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The article discusses two wireless modalities, the far-field and near-field, terms that refer to the distance between the source and the device as a function of the powering frequency. Also discussed is the new mid-field wireless power transfer technique which enables the highest power transfer efficiency at deep implantation depths compared with far-field and near-field techniques. Full-wave analytical and numerical techniques have been used to derive the optimum frequency and current density.

After an amputation, advanced prosthetic limbs can be used to interface with the nervous system and restore motor function. Despite numerous breakthroughs in the field, many of the recent research advancements have not been widely integrated into clinical practice. This review highlights recent innovations in neuromuscular implants—specifically those that interface with skeletal muscle—which could improve the clinical translation of prosthetic technologies. Skeletal muscle provides a physiologic gateway to harness and amplify signals from the nervous system. Recent surgical advancements in muscle reinnervation surgeries leverage the "bio‐amplification" capabilities of muscle, enabling more intuitive control over a greater number of degrees of freedom in prosthetic limbs than previously achieved. We anticipate that state‐of‐the‐art implantable neuromuscular interfaces that integrate well with skeletal muscle and novel surgical interventions will provide a long‐term solution for controlling advanced prostheses. Flexible electrodes are expected to play a crucial role in reducing foreign body responses and improving the longevity of the interface. Additionally, innovations in device miniaturization and ongoing exploration of shape memory polymers could simplify surgical procedures for implanting such interfaces. Once implanted, wireless strategies for powering and transferring data from the interface can eliminate bulky external wires, reduce infection risk, and enhance day‐to‐day usability. By outlining the current limitations of neuromuscular interfaces along with potential future directions, this review aims to guide continued research efforts and future collaborations between engineers and specialists in the field of neuromuscular and musculoskeletal medicine. [ABSTRACT FROM AUTHOR]

Objective: To investigate how prolonged seizure activity affects cardiorespiratory function and activity of pre‐Bötzinger complex, leading to sudden death. Methods: Urethane‐anesthetized female Long‐Evans rats were implanted with nasal thermocouple; venous and arterial cannulae; and electrodes for electrocardiography (ECG) and hippocampal, cortical, and brainstem recording. Kainic acid injection into the ventral hippocampus induced status epilepticus. Results: Seizures caused hypertension, tachycardia, and tachypnea punctuated by recurrent transient apneas. Salivation increased considerably: in 11 of 12 rats, liquid with alkaline pH consistent with saliva was expelled from the mouth. Most transient apneas were obstructive: nasal airflow ceased, while, in 83%, efforts to breathe persisted as continued rhythmic activity of respiratory pre‐Bötzinger neurons, inspiratory electromyography (EMG), and excursions of the chest wall and abdomen. Blood pressure oscillated in time with respiratory efforts. This pattern also occurred in a minority of cases (16%) of incomplete apnea, but not in rare cases (1%) of transient central apneas. During transient obstructive apneas, the frequency of all inspiratory efforts decreased abruptly by ~30%, suggesting a resetting of the central respiratory rhythm generator. Twenty‐two of thirty‐one rats died, due either to obstructive apnea (12) or central apnea following progressive slowing of respiration (10). Most rats dying of central apnea had experienced several transient obstructive apneas. Negative DC field potential shifts of the brainstem followed the final breath, consistent with previous reports on spreading depolarization in mouse models. Timing suggests that the DC shift is a consequence rather than cause of respiratory collapse. Cardiac activity continued for tens of seconds. Significance: Seizure activity in forebrain induces pronounced autonomic activation and disrupts activity in medullary respiratory centers, resulting in death from either obstructive or central apnea. These results directly inform mechanisms of death in status epilepticus, and indirectly provide clues to mechanisms of sudden unexpected death in epilepsy (SUDEP). [ABSTRACT FROM AUTHOR]

The general coupling matrix representation of bandpass filter (BPF) circuits is a widely used technique that has simplified the analysis and optimization of complex microwave filters. In this paper, we demonstrate a novel application of the general coupling matrix for modeling wireless power-transfer (WPT) systems based on the BPF model of magnetically coupled resonators. Compared to other methods of WPT analysis, our model simplifies accommodation of complex loads and provides direct expressions for impedance matching (IM) in WPT systems. Using this tool, we achieve optimal IM for two resonator systems with a complex load, thus achieving the greatest possible power-transfer efficiency (PTE). Furthermore, our model reveals additional design constraints for optimizing PTE in coupled resonator systems exhibiting low quality factor and small interresonator coupling. Overall, this paper introduces a new, versatile framework for the analysis and optimization of coupled resonator WPT systems. Experimental results are presented, verifying the optimal IM design process. [ABSTRACT FROM PUBLISHER]

