An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm.

BACKGROUND: Blepharospasm is treated with botulinum toxin, but obtaining satisfactory results is sometimes challenging. OBJECTIVE: The aim is to conduct an exploratory trial of oral dipraglurant for blepharospasm. METHODS: This study was an exploratory, phase 2a, randomized, double-blind, placebo-controlled trial of 15 participants who were assigned to receive a placebo or dipraglurant (50 or 100 mg) and assessed over 2 days, 1 and 2 hours following dosing. Outcome measures included multiple scales rated by clinicians or participants, digital video, and a wearable sensor. RESULTS: Dipraglurant was well tolerated, with no obvious impact on any of the measurement outcomes. Power analyses suggested fewer subjects would be required for studies using a within-subject versus independent group design, especially for certain measures. Some outcome measures appeared more suitable than others. CONCLUSION: Although dipraglurant appeared well tolerated, it did not produce a trend for clinical benefit. The results provide valuable information for planning further trials in blepharospasm. © 2024 International Parkinson and Movement Disorder Society.

Ultrathin Crystalline Silicon Nano and Micro Membranes with High Areal Density for Low-Cost Flexible Electronics.

Ultrathin crystalline silicon is widely used as an active material for high-performance, flexible, and stretchable electronics, from simple passive and active components to complex integrated circuits, due to its excellent electrical and mechanical properties. However, in contrast to conventional silicon wafer-based devices, ultrathin crystalline silicon-based electronics require an expensive and rather complicated fabrication process. Although silicon-on-insulator (SOI) wafers are commonly used to obtain a single layer of crystalline silicon, they are costly and difficult to process. Therefore, as an alternative to SOI wafers-based thin layers, here, a simple transfer method is proposed for printing ultrathin multiple crystalline silicon sheets with thicknesses between 300 nm to 13 µm and high areal density (>90%) from a single mother wafer. Theoretically, the silicon nano/micro membrane can be generated until the mother wafer is completely consumed. In addition, the electronic applications of silicon membranes are successfully demonstrated through the fabrication of a flexible solar cell and flexible NMOS transistor arrays.

Experimental Study: Deep Learning-Based Fall Monitoring among Older Adults with Skin-Wearable Electronics.

Older adults are more vulnerable to falling due to normal changes due to aging, and their falls are a serious medical risk with high healthcare and societal costs. However, there is a lack of automatic fall detection systems for older adults. This paper reports (1) a wireless, flexible, skin-wearable electronic device for both accurate motion sensing and user comfort, and (2) a deep learning-based classification algorithm for reliable fall detection of older adults. The cost-effective skin-wearable motion monitoring device is designed and fabricated using thin copper films. It includes a six-axis motion sensor and is directly laminated on the skin without adhesives for the collection of accurate motion data. To study accurate fall detection using the proposed device, different deep learning models, body locations for the device placement, and input datasets are investigated using motion data based on various human activities. Our results indicate the optimal location to place the device is the chest, achieving accuracy of more than 98% for falls with motion data from older adults. Moreover, our results suggest a large motion dataset directly collected from older adults is essential to improve the accuracy of fall detection for the older adult population.

Wireless, intraoral hybrid electronics for real-time quantification of sodium intake toward hypertension management.

Recent wearable devices offer portable monitoring of biopotentials, heart rate, or physical activity, allowing for active management of human health and wellness. Such systems can be inserted in the oral cavity for measuring food intake in regard to controlling eating behavior, directly related to diseases such as hypertension, diabetes, and obesity. However, existing devices using plastic circuit boards and rigid sensors are not ideal for oral insertion. A user-comfortable system for the oral cavity requires an ultrathin, low-profile, and soft electronic platform along with miniaturized sensors. Here, we introduce a stretchable hybrid electronic system that has an exceptionally small form factor, enabling a long-range wireless monitoring of sodium intake. Computational study of flexible mechanics and soft materials provides fundamental aspects of key design factors for a tissue-friendly configuration, incorporating a stretchable circuit and sensor. Analytical calculation and experimental study enables reliable wireless circuitry that accommodates dynamic mechanical stress. Systematic in vitro modeling characterizes the functionality of a sodium sensor in the electronics. In vivo demonstration with human subjects captures the device feasibility for real-time quantification of sodium intake, which can be used to manage hypertension.

Soft Wireless Bioelectronics and Differential Electrodermal Activity for Home Sleep Monitoring.

