Large-scale smart bioreactor with fully integrated wireless multivariate sensors and electronics for long-term in situ monitoring of stem cell culture.

Achieving large-scale, cost-effective, and reproducible manufacturing of stem cells with the existing devices is challenging. Traditional single-use cell-bag bioreactors, limited by their rigid and single-point sensors, struggle with accuracy and scalability for high-quality cell manufacturing. Here, we introduce a smart bioreactor system that enables multi-spatial sensing for real-time, wireless culture monitoring. This scalable system includes a low-profile, label-free thin-film sensor array and electronics integrated with a flexible cell bag, allowing for simultaneous assessment of culture properties such as pH, dissolved oxygen, glucose, and temperature, to receive real-time feedback for up to 30 days. The experimental results show the accurate monitoring of time-dynamic and spatial variations of stem cells and myoblast cells with adjustable carriers from a plastic dish to a 2-liter cell bag. These advances open up the broad applicability of the smart sensing system for large-scale, lower-cost, reproducible, and high-quality engineered cell manufacturing for broad clinical use.

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 portable continuous real-time auscultation with a soft wearable stethoscope designed for automated disease diagnosis.

Modern auscultation, using digital stethoscopes, provides a better solution than conventional methods in sound recording and visualization. However, current digital stethoscopes are too bulky and nonconformal to the skin for continuous auscultation. Moreover, motion artifacts from the rigidity cause friction noise, leading to inaccurate diagnoses. Here, we report a class of technologies that offers real-time, wireless, continuous auscultation using a soft wearable system as a quantitative disease diagnosis tool for various diseases. The soft device can detect continuous cardiopulmonary sounds with minimal noise and classify real-time signal abnormalities. A clinical study with multiple patients and control subjects captures the unique advantage of the wearable auscultation method with embedded machine learning for automated diagnoses of four types of lung diseases: crackle, wheeze, stridor, and rhonchi, with a 95% accuracy. The soft system also demonstrates the potential for a sleep study by detecting disordered breathing for home sleep and apnea detection.

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.

Advances in Microsensors and Wearable Bioelectronics for Digital Stethoscopes in Health Monitoring and Disease Diagnosis.

Acoustic stethoscopes have demonstrated beneficial factors aiding diagnosis from the doctors with accurate body sounds. Still, the conventional acoustic stethoscopes require a substantial amount of clinical experience and hearing skills for the physicians to accurately diagnose symptoms from abnormal sounds. Especially for cardiopulmonary systems, it is crucial to collect sounds with precision since they contain valuable information in specific frequency ranges for various sounds. This review paper summarizes recent advances and technical developments in microsensors, circuits, chips, and integrated electronics for fabricating different digital stethoscopes that offer portable detection of body sounds. They solve the limitations of conventional stethoscopes, aiming for wireless auscultation in digitized medicine. Overall, this comprehensive review will help researchers design and develop new wearable electronics and digital stethoscopes for advancing human healthcare, continuous monitoring, and better diagnosis.

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.

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.

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.

Printed, Wireless, Soft Bioelectronics and Deep Learning Algorithm for Smart Human-Machine Interfaces.

Recent advances in flexible materials and wearable electronics offer a noninvasive, high-fidelity recording of biopotentials for portable healthcare, disease diagnosis, and machine interfaces. Current device-manufacturing methods, however, still heavily rely on the conventional cleanroom microfabrication that requires expensive, time-consuming, and complicated processes. Here, we introduce an additive nanomanufacturing technology that explores a contactless direct printing of aerosol nanomaterials and polymers to fabricate stretchable sensors and multilayered wearable electronics. Computational and experimental studies prove the mechanical flexibility and reliability of soft electronics, considering direct mounting to the deformable human skin with a curvilinear surface. The dry, skin-conformal graphene biosensor, without the use of conductive gels and aggressive tapes, offers an enhanced biopotential recording on the skin and multiple uses (over ten times) with consistent measurement of electromyograms. The combination of soft bioelectronics and deep learning algorithm allows classifying six classes of muscle activities with an accuracy of over 97%, which enables wireless, real-time, continuous control of external machines such as a robotic hand and a robotic arm. Collectively, the comprehensive study of nanomaterials, flexible mechanics, system integration, and machine learning shows the potential of the printed bioelectronics for portable, smart, and persistent human-machine interfaces.