Objective: Heart disease is the leading cause of death worldwide. Hypertension is an important precursor and the most common risk factor to heart failure. While some patients can control their high blood pressure with pharmaceuticals, many suffer from resistant hypertension, where antihypertensive medications do not achieve the desired outcome. Electrical stimulation is an emerging therapy to modulate blood pressure and integrating it with closed-loop feedback can improve blood pressure control. Methods: We design and fabricate two application-specific integrated circuits (ASICs) for stimulation and pressure sensing using TSMC's 180 nm MS RF G process. We create a closed-loop system by integrating the ASICs with a microscale pressure sensor and a custom-built Python script and test the full system in six Long Evans rats using vagus nerve stimulation. Results: After calibration and benchtop verification, we prove the functionality of the system in lowering, and maintaining a desired blood pressure in vivo. The system effectively monitors pressure and stimulates when that pressure exceeds the user-determined threshold. Conclusion: By combining this stimulation therapy with a pressure sensor, we present a novel closed-loop, electroceutical system that has the potential to monitor and modulate blood pressure. Significance: We present a drug-free, potentially side-effect-free electroceutical therapeutic for managing resistant hypertension. [ABSTRACT FROM AUTHOR]

Far-field RF powering is an attractive solution to the challenge of remotely powering devices implanted in living tissue. The purpose of this study is to characterize the peak obtainable power levels in a wireless myoelectric sensor implanted in a patient while maintaining safe local temperature and RF powering conditions. This can serve as a guide for the design of onboard electronics in related medical implants and provide motivation for more efficient power management strategies for implantable integrated circuits. Safe powering conditions and peak received power levels are established using a simplified theoretical analysis and Federal Communications Commission-established limits for radiating antennas. These conditions are subsequently affirmed and improved upon using the finite-element method and temperature modeling in bovine muscle. [ABSTRACT FROM PUBLISHER]

Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. Furthermore, cultures of chick dorsal root ganglia in gels of hyaluronic acid or chondroitin sulfate revealed enhanced growth in chondroitin sulfate gels only upon addition of peptide. Taken together, these results suggest a synergistic nerve growth factor-binding activity between this peptide and chondroitin sulfate. [ABSTRACT FROM AUTHOR]

