Toward an energy-efficient high-voltage compliant visual intracortical multichannel stimulator

ABSTRACT: We present, in this paper, a new multichip system aimed toward building an implantable visual intracortical stimulation device. The objective is to deliver energy-optimum pulse patterns to neural sites with needed compliance voltage across high electrode–tissue interface impedance of implantable microelectrodes. The first chip is an energy-efficient stimuli generator (SG), and the second one is a high-impedance microelectrode array driver (MED) output stage. The fourchannel SG produces rectangular, half-sine, plateau-sine, and other types of current pulse with stimulation current ranging from 2.32 to 220 μA per channel. The microelectrode array driver is able to deliver 20 V per anodic or cathodic phase across the microelectrode–tissue interface for ±13 V power supplies. The MED supplies different current levels with the maximum value of 400 μA per input and 100 μA per output channel simultaneously to 8–16 stimulation sites through microelectrodes, connected either in bipolar or monopolar configuration. Both chips receive power via inductive link and data through capacitive coupling. The SG and MED chips have been fabricated in 0.13-μm CMOS and 0.8-μm 5-/20-V CMOS/double-diffused metal-oxidesemiconductor technologies. The measured dc power budgets consumed by low- and mid-voltage chips are 2.56 and 2.1 mW consecutively. The system, modular in architecture, is interfaced with a newly developed platinum-coated pyramidal microelectrode array. In vitro test results with 0.9% phosphate buffer saline show the microelectrode impedance of 70 Ωk at 1 kHz

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

Distributed Sensing and Stimulation Systems Towards Sense of Touch Restoration in Prosthetics

Modern prostheses aim at restoring the functional and aesthetic characteristics of the lost limb. To foster prosthesis embodiment and functionality, it is necessary to restitute both volitional control and sensory feedback. Contemporary feedback interfaces presented in research use few sensors and stimulation units to feedback at most two discrete feedback variables (e.g. grasping force and aperture), whereas the human sense of touch relies on a distributed network of mechanoreceptors providing high-fidelity spatial information. To provide this type of feedback in prosthetics, it is necessary to sense tactile information from artificial skin placed on the prosthesis and transmit tactile feedback above the amputation in order to map the interaction between the prosthesis and the environment. This thesis proposes the integration of distributed sensing systems (e-skin) to acquire tactile sensation, and non-invasive multichannel electrotactile feedback and virtual reality to deliver high-bandwidth information to the user. Its core focus addresses the development and testing of close-loop sensory feedback human-machine interface, based on the latest distributed sensing and stimulation techniques for restoring the sense of touch in prosthetics. To this end, the thesis is comprised of two introductory chapters that describe the state of art in the field, the objectives and the used methodology and contributions; as well as three studies distributed over stimulation system level and sensing system level. The first study presents the development of close-loop compensatory tracking system to evaluate the usability and effectiveness of electrotactile sensory feedback in enabling real-time close-loop control in prosthetics. It examines and compares the subject\u2019s adaptive performance and tolerance to random latencies while performing the dynamic control task (i.e. position control) and simultaneously receiving either visual feedback or electrotactile feedback for communicating the momentary tracking error. Moreover, it reported the minimum time delay needed for an abrupt impairment of users\u2019 performance. The experimental results have shown that electrotactile feedback performance is less prone to changes with longer delays. However, visual feedback drops faster than electrotactile with increased time delays. This is a good indication for the effectiveness of electrotactile feedback in enabling close- loop control in prosthetics, since some delays are inevitable. The second study describes the development of a novel non-invasive compact multichannel interface for electrotactile feedback, containing 24 pads electrode matrix, with fully programmable stimulation unit, that investigates the ability of able-bodied human subjects to localize the electrotactile stimulus delivered through the electrode matrix. Furthermore, it designed a novel dual parameter -modulation (interleaved frequency and intensity) and compared it to conventional stimulation (same frequency for all pads). In addition and for the first time, it compared the electrotactile stimulation to mechanical stimulation. More, it exposes the integration of virtual prosthesis with the developed system in order to achieve better user experience and object manipulation through mapping the acquired real-time collected tactile data and feedback it simultaneously to the user. The experimental results demonstrated that the proposed interleaved coding substantially improved the spatial localization compared to same-frequency stimulation. Furthermore, it showed that same-frequency stimulation was equivalent to mechanical stimulation, whereas the performance with dual-parameter modulation was significantly better. The third study presents the realization of a novel, flexible, screen- printed e-skin based on P(VDF-TrFE) piezoelectric polymers, that would cover the fingertips and the palm of the prosthetic hand (particularly the Michelangelo hand by Ottobock) and an assistive sensorized glove for stroke patients. Moreover, it developed a new validation methodology to examine the sensors behavior while being solicited. The characterization results showed compatibility between the expected (modeled) behavior of the electrical response of each sensor to measured mechanical (normal) force at the skin surface, which in turn proved the combination of both fabrication and assembly processes was successful. This paves the way to define a practical, simplified and reproducible characterization protocol for e-skin patches In conclusion, by adopting innovative methodologies in sensing and stimulation systems, this thesis advances the overall development of close-loop sensory feedback human-machine interface used for restoration of sense of touch in prosthetics. Moreover, this research could lead to high-bandwidth high-fidelity transmission of tactile information for modern dexterous prostheses that could ameliorate the end user experience and facilitate it acceptance in the daily life

