Harnessing metamaterials for efficient wireless power transfer for implantable medical devices.

Wireless power transfer (WPT) within the human body can enable long-lasting medical devices but poses notable challenges, including absorption by biological tissues and weak coupling between the transmitter (Tx) and receiver (Rx). In pursuit of more robust and efficient wireless power, various innovative strategies have emerged to optimize power transfer efficiency (PTE). One such groundbreaking approach stems from the incorporation of metamaterials, which have shown the potential to enhance the capabilities of conventional WPT systems. In this review, we delve into recent studies focusing on WPT systems that leverage metamaterials to achieve increased efficiency for implantable medical devices (IMDs) in the electromagnetic paradigm. Alongside a comparative analysis, we also outline current challenges and envision potential avenues for future advancements.

Circuit-Level Modeling and Simulation of Wireless Sensing and Energy Harvesting With Hybrid Magnetoelectric Antennas for Implantable Neural Devices.

A magnetoelectric antenna (ME) can exhibit the dual capabilities of wireless energy harvesting and sensing at different frequencies. In this article, a behavioral circuit model for hybrid ME antennas is described to emulate the radio frequency (RF) energy harvesting and sensing operations during circuit simulations. The ME antenna of this work is interfaced with a CMOS energy harvester chip towards the goal of developing a wireless communication link for fully integrated implantable devices. One role of the integrated system is to receive pulse-modulated power from a nearby transmitter, and another role is to sense and transmit low-magnitude neural signals. The measurements reported in this paper are the first results that demonstrate simultaneous low-frequency wireless magnetic sensing and high-frequency wireless energy harvesting at two different frequencies with one dual-mode ME antenna. The proposed behavioral ME antenna model can be utilized during design optimizations of energy harvesting circuits. Measurements were performed to validate the wireless power transfer link with an ME antenna having a 2.57 GHz resonance frequency connected to an energy harvester chip designed in 65nm CMOS technology. Furthermore, this dual-mode ME antenna enables concurrent sensing using a carrier signal with a frequency that matches the second 63.63 MHz resonance mode. A wireless test platform has been developed for evaluation of ME antennas as a tool for neural implant design, and this prototype system was utilized to provide first experimental results with the transmission of magnetically modulated action potential waveforms.

Machine-Learning Methods for Speech and Handwriting Detection Using Neural Signals: A Review.

Brain-Computer Interfaces (BCIs) have become increasingly popular in recent years due to their potential applications in diverse fields, ranging from the medical sector (people with motor and/or communication disabilities), cognitive training, gaming, and Augmented Reality/Virtual Reality (AR/VR), among other areas. BCI which can decode and recognize neural signals involved in speech and handwriting has the potential to greatly assist individuals with severe motor impairments in their communication and interaction needs. Innovative and cutting-edge advancements in this field have the potential to develop a highly accessible and interactive communication platform for these people. The purpose of this review paper is to analyze the existing research on handwriting and speech recognition from neural signals. So that the new researchers who are interested in this field can gain thorough knowledge in this research area. The current research on neural signal-based recognition of handwriting and speech has been categorized into two main types: invasive and non-invasive studies. We have examined the latest papers on converting speech-activity-based neural signals and handwriting-activity-based neural signals into text data. The methods of extracting data from the brain have also been discussed in this review. Additionally, this review includes a brief summary of the datasets, preprocessing techniques, and methods used in these studies, which were published between 2014 and 2022. This review aims to provide a comprehensive summary of the methodologies used in the current literature on neural signal-based recognition of handwriting and speech. In essence, this article is intended to serve as a valuable resource for future researchers who wish to investigate neural signal-based machine-learning methods in their work.

Fabrication and Assembly Techniques for Sub-mm Battery-Free Epicortical Implants.

Over the past three decades, we have seen significant advances in the field of wireless implantable medical devices (IMDs) that can interact with the nervous system. To further improve the stability, safety, and distribution of these interfaces, a new class of implantable devices is being developed: single-channel, sub-mm scale, and wireless microelectronic devices. In this research, we describe a new and simple technique for fabricating and assembling a sub-mm, wirelessly powered stimulating implant. The implant consists of an ASIC measuring 900 × 450 × 80 µm3, two PEDOT-coated microelectrodes, an SMD inductor, and a SU-8 coating. The microelectrodes and SMD are directly mounted onto the ASIC. The ultra-small device is powered using electromagnetic (EM) waves in the near-field using a two-coil inductive link and demonstrates a maximum achievable power transfer efficiency (PTE) of 0.17% in the air with a coil separation of 0.5 cm. In vivo experiments conducted on an anesthetized rat verified the efficiency of stimulation.