Sleep is an essential element to human life, restoring the brain and body from accumulated fatigue from daily activities. Quantitative monitoring of daily sleep quality can provide critical feedback to evaluate human health and life patterns. However, the existing sleep assessment system using polysomnography is not available for a home sleep evaluation, while it requires multiple sensors, tabletop electronics, and sleep specialists. More importantly, the mandatory sleep in a designated lab facility disrupts a subject's regular sleep pattern, which does not capture one's everyday sleep behaviors. Recent studies report that galvanic skin response (GSR) measured on the skin can be one indicator to evaluate the sleep quality daily at home. However, the available GSR detection devices require rigid sensors wrapped on fingers along with separate electronic components for data acquisition, which can interrupt the normal sleep conditions. Here, we report a new class of materials, sensors, electronics, and packaging technologies to develop a wireless, soft electronic system that can measure GSR on the wrist. The single device platform that avoids wires, rigid sensors, and straps offers the maximum comfort to wear on the skin and minimize disruption of a subject's sleep. A nanomaterial GSR sensor, printed on a soft elastomeric membrane, can have intimate contact with the skin to reduce motion artifact during sleep. A multi-layered flexible circuit mounted on top of the sensor provides a wireless, continuous, real-time recording of GSR to classify sleep stages, validated by the direct comparison with the standard method that measures other physiological signals. Collectively, the soft bioelectronic system shows great potential to be working as a portable, at-home sensor system for assessing sleep quality before a hospital visit.

Development of Flexible Ion-Selective Electrodes for Saliva Sodium Detection.

Saliva can be used for health monitoring with non-invasive wearable systems. Such devices, including electrochemical sensors, may provide a safe, fast, and cost-efficient way of detecting target ions. Although salivary ions are known to reflect those in blood, no available clinical device can detect essential ions directly from saliva. Here, we introduce an all-solid-state, flexible film sensor that allows highly accurate detection of sodium levels in saliva, comparable to those in blood. The wireless film sensor system can successfully measure sodium ions from a small volume of infants' saliva (<400 µL), demonstrating its potential as a continuous health monitor. This study includes the structural characterization and error analysis of a carbon/elastomer-based ion-selective electrode and a reference electrode to confirm the signal reliability. The sensor, composed of a pair of the electrodes, shows good sensitivity (58.9 mV/decade) and selectivity (log K = -2.68 for potassium), along with a broad detection range of 5 × 10-5 ≈ 1 M with a low detection limit of 4.27 × 10-5 M. The simultaneous comparison between the film sensor and a commercial electrochemical sensor demonstrates the accuracy of the flexible sensor and a positive correlation in saliva-to-blood sodium levels. Collectively, the presented study shows the potential of the wireless ion-selective sensor system for a non-invasive, early disease diagnosis with saliva.

Thin dielectric-layer-enabled low-voltage operation of fully printed flexible carbon nanotube thin-film transistors.

The quality of printable dielectric layer has become one of the major obstacles to achieving high-performance fully printed transistors. A thick dielectric layer will require high gate voltage to switch the transistors on and off, which will cause high power dissipation in printed devices. In response to this challenge, fully printed carbon nanotube (CNT)-based thin-film transistors (TFTs) have been fabricated on flexible membranes such as polyimide and liquid crystal polymer using aerosol jet printing. These devices can be operated at bias voltages below ±10 V (drain/gate voltages around ±6 V). This is much smaller than the previously reported values for fully printed CNT-TFTs because of using xdi-dcs (mixture of poly(vinylphenol)/poly (methylsilsesquioxane)) as the dielectric and using a single printing method. The lower voltage is a consequence of a thin dielectric layer (∼300 nm) and good uniformity in the printed CNT network. The printed CNT-TFTs show on/off ratio >105, and mobility >5 cm2V-1s-1. Layer-by-layer deposition of CNT allows highly uniform and dense network formation, and the optimization of the xdi-dcs concentration using natural butyl alcohol provides high-yield printing of a thin dielectric layer. Collectively, this work shows the potential of using fully printed CNT-TFTs in various flexible electronic applications such as wearable sensors, actuators, artificial skin, displays and wireless tags and antennas.

Wireless, Flexible, Ion-Selective Electrode System for Selective and Repeatable Detection of Sodium.