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

High-Density 3D Pyramid-Shaped Microelectrode Arrays for Brain-Machine Interface Applications

RÉSUMÉ Les dispositifs médicaux dédiés aux enregistrements des activités neuronales et à la stimulation de tissus nerveux sont appelés interfaces cerveau-machines. Ils offrent un potentiel important pour restaurer diverses fonctions neurologiques perdues. Un élément clé dans la mise en œuvre des dispositifs est le réseau de microélectrodes (MEAs pour MicroElectrode Arrays en anglais) servant d’interface avec les tissus nerveux. Les MEA jouent un rôle important dans les implants lors d’expérimentations chroniques, ils doivent être fiables, stables et efficaces pour l'enregistrement et la stimulation à long terme. Les propriétés électrochimiques et la compatibilité biologique des microélectrodes sont des facteurs essentiels qui doivent être prises en compte lors de leur conception et fabrication. La présente thèse traite de la conception et la fabrication de MEA en silicium micro-usiné à haute densité et en forme de pyramides qui sont destinés à l’enregistrement et la stimulation intracorticals 3D. Nous nous concentrons principalement sur les techniques de microfabrication des électrodes et le développement de procédure du revêtement de matériaux nécessaires pour la biocompatibilité et protection des dispositifs implantables. Nous élaborons des microélectrodes à hauteur variable pour enregistrer des signaux neuronaux, sans perdre la capacité de microstimulation et tout en maintenant des impédances de faibles valeurs. Cette caractéristique est obtenue en modifiant la géométrie et la composition de matériaux utilisés, ce qui facilite l'injection de charge et la résolution spatiale élevée. Nous présentons une nouvelle technique de micro-usinage 3D à nombre réduit de masques comparé aux techniques existantes. Nous décrivons la mise en œuvre d’un MEA à haute densité (25 électrodes / 1,96 mm2) et à différentes longueurs d’électrodes. En outre, une nouvelle technique de masquage à base de film sec a été développée pour obtenir de très petites surfaces actives pour les microélectrodes qui sont à hauteur variable. Nous avons réduit les étapes du procédé de masquage de 14 à 6 par rapport à la méthode classique de masquage utilisé dans la littérature. Nous avons ensuite effectué, pour la première fois, une croissance directe sélective de nanotubes de carbone sur les têtes de microélectrodes de longueurs variables en utilisant la technique du dépôt chimique en phase vapeur assisté par plasma (Plasma-Enhanced Chemical Vapor Deposition - PECVD).----------ABSTRACT Neuroprosthetic devices that can record neural activities and stimulate the central nervous system (CNS), called brain-machine interfaces (BMI), offer significant potential to restore various lost neurologic functions. A key element in functions restoration is Microelectrode arrays (MEAs) implanted in neural tissues. MEAs, which act as an interface between bioelectronic devices and neural tissues, play an important role in chronic implants and must be reliable, stable, and efficient for long-term recording and stimulation. Electrochemical properties and biological compatibility of chronic microelectrodes are essential factors that must be taken into account in their design and fabrication. The present thesis deals with the design and fabrication of silicon micromachined, high-density, pyramid-shaped neural MEAs for intracortical 3D recording and stimulation. The focused is mainly on the MEAs fabrication techniques and development of coating materials process required with implantable devices with an ultimate purpose: elaborate variable-height microelectrodes to obtain consistent recording signals from small groups of neurons without losing microstimulation capabilities, while maintaining low-impedance pathways for charge injection, high charge transfer, and high-spatial resolution by altering the geometries and material compositions of the array. In the first part of the thesis, we present a new 3D micromachining technique with a single masking step in a time and cost effective manner. A high density 25 electrodes/ 1.96 mm2 MEA with varying lengths electrodes to access neurons that are located in different depths of cortical tissue was designed and fabricated. Furthermore, a novel dry-film based masking technique for procuring extremely small active area for variable-height electrodes has been developed. With this technology, we have reduced the masking process steps from 14 to 6 compared to the conventional masking method. We have then reported for the first time a selective direct growth of carbon nanotubes (CNTs) on the tips of 3D MEAs using Plasma Enhanced Chemical Vapor Deposition (PECVD) that could enhance electrical properties of the electrodes significantly. The CNT coating led to a 5-fold decrease in impedance and a 600-fold increase in charge transfer compared with Pt electrode. Finally, we have highlighted the importance of the coating MEAs with bioactive molecules (Poly-D-lysine) and polyethylene glycol (PEG) hydrogels to minimize the immune response of the neural tissue to implanted MEAs by in vitro cell-culture tests

