At-home wireless sleep monitoring patches for the clinical assessment of sleep quality and sleep apnea.

Although many people suffer from sleep disorders, most are undiagnosed, leading to impairments in health. The existing polysomnography method is not easily accessible; it's costly, burdensome to patients, and requires specialized facilities and personnel. Here, we report an at-home portable system that includes wireless sleep sensors and wearable electronics with embedded machine learning. We also show its application for assessing sleep quality and detecting sleep apnea with multiple patients. Unlike the conventional system using numerous bulky sensors, the soft, all-integrated wearable platform offers natural sleep wherever the user prefers. In a clinical study, the face-mounted patches that detect brain, eye, and muscle signals show comparable performance with polysomnography. When comparing healthy controls to sleep apnea patients, the wearable system can detect obstructive sleep apnea with an accuracy of 88.5%. Furthermore, deep learning offers automated sleep scoring, demonstrating portability, and point-of-care usability. At-home wearable electronics could ensure a promising future supporting portable sleep monitoring and home healthcare.

Soft Wireless Headband Bioelectronics and Electrooculography for Persistent Human-Machine Interfaces.

Recent advances in wearable technologies have enabled ways for people to interact with external devices, known as human-machine interfaces (HMIs). Among them, electrooculography (EOG), measured by wearable devices, is used for eye movement-enabled HMI. Most prior studies have utilized conventional gel electrodes for EOG recording. However, the gel is problematic due to skin irritation, while separate bulky electronics cause motion artifacts. Here, we introduce a low-profile, headband-type, soft wearable electronic system with embedded stretchable electrodes, and a flexible wireless circuit to detect EOG signals for persistent HMIs. The headband with dry electrodes is printed with flexible thermoplastic polyurethane. Nanomembrane electrodes are prepared by thin-film deposition and laser cutting techniques. A set of signal processing data from dry electrodes demonstrate successful real-time classification of eye motions, including blink, up, down, left, and right. Our study shows that the convolutional neural network performs exceptionally well compared to other machine learning methods, showing 98.3% accuracy with six classes: the highest performance till date in EOG classification with only four electrodes. Collectively, the real-time demonstration of continuous wireless control of a two-wheeled radio-controlled car captures the potential of the bioelectronic system and the algorithm for targeting various HMI and virtual reality applications.

Fully Screen-Printed PI/PEG Blends Enabled Patternable Electrodes for Scalable Manufacturing of Skin-Conformal, Stretchable, Wearable Electronics.

Recent advances in soft materials and nano-microfabrication have enabled the development of flexible wearable electronics. At the same time, printing technologies have been demonstrated to be efficient and compatible with polymeric materials for manufacturing wearable electronics. However, wearable device manufacturing still counts on a costly, complex, multistep, and error-prone cleanroom process. Here, we present fully screen-printable, skin-conformal electrodes for low-cost and scalable manufacturing of wearable electronics. The screen printing of the polyimide (PI) layer enables facile, low-cost, scalable, high-throughput manufacturing. PI mixed with poly(ethylene glycol) exhibits a shear-thinning behavior, significantly improving the printability of PI. The premixed Ag/AgCl ink is then used for conductive layer printing. The serpentine pattern of the screen-printed electrode accommodates natural deformation under stretching (30%) and bending conditions (180°), which are verified by computational and experimental studies. Real-time wireless electrocardiogram monitoring is also successfully demonstrated using the printed electrodes with a flexible printed circuit. The algorithm developed in this study can calculate accurate heart rates, respiratory rates, and heart rate variability metrics for arrhythmia detection.

Automatic and Accurate Sleep Stage Classification via a Convolutional Deep Neural Network and Nanomembrane Electrodes.