Magnetic temporal interference for noninvasive and focal brain stimulation.

Objective. Noninvasive focal stimulation of deep brain regions has been a major goal for neuroscience and neuromodulation in the past three decades. Transcranial magnetic stimulation (TMS), for instance, cannot target deep regions in the brain without activating the overlying tissues and has poor spatial resolution. In this manuscript, we propose a new concept that relies on the temporal interference (TI) of two high-frequency magnetic fields generated by two electromagnetic solenoids.Approach. To illustrate the concept, custom solenoids were fabricated and optimized to generate temporal interfering electric fields for rodent brain stimulation. C-Fos expression was used to track neuronal activation.Main result. C-Fos expression was not present in regions impacted by only one high-frequency magnetic field indicating ineffective recruitment of neural activity in non-target regions. In contrast, regions impacted by two fields that interfere to create a low-frequency envelope display a strong increase in c-Fos expression.Significance. Therefore, this magnetic temporal interference solenoid-based system provides a framework to perform further stimulation studies that would investigate the advantages it could bring over conventional TMS systems.

A 30% Efficient High-Output Voltage Fully Integrated Self-Biased Gate RF Rectifier Topology for Neural Implants.

This paper presents a fully integrated RF energy harvester (EH) with 30% end-to-end power harvesting efficiency (PHE) and supports high output voltage operation, up to 9.3V, with a 1.07 GHz input and under the electrode model for neural applications. The EH is composed of a novel 10-stage self-biased gate (SBG) rectifier with an on-chip matching network. The SBG topology elevates the gate-bias of transistors in a non-linear manner to enable higher conductivity. The design also achieves >20% PHE range of 12-dB. The design was fabricated in 65 nm CMOS technology and occupies an area of 0.0732-mm2 with on-chip matching network. In addition to standalone EH characterization measurement results, animal tissue stimulation test was performed to evaluate its performance in a realistic neural implant application.

Analysis and Design Methodology of RF Energy Harvesting Rectifier Circuit for Ultra-Low Power Applications.

This paper reviews and analyses the design of popular radio frequency energy harvesting systems and proposes a method to qualitatively and quantitatively analyze their circuit architectures using new square-wave approximation method. This approach helps in simplifying design analysis. Using this analysis, we can establish no load output voltage characteristics, upper limit on rectifier efficiency, and maximum power characteristics of a rectifier. This paper will help guide the design of RF energy harvesting rectifier circuits for radio frequency identification (RFIDs), the Internet of Things (IoTs), wearable, and implantable medical device applications. Different application scenarios are explained in the context of design challenges, and corresponding design considerations are discussed in order to evaluate their performance. The pros and cons of different rectifier topologies are also investigated. In addition to presenting the popular rectifier topologies, new measurement results of these energy harvester topologies, fabricated in 65nm, 130nm and 180nm CMOS technologies are also presented.

COVID-19 epidemiology and changes in health service utilization in Azraq and Zaatari refugee camps in Jordan: A retrospective cohort study.

