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.

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.

Flexible low-profile external ventricular drain catheter for real-time brain monitoring.

External ventricular drainage is one of the most common neurosurgical procedures in the world for acute hydrocephalus, which must be performed carefully by a neurosurgeon. Although various neuromonitoring external ventricular drain (EVD) catheters have been utilized, they still suffer from rigidity and bulkiness to mitigate post-EVD placement trauma. Here, we introduce a flexible and low-profile smart EVD catheter using a class of technologies with sensitive electrical materials, seamless integration, and flexible mechanics, which serves as a highly soft and minimally invasive device to monitor electrical brain signals. This device reliably captures biopotentials in real time while exhibiting remarkable flexibility and reliability. The seamless integration of its sensory system promises a minimally invasive EVD placement on brain tissue. This work validates the device's distinct characteristics and performances through in vitro experiments and computational analysis. Collectively, this device's exceptional patient- and user-friendly attributes highlight its potential as one of the most practical EVD catheters.

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.

Synthesis of shape-programmable elastomer for a bioresorbable, wireless nerve stimulator.

Materials that have the ability to manipulate shapes in response to stimuli such as heat, light, humidity and magnetism offer a means for versatile, sophisticated functions in soft robotics or biomedical implants, while such a reactive transformation has certain drawbacks including high operating temperatures, inherent rigidity and biological hazard. Herein, we introduce biodegradable, self-adhesive, shape-transformable poly (L-lactide-co-ε-caprolactone) (BSS-PLCL) that can be triggered via thermal stimulation near physiological temperature (∼38 °C). Chemical inspections confirm the fundamental properties of the synthetic materials in diverse aspects, and study on mechanical and biochemical characteristics validates exceptional stretchability up to 800 % and tunable dissolution behaviors under biological conditions. The integration of the functional polymer with a bioresorbable electronic system highlights potential for a wide range of biomedical applications.

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.

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.

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.

Cloud-Integrated Smart Nanomembrane Wearables for Remote Wireless Continuous Health Monitoring of Postpartum Women.

Noncommunicable diseases (NCD), such as obesity, diabetes, and cardiovascular disease, are defining healthcare challenges of the 21st century. Medical infrastructure, which for decades sought to reduce the incidence and severity of communicable diseases, has proven insufficient in meeting the intensive, long-term monitoring needs of many NCD disease patient groups. In addition, existing portable devices with rigid electronics are still limited in clinical use due to unreliable data, limited functionality, and lack of continuous measurement ability. Here, a wearable system for at-home cardiovascular monitoring of postpartum women-a group with urgently unmet NCD needs in the United States-using a cloud-integrated soft sternal device with conformal nanomembrane sensors is introduced. A supporting mobile application provides device data to a custom cloud architecture for real-time waveform analytics, including medical device-grade blood pressure prediction via deep learning, and shares the results with both patient and clinician to complete a robust and highly scalable remote monitoring ecosystem. Validated in a month-long clinical study with 20 postpartum Black women, the system demonstrates its ability to remotely monitor existing disease progression, stratify patient risk, and augment clinical decision-making by informing interventions for groups whose healthcare needs otherwise remain unmet in standard clinical practice.

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.

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.

Skin preparation-free, stretchable microneedle adhesive patches for reliable electrophysiological sensing and exoskeleton robot control.

High-fidelity and comfortable recording of electrophysiological (EP) signals with on-the-fly setup is essential for health care and human-machine interfaces (HMIs). Microneedle electrodes allow direct access to the epidermis and eliminate time-consuming skin preparation. However, existing microneedle electrodes lack elasticity and reliability required for robust skin interfacing, thereby making long-term, high-quality EP sensing challenging during body movement. Here, we introduce a stretchable microneedle adhesive patch (SNAP) providing excellent skin penetrability and a robust electromechanical skin interface for prolonged and reliable EP monitoring under varying skin conditions. Results demonstrate that the SNAP can substantially reduce skin contact impedance under skin contamination and enhance wearing comfort during motion, outperforming gel and flexible microneedle electrodes. Our wireless SNAP demonstration for exoskeleton robot control shows its potential for highly reliable HMIs, even under time-dynamic skin conditions. We envision that the SNAP will open new opportunities for wearable EP sensing and its real-world applications in HMIs.

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.

Advances in Wireless, Batteryless, Implantable Electronics for Real-Time, Continuous Physiological Monitoring.

This review summarizes recent progress in developing wireless, batteryless, fully implantable biomedical devices for real-time continuous physiological signal monitoring, focusing on advancing human health care. Design considerations, such as biological constraints, energy sourcing, and wireless communication, are discussed in achieving the desired performance of the devices and enhanced interface with human tissues. In addition, we review the recent achievements in materials used for developing implantable systems, emphasizing their importance in achieving multi-functionalities, biocompatibility, and hemocompatibility. The wireless, batteryless devices offer minimally invasive device insertion to the body, enabling portable health monitoring and advanced disease diagnosis. Lastly, we summarize the most recent practical applications of advanced implantable devices for human health care, highlighting their potential for immediate commercialization and clinical uses.