Sleep stage classification is an essential process of diagnosing sleep disorders and related diseases. Automatic sleep stage classification using machine learning has been widely studied due to its higher efficiency compared with manual scoring. Typically, a few polysomnography data are selected as input signals, and human experts label the corresponding sleep stages manually. However, the manual process includes human error and inconsistency in the scoring and stage classification. Here, we present a convolutional neural network (CNN)-based classification method that offers highly accurate, automatic sleep stage detection, validated by a public dataset and new data measured by wearable nanomembrane dry electrodes. First, our study makes a training and validation model using a public dataset with two brain signal and two eye signal channels. Then, we validate this model with a new dataset measured by a set of nanomembrane electrodes. The result of the automatic sleep stage classification shows that our CNN model with multi-taper spectrogram pre-processing achieved 88.85% training accuracy on the validation dataset and 81.52% prediction accuracy on our laboratory dataset. These results validate the reliability of our classification method on the standard polysomnography dataset and the transferability of our CNN model for other datasets measured with the wearable electrodes.

Soft Wireless Bioelectronics Designed for Real-Time, Continuous Health Monitoring of Farmworkers.

Hotter summers caused by global warming and increased workload and duration are endangering the health of farmworkers, a high-risk population for heat-related illness (HRI), and deaths. Although prior studies using wearable sensors show the feasibility of employing field-collected data for HRI monitoring, existing devices still have limitations, such as data loss from motion artifacts, device discomfort from rigid electronics, difficulties with administering ingestible sensors, and low temporal resolution. Here, this paper introduces a wireless, wearable bioelectronic system with functionalities for continuous monitoring of skin temperature, electrocardiograms (ECG), heart rates (HR), and activities, configured in a single integrated package. Advanced nanomanufacturing based on laser machining allows rapid device fabrication and direct incorporation of sensors with a highly breathable substrate, allowing for managing excessive sweating and multimodal stresses. To validate the device's performance in agricultural settings, the device is applied to multiple farmworkers at various operations, including fernery, nursery, and crop. The accurate data recording, including high-fidelity ECG (signal-to-noise ratio: >20 dB), accurate HR (r = 0.89, r2 = 0.65 in linear correlation), and reliable temperature/activity, confirms the device's capability for multiparameter health monitoring of farmworkers.

At-home wireless monitoring of acute hemodynamic disturbances to detect sleep apnea and sleep stages via a soft sternal patch.

Obstructive sleep apnea (OSA) affects more than 900 million adults globally and can create serious health complications when untreated; however, 80% of cases remain undiagnosed. Critically, current diagnostic techniques are fundamentally limited by low throughputs and high failure rates. Here, we report a wireless, fully integrated, soft patch with skin-like mechanics optimized through analytical and computational studies to capture seismocardiograms, electrocardiograms, and photoplethysmograms from the sternum, allowing clinicians to investigate the cardiovascular response to OSA during home sleep tests. In preliminary trials with symptomatic and control subjects, the soft device demonstrated excellent ability to detect blood-oxygen saturation, respiratory effort, respiration rate, heart rate, cardiac pre-ejection period and ejection timing, aortic opening mechanics, heart rate variability, and sleep staging. Last, machine learning is used to autodetect apneas and hypopneas with 100% sensitivity and 95% precision in preliminary at-home trials with symptomatic patients, compared to data scored by professionally certified sleep clinicians.

Wireless Soft Scalp Electronics and Virtual Reality System for Motor Imagery-Based Brain-Machine Interfaces.

Motor imagery offers an excellent opportunity as a stimulus-free paradigm for brain-machine interfaces. Conventional electroencephalography (EEG) for motor imagery requires a hair cap with multiple wired electrodes and messy gels, causing motion artifacts. Here, a wireless scalp electronic system with virtual reality for real-time, continuous classification of motor imagery brain signals is introduced. This low-profile, portable system integrates imperceptible microneedle electrodes and soft wireless circuits. Virtual reality addresses subject variance in detectable EEG response to motor imagery by providing clear, consistent visuals and instant biofeedback. The wearable soft system offers advantageous contact surface area and reduced electrode impedance density, resulting in significantly enhanced EEG signals and classification accuracy. The combination with convolutional neural network-machine learning provides a real-time, continuous motor imagery-based brain-machine interface. With four human subjects, the scalp electronic system offers a high classification accuracy (93.22 ± 1.33% for four classes), allowing wireless, real-time control of a virtual reality game.

Real-Time Functional Assay of Volumetric Muscle Loss Injured Mouse Masseter Muscles via Nanomembrane Electronics.

