Improving the mechanistic study of neuromuscular diseases through the development of a fully wireless and implantable recording device

Neuromuscular diseases manifest by a handful of known phenotypes affecting the peripheral nerves, skeletal muscle fibers, and neuromuscular junction. Common signs of these diseases include demyelination, myasthenia, atrophy, and aberrant muscle activity—all of which may be tracked over time using one or more electrophysiological markers. Mice, which are the predominant mammalian model for most human diseases, have been used to study congenital neuromuscular diseases for decades. However, our understanding of the mechanisms underlying these pathologies is still incomplete. This is in part due to the lack of instrumentation available to easily collect longitudinal, in vivo electrophysiological activity from mice. There remains a need for a fully wireless, batteryless, and implantable recording system that can be adapted for a variety of electrophysiological measurements and also enable long-term, continuous data collection in very small animals. To meet this need a miniature, chronically implantable device has been developed that is capable of wirelessly coupling energy from electromagnetic fields while implanted within a body. This device can both record and trigger bioelectric events and may be chronically implanted in rodents as small as mice. This grants investigators the ability to continuously observe electrophysiological changes corresponding to disease progression in a single, freely behaving, untethered animal. The fully wireless closed-loop system is an adaptable solution for a range of long-term mechanistic and diagnostic studies in rodent disease models. Its high level of functionality, adjustable parameters, accessible building blocks, reprogrammable firmware, and modular electrode interface offer flexibility that is distinctive among fully implantable recording or stimulating devices. The key significance of this work is that it has generated novel instrumentation in the form of a fully implantable bioelectric recording device having a much higher level of functionality than any other fully wireless system available for mouse work. This has incidentally led to contributions in the areas of wireless power transfer and neural interfaces for upper-limb prosthesis control. Herein the solution space for wireless power transfer is examined including a close inspection of far-field power transfer to implanted bioelectric sensors. Methods of design and characterization for the iterative development of the device are detailed. Furthermore, its performance and utility in remote bioelectric sensing applications is demonstrated with humans, rats, healthy mice, and mouse models for degenerative neuromuscular and motoneuron diseases

An Implantable Peripheral Nerve Recording and Stimulation System for Experiments on Freely Moving Animal Subjects

A new study with rat sciatic nerve model for peripheral nerve interfacing is presented using a fully-implanted inductively-powered recording and stimulation system in a wirelessly-powered standard homecage that allows animal subjects move freely within the homecage. The Wireless Implantable Neural Recording and Stimulation (WINeRS) system offers 32-channel peripheral nerve recording and 4-channel current-controlled stimulation capabilities in a 3 × 1.5 × 0.5 cm3 package. A bi-directional data link is established by on-off keying pulse-position modulation (OOK-PPM) in near field for narrow-band downlink and 433 MHz OOK for wideband uplink. An external wideband receiver is designed by adopting a commercial software defined radio (SDR) for a robust wideband data acquisition on a PC. The WINeRS-8 prototypes in two forms of battery-powered headstage and wirelessly-powered implant are validated in vivo, and compared with a commercial system. In the animal study, evoked compound action potentials were recorded to verify the stimulation and recording capabilities of the WINeRS-8 system with 32-ch penetrating and 4-ch cuff electrodes on the sciatic nerve of awake freely-behaving rats. Compared to the conventional battery-powered system, WINeRS can be used in closed-loop recording and stimulation experiments over extended periods without adding the burden of carrying batteries on the animal subject or interrupting the experiment

Wireless Power Transfer Techniques for Implantable Medical Devices:A Review

Wireless power transfer (WPT) systems have become increasingly suitable solutions for the electrical powering of advanced multifunctional micro-electronic devices such as those found in current biomedical implants. The design and implementation of high power transfer efficiency WPT systems are, however, challenging. The size of the WPT system, the separation distance between the outside environment and location of the implanted medical device inside the body, the operating frequency and tissue safety due to power dissipation are key parameters to consider in the design of WPT systems. This article provides a systematic review of the wide range of WPT systems that have been investigated over the last two decades to improve overall system performance. The various strategies implemented to transfer wireless power in implantable medical devices (IMDs) were reviewed, which includes capacitive coupling, inductive coupling, magnetic resonance coupling and, more recently, acoustic and optical powering methods. The strengths and limitations of all these techniques are benchmarked against each other and particular emphasis is placed on comparing the implanted receiver size, the WPT distance, power transfer efficiency and tissue safety presented by the resulting systems. Necessary improvements and trends of each WPT techniques are also indicated per specific IMD