BACKGROUND: The effects of the Coronavirus Disease 2019 (COVID-19) pandemic in humanitarian contexts are not well understood. Specific vulnerabilities in such settings raised concerns about the ability to respond and maintain essential health services. This study describes the epidemiology of COVID-19 in Azraq and Zaatari refugee camps in Jordan (population: 37,932 and 79,034, respectively) and evaluates changes in routine health services during the COVID-19 pandemic. METHODS AND FINDINGS: We calculate the descriptive statistics of COVID-19 cases in the United Nations High Commissioner for Refugees (UNHCR)'s linelist and adjusted odds ratios (aORs) for selected outcomes. We evaluate the changes in health services using monthly routine data from UNHCR's health information system (HIS; January 2018 to March 2021) and apply interrupted time series analysis with a generalized additive model and negative binomial (NB) distribution, accounting for long-term trends and seasonality, reporting results as incidence rate ratios (IRRs). COVID-19 cases were first reported on September 8 and September 13, 2020 in Azraq and Zaatari camps, respectively, 6 months after the first case in Jordan. Incidence rates (IRs) were lower in camps than neighboring governorates (by 37.6% in Azraq (IRR: 0.624, 95% confidence interval [CI]: [0.584 to 0.666], p-value: <0.001) and 40.2% in Zaatari (IRR: 0.598, 95% CI: [0.570, 0.629], p-value: <0.001)) and lower than Jordan (by 59.7% in Azraq (IRR: 0.403, 95% CI: [0.378 to 0.430], p-value: <0.001) and by 63.3% in Zaatari (IRR: 0.367, 95% CI: [0.350 to 0.385], p-value: <0.001)). Characteristics of cases and risk factors for negative disease outcomes were consistent with increasing COVID-19 evidence. The following health services reported an immediate decline during the first year of COVID-19: healthcare utilization (by 32% in Azraq (IRR: 0.680, 95% CI [0.549 to 0.843], p-value < 0.001) and by 24.2% in Zaatari (IRR: 0.758, 95% CI [0.577 to 0.995], p-value = 0.046)); consultations for respiratory tract infections (RTIs; by 25.1% in Azraq (IRR: 0.749, 95% CI: [0.596 to 0.940], p-value = 0.013 and by 37.5% in Zaatari (IRR: 0.625, 95% CI: [0.461 to 0.849], p-value = 0.003)); and family planning (new and repeat family planning consultations decreased by 47.4% in Azraq (IRR: 0.526, 95% CI: [0.376 to 0.736], p-value = <0.001) and 47.6% in Zaatari (IRR: 0.524, 95% CI: [0.312 to 0.878], p-value = 0.014)). Maternal and child health services as well as noncommunicable diseases did not show major changes compared to pre-COVID-19 period. Conducting interrupted time series analyses in volatile settings such refugee camps can be challenging as it may be difficult to meet some analytical assumptions and to mitigate threats to validity. The main limitation of this study relates therefore to possible unmeasured confounding. CONCLUSIONS: COVID-19 transmission was lower in camps than outside of camps. Refugees may have been affected from external transmission, rather than driving it. Various types of health services were affected differently, but disruptions appear to have been limited in the 2 camps compared to other noncamp settings. These insights into Jordan's refugee camps during the first year of the COVID-19 pandemic set the stage for follow-up research to investigate how infection susceptibility evolved over time, as well as which mitigation strategies were more successful and accepted.

Scaling the Children Immunization App (CIMA) to Support Child Refugees and Parents in the Time of the COVID-19 Pandemic: A Social Capital Approach to Scale a Smartphone Application in Zaatari Camp, Jordan.

BACKGROUND: Children vaccination is a key intervention for their survival, especially among refugees. Yet, children vaccination registration is done manually in refugees camps and there is no possibility to send reminders to parents to come back on time. We aimed to boost the parental registration of children's vaccination records on a Children Immunization app (CIMA) while also availing the parents with useful parenting skills under COVID-19-related stress. METHODS: We incorporated United Nations Office on Drugs and Crime (UNODC) Parenting Skills under COVID-19 information material, through CIMA in Arabic and English languages. We recruited 1100 children in February-March 2021, through a community health promotion dissemination approach. A team of two nurses from the local population and two volunteers (one trained nurse and one trained social worker), from the camp, was formed. They promoted the CIMA app at two clinics and through households visits in Zaatari refugee camp. Qualitative data on impressions and observations of the interactions with the Zaatari camp community were also collected. RESULTS: A total of 1100 children, up to 15 months of age, eligible for vaccination were enrolled in CIMA, whereby the staff explained the content of the app in terms of vaccination schedule, health promotion materials for vaccination and parenting skills to their caregivers. During the household visits, the volunteers identified a total of 70 children that have incomplete history of vaccination records (n = 42/70 girls, 60%). Also, opportunities and challenges for scaling the app were documented. CONCLUSION: The scaling of CIMA as an innovative means of dissemination of risk and health information in challenging context such as refugee camps was feasible. In the context of vaccination needs for children, in refugee settings, such a need is more eminent, particularly in the context of COVID-19.

Magnetoelectric (ME) Antenna for On-chip Implantable Energy Harvesting.

A novel magnetoelectric (ME) antenna is fabricated to be integrated to the on-chip energy harvesting circuit for brain-computer interface applications. The proposed ME antenna resonates at the frequency of 2.57 GHz while providing a bandwidth of 3.37 MHz. The proposed rectangular ME antenna wireless power transfer efficiency is 0.304 %, which is considerably higher than that of micro-coils.Clinical Relevance- This provides a suitable energy harvesting efficiency for wirelessly powering up the brain implant devices.

Injectable wireless microdevices: challenges and opportunities.

