A physicochemical-sensing electronic skin for stress response monitoring.

Approaches to quantify stress responses typically rely on subjective surveys and questionnaires. Wearable sensors can potentially be used to continuously monitor stress-relevant biomarkers. However, the biological stress response is spread across the nervous, endocrine, and immune systems, and the capabilities of current sensors are not sufficient for condition-specific stress response evaluation. Here we report an electronic skin for stress response assessment that non-invasively monitors three vital signs (pulse waveform, galvanic skin response and skin temperature) and six molecular biomarkers in human sweat (glucose, lactate, uric acid, sodium ions, potassium ions and ammonium). We develop a general approach to prepare electrochemical sensors that relies on analogous composite materials for stabilizing and conserving sensor interfaces. The resulting sensors offer long-term sweat biomarker analysis of over 100 hours with high stability. We show that the electronic skin can provide continuous multimodal physicochemical monitoring over a 24-hour period and during different daily activities. With the help of a machine learning pipeline, we also show that the platform can differentiate three stressors with an accuracy of 98.0%, and quantify psychological stress responses with a confidence level of 98.7%.

A wearable aptamer nanobiosensor for non-invasive female hormone monitoring.

Personalized monitoring of female hormones (for example, oestradiol) is of great interest in fertility and women's health. However, existing approaches usually require invasive blood draws and/or bulky analytical laboratory equipment, making them hard to implement at home. Here we report a skin-interfaced wearable aptamer nanobiosensor based on target-induced strand displacement for automatic and non-invasive monitoring of oestradiol via in situ sweat analysis. The reagentless, amplification-free and 'signal-on' detection approach coupled with a gold nanoparticle-MXene-based detection electrode offers extraordinary sensitivity with an ultra-low limit of detection of 0.14 pM. This fully integrated system is capable of autonomous sweat induction at rest via iontophoresis, precise microfluidic sweat sampling controlled via capillary bursting valves, real-time oestradiol analysis and calibration with simultaneously collected multivariate information (that is, temperature, pH and ionic strength), as well as signal processing and wireless communication with a user interface (for example, smartphone). We validated the technology in human participants. Our data indicate a cyclical fluctuation in sweat oestradiol during menstrual cycles, and a high correlation between sweat and blood oestradiol was identified. Our study opens up the potential for wearable sensors for non-invasive, personalized reproductive hormone monitoring.

Direct methane protonic ceramic fuel cells with self-assembled Ni-Rh bimetallic catalyst.

Direct methane protonic ceramic fuel cells are promising electrochemical devices that address the technical and economic challenges of conventional ceramic fuel cells. However, Ni, a catalyst of protonic ceramic fuel cells exhibits sluggish reaction kinetics for CH4 conversion and a low tolerance against carbon-coking, limiting its wider applications. Herein, we introduce a self-assembled Ni-Rh bimetallic catalyst that exhibits a significantly high CH4 conversion and carbon-coking tolerance. It enables direct methane protonic ceramic fuel cells to operate with a high maximum power density of ~0.50 W·cm-2 at 500 °C, surpassing all other previously reported values from direct methane protonic ceramic fuel cells and even solid oxide fuel cells. Moreover, it allows stable operation with a degradation rate of 0.02%·h-1 at 500 °C over 500 h, which is ~20-fold lower than that of conventional protonic ceramic fuel cells (0.4%·h-1). High-resolution in-situ surface characterization techniques reveal that high-water interaction on the Ni-Rh surface facilitates the carbon cleaning process, enabling sustainable long-term operation.

3D-printed epifluidic electronic skin for machine learning-powered multimodal health surveillance.

The amalgamation of wearable technologies with physiochemical sensing capabilities promises to create powerful interpretive and predictive platforms for real-time health surveillance. However, the construction of such multimodal devices is difficult to be implemented wholly by traditional manufacturing techniques for at-home personalized applications. Here, we present a universal semisolid extrusion-based three-dimensional printing technology to fabricate an epifluidic elastic electronic skin (e3-skin) with high-performance multimodal physiochemical sensing capabilities. We demonstrate that the e3-skin can serve as a sustainable surveillance platform to capture the real-time physiological state of individuals during regular daily activities. We also show that by coupling the information collected from the e3-skin with machine learning, we were able to predict an individual's degree of behavior impairments (i.e., reaction time and inhibitory control) after alcohol consumption. The e3-skin paves the path for future autonomous manufacturing of customizable wearable systems that will enable widespread utility for regular health monitoring and clinical applications.

