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 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 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.

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.

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.

Ethical Considerations of Wearable Technologies in Human Research.

Wearable technologies hold great promise for disease diagnosis and patient care. Despite the flourishing research activities in this field, only a handful of wearable devices are commercialized and cleared for medical usage. The successful translation of current proof-of-concept prototypes requires extensive in-human testing. There is a lag between current standards and operation protocols to guide the responsible and ethical conduct of researchers in such in-human studies and the rapid development of the field. This essay presents relevant ethical concerns in early-stage human research from a researcher's perspective.

Spray-on magnetic skin for robotic actuation.

A minimalist robot construction strategy offers versatility and compatibility in actuating diverse objects on demand.

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.

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.