In the past three decades, we have witnessed unprecedented progress in wireless implantable medical devices that can monitor physiological parameters and interface with the nervous system. These devices are beginning to transform healthcare. To provide an even more stable, safe, effective, and distributed interface, a new class of implantable devices is being developed; injectable wireless microdevices. Thanks to recent advances in micro/nanofabrication techniques and powering/communication methodologies, some wireless implantable devices are now on the scale of dust (< 0.5 mm), enabling their full injection with minimal insertion damage. Here we review state-of-the-art fully injectable microdevices, discuss their injection techniques, and address the current challenges and opportunities for future developments.

The development of microfabricated solenoids with magnetic cores for micromagnetic neural stimulation.

Electrical stimulation via invasive microelectrodes is commonly used to treat a wide range of neurological and psychiatric conditions. Despite its remarkable success, the stimulation performance is not sustainable since the electrodes become encapsulated by gliosis due to foreign body reactions. Magnetic stimulation overcomes these limitations by eliminating the need for a metal-electrode contact. Here, we demonstrate a novel microfabricated solenoid inductor (80 µm × 40 µm) with a magnetic core that can activate neuronal tissue. The characterization and proof-of-concept of the device raise the possibility that micromagnetic stimulation solenoids that are small enough to be implanted within the brain may prove to be an effective alternative to existing electrode-based stimulation devices for chronic neural interfacing applications.

Tracking the Migration of Injectable Microdevices in the Rodent Brain Using a 9.4T Magnetic Resonance Imaging Scanner.

Wirelessly powered microdevices are being miniaturized to improve safety, longevity, and spatial resolution in a wide range of biomedical applications. Some wireless microdevices have reached a point where they can be injected whole into the central nervous system. However, the state-of-the-art floating microdevices have not yet been tested in chronic brain applications, and there is a growing concern that the implants might migrate through neural tissue over time. Using a 9.4T MRI scanner, we attempt to address the migration question by tracking ultra-small devices injected in different areas of the brain (cortico-subcortical) of rats over 5 months. We demonstrate that injectable microdevices smaller than 0.01 mm3 remain anchored in the brain at the targeted injection site over this time period. Based on CD68 (microglia) and GFAP (astrocytes) immunoreactivity to the microdevice, we hypothesize that glial scar formation is preventing the migration of chronically implanted microdevices in the brain over time.

Ultra-compact dual-band smart NEMS magnetoelectric antennas for simultaneous wireless energy harvesting and magnetic field sensing.

Ultra-compact wireless implantable medical devices are in great demand for healthcare applications, in particular for neural recording and stimulation. Current implantable technologies based on miniaturized micro-coils suffer from low wireless power transfer efficiency (PTE) and are not always compliant with the specific absorption rate imposed by the Federal Communications Commission. Moreover, current implantable devices are reliant on differential recording of voltage or current across space and require direct contact between electrode and tissue. Here, we show an ultra-compact dual-band smart nanoelectromechanical systems magnetoelectric (ME) antenna with a size of 250 × 174 µm2 that can efficiently perform wireless energy harvesting and sense ultra-small magnetic fields. The proposed ME antenna has a wireless PTE 1-2 orders of magnitude higher than any other reported miniaturized micro-coil, allowing the wireless IMDs to be compliant with the SAR limit. Furthermore, the antenna's magnetic field detectivity of 300-500 pT allows the IMDs to record neural magnetic fields.

A simple method for implanting free-floating microdevices into the nervous tissue.

Objective. Free-floating implantable neural interfaces are an emerging powerful paradigm for mapping and modulation of brain activity. Minuscule wirelessly-powered devices have the potential to provide minimally-invasive interactions with neurons in chronic research and medical applications. However, these devices face a seemingly simple problem-how can they be placed into nervous tissue rapidly, efficiently and in an essentially arbitrary location?Approach. We introduce a novel injection tool and describe a controlled injection approach that minimizes damage to the tissue.Main results.To validate the needle injectable tool and the presented delivery approach, we evaluate the spatial precision and rotational alignment of the microdevices injected into agarose, brain, and sciatic nerve with the aid of tissue clearing and MRI imaging. In this research, we limited the number of injections into the brain to four per rat as we are using microdevices that are designed for an adult head size on a rat model. We then present immunohistology data to assess the damage caused by the needle.Significance. By virtue of its simplicity, the proposed injection method can be used to inject microdevices of all sizes and shapes and will do so in a fast, minimally-invasive, and cost-effective manner. As a result, the introduced technique can be broadly used to accelerate the validation of these next-generation types of electrodes in animal models.

A Compact Free-Floating Device for Passive Charge-Balanced Neural Stimulation using PEDOT/CNT microelectrodes.

