Self-rectifying magnetoelectric metamaterials for remote neural stimulation and motor function restoration.

Magnetoelectric materials convert magnetic fields into electric fields. These materials are often used in wireless electronic and biomedical applications. For example, magnetoelectrics could enable the remote stimulation of neural tissue, but the optimal resonance frequencies are typically too high to stimulate neural activity. Here we describe a self-rectifying magnetoelectric metamaterial for a precisely timed neural stimulation. This metamaterial relies on nonlinear charge transport across semiconductor layers that allow the material to generate a steady bias voltage in the presence of an alternating magnetic field. We generate arbitrary pulse sequences with time-averaged voltage biases in excess of 2 V. As a result, we can use magnetoelectric nonlinear metamaterials to wirelessly stimulate peripheral nerves to restore a sensory reflex in an anaesthetized rat model and restore signal propagation in a severed nerve with latencies of less than 5 ms. Overall, these results showing the rational design of magnetoelectric metamaterials support applications in advanced biotechnology and electronics.

Magnetoelectric Bio-Implants Powered and Programmed by a Single Transmitter for Coordinated Multisite Stimulation.

This paper presents a hardware platform including stimulating implants wirelessly powered and controlled by a shared transmitter for coordinated leadless multisite stimulation. The adopted novel single-transmitter, multiple-implant structure can flexibly deploy stimuli, improve system efficiency, easily scale stimulating channel quantity and relieve efforts in device synchronization. In the proposed system, a wireless link leveraging magnetoelectric effects is co-designed with a robust and efficient system-on-chip to enable reliable operation and individual programming of every implant. Each implant integrates a 0.8-mm2 chip, a 6-mm2 magnetoelectric film, and an energy storage capacitor within a 6.2-mm3 size. Magnetoelectric power transfer is capable of safely transmitting milliwatt power to devices placed several centimeters away from the transmitter coil, maintaining good efficiency with size constraints and tolerating 60-degree, 1.5-cm misalignment in angular and lateral movement. The SoC robustly operates with 2-V source amplitude variations that spans a 40-mm transmitter-implant distance change, realizes individual addressability through physical unclonable function IDs, and achieves 90% efficiency for 1.5-to-3.5-V stimulation with fully programmable stimulation parameters.

Distributed sensor and actuator networks for closed-loop bioelectronic medicine.

Designing implantable bioelectronic systems that continuously monitor physiological functions and simultaneously provide personalized therapeutic solutions for patients remains a persistent challenge across many applications ranging from neural systems to bioelectronic organs. Closed-loop systems typically consist of three functional blocks, namely, sensors, signal processors and actuators. An effective system, that can provide the necessary therapeutics, tailored to individual physiological factors requires a distributed network of sensors and actuators. While significant progress has been made, closed-loop systems still face many challenges before they can truly be considered as long-term solutions for many diseases. In this review, we consider three important criteria where materials play a critical role to enable implantable closed-loop systems: Specificity, Biocompatibility and Connectivity. We look at the progress made in each of these fields with respect to a specific application and outline the challenges in creating bioelectronic technologies for the future.

A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves.

Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via a digitally programmable 1 mm × 0.8 mm system-on-a-chip. Implantation of the device directly on top of the sciatic nerve in rats and near a femoral artery in pigs (with a stimulation lead introduced into a blood vessel through a catheter) allowed for wireless stimulation of the animals' sciatic and femoral nerves. Minimally invasive magnetoelectric implants may allow for the stimulation of nerves without the need for open surgery or the implantation of battery-powered pulse generators.

All That Coughs Is Not COVID-19: A Delayed Diagnosis of Disseminated Coccidioidomycosis Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Coccidioides immitis (and Coccidioides posadasii) are endemic fungi of the southwestern United States and northern Mexico. Uncomplicated, symptomatic Coccidioides infection most commonly causes a self-limited pneumonia; however, immunocompromised patients can manifest severe pneumonia with an additional risk of dissemination to bone, joints, soft tissues, and in the most severe cases, the central nervous system. In 2020, clinicians were challenged with a previously unseen volume of acute respiratory complaints as a result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We present a patient with respiratory failure secondary to SARS-CoV-2 who experienced prolonged hypoxia and neurologic deterioration, eventually leading to a diagnosis of occult disseminated coccidiomycosis involving meningitis, miliary-pattern pneumonia, and cutaneous lesions.

