Wireless networks of injectable microelectronic stimulators based on rectification of volume conducted high frequency currents

Objective. To develop and in vivo demonstrate threadlike wireless implantable neuromuscular microstimulators that are digitally addressable. Approach. These devices perform, through its two electrodes, electronic rectification of innocuous high frequency current bursts delivered by volume conduction via epidermal textile electrodes. By avoiding the need of large components to obtain electrical energy, this approach allows the development of thin devices that can be intramuscularly implanted by minimally invasive procedures such as injection. For compliance with electrical safety standards, this approach requires a minimum distance, in the order of millimeters or a very few centimeters, between the implant electrodes. Additionally, the devices must cause minimal mechanical damage to tissues, avoid dislocation and be adequate for long-term implantation. Considering these requirements, the implants were conceived as tubular and flexible devices with two electrodes at opposite ends and, at the middle section, a hermetic metallic capsule housing the electronics. Main results. The developed implants have a submillimetric diameter (0.97 mm diameter, 35 mm length) and consist of a microcircuit, which contains a single custom-developed integrated circuit, housed within a titanium capsule (0.7 mm diameter, 6.5 mm length), and two platinum–iridium coils that form two electrodes (3 mm length) located at opposite ends of a silicone body. These neuromuscular stimulators are addressable, allowing to establish a network of microstimulators that can be controlled independently. Their operation was demonstrated in an acute study by injecting a few of them in the hind limb of anesthetized rabbits and inducing controlled and independent contractions. Significance. These results show the feasibility of manufacturing threadlike wireless addressable neuromuscular stimulators by using fabrication techniques and materials well established for chronic electronic implants. Although long-term operation still must be demonstrated, the obtained results pave the way to the clinical development of advanced motor neuroprostheses formed by dense networks of such wireless devices.European Research Council (ERC) 724244ICREA under the ICREA Academia programm

Construction of injectable wireless microstimulators based on rectification of volume conducted high frequency currents

Functional neuromuscular stimulation (FNS) refers to the delivery of electrical stimuli to nerves or muscles to enhance, modify or restore motor functions. Despite their invasiveness, implantable systems for FNS offer key advantages over surface and percutaneous systems in terms of selectivity and safety. Most implantable FNS systems consist of a relatively bulky subcutaneous pulse genera-tor connected through leads to electrodes at the target stimulation sites. In the case of FNS systems for restoring motor functions in patients with paralysis, the leads are long and the electrodes are distributed over large and mobile body parts, thus making them highly invasive and prone to failure. Miniaturized wireless implantable stimulators represent a safer and more reliable alternative. By integrating all the components in the same device, long leads are avoided and minimally invasive implantation procedures are enabled. In this thesis, architectures and construction methods were devised to implement thin (diameter < 1 mm), flexible and biocompatible wireless microstimulators whose operation principle is based in rectifying high frequency currents delivered to tissues by volume conduction. These threadlike devices, which were successfully in vivo assayed, are intended to be deployed by injection forming a dense network of intramuscular addressable stimulators for the development of motor neuroprostheses. They were implemented adapting techniques well accepted in industry to facilitate early clinical adoption. A noteworthy feature of their construction is the inclusion of a biterminal hermetic metallic capsule housing the sophisticated microelectronic circuitry required for their operation. The applicability of the same technology and operation methods to an alternative clinical field was also explored in the scope of this thesis through the development and in vivo assay proof-of-concept novel leadless microstimulators. Furthermore, this thesis has contributed to the development of refined computer models to characterize the stimulation method previously described.La estimulación neuromuscular funcional (FNS) se refiere a la aplicación de estímulos eléctricos a nervios o músculos para mejorar, modificar o restaurar fun-ciones motoras. A pesar de ser invasivos, los sistemas implantables para FNS ofrecen ventajas en selectividad y seguridad sobre los superficiales y percutáneos. La mayoría de los sistemas FNS implantables consisten en un generador de pulsos subcutáneo relativamente voluminoso conectado por cables a electrodos en los puntos de estimulación. En el caso de sistemas FNS para restaurar funciones motoras en pacientes con parálisis, los cables son largos y los electrodos están distribuidos por partes del cuerpo grandes y móviles, haciéndolos altamente invasivos y propensos a fallar. Estimuladores implantables inalámbricos miniaturizados representan una alternativa más segura y confiable. Al integrar todos los componentes en el mismo dispositivo, se evitan los cables largos y se habilitan procedimientos de implantación mínimamente invasivos. En esta tesis se han diseñado arquitecturas y métodos de construcción para implementar microestimuladores inalámbricos delgados (diámetro < 1 mm), flexibles y biocompatibles basados en la rectificación de corrientes de alta frecuencia aplicadas a los tejidos por conducción volumétrica. Estos dispositivos filiformes, ensayados con éxito in vivo, serían implantados mediante inyección formando una densa red de estimuladores direccionables intramusculares para desarrollar neuroprótesis motoras. Éstos se han implementado adaptando técnicas bien aceptadas en la industria para facilitar la adopción clínica temprana. Una característica notable de su construcción es la inclusión de una cápsula metálica hermética biterminal que aloja los sofisticados circuitos microelectrónicos necesarios para su funcionamiento. La aplicabilidad de la misma tecnología y métodos de operación a un campo clínico alternativo también se ha explorado en esta tesis mediante el desarrollo y prueba de concepto in vivo de novedosos microestimuladores sin cables. Además, esta tesis ha contribuido al desarrollo de modelos informáticos refinados para caracterizar el método de estimulación descrito anteriormente

