First-in-human demonstration of floating EMG sensors and stimulators wirelessly powered and operated by volume conduction.

BACKGROUND: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. METHODS: A proof-of-concept device, consisting of implantable thin-film electrodes and a nonimplantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. RESULTS: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. CONCLUSIONS: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.

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.

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

Objective.To develop andin vivodemonstrate 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.

Floating EMG sensors and stimulators wirelessly powered and operated by volume conduction for networked neuroprosthetics.

BACKGROUND: Implantable neuroprostheses consisting of a central electronic unit wired to electrodes benefit thousands of patients worldwide. However, they present limitations that restrict their use. Those limitations, which are more adverse in motor neuroprostheses, mostly arise from their bulkiness and the need to perform complex surgical implantation procedures. Alternatively, it has been proposed the development of distributed networks of intramuscular wireless microsensors and microstimulators that communicate with external systems for analyzing neuromuscular activity and performing stimulation or controlling external devices. This paradigm requires the development of miniaturized implants that can be wirelessly powered and operated by an external system. To accomplish this, we propose a wireless power transfer (WPT) and communications approach based on volume conduction of innocuous high frequency (HF) current bursts. The currents are applied through external textile electrodes and are collected by the wireless devices through two electrodes for powering and bidirectional digital communications. As these devices do not require bulky components for obtaining power, they may have a flexible threadlike conformation, facilitating deep implantation by injection. METHODS: We report the design and evaluation of advanced prototypes based on the above approach. The system consists of an external unit, floating semi-implantable devices for sensing and stimulation, and a bidirectional communications protocol. The devices are intended for their future use in acute human trials to demonstrate the distributed paradigm. The technology is assayed in vitro using an agar phantom, and in vivo in hindlimbs of anesthetized rabbits. RESULTS: The semi-implantable devices were able to power and bidirectionally communicate with the external unit. Using 13 commands modulated in innocuous 3 MHz HF current bursts, the external unit configured the sensing and stimulation parameters, and controlled their execution. Raw EMG was successfully acquired by the wireless devices at 1 ksps. CONCLUSIONS: The demonstrated approach overcomes key limitations of existing neuroprostheses, paving the way to the development of distributed flexible threadlike sensors and stimulators. To the best of our knowledge, these devices are the first based on WPT by volume conduction that can work as EMG sensors and as electrical stimulators in a network of wireless devices.

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%.

Interleaved intramuscular stimulation with minimally overlapping electrodes evokes smooth and fatigue resistant forces.

OBJECTIVE: It is known that multi-site interleaved stimulation generates less muscle fatigue compared to single-site synchronous stimulation. However, in the limited number of studies in which intramuscular electrodes were used, the fatigue reduction associated with interleaved stimulation could not consistently be achieved. We hypothesize that this could be due to the inability to place the intramuscular electrodes used in interleaved stimulation in locations that minimize overlap amongst the motor units activated by the electrodes. Our objective in the present study was to use independent intramuscular electrodes to compare fatigue induced by interleaved stimulation with that generated by synchronous stimulation at the same initial force and ripple. APPROACH: In the medial gastrocnemius muscle of an anesthetized rabbit (n = 3), ten intramuscular hook wire electrodes were inserted at different distances from the nerve entry. Overlap was measured using the refractory technique and only three electrodes were found to be highly independent. After ensuring that forces obtained by both stimulation modalities had the same ripple and magnitude, fatigue induced during interleaved stimulation across three independent distal electrodes was compared to that obtained by synchronously delivering pulses to a single proximal electrode. MAIN RESULTS: Contractions evoked by interleaved stimulation exhibited less fatigue than those evoked by synchronous stimulation. Twitch force recruitment curves collected from each of the ten intramuscular electrodes showed frequent intermediate plateaus and the force value at these plateaus decreased as the distance between the electrode and nerve entry increased. SIGNIFICANCE: The results indicate that interleaved intramuscular stimulation is preferred over synchronous intramuscular stimulation when fatigue-resistant and smooth forces are desired. In addition, the results suggest that the large muscle compartments innervated by the primary intramuscular nerve branches give rise to progressively smaller independent compartments in subsequent nerve divisions.

Demonstration of 2-mm-Thick Microcontrolled Injectable Stimulators Based on Rectification of High Frequency Current Bursts.