Wearable wireless power systems for 'ME-BIT' magnetoelectric-powered bio implants.

Objective.Compared to biomedical devices with implanted batteries, wirelessly powered technologies can be longer-lasting, less invasive, safer, and can be miniaturized to access difficult-to-reach areas of the body. Magnetic fields are an attractive wireless power transfer modality for such bioelectronic applications because they suffer negligible absorption and reflection in biological tissues. However, current solutions using magnetic fields for mm sized implants either operate at high frequencies (>500 kHz) or require high magnetic field strengths (>10 mT), which restricts the amount of power that can be transferred safely through tissue and limits the development of wearable power transmitter systems. Magnetoelectric (ME) materials have recently been shown to provide a wireless power solution for mm-sized neural stimulators. These ME transducers convert low magnitude (<1 mT) and low-frequency (∼300 kHz) magnetic fields into electric fields that can power custom integrated circuits or stimulate nearby tissue.Approach.Here we demonstrate a battery-powered wearable magnetic field generator that can power a miniaturized MagnetoElectric-powered Bio ImplanT 'ME-BIT' that functions as a neural stimulator. The wearable transmitter weighs less than 0.5 lbs and has an approximate battery life of 37 h.Main results.We demonstrate the ability to power a millimeter-sized prototype 'ME-BIT' at a distance of 4 cm with enough energy to electrically stimulate a rat sciatic nerve. We also find that the system performs well under translational misalignment and identify safe operating ranges according to the specific absorption rate limits set by the IEEE Std 95.1-2019.Significance.These results validate the feasibility of a wearable system that can power miniaturized ME implants that can be used for different neuromodulation applications.

MagNI: A Magnetoelectrically Powered and Controlled Wireless Neurostimulating Implant.

This paper presents the first wireless and programmable neural stimulator leveraging magnetoelectric (ME) effects for power and data transfer. Thanks to low tissue absorption, low misalignment sensitivity and high power transfer efficiency, the ME effect enables safe delivery of high power levels (a few milliwatts) at low resonant frequencies (  âˆ¼ 250 kHz) to mm-sized implants deep inside the body (30-mm depth). The presented MagNI (Magnetoelectric Neural Implant) consists of a 1.5-mm 2 180-nm CMOS chip, an in-house built 4 × 2 mm ME film, an energy storage capacitor, and on-board electrodes on a flexible polyimide substrate with a total volume of 8.2 mm 3. The chip with a power consumption of 23.7  µW includes robust system control and data recovery mechanisms under source amplitude variations (1-V variation tolerance). The system delivers fully-programmable bi-phasic current-controlled stimulation with patterns covering 0.05-to-1.5-mA amplitude, 64-to-512- µs pulse width, and 0-to-200-Hz repetition frequency for neurostimulation.

Magnetoelectric Materials for Miniature, Wireless Neural Stimulation at Therapeutic Frequencies.

A major challenge for miniature bioelectronics is wireless power delivery deep inside the body. Electromagnetic or ultrasound waves suffer from absorption and impedance mismatches at biological interfaces. On the other hand, magnetic fields do not suffer these losses, which has led to magnetically powered bioelectronic implants based on induction or magnetothermal effects. However, these approaches have yet to produce a miniature stimulator that operates at clinically relevant high frequencies. Here, we show that an alternative wireless power method based on magnetoelectric (ME) materials enables miniature magnetically powered neural stimulators that operate up to clinically relevant frequencies in excess of 100 Hz. We demonstrate that wireless ME stimulators provide therapeutic deep brain stimulation in a freely moving rodent model for Parkinson's disease and that these devices can be miniaturized to millimeter-scale and fully implanted. These results suggest that ME materials are an excellent candidate to enable miniature bioelectronics for clinical and research applications.