Physically defined long-term and short-term synapses for the development of reconfigurable analog-type operators capable of performing health care tasks.

Extracting valuable information from the overflowing data is a critical yet challenging task. Dealing with high volumes of biometric data, which are often unstructured, nonstatic, and ambiguous, requires extensive computer resources and data specialists. Emerging neuromorphic computing technologies that mimic the data processing properties of biological neural networks offer a promising solution for handling overflowing data. Here, the development of an electrolyte-gated organic transistor featuring a selective transition from short-term to long-term plasticity of the biological synapse is presented. The memory behaviors of the synaptic device were precisely modulated by restricting ion penetration through an organic channel via photochemical reactions of the cross-linking molecules. Furthermore, the applicability of the memory-controlled synaptic device was verified by constructing a reconfigurable synaptic logic gate for implementing a medical algorithm without further weight-update process. Last, the presented neuromorphic device demonstrated feasibility to handle biometric information with various update periods and perform health care tasks.

A wireless patch for the monitoring of C-reactive protein in sweat.

The quantification of protein biomarkers in blood at picomolar-level sensitivity requires labour-intensive incubation and washing steps. Sensing proteins in sweat, which would allow for point-of-care monitoring, is hindered by the typically large interpersonal and intrapersonal variations in its composition. Here we report the design and performance of a wearable and wireless patch for the real-time electrochemical detection of the inflammatory biomarker C-reactive (CRP) protein in sweat. The device integrates iontophoretic sweat extraction, microfluidic channels for sweat sampling and for reagent routing and replacement, and a graphene-based sensor array for quantifying CRP (via an electrode functionalized with anti-CRP capture antibodies-conjugated gold nanoparticles), ionic strength, pH and temperature for the real-time calibration of the CRP sensor. In patients with chronic obstructive pulmonary disease, with active or past infections or who had heart failure, the elevated concentrations of CRP measured via the patch correlated well with the protein's levels in serum. Wearable biosensors for the real-time sensitive analysis of inflammatory proteins in sweat may facilitate the management of chronic diseases.

A Computationally Assisted Approach for Designing Wearable Biosensors toward Non-Invasive Personalized Molecular Analysis.

Wearable sweat sensors have the potential to revolutionize precision medicine as they can non-invasively collect molecular information closely associated with an individual's health status. However, the majority of clinically relevant biomarkers cannot be continuously detected in situ using existing wearable approaches. Molecularly imprinted polymers (MIPs) are a promising candidate to address this challenge but haven't yet gained widespread use due to their complex design and optimization process yielding variable selectivity. Here, QuantumDock is introduced, an automated computational framework for universal MIP development toward wearable applications. QuantumDock utilizes density functional theory to probe molecular interactions between monomers and the target/interferent molecules to optimize selectivity, a fundamentally limiting factor for MIP development toward wearable sensing. A molecular docking approach is employed to explore a wide range of known and unknown monomers, and to identify the optimal monomer/cross-linker choice for subsequent MIP fabrication. Using an essential amino acid phenylalanine as the exemplar, experimental validation of QuantumDock is performed successfully using solution-synthesized MIP nanoparticles coupled with ultraviolet-visible spectroscopy. Moreover, a QuantumDock-optimized graphene-based wearable device is designed that can perform autonomous sweat induction, sampling, and sensing. For the first time, wearable non-invasive phenylalanine monitoring is demonstrated in human subjects toward personalized healthcare applications.

Skin-Interfaced Wearable Sweat Sensors for Precision Medicine.

Wearable sensors hold great potential in empowering personalized health monitoring, predictive analytics, and timely intervention toward personalized healthcare. Advances in flexible electronics, materials science, and electrochemistry have spurred the development of wearable sweat sensors that enable the continuous and noninvasive screening of analytes indicative of health status. Existing major challenges in wearable sensors include: improving the sweat extraction and sweat sensing capabilities, improving the form factor of the wearable device for minimal discomfort and reliable measurements when worn, and understanding the clinical value of sweat analytes toward biomarker discovery. This review provides a comprehensive review of wearable sweat sensors and outlines state-of-the-art technologies and research that strive to bridge these gaps. The physiology of sweat, materials, biosensing mechanisms and advances, and approaches for sweat induction and sampling are introduced. Additionally, design considerations for the system-level development of wearable sweat sensing devices, spanning from strategies for prolonged sweat extraction to efficient powering of wearables, are discussed. Furthermore, the applications, data analytics, commercialization efforts, challenges, and prospects of wearable sweat sensors for precision medicine are discussed.