Power transfer by volume conduction: in vitro validated analytical models predict DC powers above 1 mw in injectable implants

Galvanic coupling, or more precisely volume conduction, has been recently studied by different research groups as a method for intrabody communications. However, only in a very few occasions its use for powering implants has been proposed and proper analyses of such capability are still lacking. We present the development and the in vitro validation of a set of analytical expressions able to estimate the maximum ac and dc powers attainable in elongated implants powered by volume conduction. In particular, the expressions do not describe the complete power transfer channel but the behavior of the implants when the presence of an electric field is assumed. The expressions and the in vitro models indicate that time-averaged powers above 1 mW can be readily obtained in very thin (diameter < 1 mm) and short (length < 15 mm) implants when ac fields that comply with safety standards are present in the tissues where the implants are located. The expressions and the in vitro models also indicate that the obtained dc power is maximized by delivering the ac field in the form of short bursts rather than continuously. The study results support the use of volume conduction as a safe option to power implants.This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme under Grant 724244. The work of Antoni Ivorra was supported by the ICREA under the ICREA Academia Programme

Injectable temperature sensors based on passive rectification of volume-conducted currents

Comunicació presentada a: 2021 IEEE Biomedical Circuits and Systems Conference (BioCAS), celebrat del 6 al 9 d'octubre de 2021 virtualmentIn situ monitoring of biomedical parameters with implantable sensors can provide information to trigger interventional or therapeutic actions. However, these sensors require bulky components for power or for interrogation that hinder miniaturization. We have proposed a wireless sensing method based in passive rectification of high frequency current bursts that flow through the tissues by volume conduction. Here we report the evaluation of a 0.98 mm-thick, passive, and flexible temperature sensor based on this method. The injectable microsensor obtained an accuracy of ±2.1%. This opens the possibility of continuous and in situ temperature sensing with minimal invasiveness.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreements No 724244 (eAXON) and 963955 (SENSO-eAXON)), and the UPF INNOValora programme, which is co-financed by the Generalitat de Catalunya and the European Regional Development Fund. Antoni Ivorra gratefully acknowledges the financial support by ICREA under the ICREA Academia programme

Wireless networks of injectable microelectronic stimulators based on rectification of volume conducted high frequency currents

