A skin-interfaced, miniaturized platform for triggered induction, capture and colorimetric multicomponent analysis of microliter volumes of sweat.

Eccrine sweat can serve as a source of biomarkers for assessing physiological health and nutritional balance, for tracking loss of essential species from the body and for evaluating exposure to hazardous substances. The growing interest in this relatively underexplored class of biofluid arises in part from its non-invasive ability for capture and analysis. The simplest devices, and the only ones that are commercially available, exploit soft microfluidic constructs and colorimetric assays with purely passive modes of operation. The most sophisticated platforms exploit batteries, electronic components and radio hardware for inducing sweat, for electrochemical evaluation of its content and for wireless transmission of this information. The work reported here introduces a technology that combines the advantages of these two different approaches, in the form of a cost-effective, easy-to-use device that supports on-demand evaluation of multiple biomarkers in sweat. This flexible, skin-interfaced, miniaturized system incorporates a hydrogel that contains an approved drug to activate eccrine sweat glands, electrodes and a simple circuit and battery to delivery this drug by iontophoresis through the surface of the skin, microfluidic channels and microreservoirs to capture the induced sweat, and multiple colorimetric assays to evaluate the concentrations of chloride, zinc, and iron. As demonstrated in healthy human participants monitored before and after a meal, such devices yield results that match those of traditional laboratory analysis techniques. Clinical studies that involve cystic fibrosis pediatric patients illustrate the use of this technology as a simple, painless, and reliable alternative to traditional hospital systems for measurements of sweat chloride.

Early Prediction of Poststroke Rehabilitation Outcomes Using Wearable Sensors.

OBJECTIVE: Inpatient rehabilitation represents a critical setting for stroke treatment, providing intensive, targeted therapy and task-specific practice to minimize a patient's functional deficits and facilitate their reintegration into the community. However, impairment and recovery vary greatly after stroke, making it difficult to predict a patient's future outcomes or response to treatment. In this study, the authors examined the value of early-stage wearable sensor data to predict 3 functional outcomes (ambulation, independence, and risk of falling) at rehabilitation discharge. METHODS: Fifty-five individuals undergoing inpatient stroke rehabilitation participated in this study. Supervised machine learning classifiers were retrospectively trained to predict discharge outcomes using data collected at hospital admission, including patient information, functional assessment scores, and inertial sensor data from the lower limbs during gait and/or balance tasks. Model performance was compared across different data combinations and was benchmarked against a traditional model trained without sensor data. RESULTS: For patients who were ambulatory at admission, sensor data improved the predictions of ambulation and risk of falling (with weighted F1 scores increasing by 19.6% and 23.4%, respectively) and maintained similar performance for predictions of independence, compared to a benchmark model without sensor data. The best-performing sensor-based models predicted discharge ambulation (community vs household), independence (high vs low), and risk of falling (normal vs high) with accuracies of 84.4%, 68.8%, and 65.9%, respectively. Most misclassifications occurred with admission or discharge scores near the classification boundary. For patients who were nonambulatory at admission, sensor data recorded during simple balance tasks did not offer predictive value over the benchmark models. CONCLUSION: These findings support the continued investigation of wearable sensors as an accessible, easy-to-use tool to predict the functional recovery after stroke. IMPACT: Accurate, early prediction of poststroke rehabilitation outcomes from wearable sensors would improve our ability to deliver personalized, effective care and discharge planning in the inpatient setting and beyond.

3D-printed epidermal sweat microfluidic systems with integrated microcuvettes for precise spectroscopic and fluorometric biochemical assays.

Systems for capture, storage and analysis of eccrine sweat can provide insights into physiological health status, quantify losses of water, electrolytes, amino acids and/or other essential species, and identify exposures to adverse environmental species or illicit drugs. Recent advances in materials and device designs serve as the basis for skin-compatible classes of microfluidic platforms and in situ colorimetric assays for precise assessments of sweat rate, sweat loss and concentrations of wide-ranging types of biomarkers in sweat. This paper presents a set of findings that enhances the performance of these systems through the use of microfluidic networks, integrated valves and microscale optical cuvettes formed by three dimensional printing in hard/soft hybrid materials systems, for accurate spectroscopic and fluorometric assays. Field studies demonstrate the capability of these microcuvette systems to evaluate the concentrations of copper, chloride, and glucose in sweat, along with the pH of sweat, with laboratory-grade accuracy and sensitivity.