Wirelessly powered implants are increasingly being developed as free-floating single-channel devices to interface with neurons directly at stimulation sites. In order to stimulate neurons in a manner that is safe to both the electrode and the surrounding tissue, charge accumulation over time needs to be avoided. The implementation of conventional charge balancing methods often leads to an increase in system complexity, power consumption or area, all of which are critical parameters in ultra-small wireless devices. The proposed charge balancing method described in this work, which relies on bipolar capacitive integrated electrodes, does not increase these parameters. The standalone wirelessly powered stimulating implant is implemented in a 130nm CMOS technology and measures 0.009 mm3.

A Miniature Wireless Silicon-on-Insulator Image Sensor for Brain Fluorescence Imaging.

Optical recording of genetically encoded calcium indicator (GECI) allows neuroscientists to study the activity of genetically labeled neuron populations, but our current tools lack the resolution, stability and are often too invasive. Here we present the design concepts, prototypes, and preliminary measurement results of a super-miniaturized wireless image sensor built using a 32nm Silicon-on-Insulator process. SOI process is optimal for wireless applications, and we can further thin the substrate to reduce overall device thickness to ~25µm and operate the pixels using back-side illumination. The proposed device is 300µm × 300µm. Our prototype is built on a 3 × 3mm die.

Cancer in Syrian refugees in Jordan and Lebanon between 2015 and 2017.

Protracted conflicts in the Middle East have led to successive waves of refugees crossing borders. Chronic, non-communicable diseases are now recognised as diseases that need to be addressed in such crises. Cancer, in particular, with its costly, multidisciplinary care, poses considerable financial and ethical challenges for policy makers. In 2014 and with funding from the United Nations High Commissioner for Refugees, we reported on cancer cases among Iraqi refugees in Jordan (2010-12) and Syria (2009-11). In this Policy Review, we provide data on 733 refugees referred to the United Nations High Commissioner for Refugees in Lebanon (2015-17) and Jordan (2016-17), analysed by cancer type, demographic risk factors, treatment coverage status, and cost. Results show the need for increased funding and evidence-based standard operating procedures across countries to ensure that patients have equitable access to care. We recommend a holistic response to humanitarian crises that includes education, screening, treatment, and palliative care for refugees and nationals and prioritises breast cancer and childhood cancers.

The Microbead: A 0.009 mm3 Implantable Wireless Neural Stimulator.

Wirelessly powered implants are increasingly being developed to interface with neurons in the brain. They often rely on microelectrode arrays, which are limited by their ability to cover large cortical surface areas and long-term stability because of their physical size and rigid configuration. Yet some clinical and research applications prioritize a distributed neural interface over one that offers high channel count. One solution to make large scale, fully specifiable, electrical stimulation/recording possible, is to disconnect the electrodes from the base, so that they can be arbitrarily placed freely in the nervous system. In this work, a wirelessly powered stimulating implant is miniaturized using a novel electrode integration technique, and its implanted depth maximized using new optimization design methods for the transmitter and receiver coils. The stimulating device is implemented in a 130 nm CMOS technology with the following characteristics: 300 µm × 300 µm × 80 µm size; optimized two-coil inductive link; and integrated circuit, electrodes and coil. The wireless and stimulation capability of the implant is demonstrated in a conductive medium, as well as in-vivo. To the best of our knowledge, the fabricated free-floating miniaturized implant has the best depth-to-volume ratio making it an excellent tool for minimally-invasive distributed neural interface, and thus could eventually complement or replace the rigid arrays that are currently the state-of-the-art in brain set-ups.

The Microbead: A Highly Miniaturized Wirelessly Powered Implantable Neural Stimulating System.

An implant that can electrically stimulate neurons across different depths and regions of the brain currently does not exist as it poses a number of obstacles that need to be solved. In order to address the challenges, this paper presents the concept of "microbead," a fully integrated wirelessly powered neural device that allows for spatially selective activation of neural tissue. The prototype chip is fabricated in 130-nm CMOS technology and currently measures 200 µm × 200 µm, which represents the smallest remotely powered stimulator to date. The system is validated experimentally in a rat by stimulating the sciatic nerve with 195-µs current pulses. To power the ultrasmall on-silicon coil, 36-dBm source power is provided to a highly optimized transmitter (Tx) coil at a coupling distance of 5 mm. In order to satisfy the strict power limit for safe use in human subjects, a pulsed powering scheme is implemented that enables a significant decrease in the average power emitted from the Tx.