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

Building And Validating Next-Generation Neurodevices Using Novel Materials, Fabrication, And Analytic Strategies

Technologies that enable scientists to record and modulate neural activity across spatial scales are advancing the way that neurological disorders are diagnosed and treated, and fueling breakthroughs in our fundamental understanding of brain function. Despite the rapid pace of technology development, significant challenges remain in realizing safe, stable, and functional interfaces between manmade electronics and soft biological tissues. Additionally, technologies that employ multimodal methods to interrogate brain function across temporal and spatial scales, from single cells to large networks, offer insights beyond what is possible with electrical monitoring alone. However, the tools and methodologies to enable these studies are still in their infancy. Recently, carbon nanomaterials have shown great promise to improve performance and multimodal capabilities of bioelectronic interfaces through their unique optical and electronic properties, flexibility, biocompatibility, and nanoscale topology. Unfortunately, their translation beyond the lab has lagged due to a lack of scalable assembly methods for incorporating such nanomaterials into functional devices. In this thesis, I leverage carbon nanomaterials to address several key limitations in the field of bioelectronic interfaces and establish scalable fabrication methods to enable their translation beyond the lab. First, I demonstrate the value of transparent, flexible electronics by analyzing simultaneous optical and electrical recordings of brain activity at the microscale using custom-fabricated graphene electronics. Second, I leverage a recently discovered 2D nanomaterial, Ti3C2 MXene, to improve the capabilities and performance of neural microelectronic devices. Third, I fabricate and validate human-scale Ti3C2 MXene epidermal electrode arrays in clinical applications. Leveraging the unique solution-processability of Ti3C2 MXene, I establish novel fabrication methods for both high-resolution microelectrode arrays and macroscale epidermal electrode arrays that are scalable and sufficiently cost-effective to allow translation of MXene bioelectronics beyond the lab and into clinical use. Thetechnologies and methodologies developed in this thesis advance bioelectronic technology for both research and clinical applications, with the goal of improving patient quality of life and illuminating complex brain dynamics across spatial scales