Skeletal muscle has a remarkable regeneration capacity to recover its structure and function after injury, except for the traumatic loss of critical muscle volume, called volumetric muscle loss (VML). Although many extremity VML models have been conducted, craniofacial VML has not been well-studied due to unavailable in vivo assay tools. Here, this paper reports a wireless, noninvasive nanomembrane system that integrates skin-wearable printed sensors and electronics for real-time, continuous monitoring of VML on craniofacial muscles. The craniofacial VML model, using biopsy punch-induced masseter muscle injury, shows impaired muscle regeneration. To measure the electrophysiology of small and round masseter muscles of active mice during mastication, a wearable nanomembrane system with stretchable graphene sensors that can be laminated to the skin over target muscles is utilized. The noninvasive system provides highly sensitive electromyogram detection on masseter muscles with or without VML injury. Furthermore, it is demonstrated that the wireless sensor can monitor the recovery after transplantation surgery for craniofacial VML. Overall, the presented study shows the enormous potential of the masseter muscle VML injury model and wearable assay tool for the mechanism study and the therapeutic development of craniofacial VML.

Recent advances in wearable sensors and portable electronics for sleep monitoring.

Despite the increasing awareness of the importance of sleep, the number of people suffering from insufficient sleep has increased every year. The gold-standard sleep assessment uses polysomnography (PSG) with various sensors to identify sleep patterns and disorders. However, due to the high cost of PSG and limited availability, many people with sleep disorders are left undiagnosed. Recent wearable sensors and electronics enable portable, continuous monitoring of sleep at home, overcoming the limitations of PSG. This report reviews the advances in wearable sensors, miniaturized electronics, and system packaging for home sleep monitoring. New devices available in the market and systems are collectively summarized based on their overall structure, form factor, materials, and sleep assessment method. It is expected that this review provides a comprehensive view of newly developed technologies and broad insights on wearable sensors and portable electronics toward advanced sleep monitoring as well as at-home sleep assessment.

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.

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.

Wireless, continuous monitoring of daily stress and management practice via soft bioelectronics.

Stress has become a significant factor, directly affecting human health. Due to the numerous sources of stress that are inevitable in daily life, effective management of stress is essential to maintain a healthy life. Recent advancements in wearable devices allow monitoring stress levels via the detection of galvanic skin response on the skin. Some of these devices show the capability of assessing stress relief methods. However, prior works have been limited in a controlled laboratory setting with a short period assessment (<1 h) of stress intervention. The existing systems' main issues include motion artifacts and discomfort caused by rigid and bulky electronics and mandatory device connection on active fingers. Here, we introduce soft, wireless, skin-like electronics (SKINTRONICS) that offers continuous, portable daily stress and management practice monitoring. The ultrathin, lightweight, all-in-one device captures the change of a subject's stress over six continuous hours during everyday activities, including desk work, cleaning, and resting. At the same time, the SKINTRONICS proves that typical stress alleviation methods (mindfulness and meditation) can reduce stress levels, even in the middle of the day, which is supported by statistical analysis. The low-profile, wireless, gel-free device shows enhanced breathability and minimized motion artifacts compared to a commercial stress monitor. Collectively, this study shows the first demonstration of soft, nanomembrane bioelectronics for long-term, continuous assessment of stress and intervention effectiveness throughout daily life.

Fully Integrated, Stretchable, Wireless Skin-Conformal Bioelectronics for Continuous Stress Monitoring in Daily Life.

Stress is one of the main causes that increase the risk of serious health problems. Recent wearable devices have been used to monitor stress levels via electrodermal activities on the skin. Although many biosensors provide adequate sensing performance, they still rely on uncomfortable, partially flexible systems with rigid electronics. These devices are mounted on either fingers or palms, which hinders a continuous signal monitoring. A fully-integrated, stretchable, wireless skin-conformal bioelectronic (referred to as "SKINTRONICS") is introduced here that integrates soft, multi-layered, nanomembrane sensors and electronics for continuous and portable stress monitoring in daily life. The all-in-one SKINTRONICS is ultrathin, highly soft, and lightweight, which overall offers an ergonomic and conformal lamination on the skin. Stretchable nanomembrane electrodes and a digital temperature sensor enable highly sensitive monitoring of galvanic skin response (GSR) and temperature. A set of comprehensive signal processing, computational modeling, and experimental study provides key aspects of device design, fabrication, and optimal placing location. Simultaneous comparison with two commercial stress monitors captures the enhanced performance of SKINTRONICS in long-term wearability, minimal noise, and skin compatibility. In vivo demonstration of continuous stress monitoring in daily life reveals the unique capability of the soft device as a real-world applicable stress monitor.