Objective. To develop and in vivo demonstrate threadlike wireless implantable neuromuscular microstimulators that are digitally addressable. Approach. These devices perform, through its two electrodes, electronic rectification of innocuous high frequency current bursts delivered by volume conduction via epidermal textile electrodes. By avoiding the need of large components to obtain electrical energy, this approach allows the development of thin devices that can be intramuscularly implanted by minimally invasive procedures such as injection. For compliance with electrical safety standards, this approach requires a minimum distance, in the order of millimeters or a very few centimeters, between the implant electrodes. Additionally, the devices must cause minimal mechanical damage to tissues, avoid dislocation and be adequate for long-term implantation. Considering these requirements, the implants were conceived as tubular and flexible devices with two electrodes at opposite ends and, at the middle section, a hermetic metallic capsule housing the electronics. Main results. The developed implants have a submillimetric diameter (0.97 mm diameter, 35 mm length) and consist of a microcircuit, which contains a single custom-developed integrated circuit, housed within a titanium capsule (0.7 mm diameter, 6.5 mm length), and two platinum–iridium coils that form two electrodes (3 mm length) located at opposite ends of a silicone body. These neuromuscular stimulators are addressable, allowing to establish a network of microstimulators that can be controlled independently. Their operation was demonstrated in an acute study by injecting a few of them in the hind limb of anesthetized rabbits and inducing controlled and independent contractions. Significance. These results show the feasibility of manufacturing threadlike wireless addressable neuromuscular stimulators by using fabrication techniques and materials well established for chronic electronic implants. Although long-term operation still must be demonstrated, the obtained results pave the way to the clinical development of advanced motor neuroprostheses formed by dense networks of such wireless devices.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 724244). A.I. gratefully acknowledges the financial support by ICREA under the ICREA Academia programme

Injectable sensors based on passive rectification of volume-conducted currents

Sensing implants that can be deployed by catheterization or by injection are preferable over implants requiring invasive surgery. However, present powering methods for active implants and present interrogation methods for passive implants require bulky parts within the implants that hinder the development of such minimally invasive devices. In this article, we propose a novel approach that potentially enables the development of passive sensing systems overcoming the limitations of previous implantable sensing systems in terms of miniaturization. In this approach implants are shaped as thread-like devices suitable for implantation by injection. Their basic structure consists of a thin elongated body with two electrodes at opposite ends and a simple and small circuit made up of a diode, a capacitor and a resistor. The interrogation method to obtain measurements from the implants consists in applying innocuous bursts of high frequency (≥1 MHz) alternating current that reach the implants by volume conduction and in capturing and processing the voltage signals that the implants produce after the bursts. As proof-of-concept, and for illustrating how to put in practice this novel approach, here we describe the development and characterization of a system for measuring the conductivity of tissues surrounding the implant. We also describe the implementation and the in vitro validation of a 0.95 mm-thick, flexible injectable implant made of off-the-shelf components. For conductivities ranging from about 0.2 to 0.8 S/m, when compared to a commercial conductivity meter, the accuracy of the implemented system was about ±10%.This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 724244). Antoni Ivorra gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. Shahid Malik would like to thank the Spanish Institute for Foreign Trade (ICEX) and the Spanish National Research Council (CSIC) for the ERASMUS (Alianza 4 Universidades) mobility grant

Powering electronic implants by high frequency volume conduction: in human validation

Objective: Wireless power transfer (WPT) is used as an alternative to batteries to accomplish miniaturization in electronic medical implants. However, established WPT methods require bulky parts within the implant or cumbersome external systems, hindering minimally invasive deployments and the development of networks of implants. As an alternative, we propose a WPT approach based on volume conduction of high frequency (HF) current bursts. These currents are applied through external electrodes and are collected by the implants through two electrodes at their opposite ends. This approach avoids bulky components, enabling the development of flexible threadlike implants. Methods: We study in humans if HF (6.78 MHz) current bursts complying with safety standards and applied through two textile electrodes strapped around a limb can provide substantial powers from pairs of implanted electrodes. Results: Time averaged electric powers obtained from needle electrodes (diameter = 0.4 mm, length = 3 mm, separation = 30 mm) inserted into arms and lower legs of five healthy participants were 5.9 ± 0.7 mW and 2.4 ± 0.3 mW respectively. We also characterize the coupling between the external system and the implants using personalized two-port impedance models generated from medical images. Conclusions: The results demonstrate that innocuous and imperceptible HF current bursts that flow through the tissues by volume conduction can be used to wirelessly power threadlike implants. Significance: This is the first time that WPT based on volume conduction is demonstrated in humans. This method overcomes the limitations of existing WPT methods in terms of minimal invasiveness and usability.This work has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant 779982 (Project EXTEND—Bidirectional Hyper-Connected Neural System). A. Ivorra gratefully acknowledges the financial support by ICREA under the ICREA Academia programme