A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals.

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals.

Sweat as a diagnostic biofluid.

Skin-interfaced microfluidic systems help assess health status and chemical exposure.

Wearable Sensors Improve Prediction of Post-Stroke Walking Function Following Inpatient Rehabilitation.

OBJECTIVE: A primary goal of acute stroke rehabilitation is to maximize functional recovery and help patients reintegrate safely in the home and community. However, not all patients have the same potential for recovery, making it difficult to set realistic therapy goals and to anticipate future needs for short- or long-term care. The objective of this study was to test the value of high-resolution data from wireless, wearable motion sensors to predict post-stroke ambulation function following inpatient stroke rehabilitation. METHOD: Supervised machine learning algorithms were trained to classify patients as either household or community ambulators at discharge based on information collected upon admission to the inpatient facility (N=33-35). Inertial measurement unit (IMU) sensor data recorded from the ankles and the pelvis during a brief walking bout at admission (10 meters, or 60 seconds walking) improved the prediction of discharge ambulation ability over a traditional prediction model based on patient demographics, clinical information, and performance on standardized clinical assessments. RESULTS: Models incorporating IMU data were more sensitive to patients who changed ambulation category, improving the recall of community ambulators at discharge from 85% to 89-93%. CONCLUSIONS: This approach demonstrates significant potential for the early prediction of post-rehabilitation walking outcomes in patients with stroke using small amounts of data from three wearable motion sensors. CLINICAL IMPACT: Accurately predicting a patient's functional recovery early in the rehabilitation process would transform our ability to design personalized care strategies in the clinic and beyond. This work contributes to the development of low-cost, clinically-implementable prognostic tools for data-driven stroke treatment.

Translational gaps and opportunities for medical wearables in digital health.

A confluence of advances in biosensor technologies, enhancements in health care delivery mechanisms, and improvements in machine learning, together with an increased awareness of remote patient monitoring, has accelerated the impact of digital health across nearly every medical discipline. Medical grade wearables-noninvasive, on-body sensors operating with clinical accuracy-will play an increasingly central role in medicine by providing continuous, cost-effective measurement and interpretation of physiological data relevant to patient status and disease trajectory, both inside and outside of established health care settings. Here, we review current digital health technologies and highlight critical gaps to clinical translation and adoption.

Sweating Rate and Sweat Chloride Concentration of Elite Male Basketball Players Measured With a Wearable Microfluidic Device Versus the Standard Absorbent Patch Method.

The purpose of this study was to compare a wearable microfluidic device and standard absorbent patch in measuring local sweating rate (LSR) and sweat chloride concentration ([Cl-]) in elite basketball players. Participants were 53 male basketball players (25 ± 3 years, 92.2 ± 10.4 kg) in the National Basketball Association's development league. Players were tested during a moderate-intensity, coach-led practice (98 ± 30 min, 21.0 ± 1.2 °C). From the right ventral forearm, sweat was collected using an absorbent patch (3M Tegaderm™ + Pad). Subsequently, LSR and local sweat [Cl-] were determined via gravimetry and ion chromatography. From the left ventral forearm, LSR and local sweat [Cl-] were measured using a wearable microfluidic device and associated smartphone application-based algorithms. Whole-body sweating rate (WBSR) was determined from pre- to postexercise change in body mass corrected for fluid/food intake (ad libitum), urine loss, and estimated respiratory water and metabolic mass loss. The WBSR values predicted by the algorithms in the smartphone application were also recorded. There were no differences between the absorbent patch and microfluidic patch for LSR (1.25 ± 0.91 mg·cm-2·min-1 vs. 1.14 ±0.78 mg·cm-2·min-1, p = .34) or local sweat [Cl-] (30.6 ± 17.3 mmol/L vs. 29.6 ± 19.4 mmol/L, p = .55). There was no difference between measured and predicted WBSR (0.97 ± 0.41 L/hr vs. 0.89 ± 0.35 L/hr, p = .22; 95% limits of agreement = 0.61 L/hr). The wearable microfluidic device provides similar LSR, local sweat [Cl-], and WBSR results compared with standard field-based methods in elite male basketball players during moderate-intensity practices.

