Flexible, Biodegradable, and Wireless Magnetoelectric Paper for Simple In Situ Personalization of Bioelectric Implants.

Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost-effective personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability. Here, a flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants is introduced. The bioelectronic paper synergistically combines i) lead-free magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field and ii) flexible and biodegradable nanofibers (NFs) that enable localization of MENs for high-selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. The effectiveness of wireless electrical stimulation in vitro through enhanced neuronal differentiation of neuron-like PC12 cells and the controllability of their microstructural orientation are shown. Also, scalability, design flexibility, and rapid customizability of the bioelectronic paper are shown by creating various 3D macrostructures using simple paper crafting techniques such as cutting and folding. This platform holds promise for simple and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.

Soft Bioelectronics for Therapeutics.

Soft bioelectronics play an increasingly crucial role in high-precision therapeutics due to their softness, biocompatibility, clinical accuracy, long-term stability, and patient-friendliness. In this review, we provide a comprehensive overview of the latest representative therapeutic applications of advanced soft bioelectronics, ranging from wearable therapeutics for skin wounds, diabetes, ophthalmic diseases, muscle disorders, and other diseases to implantable therapeutics against complex diseases, such as cardiac arrhythmias, cancer, neurological diseases, and others. We also highlight key challenges and opportunities for future clinical translation and commercialization of soft therapeutic bioelectronics toward personalized medicine.

Hydrogel Bioelectronics for Health Monitoring.

Hydrogels are considered an ideal platform for personalized healthcare due to their unique characteristics, such as their outstanding softness, appealing biocompatibility, excellent mechanical properties, etc. Owing to the high similarity between hydrogels and biological tissues, hydrogels have emerged as a promising material candidate for next generation bioelectronic interfaces. In this review, we discuss (i) the introduction of hydrogel and its traditional applications, (ii) the work principles of hydrogel in bioelectronics, (iii) the recent advances in hydrogel bioelectronics for health monitoring, and (iv) the outlook for future hydrogel bioelectronics' development.

Regenerative bioelectronics: A strategic roadmap for precision medicine.

In the past few decades, stem cell-based regenerative engineering has demonstrated its significant potential to repair damaged tissues and to restore their functionalities. Despite such advancement in regenerative engineering, the clinical translation remains a major challenge. In the stance of personalized treatment, the recent progress in bioelectronic medicine likewise evolved as another important research domain of larger significance for human healthcare. Over the last several years, our research group has adopted biomaterials-based regenerative engineering strategies using innovative bioelectronic stimulation protocols based on either electric or magnetic stimuli to direct cellular differentiation on engineered biomaterials with a range of elastic stiffness or functional properties (electroactivity/magnetoactivity). In this article, the role of bioelectronics in stem cell-based regenerative engineering has been critically analyzed to stimulate futuristic research in the treatment of degenerative diseases as well as to address some fundamental questions in stem cell biology. Built on the concepts from two independent biomedical research domains (regenerative engineering and bioelectronic medicine), we propose a converging research theme, 'Regenerative Bioelectronics'. Further, a series of recommendations have been put forward to address the current challenges in bridging the gap in stem cell therapy and bioelectronic medicine. Enacting the strategic blueprint of bioelectronic-based regenerative engineering can potentially deliver the unmet clinical needs for treating incurable degenerative diseases.

Design of stretchable and self-powered sensing device for portable and remote trace biomarkers detection.

Timely and remote biomarker detection is highly desired in personalized medicine and health protection but presents great challenges in the devices reported so far. Here, we present a cost-effective, flexible and self-powered sensing device for H2S biomarker analysis in various application scenarios based on the structure of galvanic cells. The sensing mechanism is attributed to the change in electrode potential resulting from the chemical adsorption of gas molecules on the electrode surfaces. Intrinsically stretchable organohydrogels are used as solid-state electrolytes to enable stable and long-term operation of devices under stretching deformation or in various environments. The resulting open-circuit sensing device exhibits high sensitivity, low detection limit, and excellent selectivity for H2S. Its application in the non-invasive halitosis diagnosis and identification of meat spoilage is demonstrated, emerging great commercial value in portable medical electronics and food security. A wireless sensory system has also been developed for remote H2S monitoring with the participation of Bluetooth and cloud technologies. This work breaks through the shortcomings in the traditional chemiresistive sensors, offering a direction and theoretical foundation for designing wearable sensors catering to other stimulus detection requirements.

