhibées. Ces contractions peuvent être accompagnées d’une augmentation de l’activité du sphincter externe. Par conséquent, cela mène à un état d’obstruction fonctionnelle de la vessie, qui induit une forte pression intravésicale à chacune des contractions réflexes et qui peut potentiellement endommager le haut appareil urinaire. Dans ce contexte, la neurostimulation est l'une des techniques les plus prometteuses pour la réhabilitation de la vessie chez les patients ayant subi une lésion de la moelle épinière. Le seul neurostimulateur implantable commercialisé, ciblant l'amélioration de la miction et ayant obtenu des résultats satisfaisants, nécessite une rhizotomie (section de certains nerfs) afin de réduire la dyssynergie entre la vessie et le sphincter. Cependant, la rhizotomie est irréversible et peut abolir les réflexes sexuels, de défécation ainsi que les sensations sacrales si encore présents dans le cas de lésions incomplètes. Afin d'éviter la rhizotomie, nous proposons une nouvelle stratégie de stimulation multi-site appliquée aux racines sacrées, et basée sur le blocage de la conduction des nerfs à l'aide d'une stimulation à haute fréquence comme alternative à la rhizotomie. Cette approche permettrait une meilleure miction en augmentant sélectivement la contraction de la vessie et en diminuant la dyssynergie. Huit expériences en phase aigüe ont étés menées sur des chiens pour vérifier la réponse de la vessie et du sphincter urétral externe à la stratégie de stimulation proposée. Le blocage à haute-fréquence (1 kHz) combiné à la stimulation basse-fréquence (30 Hz), a augmenté la différence de pression intra-vésicale/intra-urétrale moyenne jusqu'à 53 cmH2O et a réduit la pression intra-urétrale moyenne jusqu'à hauteur de 86 % relativement au niveau de référence. Dans l’objectif de tester la stratégie de neurostimulation proposée avec des expériences animales en phase chronique, un dispositif de neurostimulation implantable est requis. Un prototype discret implémentant cette stratégie de stimulation a été réalisé en utilisant uniquement des composants discrets disponibles commercialement. Ce prototype est capable de générer des impulsions à une fréquence aussi basse que 18 Hz tout en générant simultanément une forme d’onde alternative à une fréquence aussi haute que 8.6 kHz, et ce sur de multiples canaux. Lorsque tous les étages de stimulation et leurs différentes sorties sont activés avec des fréquences d’impulsions (2 mA, 217 μs) et de sinusoïdes de 30 Hz et 1 kHz respectivement, la consommation de puissance totale est autour de 4.5 mA (rms). Avec 50 mW de puissance inductive disponible par exemple et 4.5 mA de consommation de courant, le régulateur haute-tension peut être réglé à 10 V permettant ainsi une stimulation de 2 mA avec une impédance nerf-électrode de 4.4 kΩ. Le nombre effectif de sorties activées et le maximum réalisable des paramètres de stimulation sont limités par l’énergie disponible fournie par le lien inductif et l’impédance des interfaces nerf-électrode. Cependant, une plus grande intégration du neurostimulateur devient de plus en plus nécessaire à des fins de miniaturisation, de réduction de consommation de puissance, et d’augmentation du nombre de canaux de stimulation. Comme première étape vers une intégration totale, nous présentons la conception d’un neurostimulateur hautement intégré et qui peut être assemblé sur un circuit imprimé de 21 mm de diamètre. Le prototype est basé sur trois circuits intégrés, dédiés et fabriqués en technologie CMOS haute-tension, ainsi qu’un FPGA miniature à faible puissance et disponible commercialement. En utilisant une approche basée sur un abaisseur de tension, où la tension induite est laissée libre jusqu’à 20 V, l’étage d’entrée de récupération de puissance inductive et de données est totalement intégré.----------ABSTRACT Spinal cord injury (SCI) is a devastating condition medically and socially. For the population of USA only, the incidence is around 10 000 new cases per year. SCI leads to different degrees of dysfunction of the lower urinary tract due to a large variety of possible lesions. With a complete lesion, there is a complete loss of sensory and motor control below the level of lesion. An incomplete lesion implies that some sensory and/or motor activity is still present. Most patients with suprasacral SCI suffer from detrusor over-activity (DO) and detrusor sphincter dyssynergia (DSD). DSD leads to high intravesical pressure, high residual urine, urinary tract infection, and deterioration of the upper urinary tract. In this context, neurostimulation is one of the most promising techniques for bladder rehabilitation in SCI patients. The only commercialized implantable neurostimulator aiming for improved micturition and having obtained satisfactory results requires rhizotomy to reduce DSD. However, rhizotomy is irreversible and may abolish sexual and defecation reflexes as well as sacral sensations, if still present in case of incomplete SCI. In order to avoid rhizotomy, we propose a new multisite stimulation strategy applied to sacral roots, and based on nerve conduction blockade using high-frequency stimulation as an alternative to rhizotomy. This approach would allow a better micturition by increasing bladder contraction selectively and decreasing dyssynergia. Eight acute dog experiments were carried out to verify the bladder and the external urethral sphincter responses to the proposed stimulation strategy. High-frequency blockade (1 kHz) combined with low-frequency stimulation (30 Hz) increased the average intravesical-intraurethral pressure difference up to 53 cmH2O and reduced the average intraurethral pressure with respect to baseline by up to 86 %. To test the proposed neurostimulation strategy during chronic animal experiments, an implantable neurostimulateur is required. A discrete prototype implementing the proposed stimulation strategy has been designed using commercially available discrete components. This prototype is capable of generating a low frequency pulse waveform as low as 18 Hz with a simultaneous high frequency alternating waveform as high as 8.6 kHz, and that over different and multiple channels