Existing implantable stimulators use powering approaches that result in stiff and bulky systems or result in systems incapable of producing the current magnitudes required for neuromuscular stimulation. This hampers their use in neuroprostheses for paralysis. We previously demonstrated an electrical stimulation method based on electronic rectification of high frequency (HF) current bursts. The implants act as rectifiers of HF current that flows through the tissues by galvanic coupling, transforming this current into low frequency current capable of performing neuromuscular stimulation. Here we developed 2 mm thick, semi-rigid, injectable and addressable stimulators made of off-the-shelf components and based on this method. The devices were tested in vitro to illustrate how they are powered by galvanic coupling. In addition they were tried in an animal model to demonstrate their ability to perform controlled electrical stimulation. The implants were deployed by injection into two antagonist muscles of an anesthetized rabbit and were addressed resulting in independent isometric contractions. Low frequency currents of 2 mA were delivered by the implants. The HF currents are safe in terms of unwanted electrostimulation and tissue heating according to standards. This indicates that the proposed electrical stimulation method will allow unprecedented levels of miniaturization for neuroprostheses.

In vivo demonstration of injectable microstimulators based on charge-balanced rectification of epidermically applied currents.

OBJECTIVE: It is possible to develop implantable microstimulators whose actuation principle is based on rectification of high-frequency (HF) current bursts supplied through skin electrodes. This has been demonstrated previously by means of devices consisting of a single diode. However, previous single diode devices caused dc currents which made them impractical for clinical applications. Here flexible thread-like stimulation implants which perform charge balance are demonstrated in vivo. APPROACH: The implants weigh 40.5 mg and they consist of a 3 cm long tubular silicone body with a diameter of 1 mm, two electrodes at opposite ends, and, within the central section of the body, an electronic circuit made up of a diode, two capacitors, and a resistor. In the present study, each implant was percutaneously introduced through a 14 G catheter into either the gastrocnemius muscle or the cranial tibial muscle of a rabbit hindlimb. Then stimulation was performed by delivering HF bursts (amplitude <60 V, frequency 1 MHz, burst repetition frequency from 10 Hz to 200 Hz, duration = 200 µs) through a pair of textile electrodes strapped around the hindlimb and either isometric plantarflexion or dorsiflexion forces were recorded. Stimulation was also assayed 1, 2 and 4 weeks after implantation. MAIN RESULTS: The implants produced bursts of rectified current whose mean value was of a few mA and were capable of causing local neuromuscular stimulation. The implants were well-tolerated during the 4 weeks. SIGNIFICANCE: Existing power supply methods, and, in particular inductive links, comprise stiff and bulky parts. This hinders the development of minimally invasive implantable devices for neuroprostheses based on electrical stimulation. The proposed methodology is intended to relieving such bottleneck. In terms of mass, thinness, and flexibility, the demonstrated implants appear to be unprecedented among the intramuscular stimulation implants ever assayed in vertebrates.

In Vivo Demonstration of Addressable Microstimulators Powered by Rectification of Epidermically Applied Currents for Miniaturized Neuroprostheses.

Electrical stimulation is used in order to restore nerve mediated functions in patients with neurological disorders, but its applicability is constrained by the invasiveness of the systems required to perform it. As an alternative to implantable systems consisting of central stimulation units wired to the stimulation electrodes, networks of wireless microstimulators have been devised for fine movement restoration. Miniaturization of these microstimulators is currently hampered by the available methods for powering them. Previously, we have proposed and demonstrated a heterodox electrical stimulation method based on electronic rectification of high frequency current bursts. These bursts can be delivered through textile electrodes on the skin. This approach has the potential to result in an unprecedented level of miniaturization as no bulky parts such as coils or batteries are included in the implant. We envision microstimulators designs based on application-specific integrated circuits (ASICs) that will be flexible, thread-like (diameters < 0.5 mm) and not only with controlled stimulation capabilities but also with sensing capabilities for artificial proprioception. We in vivo demonstrate that neuroprostheses composed of addressable microstimulators based on this electrical stimulation method are feasible and can perform controlled charge-balanced electrical stimulation of muscles. We developed miniature external circuit prototypes connected to two bipolar probes that were percutaneously implanted in agonist and antagonist muscles of the hindlimb of an anesthetized rabbit. The electronic implant architecture was able to decode commands that were amplitude modulated on the high frequency (1 MHz) auxiliary current bursts. The devices were capable of independently stimulating the target tissues, accomplishing controlled dorsiflexion and plantarflexion joint movements. In addition, we numerically show that the high frequency current bursts comply with safety standards both in terms of tissue heating and unwanted electro-stimulation. We demonstrate that addressable microstimulators powered by rectification of epidermically applied currents are feasible.