Background: A serious complication with drug-eluting coronary stents is late thrombosis, caused by exposed stent struts not covered by endothelial cells in the healing process. Real-time detection of this healing process could guide physicians for more individualized anti-platelet therapy. Here we present work towards developing a sensor to detect this healing process. Sensors on several stent struts could give information about the heterogeneity of healing across the stent. Methods: A piezoelectric microcantilever was insulated with parylene and demonstrated as an endothelialization detector for incorporation within an active coronary stent. After initial characterization, endothelial cells were plated onto the cantilever surface. After they attached to the surface, they caused an increase in mass, and thus a decrease in the resonant frequencies of the cantilever. This shift was then detected electrically with an LCR meter. The self-sensing, self-actuating cantilever does not require an external, optical detection system, thus allowing for implanted applications. Results: A cell density of 1300 cells/mm2 on the cantilever surface is detected. Conclusions: We have developed a self-actuating, self-sensing device for detecting the presence of endothelial cells on a surface. The device is biocompatible and functions reliably in ionic liquids, making it appropriate for implantable applications. This sensor can be placed along the struts of a coronary stent to detect when the struts have been covered with a layer of endothelial cells and are no longer available surfaces for clot formation. Anti-platelet therapy can be adjusted in real-time with respect to a patient's level of healing and hemorrhaging risks. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the safety and efficacy of the IOPTx™ system – a novel wearable, electroceutical treatment to lower intraocular pressure. Methods: Patients wear the customized contact lens and spectacles of the IOPTx™ system and undergo three 15-minute randomized stimulation trials at different stimulus amplitudes with 15 minutes of rest in between. The parameters for the stimulation trials include a frequency of 50 Hz, a pulse width of 100 µs, and current amplitudes between 90–150 µA. The optometrist measures the intraocular pressure (IOP) before, immediately after, and 15 minutes after the trial, and performs topography, a slit eye examination, and specular microscopy before and after the entire study to check the health of the eye and confirm the safety of the system. Results: The IOPTx™ system successfully modulates a patient's IOP. By testing various currents, we create individual tuning curves examining the effect of the stimulation amplitude on the change in IOP. Each patient may have an optimal dose-response curve and by normalizing to this value, the IOPTx™ system decreased IOP by an average of 17.7% with fifteen minutes of therapy. No Adverse Events or Adverse Device Effects occurred.Conclusions: The results of this clinical case series provide preliminary evidence of efficacy and safety of the IOPTx™ system and its potential usefulness to lower IOP in glaucoma and ocular hypertension. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that death with physiological parallels to human cases of sudden unexpected death in epilepsy (SUDEP) can be induced in seizing rats by ictal activation of oxygen‐conserving reflexes (OCRs). Methods: Urethane‐anesthetized female Long‐Evans rats were implanted with electrodes for electrocardiography (ECG), electrocorticography (ECoG), and respiratory thermocouple; venous and arterial cannulas; and a laryngoscope guide and cannula or nasal cannula for activation of the laryngeal chemoreflex (LCR) or mammalian diving reflex (MDR), respectively. Kainic acid injection, either systemic or into the ventral hippocampus, induced prolonged acute seizures. Results: Reflex challenges during seizures caused sudden death in 18 of 20 rats—all MDR rats (10) and all but two LCR rats (8) failed to recover from ictal activation of OCRs and died within minutes of the reflexes. By comparison, 4 of 4 control (ie, nonseizing) rats recovered from 64 induced diving reflexes (16 per rat), and 4 of 4 controls recovered from 64 induced chemoreflexes (16 per rat). Multiple measures were consistent with reports of human SUDEP. Terminal central apnea preceded terminal asystole in all cases. Heart and respiratory rate fluctuations that paralleled those seen in human SUDEP occurred during OCR‐induced sudden death, and mean arterial pressure (MAP) was predictive of death, showing a 17 or 15 mm Hg drop (MDR and LCR, respectively) in the 20 s window centered on the time of brain death. OCR activation was never fatal in nonseizing rats. Significance: These results present a method of inducing sudden death in two seizure models that show pathophysiology consistent with that observed in human cases of SUDEP. This proposed mechanism directly informs previous findings by our group and others in the field; provides a repeatable, inducible animal model for the study of sudden death; and offers a potential explanation for observations made in cases of human SUDEP. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) has been on the forefront of inflammatory disorder research and has yielded many promising results. Questions remain, however, about the biological mechanisms of such treatments and the inconsistencies in the methods used in research efforts. Here, we aimed to clarify the inflammatory response to intraperitoneal (IP) injections of lipopolysaccharide (LPS) in rats, while analyzing corresponding effects of electrical stimulation to subdiaphragmatic branches (anterior gastric, accessory celiac, and hepatic) of the left vagus nerve. We accomplished an in-depth characterization of the time-varying cytokine cascade response in the serum of 58 rats to an acute IP LPS challenge over a 330-minute period by utilizing curve-fitting and starting point-alignment methods. We then explored the post-LPS neuromodulation effects of electrically stimulating individually cuffed subdiaphragmatic branches. Through our analysis, we found there to be a consistent order of IP LPS cytokine response (IL-10, TNF-α, GM-CSF, IL-17F, IL-6, IL-22, INF-γ). Apart from IL-10, the IP cytokine cascade was more variable in starting time and occurred later than in previously recorded intravenous (IV) challenges. We also found distinct regulatory effects on multiple cytokine levels by each of the three subdiaphragmatic stimulation subsets. While the time-variability of IP LPS use in rats complicates its utility, we have shown it to be a practical, arguably more physiologically relevant method than IV in rats when our methods are used. More importantly, we have shown that selective subdiaphragmatic neurostimulation can be utilized to selectively induce specific effects on inflammation in the body. [ABSTRACT FROM AUTHOR]