A Skin-Interfaced, Miniaturized Microfluidic Analysis and Delivery System for Colorimetric Measurements of Nutrients in Sweat and Supply of Vitamins Through the Skin.

Nutrients play critical roles in maintaining core physiological functions and in preventing diseases. Technologies for delivering these nutrients and for monitoring their concentrations can help to ensure proper nutritional balance. Eccrine sweat is a potentially attractive class of biofluid for monitoring purposes due to the ability to capture sweat easily and noninvasively from nearly any region of the body using skin-integrated microfluidic technologies. Here, a miniaturized system of this type is presented that allows simple, rapid colorimetric assessments of the concentrations of multiple essential nutrients in sweat, simultaneously and without any supporting electronics - vitamin C, calcium, zinc, and iron. A transdermal patch integrated directly with the microfluidics supports passive, sustained delivery of these species to the body throughout a period of wear. Comparisons of measurement results to those from traditional lab analysis methods demonstrate the accuracy and reliability of this platform. On-body tests with human subjects reveal correlations between the time dynamics of concentrations of these nutrients in sweat and those of the corresponding concentrations in blood. Studies conducted before and after consuming certain foods and beverages highlight practical capabilities in monitoring nutritional balance, with strong potential to serve as a basis for guiding personalized dietary choices.

Age-related degradation of tectorial membrane dynamics with loss of CEACAM16.

Studies of genetic disorders of sensorineural hearing loss have been instrumental in delineating mechanisms that underlie the remarkable sensitivity and selectivity that are hallmarks of mammalian hearing. For example, genetic modifications of TECTA and TECTB, which are principal proteins that comprise the tectorial membrane (TM), have been shown to alter auditory thresholds and frequency tuning in ways that can be understood in terms of changes in the mechanical properties of the TM. Here, we investigate effects of genetic modification targeting CEACAM16, a third important TM protein. Loss of CEACAM16 has been recently shown to lead to progressive reductions in sensitivity. Whereas age-related hearing losses have previously been linked to changes in sensory receptor cells, the role of the TM in progressive hearing loss is largely unknown. Here, we show that TM stiffness and viscosity are significantly reduced in adult mice that lack functional CEACAM16 relative to age-matched wild-type controls. By contrast, these same mechanical properties of TMs from juvenile mice that lack functional CEACAM16 are more similar to those of wild-type mice. Thus, changes in hearing phenotype align with changes in TM material properties and can be understood in terms of the same TM wave properties that were previously used to characterize modifications of TECTA and TECTB. These results demonstrate that CEACAM16 is essential for maintaining TM mechanical and wave properties, which in turn are necessary for sustaining the remarkable sensitivity and selectivity of mammalian hearing with increasing age.

State of Sweat: Emerging Wearable Systems for Real-Time, Noninvasive Sweat Sensing and Analytics.

Skin-interfaced wearable systems with integrated colorimetric assays, microfluidic channels, and electrochemical sensors offer powerful capabilities for noninvasive, real-time sweat analysis. This Perspective details recent progress in the development and translation of novel wearable sensors for personalized assessment of sweat dynamics and biomarkers, with precise sampling and real-time analysis. Sensor accuracy, system ruggedness, and large-scale deployment in remote environments represent key opportunity areas, enabling broad deployment in the context of field studies, clinical trials, and recent commercialization. On-body measurements in these contexts show good agreement compared to conventional laboratory-based sweat analysis approaches. These device demonstrations highlight the utility of biochemical sensing platforms for personalized assessment of performance, wellness, and health across a broad range of applications.

Development and feasibility of a Configurable Assessment Messaging Platform for Interventions (CAMPI).