A fully-programmable neural interface for multi-polar, multi-channel stimulation strategies

Accepted versio

A Fully Implantable Opto-Electro Closed-Loop Neural Interface for Motor Neuron Disease Studies

This paper presents a fully implantable closed-loop device for use in freely moving rodents to investigate new treatments for motor neuron disease. The 0.18 µm CMOS integrated circuit comprises 4 stimulators, each featuring 16 channels for optical and electrical stimulation using arbitrary current waveforms at frequencies from 1.5 Hz to 50 kHz, and a bandwidth programmable front-end for neural recording. The implant uses a Qi wireless inductive link which can deliver >100 mW power at a maximum distance of 2 cm for a freely moving rodent. A backup rechargeable battery can support 10 mA continuous stimulation currents for 2.5 hours in the absence of an inductive power link. The implant is controlled by a graphic user interface with broad programmable parameters via a Bluetooth low energy bidirectional data telemetry link. The encapsulated implant is 40 mm × 20 mm × 10 mm. Measured results are presented showing the electrical performance of the electronics and the packaging method

Integrated Electronics for Wireless Imaging Microsystems with CMUT Arrays

Integration of transducer arrays with interface electronics in the form of single-chip CMUT-on-CMOS has emerged into the field of medical ultrasound imaging and is transforming this field. It has already been used in several commercial products such as handheld full-body imagers and it is being implemented by commercial and academic groups for Intravascular Ultrasound and Intracardiac Echocardiography. However, large attenuation of ultrasonic waves transmitted through the skull has prevented ultrasound imaging of the brain. This research is a prime step toward implantable wireless microsystems that use ultrasound to image the brain by bypassing the skull. These microsystems offer autonomous scanning (beam steering and focusing) of the brain and transferring data out of the brain for further processing and image reconstruction. The objective of the presented research is to develop building blocks of an integrated electronics architecture for CMUT based wireless ultrasound imaging systems while providing a fundamental study on interfacing CMUT arrays with their associated integrated electronics in terms of electrical power transfer and acoustic reflection which would potentially lead to more efficient and high-performance systems. A fully wireless architecture for ultrasound imaging is demonstrated for the first time. An on-chip programmable transmit (TX) beamformer enables phased array focusing and steering of ultrasound waves in the transmit mode while its on-chip bandpass noise shaping digitizer followed by an ultra-wideband (UWB) uplink transmitter minimizes the effect of path loss on the transmitted image data out of the brain. A single-chip application-specific integrated circuit (ASIC) is de- signed to realize the wireless architecture and interface with array elements, each of which includes a transceiver (TRX) front-end with a high-voltage (HV) pulser, a high-voltage T/R switch, and a low-noise amplifier (LNA). Novel design techniques are implemented in the system to enhance the performance of its building blocks. Apart from imaging capability, the implantable wireless microsystems can include a pressure sensing readout to measure intracranial pressure. To do so, a power-efficient readout for pressure sensing is presented. It uses pseudo-pseudo differential readout topology to cut down the static power consumption of the sensor for further power savings in wireless microsystems. In addition, the effect of matching and electrical termination on CMUT array elements is explored leading to new interface structures to improve bandwidth and sensitivity of CMUT arrays in different operation regions. Comprehensive analysis, modeling, and simulation methodologies are presented for further investigation.Ph.D

VLSI Circuits for Bidirectional Neural Interfaces

Medical devices that deliver electrical stimulation to neural tissue are important clinical tools that can augment or replace pharmacological therapies. The success of such devices has led to an explosion of interest in the field, termed neuromodulation, with a diverse set of disorders being targeted for device-based treatment. Nevertheless, a large degree of uncertainty surrounds how and why these devices are effective. This uncertainty limits the ability to optimize therapy and gives rise to deleterious side effects. An emerging approach to improve neuromodulation efficacy and to better understand its mechanisms is to record bioelectric activity during stimulation. Understanding how stimulation affects electrophysiology can provide insights into disease, and also provides a feedback signal to autonomously tune stimulation parameters to improve efficacy or decrease side-effects. The aims of this work were taken up to advance the state-of-the-art in neuro-interface technology to enable closed-loop neuromodulation therapies. Long term monitoring of neuronal activity in awake and behaving subjects can provide critical insights into brain dynamics that can inform system-level design of closed-loop neuromodulation systems. Thus, first we designed a system that wirelessly telemetered electrocorticography signals from awake-behaving rats. We hypothesized that such a system could be useful for detecting sporadic but clinically relevant electrophysiological events. In an 18-hour, overnight recording, seizure activity was detected in a pre-clinical rodent model of global ischemic brain injury. We subsequently turned to the design of neurostimulation circuits. Three critical features of neurostimulation devices are safety, programmability, and specificity. We conceived and implemented a neurostimulator architecture that utilizes a compact on-chip circuit for charge balancing (safety), digital-to-analog converter calibration (programmability) and current steering (specificity). Charge balancing accuracy was measured at better than 0.3%, the digital-to-analog converters achieved 8-bit resolution, and physiological effects of current steering stimulation were demonstrated in an anesthetized rat. Lastly, to implement a bidirectional neural interface, both the recording and stimulation circuits were fabricated on a single chip. In doing so, we implemented a low noise, ultra-low power recording front end with a high dynamic range. The recording circuits achieved a signal-to-noise ratio of 58 dB and a spurious-free dynamic range of better than 70 dB, while consuming 5.5 μW per channel. We demonstrated bidirectional operation of the chip by recording cardiac modulation induced through vagus nerve stimulation, and demonstrated closed-loop control of cardiac rhythm

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