We report a wireless energy harvesting and telemetry storage system in 180 nm CMOS technology, demonstrated in situ in rat carcass. The implantable device has dimensions 13 mm × 15 mm and stores 87.5 mJ, providing a self-powering time of 8.5 s transmitting through tissue. We utilize an all-solid-state flexible supercapacitor of breakdown voltage 0.8 V and capacitance 400 mF to harvest incoming wireless power, followed by a boost converter CMOS that drives an active wireless transmitter at 1.5 V at 2.4 GHz in the industrial, scientific, and medical (ISM) band. The DC/DC converter component and switching frequency selection were guided by genetic algorithm analysis and use digital feedback to control the pulse width modulation (PWM), which slowly modifies the duty cycle to control output voltage fluctuations. This implantable medical device system presents the roadmap for batteryless energy harvesting in vivo and in clinical environments, exhibiting the highest operating storage density of 450 μJ/mm2 reported to date. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor α (TNF-α) is linked to several chronic inflammatory diseases. Electrical vagus nerve stimulation reduces serum TNF-α levels but may cause chronic nerve damage and requires surgery. Alternatively, we proposed focused ultrasound stimulation of the vagus nerve (uVNS), which can be applied non-invasively. In this study, we induced an inflammatory response in rats using lipopolysaccharides (LPS) and collected blood to analyze the effects of uVNS on cytokine concentrations. We applied one or three 5-min pulsed focused ultrasound stimulation treatments to the vagus nerve (250 kHz, ISPPA = 3 W/cm2). Animals receiving a single ultrasound application had an average reduction in TNF-α levels of 19%, similar to the 16% reduction observed in electrically stimulated animals. With multiple applications, uVNS therapy statistically reduced serum TNF-α levels by 73% compared with control animals without any observed damage to the nerve. These findings suggest that uVNS is a suitable way to attenuate TNF-α levels. [ABSTRACT FROM AUTHOR]

Highlights • Flexible glucose sensor with mechanical stress robustness is proposed. • Linear (0.002∼66 mM) and sensitive (5.67 μAmM−1 cm-2) behavior to glucose concentrations is presented. • Integration of the electrochemical device with a custom designed IC for system level design is demonstrated. Abstract Glucose is a central substance in the human metabolism, and its concentration in human body fluid can reflect various diseases and organ malfunctions. We demonstrate a thin, flexible sensor and an associated wireless readout integrated circuit (IC) that can be used to continuously monitor glucose level over a very wide glucose concentration range. The sensor is fabricated on flexible and robust graphene petals deposited on thin carbon fibers with biocompatible materials. Graphene petals offer sensitivity of 5.67 μAmM−1 cm-2 with a sensing range from 2 μM to 66 mM. Mechanical properties of the graphene petals provide a sensor lifetime exceeding four weeks. The readout IC harvests magnetic energy from a nearby power source, acquires glucose information, and wirelessly transmits data to the user. Linearity of analog/digital circuit blocks are verified by amperometric glucose measurements while consuming less than 21μW. The sensor and readout system can be readily integrated with other sensors or drug-delivery actuators for diagnosis and therapies for diabetes. [ABSTRACT FROM AUTHOR]

Highlights • Sudden deaths in the acute KA model are preceded by a pH change in the esophagus. • When the esophagus is blocked sudden deaths are no longer observed. • Acid induced laryngospasm may cause some deaths in epilepsy. Abstract Objective Recent research suggests that obstructive laryngospasm and consequent respiratory arrest may be a mechanism in sudden unexpected death in epilepsy. We sought to test a new hypothesis that this laryngospasm is caused by seizures driving reflux of stomach acid into the larynx, rather than spontaneous pathological activity in the recurrent laryngeal nerve. Approach We used an acute kainic acid model under urethane anesthesia to observe seizure activity in Long−Evans rats. We measured the pH in the esophagus and respiratory activity. In a subset of experiments, we blocked acid movement up the esophagus with a balloon catheter. Main results In all cases of sudden death, terminal apnea was preceded by a large pH drop from 7 to 2 in the esophagus. In several animals we observed acidic fluid exiting the mouth, sometimes in large quantities. In animals where acid movement was blocked, sudden deaths did not occur. No acid was detected in controls. Significance The results suggest that acid movement up the esophagus is a trigger for sudden death in KA induced seizures. The fact that blocking acid also eliminates sudden death implies causation. These results may provide insight to the mechanism of SUDEP in humans. [ABSTRACT FROM AUTHOR]

Transfer printing of thin-film nanoelectronics from their fabrication wafer commonly requires chemical etching on the sacrifice of wafer but is also limited by defects with a low yield. Here, we introduce a wafer-recyclable, environment-friendly transfer printing process that enables the wafer-scale separation of high-performance thinfilm nanoelectronics from their fabrication wafer in a defect-free manner that enables multiple reuses of the wafer. The interfacial delamination is enabled through a controllable cracking phenomenon in a water environment at room temperature. The physically liberated thin-film nanoelectronics can be then pasted onto arbitrary places of interest, thereby endowing the particular surface with desirable add-on electronic features. Systematic experimental, theoretical, and computational studies reveal the underlying mechanics mechanism and guide manufacturability for the transfer printing process in terms of scalability, controllability, and reproducibility. [ABSTRACT FROM AUTHOR]