Wireless, flexible, ion-selective electrodes (ISEs) are of great interest in the development of wearable health monitors and clinical systems. Existing film-based electrochemical sensors, however, still have practical limitations due to poor electrical contact and material-interfacial leakage. Here, we introduce a wireless, flexible film-based system with a highly selective, stable, and reliable sodium sensor. A flexible and hydrophobic composite with carbon black and soft elastomer serves as an ion-to-electron transducer offering cost efficiency, design simplicity, and long-term stability. The sensor package demonstrates repeatable analysis of selective sodium detection in saliva with good sensitivity (56.1 mV/decade), stability (0.53 mV/h), and selectivity coefficient of sodium against potassium (-3.0). The film ISEs have an additional membrane coating that provides reinforced stability for the sensor upon mechanical bending. Collectively, the comprehensive study of materials, surface chemistry, and sensor design in this work shows the potential of the wireless flexible sensor system for low-profile wearable applications.

Soft, curved electrode systems capable of integration on the auricle as a persistent brain-computer interface.

Recent advances in electrodes for noninvasive recording of electroencephalograms expand opportunities collecting such data for diagnosis of neurological disorders and brain-computer interfaces. Existing technologies, however, cannot be used effectively in continuous, uninterrupted modes for more than a few days due to irritation and irreversible degradation in the electrical and mechanical properties of the skin interface. Here we introduce a soft, foldable collection of electrodes in open, fractal mesh geometries that can mount directly and chronically on the complex surface topology of the auricle and the mastoid, to provide high-fidelity and long-term capture of electroencephalograms in ways that avoid any significant thermal, electrical, or mechanical loading of the skin. Experimental and computational studies establish the fundamental aspects of the bending and stretching mechanics that enable this type of intimate integration on the highly irregular and textured surfaces of the auricle. Cell level tests and thermal imaging studies establish the biocompatibility and wearability of such systems, with examples of high-quality measurements over periods of 2 wk with devices that remain mounted throughout daily activities including vigorous exercise, swimming, sleeping, and bathing. Demonstrations include a text speller with a steady-state visually evoked potential-based brain-computer interface and elicitation of an event-related potential (P300 wave).

Recent Advances in Nanoparticle Concentration and Their Application in Viral Detection Using Integrated Sensors.

Early disease diagnostics require rapid, sensitive, and selective detection methods for target analytes. Specifically, early viral detection in a point-of-care setting is critical in preventing epidemics and the spread of disease. However, conventional methods such as enzyme-linked immunosorbent assays or cell cultures are cumbersome and difficult for field use due to the requirements of extensive lab equipment and highly trained personnel, as well as limited sensitivity. Recent advances in nanoparticle concentration have given rise to many novel detection methodologies, which address the shortcomings in modern clinical assays. Here, we review the primary, well-characterized methods for nanoparticle concentration in the context of viral detection via diffusion, centrifugation and microfiltration, electric and magnetic fields, and nano-microfluidics. Details of the concentration mechanisms and examples of related applications provide valuable information to design portable, integrated sensors. This study reviews a wide range of concentration techniques and compares their advantages and disadvantages with respect to viral particle detection. We conclude by highlighting selected concentration methods and devices for next-generation biosensing systems.

A Simulation Study of a Radiofrequency Localization System for Tracking Patient Motion in Radiotherapy.

One of the most widely used tools in cancer treatment is external beam radiotherapy. However, the major risk involved in radiotherapy is excess radiation dose to healthy tissue, exacerbated by patient motion. Here, we present a simulation study of a potential radiofrequency (RF) localization system designed to track intrafraction motion (target motion during the radiation treatment). This system includes skin-wearable RF beacons and an external tracking system. We develop an analytical model for direction of arrival measurement with radio frequencies (GHz range) for use in a localization estimate. We use a Monte Carlo simulation to investigate the relationship between a localization estimate and angular resolution of sensors (signal receivers) in a simulated room. The results indicate that the external sensor needs an angular resolution of about 0.03 degrees to achieve millimeter-level localization accuracy in a treatment room. This fundamental study of a novel RF localization system offers the groundwork to design a radiotherapy-compatible patient positioning system for active motion compensation.

Ultrathin conformal devices for precise and continuous thermal characterization of human skin.