Tailoring the Electron Trapping Effect of a Biocompatible Triboelectric Hydrogel by Graphene Oxide Incorporation towards Self-Powered Medical Electronics.

Triboelectric nanogenerators (TENGs) are associated with several drawbacks that limit their application in the biomedical field, including toxicity, thrombogenicity, and poor performance in the presence of fluids. By proposing the use of a hemo/biocompatible hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), this study bypasses these barriers. In contact-separation mode, using polytetrafluoroethylene (PTFE) as a reference, pHEMA generates an output of 100.0 V, under an open circuit, 4.7 µA, and 0.68 W/m2 for an internal resistance of 10 MΩ. Our findings unveil that graphene oxide (GO) can be used to tune pHEMA's triboelectric properties in a concentration-dependent manner. At the lowest measured concentration (0.2% GO), the generated outputs increase to 194.5 V, 5.3 µA, and 1.28 W/m2 due to the observed increase in pHEMA's surface roughness, which expands the contact area. Triboelectric performance starts to decrease as GO concentration increases, plateauing at 11% volumetric, where the output is 51 V, 1.76 µA, and 0.17 W/m2 less than pHEMA's. Increases in internal resistance, from 14 ΩM to greater than 470 ΩM, ζ-potential, from -7.3 to -0.4 mV, and open-circuit characteristic charge decay periods, from 90 to 120 ms, are all observed in conjunction with this phenomenon, which points to GO function as an electron trapping site in pHEMA's matrix. All of the composites can charge a 10 µF capacitor in 200 s, producing a voltage between 0.25 and 3.5 V and allowing the operation of at least 20 LEDs. The triboelectric output was largely steady throughout the 3.33 h durability test. Voltage decreases by 38% due to contact-separation frequency, whereas current increases by 77%. In terms of pressure, it appears to have little effect on voltage but boosts current output by 42%. Finally, pHEMA and pHEMA/GO extracts were cytocompatible toward fibroblasts. According to these results, pHEMA has a significant potential to function as a biomaterial to create bio/hemocompatible TENGs and GO to precisely control its triboelectric outputs.

A universal interface for plug-and-play assembly of stretchable devices.

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.

Powering Electronic Implants by High Frequency Volume Conduction: In Human Validation.

OBJECTIVE: Wireless power transfer (WPT) is used as an alternative to batteries to accomplish miniaturization in electronic medical implants. However, established WPT methods require bulky parts within the implant or cumbersome external systems, hindering minimally invasive deployments and the development of networks of implants. As an alternative, we propose a WPT approach based on volume conduction of high frequency (HF) current bursts. These currents are applied through external electrodes and are collected by the implants through two electrodes at their opposite ends. This approach avoids bulky components, enabling the development of flexible threadlike implants. METHODS: We study in humans if HF (6.78 MHz) current bursts complying with safety standards and applied through two textile electrodes strapped around a limb can provide substantial powers from pairs of implanted electrodes. RESULTS: Time averaged electric powers obtained from needle electrodes (diameter = 0.4 mm, length = 3 mm, separation = 30 mm) inserted into arms and lower legs of five healthy participants were 5.9 ± 0.7 mW and 2.4 ± 0.3 mW respectively. We also characterize the coupling between the external system and the implants using personalized two-port impedance models generated from medical images. CONCLUSIONS: The results demonstrate that innocuous and imperceptible HF current bursts that flow through the tissues by volume conduction can be used to wirelessly power threadlike implants. SIGNIFICANCE: This is the first time that WPT based on volume conduction is demonstrated in humans. This method overcomes the limitations of existing WPT methods in terms of minimal invasiveness and usability.

[Retrospective Analysis of Common Faults and Maintenance Strategies of Medical Electronic Endoscope].

Medical electronic endoscope is one of the indispensable tools in medical diagnosis and treatment. With the development of science and technology, electronic endoscope has higher safety and accuracy than traditional optical endoscope. Due to the sophisticated construction and high price, hospitals spend a lot of money on maintenance every year. In order to prolong the working life of electronic endoscope, reduce the incidence of artificial failure and save hospital costs, this study made a retrospective analysis on the common faults of electronic endoscope, and summarized the maintenance strategies for reference.