Breathable, large-area epidermal electronic systems for recording electromyographic activity during operant conditioning of H-reflex.

Operant conditioning of Hoffmann's reflex (H-reflex) is a non-invasive and targeted therapeutic intervention for patients with movement disorders following spinal cord injury. The reflex-conditioning protocol uses electromyography (EMG) to measure reflexes from specific muscles elicited using transcutaneous electrical stimulation. Despite recent advances in wearable electronics, existing EMG systems that measure muscle activity for operant conditioning of spinal reflexes still use rigid metal electrodes with conductive gels and aggressive adhesives, while requiring precise positioning to ensure reliability of data across experimental sessions. Here, we present the first large-area epidermal electronic system (L-EES) and demonstrate its use in every step of the reflex-conditioning protocol. The L-EES is a stretchable and breathable composite of nanomembrane electrodes (16 electrodes in a four by four array), elastomer, and fabric. The nanomembrane electrode array enables EMG recording from a large surface area on the skin and the breathable elastomer with fabric is biocompatible and comfortable for patients. We show that L-EES can record direct muscle responses (M-waves) and H-reflexes, both of which are comparable to those recorded using conventional EMG recording systems. In addition, L-EES may improve the reflex-conditioning protocol; it has potential to automatically optimize EMG electrode positioning, which may reduce setup time and error across experimental sessions.

All-printed nanomembrane wireless bioelectronics using a biocompatible solderable graphene for multimodal human-machine interfaces.

Recent advances in nanomaterials and nano-microfabrication have enabled the development of flexible wearable electronics. However, existing manufacturing methods still rely on a multi-step, error-prone complex process that requires a costly cleanroom facility. Here, we report a new class of additive nanomanufacturing of functional materials that enables a wireless, multilayered, seamlessly interconnected, and flexible hybrid electronic system. All-printed electronics, incorporating machine learning, offers multi-class and versatile human-machine interfaces. One of the key technological advancements is the use of a functionalized conductive graphene with enhanced biocompatibility, anti-oxidation, and solderability, which allows a wireless flexible circuit. The high-aspect ratio graphene offers gel-free, high-fidelity recording of muscle activities. The performance of the printed electronics is demonstrated by using real-time control of external systems via electromyograms. Anatomical study with deep learning-embedded electrophysiology mapping allows for an optimal selection of three channels to capture all finger motions with an accuracy of about 99% for seven classes.

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 Nanomembrane Sensors and Flexible Hybrid Bioelectronics for Wireless Quantification of Blepharospasm.

Blepharospasm (BL) is characterized by involuntary closures of the eyelids due to spasms of the orbicularis oculi muscle. The gold standard for clinical evaluation of BL involves visual inspection for manual rating scales. This approach is highly subjective and error prone. Unfortunately, there are currently no simple quantitative systems for accurate and objective diagnostics of BL. Here, we introduce a soft, flexible hybrid bioelectronic system that offers highly conformal, gentle lamination on the skin, while enabling wireless, quantitative detection of electrophysiological signals. Computational and experimental studies of soft materials and flexible mechanics provide a set of key fundamental design factors for a low-profile bioelectronic system. The nanomembrane soft electrodes, mounted around the eyes, are capable of accurately measuring clinical symptoms, including the frequency of blinking, the duration of eye closures during spasms, as well as combinations of blinking and spasms. The use of a deep-learning, convolutional neural network, with the bioelectronics offers objective, real-time classification of key pathological features in BL. The wearable bioelectronics outperform the conventional manual clinical rating, as shown by a pilot study with 13 patients. In vivo demonstration of the bioelectronics with these patients indicates the device as an easy-to-use solution for objective quantification of BL.