Conformable transistors for bioelectronics

The diversity of network disruptions that occur in patients with neuropsychiatric disorders creates a strong demand for personalized medicine. Such approaches often take the form of implantable bioelectronic devices that are capable of monitoring pathophysiological activity for identifying biomarkers to allow for local and responsive delivery of intervention. They are also required to transmit this data outside of the body for evaluation of the treatment’s efficacy. However, the ability to perform these demanding electronic functions in the complex physiological environment with minimum disruption to the biological tissue remains a big challenge. An optimal fully implantable bioelectronic device would require each component from the front-end to the data transmission to be conformable and biocompatible. For this reason, organic material-based conformable electronics are ideal candidates for components of bioelectronic circuits due to their inherent flexibility, and soft nature. In this work, first an organic mixed-conducting particulate composite material (MCP) able to form functional electronic components and non-invasively acquire high–spatiotemporal resolution electrophysiological signals by directly interfacing human skin is presented. Secondly, we introduce organic electrochemical internal ion-gated transistors (IGTs) as a high-density, high-amplification sensing component as well as a low leakage, high-speed processing unit. Finally, a novel wireless, battery-free strategy for electrophysiological signal acquisition, processing, and transmission that employs IGTs and an ionic communication circuit (IC) is introduced. We show that the wirelessly-powered IGTs are able to acquire and modulate neurophysiological data in-vivo and transmit them transdermally, eliminating the need for any hard Si-based electronics in the implant

Doctor of Philosophy

dissertationToday, we are implanting electrodes into many different parts of the peripheral and central nervous systems for the purpose of restoring function to people with nerve injury or disease. As technology and manufacturing continue to become more advanced, ne

Electronic bidirectional interfaces to the peripheral nervous system for prosthetic applications

The research presented in this thesis concerns the field of bioelectronics, in particular the work has been focused on the development of special electronic devices for neural signal acquisition and Peripheral Nervous System (PNS) stimulation. The final aim of the project in which this work is involved is in fact the realization of a prosthetic hand controlled using neural signals. The commercially available prosthesis are based on Electromyographic (EMG) signals, their use implies unnatural movements for the patient that needs a special training to develop the control capabilities over the mechanical limb. The proposed approach offers a number of advantages compared to the traditional prosthesis, first because the signals used are the same used to control the biologic limb, allowing a more comfortable solution for the patient that gets closer to feel the robotic hand as a natural extension of his/her body. Secondly, placing temperature and pressure sensors on the limb surface, it is possible to trasduce such information in an electrical current that, injected into the PNS, can restore the sensory feedback in amputees. The final goal of this research is the development of a fully implantable device able to perform a bidirectional communication between the robotic hand and the patient. Due to small area, low noise and low power constraints, the only possible way to reach this aim is the design of a full custom Integrated Circuit (IC). However a preliminary evaluation of the key design features, such as neural signal amplitudes and frequencies as well as stimulation shape parameters, is necessary in order to define clearly and precisely the design specifications. A low-cost and short implementation time device is then needed for this aim, the Components Off The Shelf (COTS) approach seems to be the best solution for this purpose. A Printed Circuit Board (PCB) with discrete components has been designed, developed and tested, the information extracted by the test results have been used to guide the IC design. The generation of electrical signals in biological cells, such as neural spikes, is possible thanks to ions that move across the cell membrane. In many applications it is important, not only to record the spikes, but also to measure these small currents in order to understand which electro-chemical processes are involved in the signal generation and to have a direct measurement of the ion channels involved in the reaction. Ion currents, in fact, play a key role in several physiological processes, in neural signal generation, but also in the maintenance of heartbeat and in muscle contraction. For this purpose, a system level implementation of a Read out circuit for ion channel current detection has been developed