Implantable Electronic Medicine Enabled by Bioresorbable Microneedles for Wireless Electrotherapy and Drug Delivery.

A combined treatment using medication and electrostimulation increases its effectiveness in comparison with one treatment alone. However, the organic integration of two strategies in one miniaturized system for practical usage has seldom been reported. This article reports an implantable electronic medicine based on bioresorbable microneedle devices that is activated wirelessly for electrostimulation and sustainable delivery of anti-inflammatory drugs. The electronic medicine is composed of a radio frequency wireless power transmission system and a drug-loaded microneedle structure, all fabricated with bioresorbable materials. In a rat skeletal muscle injury model, periodic electrostimulation regulates cell behaviors and tissue regeneration while the anti-inflammatory drugs prevent inflammation, which ultimately enhance the skeletal muscle regeneration. Finally, the electronic medicine is fully bioresorbable, excluding the second surgery for device removal.

[Discussion on Design of Comprehensive Verification and Evaluation Schemes for Electrocardiogram Medical Electronic Instruments].

This study introduced the current testing content and standards of ECG medical electronic instruments, combined with actual clinical needs, and discussed the comprehensive verification and evaluation protocol for ECG medical electronic instruments. The protocol mainly includes hardware performance testing, automatic diagnostic function testing and clinical application evaluation. The protocol emphasizes the clinical practicality and importance of the comprehensive verification and evaluation program, and provides a reference for the institutions involved in the program.

A method for in vivo treatment verification of IMRT and VMAT based on electronic portal imaging device.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) and volume-modulated arc therapy (VMAT) are rather complex treatment techniques and require patient-specific quality assurance procedures. Electronic portal imaging devices (EPID) are increasingly used in the verification of radiation therapy (RT). This work aims to develop a novel model to predict the EPID transmission image (TI) with fluence maps from the RT plan. The predicted TI is compared with the measured TI for in vivo treatment verification. METHODS: The fluence map was extracted from the RT plan and corrections of penumbra, response, global field output, attenuation, and scatter were applied before the TI was calculated. The parameters used in the model were calculated separately for central axis and off-axis points using a series of EPID measurement data. Our model was evaluated using a CIRS thorax phantom and 20 clinical plans (10 IMRT and 10 VMAT) optimized for head and neck, breast, and rectum treatments. RESULTS: Comparisons of the predicted and measured images were carried out using a global gamma analysis of 3%/2 mm (10% threshold) to validate the accuracy of the model. The gamma pass rates for IMRT and VMAT were greater than 97.2% and 94.5% at 3%/2 mm, respectively. CONCLUSION: We have developed an accurate and straightforward EPID-based quality assurance model that can potentially be used for in vivo treatment verification of the IMRT and VMAT delivery.

Disinvestment in the presence of uncertainty: Description of a novel, multi-group, disinvestment trial design and protocol for an application to reduce or cease use of mobilisation alarms for preventing falls in hospitals.

Disinvestment is the removal or reduction of previously provided practices or services, and has typically been undertaken where a practice or service has been clearly shown to be ineffective, inefficient and/or harmful. However, practices and services that have uncertain evidence of effectiveness, efficiency and safety can also be considered as candidates for disinvestment. Disinvestment from these practices and services is risky as they may yet prove to be beneficial if further evidence becomes available. A novel research approach has previously been described for this situation, allowing disinvestment to take place while simultaneously generating evidence previously missing from consideration. In this paper, we describe how this approach can be expanded to situations where three or more conditions are of relevance, and describe the protocol for a trial examining the reduction and elimination of use of mobilisation alarms on hospital wards to prevent patient falls. Our approach utilises a 3-group, concurrent, non-inferiority, stepped wedge, randomised design with an embedded parallel, cluster randomised design. Eighteen hospital wards with high rates of alarm use (≥3%) will be paired within their health service and randomly allocated to a calendar month when they will transition to a "Reduced" (<3%) or "Eliminated" (0%) mobilisation alarm condition. Dynamic randomisation will be used to determine which ward in each pair will be allocated to either the reduced or eliminated condition to promote equivalence between wards for the embedded parallel, cluster randomised component of the design. A project governance committee will set non-inferiority margins. The primary outcome will be rates of falls. Secondary clinical, process, safety, and economic outcomes will be collected and a concurrent economic evaluation undertaken.