Precision thermometry of the skin can, together with other measurements, provide clinically relevant information about cardiovascular health, cognitive state, malignancy and many other important aspects of human physiology. Here, we introduce an ultrathin, compliant skin-like sensor/actuator technology that can pliably laminate onto the epidermis to provide continuous, accurate thermal characterizations that are unavailable with other methods. Examples include non-invasive spatial mapping of skin temperature with millikelvin precision, and simultaneous quantitative assessment of tissue thermal conductivity. Such devices can also be implemented in ways that reveal the time-dynamic influence of blood flow and perfusion on these properties. Experimental and theoretical studies establish the underlying principles of operation, and define engineering guidelines for device design. Evaluation of subtle variations in skin temperature associated with mental activity, physical stimulation and vasoconstriction/dilation along with accurate determination of skin hydration through measurements of thermal conductivity represent some important operational examples.

Skin-interfacing wearable biosensors for smart health monitoring of infants and neonates.

Health monitoring of infant patients in intensive care can be especially strenuous for both the patient and their caregiver, as testing setups involve a tangle of electrodes, probes, and catheters that keep the patient bedridden. This has typically involved expensive and imposing machines, to track physiological metrics such as heart rate, respiration rate, temperature, blood oxygen saturation, blood pressure, and ion concentrations. However, in the past couple of decades, research advancements have propelled a world of soft, wearable, and non-invasive systems to supersede current practices. This paper summarizes the latest advancements in neonatal wearable systems and the different approaches to each branch of physiological monitoring, with an emphasis on smart skin-interfaced wearables. Weaknesses and shortfalls are also addressed, with some guidelines provided to help drive the further research needed.

Continuous real-time assessment of acute cognitive stress from cardiac mechanical signals captured by a skin-like patch.

The inability to objectively quantify cognitive stress in real-time with wearable devices is a crucial unsolved problem with serious negative consequences for dementia and mental disability patients and those seeking to improve their quality of life. Here, we introduce a skin-like, wireless sternal patch that captures changes in cardiac mechanics due to stress manifesting in the seismocardiogram (SCG) signals. Judicious optimization of the device's micro-structured interconnections and elastomer integration yields a device that sufficiently matches the skin's mechanics, robustly yet gently adheres to the skin without aggressive tapes, and captures planar and longitudinal SCG waves well. The device transmits SCG beats in real-time to a user's device, where derived features relate to the heartbeat's mechanical morphology. The signals are assessed by a series of features in a support vector machine regressor. Controlled studies, compared to gold standard cortisol and following the validated imaging test, show an R-squared correlation of 0.79 between the stress prediction and cortisol change, significantly improving over prior works. Likewise, the system demonstrates excellent robustness to external temperature and physical recovery status while showing excellent accuracy and wearability in full-day use.

Recent advances in implantable sensors and electronics using printable materials for advanced healthcare.

This review article focuses on the recent printing technological progress in healthcare, underscoring the significant potential of implantable devices across diverse applications. Printing technologies have widespread use in developing health monitoring devices, diagnostic systems, and surgical devices. Recent years have witnessed remarkable progress in fabricating low-profile implantable devices, driven by advancements in printing technologies and nanomaterials. The importance of implantable biosensors and bioelectronics is highlighted, specifically exploring printing tools using bio-printable inks for practical applications, including a detailed examination of fabrication processes and essential parameters. This review also justifies the need for mechanical and electrical compatibility between bioelectronics and biological tissues. In addition to technological aspects, this article delves into the importance of appropriate packaging methods to enhance implantable devices' performance, compatibility, and longevity, which are made possible by integrating cutting-edge printing technology. Collectively, we aim to shed light on the holistic landscape of implantable biosensors and bioelectronics, showcasing their evolving role in advancing healthcare through innovative printing technologies.

Recent advances in soft, implantable electronics for dynamic organs.

Unlike conventional rigid counterparts, soft and stretchable electronics forms crack- or defect-free conformal interfaces with biological tissues, enabling precise and reliable interventions in diagnosis and treatment of human diseases. Intrinsically soft and elastic materials, and device designs of innovative configurations and structures leads to the emergence of such features, particularly, the mechanical compliance provides seamless integration into continuous movements and deformations of dynamic organs such as the bladder and heart, without disrupting natural physiological functions. This review introduces the development of soft, implantable electronics tailored for dynamic organs, covering various materials, mechanical design strategies, and representative applications for the bladder and heart, and concludes with insights into future directions toward clinically relevant tools.

Biosignal-integrated robotic systems with emerging trends in visual interfaces: A systematic review.