A stretchable wireless wearable bioelectronic system for multiplexed monitoring and combination treatment of infected chronic wounds.

Chronic nonhealing wounds are one of the major and rapidly growing clinical complications all over the world. Current therapies frequently require emergent surgical interventions, while abuse and misapplication of therapeutic drugs often lead to an increased morbidity and mortality rate. Here, we introduce a wearable bioelectronic system that wirelessly and continuously monitors the physiological conditions of the wound bed via a custom-developed multiplexed multimodal electrochemical biosensor array and performs noninvasive combination therapy through controlled anti-inflammatory antimicrobial treatment and electrically stimulated tissue regeneration. The wearable patch is fully biocompatible, mechanically flexible, stretchable, and can conformally adhere to the skin wound throughout the entire healing process. Real-time metabolic and inflammatory monitoring in a series of preclinical in vivo experiments showed high accuracy and electrochemical stability of the wearable patch for multiplexed spatial and temporal wound biomarker analysis. The combination therapy enabled substantially accelerated cutaneous chronic wound healing in a rodent model.

An autonomous wearable biosensor powered by a perovskite solar cell.

Wearable sweat sensors can potentially be used to continuously and non-invasively monitor physicochemical biomarkers that contain information related to disease diagnostics and fitness tracking. However, the development of such autonomous sensors faces a number of challenges including achieving steady sweat extraction for continuous and prolonged monitoring, and addressing the high power demands of multifunctional and complex analysis. Here we report an autonomous wearable biosensor that is powered by a perovskite solar cell and can provide continuous and non-invasive metabolic monitoring. The device uses a flexible quasi-two-dimensional perovskite solar cell module that provides ample power under outdoor and indoor illumination conditions (power conversion efficiency exceeding 31% under indoor light illumination). We show that the wearable device can continuously collect multimodal physicochemical data - glucose, pH, sodium ions, sweat rate, and skin temperature - across indoor and outdoor physical activities for over 12 hours.

A wearable electrochemical biosensor for the monitoring of metabolites and nutrients.

Wearable non-invasive biosensors for the continuous monitoring of metabolites in sweat can detect a few analytes at sufficiently high concentrations, typically during vigorous exercise so as to generate sufficient quantity of the biofluid. Here we report the design and performance of a wearable electrochemical biosensor for the continuous analysis, in sweat during physical exercise and at rest, of trace levels of multiple metabolites and nutrients, including all essential amino acids and vitamins. The biosensor consists of graphene electrodes that can be repeatedly regenerated in situ, functionalized with metabolite-specific antibody-like molecularly imprinted polymers and redox-active reporter nanoparticles, and integrated with modules for iontophoresis-based sweat induction, microfluidic sweat sampling, signal processing and calibration, and wireless communication. In volunteers, the biosensor enabled the real-time monitoring of the intake of amino acids and their levels during physical exercise, as well as the assessment of the risk of metabolic syndrome (by correlating amino acid levels in serum and sweat). The monitoring of metabolites for the early identification of abnormal health conditions could facilitate applications in precision nutrition.

All-printed soft human-machine interface for robotic physicochemical sensing.

Ultrasensitive multimodal physicochemical sensing for autonomous robotic decision-making has numerous applications in agriculture, security, environmental protection, and public health. Previously reported robotic sensing technologies have primarily focused on monitoring physical parameters such as pressure and temperature. Integrating chemical sensors for autonomous dry-phase analyte detection on a robotic platform is rather extremely challenging and substantially underdeveloped. Here, we introduce an artificial intelligence-powered multimodal robotic sensing system (M-Bot) with an all-printed mass-producible soft electronic skin-based human-machine interface. A scalable inkjet printing technology with custom-developed nanomaterial inks was used to manufacture flexible physicochemical sensor arrays for electrophysiology recording, tactile perception, and robotic sensing of a wide range of hazardous materials including nitroaromatic explosives, pesticides, nerve agents, and infectious pathogens such as SARS-CoV-2. The M-Bot decodes the surface electromyography signals collected from the human body through machine learning algorithms for remote robotic control and can perform in situ threat compound detection in extreme or contaminated environments with user-interactive tactile and threat alarm feedback. The printed electronic skin-based robotic sensing technology can be further generalized and applied to other remote sensing platforms. Such diversity was validated on an intelligent multimodal robotic boat platform that can efficiently track the source of trace amounts of hazardous compounds through autonomous and intelligent decision-making algorithms. This fully printed human-machine interactive multimodal sensing technology could play a crucial role in designing future intelligent robotic systems and can be easily reconfigured toward numerous practical wearable and robotic applications.