Finding New Ways To Treat Tremors.

An estimated ten million people in the United States have a condition known as essential tremor (ET). Yet although it's been recognized for over a century-it was originally known as senile tremor-there is relatively little awareness of it as a distinct medical condition. Sometimes mistaken for Parkinson's disease, ET can lead to shaking of the arms and hands, and sometimes the head or torso. When severe, it can interfere with eating or drinking, writing, dressing, and even make some tasks impossible. Now, new approaches for treating the condition are emerging, potentially offering options to many patients whose life activities have been curtailed by ET.

Interfacial polarization of in vivo rat sciatic nerve with crush injury studied via broadband dielectric spectroscopy.

Electrical stimulation is one of the candidates for elongation-driven regeneration of damaged peripheral nerves. Different organs and tissues have an inherent cell structure and size. This leads to variation in the tissue-specific electrical properties of the frequency of interfacial polarization. Although nervous tissues have a membrane potential, the electrical reaction inside these tissues following electrical stimulation from outside remains unexplored. Furthermore, the pathophysiological reaction of an injured nerve is unclear. Here, we investigated the electrical reaction of injured and non-injured rat sciatic nerves via broadband dielectric spectroscopy. Crush injured and non-injured sciatic nerves of six 12-week-old male Lewis rats were used, 6 days after infliction of the injury. Both sides of the nerves (with and without injury) were exposed, and impedance measurements were performed at room temperature (approximately 25°C) at frequencies ranging from 100 mHz to 5.5 MHz and electric potential ranging from 0.100 to 1.00 V. The measured interfacial polarization potentially originated from the polarization by ion transport around nerve membranes at frequencies between 3.2 kHz and 1.6 MHz. The polarization strength of the injured nerves was smaller than that of non-injured nerves. However, the difference in polarization between injured and non-injured nerves might be caused by inflammation and edema. The suitable frequency range of the interfacial polarization can be expected to be critical for electrical stimulation of injured peripheral nerves.

Printable graphene BioFETs for DNA quantification in Lab-on-PCB microsystems.

Lab-on-Chip is a technology that aims to transform the Point-of-Care (PoC) diagnostics field; nonetheless a commercial production compatible technology is yet to be established. Lab-on-Printed Circuit Board (Lab-on-PCB) is currently considered as a promising candidate technology for cost-aware but simultaneously high specification applications, requiring multi-component microsystem implementations, due to its inherent compatibility with electronics and the long-standing industrial manufacturing basis. In this work, we demonstrate the first electrolyte gated field-effect transistor (FET) DNA biosensor implemented on commercially fabricated PCB in a planar layout. Graphene ink was drop-casted to form the transistor channel and PNA probes were immobilized on the graphene channel, enabling label-free DNA detection. It is shown that the sensor can selectively detect the complementary DNA sequence, following a fully inkjet-printing compatible manufacturing process. The results demonstrate the potential for the effortless integration of FET sensors into Lab-on-PCB diagnostic platforms, paving the way for even higher sensitivity quantification than the current Lab-on-PCB state-of-the-art of passive electrode electrochemical sensing. The substitution of such biosensors with our presented FET structures, promises further reduction of the time-to-result in microsystems combining sequential DNA amplification and detection modules to few minutes, since much fewer amplification cycles are required even for low-abundance nucleic acid targets.

Accuracy of soft tissue balancing in total knee arthroplasty using surgeon-defined assessment versus a gap-balancer or electronic sensor.