Objective:The goal of this paper is to create a large wireless powering arena for powering small devices implanted in freely behaving rodents. Methods: We design a cavity resonator based wireless power transfer (WPT) system and utilize our previously developed optimal impedance matching methodology to achieve effective WPT performance for operating sophisticated implantable devices, made with miniature receive coils (<8 mm in diameter), within a large volume (dimensions: 60.96 cm × 60.96 cm × 30 cm). We provide unique cavity design and construction methods which maintains electromagnetic performance of the cavity while promoting its utility as a large animal husbandry environment. In addition, we develop a biaxial receive resonator system to address device orientation insensitivity within the cavity environment. Functionality is demonstrated with chronic experiments involving rats implanted with our custom designed bioelectric recording device. Results: We demonstrate an average powering fidelity of 93.53% over nine recording sessions across nine weeks, indicating nearly continuous device operation for a freely behaving rat within the large cavity resonator space. Conclusion: We have developed and demonstrated a cavity resonator based WPT system for long term experiments involving freely behaving small animals. Significance: This cavity resonator based WPT system offers an effective and simple method for wirelessly powering miniaturized devices implanted in freely moving small animals within the largest space. [ABSTRACT FROM PUBLISHER]

• Oxygen-conserving reflex (OCR) activation in rats after carotid body (CB) denervation reliably induces sudden death. • Oxygen-conserving reflex in rat models of epilepsy induces death, but electrical CB stimulation prevents death. • Oxygen-conserving reflex-mediated death shares multiple physiological parallels with human SUDEP. • Oxygen-conserving reflex activation in non-seizing rats with intact CB never leads to sudden death. • The CB plays a vital role in restoring respiratory drive following OCR activation. To investigate carotid body (CB) mechanisms related to sudden death during seizure. Ictal activation of oxygen-conserving reflexes (OCRs) can trigger fatal cardiorespiratory collapse in seizing rats, which presents like human sudden unexpected death in epilepsy (SUDEP). The CB is strongly implicated in OCR pathways; we hypothesize that modulating CB activity will provide insight into these mechanisms of death. Long-Evans rats were anesthetized with urethane. Recordings included: electrocorticography, electrocardiography, respiration via nasal thermocouple, and blood pressure (BP). The mammalian diving reflex (MDR) was activated by cold water delivered through a nasal cannula. Reflex and stimulation trials were repeated up to 16 times (4 pre-intervention, 12 post-intervention) or until death. In some animals, one or both carotid bodies were denervated. In some animals, the CB was electrically stimulated, both with and without MDR. Seizures were induced with kainic acid (KA). Animals without seizure and with no CB modulation survived all reflexes. Non-seizing animals with CB denervation survived 7.1 ± 5.4 reflexes before death, and only 1 of 7 survived past the 12-trial threshold. Electrical CB stimulation without seizure and without reflex caused significant tachypnea and hypotension. Electrical CB stimulation with seizure and without reflex required higher amplitudes to replicate the physiological responses seen outside seizure. Seizing animals without CB intervention survived 3.2 ± 3.6 trials (per-reflex survival rate 42.0% ± 44.4%), and 0 of 7 survived past the 12-trial threshold. Seizing animals with electrical CB stimulation survived 10.5 ± 4.7 ictal trials (per-reflex survival rate 86.3% ± 35.0%), and 6 of 8 survived past the 12-trial threshold. These results suggest that, during seizure, the ability of the CB to stimulate a restart of respiration is impaired. The CB and its afferents may be relevant to fatal ictal apnea and SUDEP in humans, and CB stimulation may be a relevant intervention technique in these deaths. [ABSTRACT FROM AUTHOR]

In a multiple-receiver wireless power transfer (WPT) system, determining the condition for uniform power distribution at a high transfer efficiency is a challenging issue. In this paper, a selective WPT technique using magnetic resonance coupling (MRC) is introduced for smart power delivery in a multiple-receiver system. The proposed method selectively and exclusively delivers power to only one designated receiver among multiple receivers, eliminating the cross-coupling effect and unbalanced power division problem across the receivers. This is achieved by separating the resonant frequencies of the receivers to isolate the coupling effects between coils. The power division ratio of the receivers is controlled by changing the duration time ratio for power transfer. In this paper, a one-transmitter three-receiver selective MRC system is designed and fabricated. The power distribution is demonstrated under impedance matched condition, showing a power transfer efficiency of 24%–29% at a very small coupling coefficient of 0.01 with a 12-mm-diameter receiver coil. Distance compensation and a one-way communication of time division multiple access are demonstrated for a multiple-receiver system, using the proposed method. [ABSTRACT FROM PUBLISHER]