INTRODUCTION: Short message service (SMS) is a widely accepted telecommunications approach used to support health informatics, including behavioral interventions, data collection, and patient-provider communication. However, SMS delivery platforms are not standardized and platforms are typically commercial "off-the-shelf" or developed "in-house." As a consequence of platform variability, implementing SMS-based interventions may be challenging for both providers and patients. Off-the-shelf SMS delivery platforms may require minimal development or technical resources from providers, but users are often limited in their functionality. Conversely, platforms that are developed in-house are often specified for individual projects, requiring specialized development and technical expertise. Patients are on the receiving end of programming and technical specification challenges; message delays or lagged data affect quality of SMS communications. To date, little work has been done to develop a generalizable SMS platform that can be scaled across health initiatives. OBJECTIVE: We propose the Configurable Assessment Messaging Platform for Interventions (CAMPI) to mitigate challenges associated with SMS intervention implementation (e.g., programming, data collection, message delivery). METHOD: CAMPI aims to optimize health data captured from a multitude of sources and enhance patient-provider communication through a technology that is simple and familiar to patients. Using representative examples from three behavioral intervention case studies implemented among diverse populations (pregnant women, young sexual minority men, and parents with young children), we describe CAMPI capabilities and feasibility. CONCLUSION: As a generalizable SMS platform, CAMPI can be scaled to meet the priorities of various health initiatives, while reducing unnecessary resource utilization and burden on providers and patients. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Soft, skin-interfaced sweat stickers for cystic fibrosis diagnosis and management.

The concentration of chloride in sweat remains the most robust biomarker for confirmatory diagnosis of cystic fibrosis (CF), a common life-shortening genetic disorder. Early diagnosis via quantitative assessment of sweat chloride allows prompt initiation of care and is critically important to extend life expectancy and improve quality of life. The collection and analysis of sweat using conventional wrist-strapped devices and iontophoresis can be cumbersome, particularly for infants with fragile skin, who often have insufficient sweat production. Here, we introduce a soft, epidermal microfluidic device ("sweat sticker") designed for the simple and rapid collection and analysis of sweat. Intimate, conformal coupling with the skin supports nearly perfect efficiency in sweat collection without leakage. Real-time image analysis of chloride reagents allows for quantitative assessment of chloride concentrations using a smartphone camera, without requiring extraction of sweat or external analysis. Clinical validation studies involving patients with CF and healthy subjects, across a spectrum of age groups, support clinical equivalence compared to existing device platforms in terms of accuracy and demonstrate meaningful reductions in rates of leakage. The wearable microfluidic technologies and smartphone-based analytics reported here establish the foundation for diagnosis of CF outside of clinical settings.

Recent progress, challenges, and opportunities for wearable biochemical sensors for sweat analysis.

Sweat is a promising, yet relatively unexplored biofluid containing biochemical information that offers broad insights into the underlying dynamic metabolic activity of the human body. The rich composition of electrolytes, metabolites, hormones, proteins, nucleic acids, micronutrients, and exogenous agents found in sweat dynamically vary in response to the state of health, stress, and diet. Emerging classes of skin-interfaced wearable sensors offer powerful capabilities for the real-time, continuous analysis of sweat produced by the eccrine glands in a manner suitable for use in athletics, consumer wellness, military, and healthcare industries. This perspective examines the rapid and continuous progress of wearable sweat sensors through the most advanced embodiments that address the fundamental challenges currently restricting widespread deployment. It concludes with a discussion of efforts to expand the overall utility of wearable sweat sensors and opportunities for commercialization, in which advances in biochemical sensor technologies will be critically important.

Skin-Interfaced Microfluidic Systems that Combine Hard and Soft Materials for Demanding Applications in Sweat Capture and Analysis.

Eccrine sweat contains a rich blend of electrolytes, metabolites, proteins, metal ions, and other biomarkers. Changes in the concentrations of these chemical species can indicate alterations in hydration status and they can also reflect health conditions such as cystic fibrosis, schizophrenia, and depression. Recent advances in soft, skin-interfaced microfluidic systems enable real-time measurement of local sweat loss and sweat biomarker concentrations, with a wide range of applications in healthcare. Uses in certain contexts involve, however, physical impacts on the body that can dynamically deform these platforms, with adverse effects on measurement reliability. The work presented here overcomes this limitation through the use of microfluidic structures constructed in relatively high modulus polymers, and designed in geometries that offer soft, system level mechanics when embedded low modulus elastomers. Analytical models and finite element analysis quantitatively define the relevant mechanics of these systems, and serve as the basis for layouts optimized to allow robust operation in demanding, rugged scenarios such as those encountered in football, while preserving mechanical stretchability for comfortable, water-tight bonding to the skin. Benchtop testing and on-body field studies of measurements of sweat loss and chloride concentration under imposed mechanical stresses and impacts demonstrate the key features of these platforms.