BACKGROUND: Soft tissue balancing is essential for the success of total knee arthroplasty (TKA) and is mainly dependent on surgeon-defined assessment (SDA) or a gap-balancer (GB). However, an electronic sensor has been developed to objectively measure the gap pressure. This study aimed to evaluate the accuracy of soft tissue balancing using SDA and GB compared with a sensor. METHODS: Forty-eight patients undergoing TKA (60 knees) were prospectively enrolled. Soft tissue balancing was sequentially performed using SDA, a GB, and an electronic sensor. We compared the SDA, GB, and sensor data to calculate the sensitivity, specificity, and accuracy at 0°, 45°, 90°, and 120° flexion. Cumulative summation (CUSUM) analysis was performed to assess the surgeon's performance during the sensor introductory phase. RESULTS: The sensitivity of SDA was 63.3%, 68.3%, 80.0%, and 80.0% at 0°, 45°, 90°, and 120°, respectively. The accuracy of the GB compared with sensor data was 76.7% and 71.7% at 0° and 90°, respectively. Cohen's kappa coefficient for the accuracy of the GB was 0.406 at 0° (moderate agreement) and 0.227 at 90° (fair agreement). The CUSUM 0° line achieved good prior performance at case 45, CUSUM 90° and 120° showed a trend toward good prior performance, while CUSUM 45° reached poor prior performance at case 8. CONCLUSION: SDA was a poor predictor of knee balance. GB improved the accuracy of soft tissue balancing, but was still less accurate than the sensor, particularly for unbalanced knees. SDA improved with ongoing use of the sensor, except at 45° flexion.

Imperceptible energy harvesting device and biomedical sensor based on ultraflexible ferroelectric transducers and organic diodes.

Energy autonomy and conformability are essential elements in the next generation of wearable and flexible electronics for healthcare, robotics and cyber-physical systems. This study presents ferroelectric polymer transducers and organic diodes for imperceptible sensing and energy harvesting systems, which are integrated on ultrathin (1-µm) substrates, thus imparting them with excellent flexibility. Simulations show that the sensitivity of ultraflexible ferroelectric polymer transducers is strongly enhanced by using an ultrathin substrate, which allows the mounting on 3D-shaped objects and the stacking in multiple layers. Indeed, ultraflexible ferroelectric polymer transducers have improved sensitivity to strain and pressure, fast response and excellent mechanical stability, thus forming imperceptible wireless e-health patches for precise pulse and blood pressure monitoring. For harvesting biomechanical energy, the transducers are combined with rectifiers based on ultraflexible organic diodes thus comprising an imperceptible, 2.5-µm thin, energy harvesting device with an excellent peak power density of 3 mW·cm-3.

Costing electronic private sector malaria surveillance in the Greater Mekong Subregion.

BACKGROUND: Private sector malaria programmes contribute to government-led malaria elimination strategies in Cambodia, Lao PDR, and Myanmar by increasing access to quality malaria services and surveillance data. However, reporting from private sector providers remains suboptimal in many settings. To support surveillance strengthening for elimination, a key programme strategy is to introduce electronic surveillance tools and systems to integrate private sector data with national systems, and enhance the use of data for decision-making. During 2013-2017, an electronic surveillance system based on open source software, District Health Information System 2 (DHIS2), was implemented as part of a private sector malaria case management and surveillance programme. The electronic surveillance system covered 16,000 private providers in Myanmar (electronic reporting conducted by 200 field officers with tablets), 710 in Cambodia (585 providers reporting through mobile app), and 432 in Laos (250 providers reporting through mobile app). METHODS: The purpose of the study was to document the costs of introducing electronic surveillance systems and mobile reporting solutions in Cambodia, Lao PDR, and Myanmar, comparing the cost in different operational settings, the cost of introduction and maintenance over time, and assessing the affordability and financial sustainability of electronic surveillance. The data collection methods included extracting data from PSI's financial and operational records, collecting data on prices and quantities of resources used, and interviewing key informants in each setting. The costing study used an ingredients-based approach and estimated both financial and economic costs. RESULTS: Annual economic costs of electronic surveillance systems were $152,805 in Laos, $263,224 in Cambodia, and $1,310,912 in Myanmar. The annual economic cost per private provider surveilled was $82 in Myanmar, $371 in Cambodia, and $354 in Laos. Cost drivers varied depending on operational settings and number of private sector outlets covered in each country; whether purchased or personal mobile devices were used; and whether electronic (mobile) reporting was introduced at provider level or among field officers who support multiple providers for case reporting. CONCLUSION: The study found that electronic surveillance comprises about 0.5-1.5% of national malaria strategic plan cost and 7-21% of surveillance budgets and deemed to be affordable and financially sustainable.