Stretchable Nanocomposite Sensors, Nanomembrane Interconnectors, and Wireless Electronics toward Feedback-Loop Control of a Soft Earthworm Robot.

Sensors that can detect external stimuli and perceive the surrounding areas could offer an ability for soft biomimetic robots to use the sensory feedback for closed-loop control of locomotion. Although various types of biomimetic robots have been developed, few systems have included integrated stretchable sensors and interconnectors with miniaturized electronics. Here, we introduce a soft, stretchable nanocomposite system with built-in wireless electronics with an aim for feedback-loop motion control of a robotic earthworm. The nanostructured strain sensor, based on a carbon nanomaterial and a low-modulus silicone elastomer, allows for seamless integration with the body of the soft robot that can accommodate large strains caused by bending, stretching, and physical interactions with obstacles. A scalable, cost-effective, and screen-printing method manufactures an array of the strain sensors that are conductive and stretchable over 100% with a gauge factor over 38. An array of nanomembrane interconnectors enables a reliable connection between soft sensors and wireless electronics while tolerating the robot's multimodal movements. A set of computational and experimental studies of soft materials, stretchable mechanics, and hybrid packaging provides the key design factors for a reliable, nanocomposite sensor system. The miniaturized wireless circuit, embedded in the robot joint, offers real-time monitoring of strain changes during the motions of a robotic segment. Collectively, the soft sensor system presented in this work shows great potential to be integrated with other flexible, stretchable electronics for applications in soft robotics, wearable devices, and human-machine interfaces.

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.

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, wireless periocular wearable electronics for real-time detection of eye vergence in a virtual reality toward mobile eye therapies.

Recent advancements in electronic packaging and image processing techniques have opened the possibility for optics-based portable eye tracking approaches, but technical and safety hurdles limit safe implementation toward wearable applications. Here, we introduce a fully wearable, wireless soft electronic system that offers a portable, highly sensitive tracking of eye movements (vergence) via the combination of skin-conformal sensors and a virtual reality system. Advancement of material processing and printing technologies based on aerosol jet printing enables reliable manufacturing of skin-like sensors, while the flexible hybrid circuit based on elastomer and chip integration allows comfortable integration with a user's head. Analytical and computational study of a data classification algorithm provides a highly accurate tool for real-time detection and classification of ocular motions. In vivo demonstration with 14 human subjects captures the potential of the wearable electronics as a portable therapy system, whose minimized form factor facilitates seamless interplay with traditional wearable hardware.

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.

Soft Materials, Stretchable Mechanics, and Optimized Designs for Body-Wearable Compliant Antennas.

Among the various methods to develop flexible wearable antennas, a serpentine, mesh structure has been a great interest because of its mechanical reliability upon applied strain. However, there is still a significant lack of design guidelines for the open-mesh concept that account for both material and electromagnetic (EM) properties of antennas. In this work, we introduce a comprehensive study of materials, mechanics, fabrication, and system integration for the development of stretchable dipole and patch antennas that have networks of two-dimensional serpentine patterns. A set of computational modeling and experimental validation of open-mesh structures provides the key design guidelines to offer the maximum mechanical stretchability and minimum effective moduli of wearable antennas. Integration of the thin-film antenna traces with various substrates captures the versatility of the deterministic fabrication and material transfer printing methods. The influence of antenna stretching on the EM properties, including return loss, electric and magnetic fields, and far-field radiation patterns, is investigated. EM characterization with mechanical stretching results in different properties of fabricated antennas. The simulation study of specific absorption rates shows a potential for safe applications of dipole and patch stretchable antennas on the human skin.