A novel integrated 3D micro‐supercapacitor is reported. A through‐via bottom electrode technique is utilized for the first time for supercapacitor fabrication, and a highly miniaturized, flexible, and all‐solid‐state micro‐supercapacitor with 3D integration capability is achieved. Module‐wise compact integration of supercapacitors and their versatile powering applications are demonstrated. This device enables high‐power energy storage in small‐scale electronics. [ABSTRACT FROM AUTHOR]

The charge storage characteristics of a composite nanoarchitecture with a highly functional 3D morphology are reported. The electrodes are formed by the electropolymerization of aniline monomers into a nanometer-thick polyaniline (PANI) film that conformally coats graphitic petals (GPs) grown by microwave plasma chemical vapor deposition (MPCVD) on conductive carbon cloth (CC). The hybrid CC/GPs/PANI electrodes yield results near the theoretical maximum capacitance for PANI of 2000 F g−1 (based on PANI mass) and a large area-normalized specific capacitance of ≈2.6 F cm−2 (equivalent to a volumetric capacitance of ≈230 F cm−3) at a low current density of 1 A g−1 (based on PANI mass). The specific capacitances remain above 1200 F g−1 (based on PANI mass) for currents up to 100 A g−1 with correspondingly high area-normalized values. The hybrid electrodes also exhibit a high rate capability with an energy density of 110 Wh kg−1 and a maximum power density of 265 kW kg−1 at a current density of 100 A g−1. Long-term cyclic stability is good (≈7% loss of initial capacitance after 2000 cycles), with coulombic efficiencies >99%. Moreover, prototype all-solid-state flexible supercapacitors fabricated from these hybrid electrodes exhibit excellent energy storage performance. [ABSTRACT FROM AUTHOR]

The rapid development of miniaturized electronic devices has led to a growing need for rechargeable micropower sources with high performance. Among different sources, electrochemical microcapacitors or microsupercapacitors provide higher power density than their counterparts and are gaining increased interest from the research and engineering communities. To date, little work has appeared on the integration of microsupercapacitors onto a chip or flexible substrates. This review provides an overview of research on microsupercapacitors, with particular emphasis on state-of-the-art graphene-based electrodes and solid-state devices on both flexible and rigid substrates. The advantages, disadvantages, and performance of graphene-based microsupercapacitors are summarized and new trends in materials, fabrication and packaging are identified. [ABSTRACT FROM AUTHOR]

As implantable devices gain more widespread use, medical device manufacturers are constantly looking for novel materials that increase and improve capability and functionality. The packaging needs to be biocompatible, but it is also highly desirable for it to be radio transparent to facilitate wireless telemetry and remote powering. Low temperature co-fired ceramics (LTCC) provide a viable solution that meets these desired specifications while also having characteristics that support ease of manufacturing such as the ability for molding, shaping, and even embedding components within the material. In this work, inductor coils used for wireless telemetry and powering are integrated into the walls of the LTCC-based package to maximize the size of the passive component while optimizing the miniaturization of the implant. The package designed and fabricated in this work consisted of inductors approximating 20 mH with a quality factor of 7.8 at 2 MHz. When compared to similar devices in the literature the LTCC inductor out performed these devices when a power-link figure of merit is used for comparison. [ABSTRACT FROM AUTHOR]

Abstract: Closed-loop neurostimulation devices that stimulate the brain to treat epileptic seizures have shown great promise in treating more than a third of the 2 million people with epilepsy in the United States alone whose seizures are currently nonresponsive to pharmaceutical treatment. Seizure detection algorithms facilitate responsive therapeutic intervention that is believed to increase the efficacy of neurostimulation by improving on its spatial and temporal specificity. Translating these signal processing algorithms into battery-powered, implantable devices poses a number of challenges that severely limit the computational power of the chosen algorithm. We propose a cascaded two-stage seizure detection algorithm that is computationally efficient (resulting in a low-power hardware implementation) without compromising on detection efficacy. Unlike traditional detection algorithms, the proposed technique does not explicitly require a “training” phase from individual to individual and, instead, relies on using features that result in distinct “patterns” at the electrographic seizure onset. We tested the algorithm on spontaneous clinical seizures recorded using depth electrodes from patients with focal intractable epilepsy and annotated by epileptologists at the University of Freiburg Medical Center, via the Freiburg database. The algorithm performs with a specificity and sensitivity of 99.82 and 87.5%, detecting seizures in less than 9.08% of their duration after onset. The proposed technique is also shown to be computationally efficient, facilitating low-power hardware implementation. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. [Copyright &y& Elsevier]