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

Intra-Body Communications for Nervous System Applications: Current Technologies and Future Directions

The Internet of Medical Things (IoMT) paradigm will enable next generation healthcare by enhancing human abilities, supporting continuous body monitoring and restoring lost physiological functions due to serious impairments. This paper presents intra-body communication solutions that interconnect implantable devices for application to the nervous system, challenging the specific features of the complex intra-body scenario. The presented approaches include both speculative and implementative methods, ranging from neural signal transmission to testbeds, to be applied to specific neural diseases therapies. Also future directions in this research area are considered to overcome the existing technical challenges mainly associated with miniaturization, power supply, and multi-scale communications.Comment: https://www.sciencedirect.com/science/article/pii/S138912862300163

Towards a Fully Implantable Closed-Loop Opto-Electro Stimulation Interface for Motor Neuron Disease Treatment

This paper presents a fully-implantable closed-loop opto-electro stimulation interface for motor neuron disease studies, designed for experiments with freely moving rodents. A low power consumption Bluetooth data link is used to wirelessly control 64 opto-electro stimulation channels and receive neural recording data. The implant is powered by a wirelessly rechargeable lithium-ion battery, which can support 2.5 hours continuous operation with a stimulation output up to 10 mA. The battery is recharged using a QI standard wireless inductive power link, which can deliver >100mW power at a distance of 2 cm. The total size of the implant system is 29 mm × 20 mm × 13 mm. Its performance is compared with the state-of-the-art

Biointegrated and wirelessly powered implantable brain devices: a review

Implantable neural interfacing devices have added significantly to neural engineering by introducing the low-frequency oscillations of small populations of neurons known as local field potential as well as high-frequency action potentials of individual neurons. Regardless of the astounding progression as of late, conventional neural modulating system is still incapable to achieve the desired chronic in vivo implantation. The real constraint emerges from mechanical and physical diffierences between implants and brain tissue that initiates an inflammatory reaction and glial scar formation that reduces the recording and stimulation quality. Furthermore, traditional strategies consisting of rigid and tethered neural devices cause substantial tissue damage and impede the natural behaviour of an animal, thus hindering chronic in vivo measurements. Therefore, enabling fully implantable neural devices, requires biocompatibility, wireless power/data capability, biointegration using thin and flexible electronics, and chronic recording properties. This paper reviews biocompatibility and design approaches for developing biointegrated and wirelessly powered implantable neural devices in animals aimed at long-term neural interfacing and outlines current challenges toward developing the next generation of implantable neural devices

Wireless Technologies for Implantable Devices

Wireless technologies are incorporated in implantable devices since at least the 1950s. With remote data collection and control of implantable devices, these wireless technologies help researchers and clinicians to better understand diseases and to improve medical treatments. Today, wireless technologies are still more commonly used for research, with limited applications in a number of clinical implantable devices. Recent development and standardization of wireless technologies present a good opportunity for their wider use in other types of implantable devices, which will significantly improve the outcomes of many diseases or injuries. This review briefly describes some common wireless technologies and modern advancements, as well as their strengths and suitability for use in implantable medical devices. The applications of these wireless technologies in treatments of orthopedic and cardiovascular injuries and disorders are described. This review then concludes with a discussion on the technical challenges and potential solutions of implementing wireless technologies in implantable devices

Beyond Tissue replacement: The Emerging role of smart implants in healthcare

Smart implants are increasingly used to treat various diseases, track patient status, and restore tissue and organ function. These devices support internal organs, actively stimulate nerves, and monitor essential functions. With continuous monitoring or stimulation, patient observation quality and subsequent treatment can be improved. Additionally, using biodegradable and entirely excreted implant materials eliminates the need for surgical removal, providing a patient-friendly solution. In this review, we classify smart implants and discuss the latest prototypes, materials, and technologies employed in their creation. Our focus lies in exploring medical devices beyond replacing an organ or tissue and incorporating new functionality through sensors and electronic circuits. We also examine the advantages, opportunities, and challenges of creating implantable devices that preserve all critical functions. By presenting an in-depth overview of the current state-of-the-art smart implants, we shed light on persistent issues and limitations while discussing potential avenues for future advancements in materials used for these devices