Wearable electrochemical biosensors in North America.

Tremendous research and commercialization efforts around the world are focused on developing novel wearable electrochemical biosensors that can noninvasively and continuously screen for biochemical markers in body fluids for the prognosis, diagnosis and management of diseases, as well as the monitoring of fitness. Researchers in North America are leading the development of innovative wearable platforms that can comfortably comply to the human body and efficiently sample fluids such as sweat, interstitial fluids, tear and saliva for the electrochemical detection of biomarkers through various sensing approaches such as potentiometric ion selective electrodes and amperometric enzymatic sensors. We start this review with a historical timeline overviewing the major milestones in the development of wearable electrochemical sensors by North American institutions. We then describe how such research efforts have led to pioneering developments and are driving the advancement and commercialization of wearable electrochemical sensors: from minimally invasive continuous glucose monitors for chronic disease management to non-invasive sweat electrolyte sensors for dehydration monitoring in fitness applications. While many countries across the globe have contributed significantly to this rapidly emerging field, their contributions are beyond the scope of this review. Furthermore, we share our perspective on the promising future of wearable electrochemical sensors in applications spanning from remote and personalized healthcare to wellness.

Morphological keys for identifying long-tailed gorals (Naemorhedus caudatus) and population composition in the Osaek Region of South Korea.

The objectives of this study were to select morphological keys for the identification of individual endangered long-tailed gorals through analysis of photographic data and to use these morphological keys to determine the number and population composition of gorals living in the Osaek Region of Seoraksan National Park. Amongst 8149 photos taken using 73 cameras in the Osaek Region, 2057 photos of faces and horns were analysed. The presence and absence of horns, shape of the horns, proportion of the ring to the length of the horn and facial colour pattern were selected as morphological keys to identify individual gorals. To verify the accuracy of the morphological keys for identifying gorals, a blind test was performed on gorals residing in the sanctuary of the Yanggu Goral Restoration Center. The test revealed that the population and age of gorals were discerned correctly by the morphological keys, but there was a 12.5% error in discriminating between sexes in gorals aged over 10 years. Fifty-six gorals were identified from 2057 pictures, based on the morphological keys and methods developed in this study. The population of 56 individuals consisted of 43 individuals aged over 2 years (subadult or adult) and 13 offspring aged less than 2 years, with a ratio of 3.3:1. Of the total 56 individuals, 45% were adults aged 10 years or older, 18% were adults aged 3-10 years, 7% were subadults aged 2-3 years, 23% were offspring aged less than 2 years and 7% were individuals aged 2 years or older, whose age and sex could not be confirmed. The sex ratio of males to females was 1.17:1, with a corrected sex ratio of 1:1 considering the 12.5% error rate for gorals aged over 10 years, amongst the 39 gorals aged over 2 years.

SARS-CoV-2 RapidPlex: A Graphene-Based Multiplexed Telemedicine Platform for Rapid and Low-Cost COVID-19 Diagnosis and Monitoring.

The COVID-19 pandemic is an ongoing global challenge for public health systems. Ultrasensitive and early identification of infection is critical in preventing widespread COVID-19 infection by presymptomatic and asymptomatic individuals, especially in the community and in-home settings. We demonstrate a multiplexed, portable, wireless electrochemical platform for ultra-rapid detection of COVID-19: the SARS-CoV-2 RapidPlex. It detects viral antigen nucleocapsid protein, IgM and IgG antibodies, as well as the inflammatory biomarker C-reactive protein, based on our mass-producible laser-engraved graphene electrodes. We demonstrate ultrasensitive, highly selective, and rapid electrochemical detection in the physiologically relevant ranges. We successfully evaluated the applicability of our SARS-CoV-2 RapidPlex platform with COVID-19-positive and COVID-19-negative blood and saliva samples. Based on this pilot study, our multiplexed immunosensor platform may allow for high-frequency at-home testing for COVID-19 telemedicine diagnosis and monitoring.

Wireless battery-free wearable sweat sensor powered by human motion.