Abstract: Implantable neural prostheses that deliver focal electrical stimulation upon demand are rapidly emerging as an alternate therapy for roughly a third of the epileptic patient population that is medically refractory. Seizure detection algorithms enable feedback mechanisms to provide focally and temporally specific intervention. Real-time feasibility and computational complexity often limit most reported detection algorithms to implementations using computers for bedside monitoring or external devices communicating with the implanted electrodes. A comparison of algorithms based on detection efficacy does not present a complete picture of the feasibility of the algorithm with limited computational power, as is the case with most battery-powered applications. We present a two-dimensional design optimization approach that takes into account both detection efficacy and hardware cost in evaluating algorithms for their feasibility in an implantable application. Detection features are first compared for their ability to detect electrographic seizures from micro-electrode data recorded from kainate-treated rats. Circuit models are then used to estimate the dynamic and leakage power consumption of the compared features. A score is assigned based on detection efficacy and the hardware cost for each of the features, then plotted on a two-dimensional design space. An optimal combination of compared features is used to construct an algorithm that provides maximal detection efficacy per unit hardware cost. The methods presented in this paper would facilitate the development of a common platform to benchmark seizure detection algorithms for comparison and feasibility analysis in the next generation of implantable neuroprosthetic devices to treat epilepsy. [ABSTRACT FROM AUTHOR]

This paper presents a fully wireless cardiac pressure sensing system. Food and Drug Administration (FDA) approved medical stents are explored as radiating structures to support simultaneous transcutaneous wireless telemetry and powering. An application-specific integrated circuit (ASIC), designed and fabricated using the Texas Instruments 130-nm CMOS process, enables wireless telemetry, remote powering, voltage regulation, and processing of pressure measurements from a microelectromechanical systems (MEMS) capacitive sensor. This paper demonstrates fully wireless-pressure-sensing functionality with an external 35-dB⋅m RF powering source across a distance of 10 cm. Measurements in a regulated pressure chamber demonstrate the ability of the cardiac system to achieve pressure resolutions of 0.5 mmHg over a range of 0-50 mmHg using a channel data-rate of 42.2 kb/s. [ABSTRACT FROM AUTHOR]

Abstract: Chronic recording electrodes are a vital tool for brain research and neural prostheses. Despite decades of advances in recording technology, probe structures and implantation methods have changed little over time. Then as now, compressive insertion methods require probes to be constructed from hard, stiff materials, such as silicon, and contain a large diameter shank to penetrate the brain, particularly for deeper structures. The chronic presence of these probes results in an electrically isolating glial scar, degrading signal quality over time. This work demonstrates a new magnetic tension-based insertion mechanism that allows for the use of soft, flexible, and thinner probe materials, overcoming the materials limitations of modern electrodes. Probes are constructed from a sharp magnetic tip attached to a flexible tether. A pulsed magnetic field is generated in a coil surrounding a glass pipette containing the electrode. The applied field pulls the electrode tip forward, accelerating the probe into the neural tissue with a penetration depth that is calibrated against the charge voltage. Mathematical modeling and agar gel insertion testing demonstrate that the electrode can be implanted to a predictable depth given system specific parameters. Trial rodent implantations resulted in discernible single-unit activity on one of the probes. The current prototype demonstrates the feasibility of a tension based, magnetically driven implantation system and opens the door to a wide variety of new minimally invasive probe materials and configurations. [Copyright &y& Elsevier]

Continuous monitoring of blood pressure from a minimally invasive device in the pulmonary artery can serve as a diagnostic and early warning system for cardiac health. The foremost challenge in such a device is the wireless transfer of data and power from within the blood vessel to an external device while maintaining unrestricted flow through the artery. We present a miniaturized system, which is attached to the outer surface of a regular or drug-eluting FDA-approved stent. When expanded, the stent maintains a patent vessel lumen while allowing contact between the electronic sensors and the blood supply. The stent-based antenna can be used for both wireless telemetry and power transfer for the implanted electronics. Using the stent platform as both a radiating antenna and a structural support allows us to take advantage of an FDA-approved device whose safety and surgical procedure are well established. The electronics package has been reduced to an area of less than 1 mm2, with a thickness under 300 μm. A minimally invasive implantation procedure allows the delivery of the stent-based implant in nearly any major vessel of the body. This article describes an initial prototype with two stents configured as a single dipole, a 2.4-GHz transmitter microchip, and a battery, and validates transcutaneous transmission through ex vivo and in vivo porcine studies. The results demonstrate the feasibility of a stent-based wireless platform for continuous monitoring of blood pressure. [ABSTRACT FROM AUTHOR]