Skin-interfaced microfluidic system with personalized sweating rate and sweat chloride analytics for sports science applications.

Advanced capabilities in noninvasive, in situ monitoring of sweating rate and sweat electrolyte losses could enable real-time personalized fluid-electrolyte intake recommendations. Established sweat analysis techniques using absorbent patches require post-collection harvesting and benchtop analysis of sweat and are thus impractical for ambulatory use. Here, we introduce a skin-interfaced wearable microfluidic device and smartphone image processing platform that enable analysis of regional sweating rate and sweat chloride concentration ([Cl-]). Systematic studies (n = 312 athletes) establish significant correlations for regional sweating rate and sweat [Cl-] in a controlled environment and during competitive sports under varying environmental conditions. The regional sweating rate and sweat [Cl-] results serve as inputs to algorithms implemented on a smartphone software application that predicts whole-body sweating rate and sweat [Cl-]. This low-cost wearable sensing approach could improve the accessibility of physiological insights available to sports scientists, practitioners, and athletes to inform hydration strategies in real-world ambulatory settings.

Soft, skin-interfaced microfluidic systems with integrated immunoassays, fluorometric sensors, and impedance measurement capabilities.

Soft microfluidic systems that capture, store, and perform biomarker analysis of microliter volumes of sweat, in situ, as it emerges from the surface of the skin, represent an emerging class of wearable technology with powerful capabilities that complement those of traditional biophysical sensing devices. Recent work establishes applications in the real-time characterization of sweat dynamics and sweat chemistry in the context of sports performance and healthcare diagnostics. This paper presents a collection of advances in biochemical sensors and microfluidic designs that support multimodal operation in the monitoring of physiological signatures directly correlated to physical and mental stresses. These wireless, battery-free, skin-interfaced devices combine lateral flow immunoassays for cortisol, fluorometric assays for glucose and ascorbic acid (vitamin C), and digital tracking of skin galvanic responses. Systematic benchtop evaluations and field studies on human subjects highlight the key features of this platform for the continuous, noninvasive monitoring of biochemical and biophysical correlates of the stress state.

Skin-interfaced soft microfluidic systems with modular and reusable electronics for in situ capacitive sensing of sweat loss, rate and conductivity.

Important insights into human health can be obtained through the non-invasive collection and detailed analysis of sweat, a biofluid that contains a wide range of essential biomarkers. Skin-interfaced microfluidic platforms, characterized by soft materials and thin geometries, offer a collection of capabilities for in situ capture, storage, and analysis of sweat and its constituents. In ambulatory uses cases, the ability to provide real-time feedback on sweat loss, rate and content, without visual inspection of the device, can be important. This paper introduces a low-profile skin-interfaced system that couples disposable microfluidic sampling devices with reusable 'stick-on' electrodes and wireless readout electronics that remain isolated from the sweat. An ultra-thin capping layer on the microfluidic platform permits high-sensitivity, contactless capacitive measurements of both sweat loss and sweat conductivity. This architecture avoids the potential for corrosion of the sensing components and eliminates the need for cleaning/sterilizing the electronics, thereby resulting in a cost-effective platform that is simple to use. Optimized electrode designs follow from a combination of extensive benchtop testing, analytical calculations and FEA simulations for two sensing configurations: (1) sweat rate and loss, and (2) sweat conductivity, which contains information about electrolyte content. Both configurations couple to a flexible, wireless electronics platform that digitizes and transmits information to Bluetooth-enabled devices. On-body field testing during physical exercise validates the performance of the system in scenarios of practical relevance to human health and performance.