Wireless wearable sweat biosensors have gained huge traction due to their potential for noninvasive health monitoring. As high energy consumption is a crucial challenge in this field, efficient energy harvesting from human motion represents an attractive approach to sustainably power future wearables. Despite intensive research activities, most wearable energy harvesters suffer from complex fabrication procedures, poor robustness, and low power density, making them unsuitable for continuous biosensing. Here, we propose a highly robust, mass-producible, and battery-free wearable platform that efficiently extracts power from body motion through a flexible printed circuit board (FPCB)-based freestanding triboelectric nanogenerator (FTENG). The judiciously engineered FTENG displays a high power output of ~416 mW m-2 Through seamless system integration and efficient power management, we demonstrate a battery-free triboelectrically driven system that is able to power multiplexed sweat biosensors and wirelessly transmit data to the user interfaces through Bluetooth during on-body human trials.

Biofuel-powered soft electronic skin with multiplexed and wireless sensing for human-machine interfaces.

Existing electronic skin (e-skin) sensing platforms are equipped to monitor physical parameters using power from batteries or near-field communication. For e-skins to be applied in the next generation of robotics and medical devices, they must operate wirelessly and be self-powered. However, despite recent efforts to harvest energy from the human body, self-powered e-skin with the ability to perform biosensing with Bluetooth communication are limited because of lack of a continuous energy source and limited power efficiency. Here, we report a flexible and fully perspiration-powered integrated electronic skin (PPES) for multiplexed metabolic sensing in situ. The battery-free e-skin contains multimodal sensors and highly efficient lactate biofuel cells that use a unique integration of zero- to three-dimensional nanomaterials to achieve high power intensity and long-term stability. The PPES delivered a record-breaking power density of 3.5 milliwatt-centimeter-2 for biofuel cells in untreated human body fluids (human sweat) and displayed a very stable performance during a 60-hour continuous operation. It selectively monitored key metabolic analytes (e.g., urea, NH4 +, glucose, and pH) and the skin temperature during prolonged physical activities and wirelessly transmitted the data to the user interface using Bluetooth. The PPES was also able to monitor muscle contraction and work as a human-machine interface for human- prosthesis walking.

Investigation of cortisol dynamics in human sweat using a graphene-based wireless mHealth system.

Understanding and assessing endocrine response to stress is crucial to human performance analysis, stress-related disorder diagnosis, and mental health monitoring. Current approaches for stress monitoring are largely based on questionnaires, which could be very subjective. To avoid stress-inducing blood sampling and to realize continuous, non-invasive, and real-time stress analysis at the molecular levels, we investigate the dynamics of a stress hormone, cortisol, in human sweat using an integrated wireless sensing device. Highly sensitive, selective, and efficient cortisol sensing is enabled by a flexible sensor array that exploits the exceptional performance of laser-induced graphene for electrochemical sensing. Herein, we report the first cortisol diurnal cycle and the dynamic stress response profile constructed from human sweat. Our pilot study demonstrates a strong empirical correlation between serum and sweat cortisol, revealing exciting opportunities offered by sweat analysis toward non-invasive dynamic stress monitoring via wearable and portable sensing platforms.

A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat.

Wearable sweat sensors have the potential to provide continuous measurements of useful biomarkers. However, current sensors cannot accurately detect low analyte concentrations, lack multimodal sensing or are difficult to fabricate at large scale. We report an entirely laser-engraved sensor for simultaneous sweat sampling, chemical sensing and vital-sign monitoring. We demonstrate continuous detection of temperature, respiration rate and low concentrations of uric acid and tyrosine, analytes associated with diseases such as gout and metabolic disorders. We test the performance of the device in both physically trained and untrained subjects under exercise and after a protein-rich diet. We also evaluate its utility for gout monitoring in patients and healthy controls through a purine-rich meal challenge. Levels of uric acid in sweat were higher in patients with gout than in healthy individuals, and a similar trend was observed in serum.

Wearable and Implantable Electronics: Moving toward Precision Therapy.

Soft wearable and implantable electronic systems have attracted tremendous attention due to their flexibility, conformability, and biocompatibility. Such favorable features are critical for reliably monitoring key biomedical and physiological information (including both biophysical and biochemical signals) and effective treatment and management of specific chronic diseases. Miniaturized, fully integrated self-powered bioelectronic devices that can harvest energy from the human body represent promising and emerging solutions for long-term, intimate, and personalized therapies. In this Perspective, we offer a brief overview of recent advances in wearable/implantable soft electronic devices and their therapeutic applications ranging from drug delivery to tissue regeneration. We also discuss the key opportunities, challenges, and future directions in this important area needed to fulfill the vision of personalized medicine.