Human-machine interfaces (HMI) are currently a trendy and rapidly expanding area of research. Interestingly, the human user does not readily observe the interface between humans and machines. Instead, interactions between the machine and electrical signals from the user's body are obscured by complex control algorithms. The result is effectively a one-way street, wherein data is only transmitted from human to machine. Thus, a gap remains in the literature: how can information be effectively conveyed to the user to enable mutual understanding between humans and machines? Here, this paper reviews recent advancements in biosignal-integrated wearable robotics, with a particular emphasis on "visualization"-the presentation of relevant data, statistics, and visual feedback to the user. This review article covers various signals of interest, such as electroencephalograms and electromyograms, and explores novel sensor architectures and key materials. Recent developments in wearable robotics are examined from control and mechanical design perspectives. Additionally, we discuss current visualization methods and outline the field's future direction. While much of the HMI field focuses on biomedical and healthcare applications, such as rehabilitation of spinal cord injury and stroke patients, this paper also covers less common applications in manufacturing, defense, and other domains.

Long-term stable pH sensor array with synergistic bilayer structure for 2D real-time mapping in cell culture monitoring.

Pursuing accurate, swift, and durable pH sensors is important across numerous fields, encompassing healthcare, environmental surveillance, and agriculture. In particular, the emphasis on real-time pH monitoring during cell cultivation has become increasingly pronounced in the current scientific environment-a crucial element being diligently researched to ensure optimal cell production. Both polyaniline (PANi) and iridium oxide (IrOx) show their worth in pH sensing, yet they come with challenges. Single-PANi-layered pH sensors often grapple with diminished sensitivity and lagging responses, while electrodeposited IrOx structures exhibit poor adhesion, leading to their separation from metallic substrates-a trait undesirable for a consistently stable, long-term pH sensor. This paper introduces a bi-layered PANi-IrOx pH sensor, strategically leveraging the advantages of both materials. The results presented here underscore the sensitivity enhancement of binary-phased framework, faster response time, and more robust structure than prior work. Through this synergistic strategy, we demonstrate the potential of integrating different phases to overcome the inherent constraints of individual materials, setting the stage for advanced pH-sensing solutions.

AR-Enabled Persistent Human-Machine Interfaces via a Scalable Soft Electrode Array.

Augmented reality (AR) is a computer graphics technique that creates a seamless interface between the real and virtual worlds. AR usage rapidly spreads across diverse areas, such as healthcare, education, and entertainment. Despite its immense potential, AR interface controls rely on an external joystick, a smartphone, or a fixed camera system susceptible to lighting. Here, an AR-integrated soft wearable electronic system that detects the gestures of a subject for more intuitive, accurate, and direct control of external systems is introduced. Specifically, a soft, all-in-one wearable device includes a scalable electrode array and integrated wireless system to measure electromyograms for real-time continuous recognition of hand gestures. An advanced machine learning algorithm embedded in the system enables the classification of ten different classes with an accuracy of 96.08%. Compared to the conventional rigid wearables, the multi-channel soft wearable system offers an enhanced signal-to-noise ratio and consistency over multiple uses due to skin conformality. The demonstration of the AR-integrated soft wearable system for drone control captures the potential of the platform technology to offer numerous human-machine interface opportunities for users to interact remotely with external hardware and software.

Machine-learned wearable sensors for real-time hand-motion recognition: toward practical applications.

Soft electromechanical sensors have led to a new paradigm of electronic devices for novel motion-based wearable applications in our daily lives. However, the vast amount of random and unidentified signals generated by complex body motions has hindered the precise recognition and practical application of this technology. Recent advancements in artificial-intelligence technology have enabled significant strides in extracting features from massive and intricate data sets, thereby presenting a breakthrough in utilizing wearable sensors for practical applications. Beyond traditional machine-learning techniques for classifying simple gestures, advanced machine-learning algorithms have been developed to handle more complex and nuanced motion-based tasks with restricted training data sets. Machine-learning techniques have improved the ability to perceive, and thus machine-learned wearable soft sensors have enabled accurate and rapid human-gesture recognition, providing real-time feedback to users. This forms a crucial component of future wearable electronics, contributing to a robust human-machine interface. In this review, we provide a comprehensive summary covering materials, structures and machine-learning algorithms for hand-gesture recognition and possible practical applications through machine-learned wearable electromechanical sensors.