Abstract: Several variations of microelectrode arrays are used to record and stimulate intracortical neuronal activity. Bypassing the immune response to maintain a stable recording interface remains a challenge. Companies and researchers are continuously altering the material compositions and geometries of the arrays in order to discover a combination that allows for a chronic and stable electrode–tissue interface. From this interface, they wish to obtain consistent quality recordings and a stable, low impedance pathway for charge injection over extended periods of time. Despite numerous efforts, no microelectrode array design has managed to evade the host immune response and remain fully functional. This study is an initial effort comparing several microelectrode arrays with fundamentally different configurations for use in an implantable epilepsy prosthesis. Specifically, NeuroNexus (Michigan) probes, Cyberkinetics (Utah) Silicon and Iridium Oxide arrays, ceramic-based thin-film microelectrode arrays (Drexel), and Tucker-Davis Technologies (TDT) microwire arrays are evaluated over a 31-day period in an animal model. Microelectrodes are compared in implanted rats through impedance, charge capacity, signal-to-noise ratio, recording stability, and elicited immune response. Results suggest significant variability within and between microelectrode types with no clear superior array. Some applications for the microelectrode arrays are suggested based on data collected throughout the longitudinal study. Additionally, specific limitations of assaying biological phenomena and comparing fundamentally different microelectrode arrays in a highly variable system are discussed with suggestions on how to improve the reliability of observed results and steps needed to develop a more standardized microelectrode design. [Copyright &y& Elsevier]

We report live animal studies that verify and quantify successful transocular transmission of data from a miniature low-power implant. To minimize damage, implantation within layers of the eye requires an ultrasmall device on a scale of just a few millimeters on each side and less than 500 μm in thickness. A high-frequency transmitter integrated circuit (IC) was designed, fabricated, and bonded onto a board containing an antenna, matching network components, and interconnects. The transmitter must achieve sufficient efficiency to draw minimal power from the limited onboard storage array while outputting a sufficiently large signal to overcome tissue-induced attenuation. Two different versions of the system were developed, one using a low-temperature co-fired ceramic material for the substrate and the other using silicon. Animal studies performed using live rabbits followed by empirical measurements verified the feasibility of a wireless telemetry scheme for a low-power miniature ocular implant. [ABSTRACT FROM AUTHOR]

Recent animal work and limited clinical data have suggested that laryngospasm may be involved in the cardiorespiratory collapse seen in sudden unexpected death in epilepsy (SUDEP). In previous work, we demonstrated in an animal model of seizures that laryngospasm and sudden death were always preceded by acid reflux into the esophagus. Here, we expand on that work by testing several techniques to prevent the acid reflux or the subsequent laryngospasm. In urethane anesthetized Long Evans rats, we used systemic kainic acid to acutely induce seizure activity. We recorded pH in the esophagus, respiration, electrocorticography activity, and measured the liquid volume in the stomach postmortem. We performed the following three interventions to attempt to prevent acid reflux or laryngospasm and gain insights into mechanisms: fasting animals for 12 h, severing the gastric nerve, and electrical stimulation of either the gastric nerve or the recurrent laryngeal nerve. Seizing animals had significantly more liquid in their stomach. Severing the gastric nerve and fasting animals significantly reduced stomach liquid volume, subsequent acid reflux, and sudden death. Laryngeal nerve stimulation can reverse laryngospasm on demand. Seizing animals are more susceptible to death from stomach acid-induced laryngospasm than nonseizing animals are to artificial acid-induced laryngospasm. These results provide insight into the mechanism of acid production and sudden obstructive apnea in this model. These techniques may have clinical relevance if this model is shown to be similar to human SUDEP. • Animals in the acute KA model have more liquid in their stomach. • The gastric nerve is necessary for acid overproduction, reflux, and sudden death. • Seizing animals die more easily from laryngospasm than nonseizing animals. [ABSTRACT FROM AUTHOR]