Soft implantable printed bioelectronic system for wireless continuous monitoring of restenosis.

Atherosclerosis is a prominent cause of coronary artery disease and broader cardiovascular diseases, the leading cause of death worldwide. Angioplasty and stenting is a common treatment, but in-stent restenosis, where the artery re-narrows, is a frequent complication. Restenosis is detected through invasive procedures and is not currently monitored frequently for patients. Here, we report an implantable vascular bioelectronic device using a newly developed miniaturized strain sensor via microneedle printing methods. A capillary-based printing system achieves high-resolution patterning of a soft, capacitive strain sensor. Ink and printing parameters are evaluated to create a fully printed sensor, while sensor design and sensing mechanism are studied to enhance sensitivity and minimize sensor size. The sensor is integrated with a wireless vascular stent, offering a biocompatible, battery-free, wireless monitoring system compatible with conventional catheterization procedures. The vascular sensing system is demonstrated in an artery model for monitoring restenosis progression. Collectively, the artery implantable bioelectronic system shows the potential for wireless, real-time monitoring of various cardiovascular diseases and stent-integrated sensing/treatments.

Easy-To-Wear Auxetic SMA Knot-Architecture for Spatiotemporal and Multimodal Haptic Feedbacks.

Wearable haptic interfaces prioritize user comfort, but also value the ability to provide diverse feedback patterns for immersive interactions with the virtual or augmented reality. Here, to provide both comfort and diverse tactile feedback, an easy-to-wear and multimodal wearable haptic auxetic fabric (WHAF) is prepared by knotting shape-memory alloy wires into an auxetic-structured fabric. This unique meta-design allows the WHAF to completely expand and contract in 3D, providing superior size-fitting and shape-fitting capabilities. Additionally, a microscale thin layer of Parylene is coated on the surface to create electrically separated zones within the WHAF, featuring zone-specified actuation for conveying diverse spatiotemporal information to users with using the WHAF alone. Depending on the body part it is worn on, the WHAF conveys either cutaneous or kinesthetic feedback, thus, working as a multimodal wearable haptic interface. As a result, when worn on the forearm, the WHAF intuitively provides spatiotemporal information to users during hands-free navigation and teleoperation in virtual reality, and when worn on the elbow, the WHAF guides users to reach the desired elbow flexion, like a personal exercise advisor.

Outdoor Worker Stress Monitoring Electronics with Nanofabric Radiative Cooler-Based Thermal Management.

Severe stress endangers outdoor workers who are in an exceedingly hot workplace. Although recent studies quantify stress levels on the human skin, they still rely on rigid, bulky sensor modules, causing data loss from motion artifacts and limited field-deployability for continuous health monitoring. Moreover, no prior work shows a wearable device that can endure heat exposure while showing continuous monitoring of a subject's stress under realistic working environments. Herein, a soft, field-deployable, wearable bioelectronic system is introduced for detecting outdoor workers' stress levels with negligible motion artifacts and controllable thermal management. A nanofabric radiative cooler (NFRC) and miniaturized sensors with a nanomembrane soft electronic platform are integrated to measure stable electrodermal activities and temperature in hot outdoor conditions. The NFRC exhibits outstanding cooling performance in sub-ambient air with high solar reflectivity and high thermal emissivity. The integrated wearable device with all embedded electronic components and the NFRC shows a lower temperature (41.1%) in sub-ambient air than the NFRC-less device while capturing improved operation time (18.2%). In vivo human study of the bioelectronics with agricultural activities demonstrates the device's capability for portable, continuous, real-time health monitoring of outdoor workers with field deployability.

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.

Fluorescent-based biodegradable microneedle sensor array for tether-free continuous glucose monitoring with smartphone application.

Continuous glucose monitoring (CGM) allows patients with diabetes to manage critical disease effectively and autonomously and prevent exacerbation. A painless, wireless, compact, and minimally invasive device that can provide CGM is essential for monitoring the health conditions of freely moving patients with diabetes. Here, we propose a glucose-responsive fluorescence-based highly sensitive biodegradable microneedle CGM system. These ultrathin and ultralight microneedle sensor arrays continuously and precisely monitored glucose concentration in the interstitial fluid with minimally invasive, pain-free, wound-free, and skin inflammation-free outcomes at various locations and thicknesses of the skin. Bioresorbability in the body without a need for device removal after use was a key characteristic of the microneedle glucose sensor. We demonstrated the potential long-term use of the bioresorbable device by applying the tether-free CGM system, thus confirming the successful detection of glucose levels based on changes in fluorescence intensity. In addition, this microneedle glucose sensor with a user-friendly designed home diagnosis system using mobile applications and portable accessories offers an advance in CGM and its applicability to other bioresorbable, wearable, and implantable monitoring device technology.

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.