Skin-conformal, soft material-enabled bioelectronic system with minimized motion artifacts for reliable health and performance monitoring of athletes.

Recent advances in biosensors, bioelectronics, and system integration allow the development of wristband-type devices for health and performance monitoring of athletes. Although these devices provide adequate sensing outputs, they suffer from signal loss due to improper contact of a rigid sensor with the skin. In addition, when a rubber band tightly secures the sensor to the skin, the gap between sensor and skin causes inevitable motion artifacts, resulting in corrupted data. Consequently, the rigidity and bulky form factor of the existing devices are not suitable for a practical use since athletes typically go through strenuous activities during training and matches. Here, we introduce a soft, wearable flexible hybrid electronics (WFHE) with integrated flexible sensors and circuits in an ultrathin, low-modulus elastomer. The thin-film bioelectronic system avoids the use of bulky, rigid sensors, while providing negligible mechanical and thermal burdens to the wearer. Enabling conformal contact between sensor and skin minimizes undesired motion artifacts. A set of computational and experimental studies of soft materials, flexible mechanics, and system packaging provides key fundamental design factors for a comfortable, reliable, waterproof bioelectronic system. Skin conformal WFHE with sparse signal reconstruction enables reliable, continuous monitoring of photoplethysmogram, heart rate, and activities of athletes. Development of a quantitative analysis between impact force and impact velocity extracted from motion acceleration provides an objective assessment of an athletic punching force. Collectively, this study shows the first demonstration of a wireless, soft, thin-film electronics for a real-time, reliable assessment of athletic health and performance.

Wireless, Skin-Like Membrane Electronics With Multifunctional Ergonomic Sensors for Enhanced Pediatric Care.

Continuous cardiac monitoring using electrocardiograms (ECG) provides a range of patient information, essential for making clinical decisions, to healthcare providers. Unfortunately, the clinical standard of ECG recording requires the use of rigid metal electrodes, conductive gels, and wired electronic devices, which often cause skin injuries and health risks for pediatric patients with underdeveloped, fragile skin. Here, we introduce a wireless, soft, comfortable electronic system that obviates the need for skin preparation, electrolyte gels, or aggressive tapes. The low-profile device incorporates a thin-film circuit and nanomembrane sensors, encapsulated in a hyperelastic elastomer. The soft elastomeric membrane offers an optimized adhesion that ensures a conformal lamination of stretchable electrodes on the skin for recording of high-fidelity biopotentials. The combined set of on-board Bluetooth module, front-end amplifier, and voltage regulator enables a real-time, long-range, wireless monitoring of physiological data, including ECG, heart rate (HR) and respiratory rate (RR). A pilot study with pediatric patients demonstrates the clinical feasibility of the device as a comfortable, reliable biopotential monitor, suggesting a new standard for safe and effective pediatric care.

Use of Superelastic Nitinol and Highly-Stretchable Latex to Develop a Tongue Prosthetic Assist Device and Facilitate Swallowing for Dysphagia Patients.

We introduce a new tongue prosthetic assist device (TPAD), which shows the first prosthetic application for potential treatment of swallowing difficulty in dysphagia patients. The native tongue has a number of complex movements that are not feasible to mimic using a single mechanical prosthetic device. In order to overcome this challenge, our device has three key features, including (1) a superelastic nitinol structure that transfers the force produced by the jaws during chewing towards the palate, (2) angled composite tubes for guiding the nitinol strips smoothly during the motion, and (3) highly stretchable thin polymeric membrane as a covering sheet in order to secure the food and fluids on top of the TPAD for easy swallowing. A set of mechanical experiments has optimized the size and angle of the guiding tubes for the TPAD. The low-profile TPAD was successfully placed in a cadaver model and its mobility effectively provided a simplistic mimic of the native tongue elevation function by applying vertical chewing motions. This is the first demonstration of a new oral device powered by the jaw motions in order to create a bulge in the middle of the mouth mimicking native tongue behavior.