Wearable Hydrogel SERS Chip Utilizing Plasmonic Trimers for Uric Acid Analysis in Sweat.

Uric acid is typically measured through blood tests, which can be inconvenient and uncomfortable for patients. Herein, we propose a wearable surface-enhanced Raman scattering (SERS) chip, incorporating a hydrogel membrane with integrated plasmonic trimers, for noninvasive monitoring of uric acid in sweat. The plasmonic trimers feature sub 5 nm nanogaps, generating strong electromagnetic fields to boost the Raman signal of surrounding molecules. Simultaneously, the hydrogel membrane pumps sweat through these gaps, efficiently capturing sweat biomarkers for SERS detection. The chip can achieve saturation adsorption of sweat within 5 min, eliminating variations in individual sweat production rates. Dynamic SERS tracking of uric acid and lactic acid levels during anaerobic exercise reveals a temporary suppression of uric acid metabolism, likely due to metabolic competition with lactic acid. Furthermore, long-term monitoring correlates well with blood test results, confirming that regular exercise helps reduce serum uric acid levels and supporting its potential in managing hyperuricemia.

Jellyfish-like Gold Nanowires as FlexoSERS Sensors for Sweat Analysis.

We introduce the FlexoSERS sensor, which is notable for its high stretchability, sensitivity, and patternability. Featuring a hierarchically oriented jellyfish-like architecture constructed from stretchable gold nanowires, this sensor provides an ultrasensitive SERS signal even under 50% strain, with an enhancement factor (EF) of 3.3 × 1010. Impressively, this heightened performance remains consistently robust across 2,500 stretch-release cycles. The integration of nanowires with 3D-printed hydrogel enables a customizable FlexoSERS sensor, facilitating localized sweat collection and detection. The FlexoSERS sensor successfully detects and quantifies uric acid (UA) in both artificial and human sweat and functions as a pH sensor with repeatability and sensitivity across a pH range of 4.2-7.8, enabling real-time sweat monitoring during exercise. In summary, the rational architectural design, scalable fabrication process, and hydrogel integration collectively position this nanowire-based FlexoSERS sensor as a highly promising platform for customizable wearable sweat diagnostics.

A Fully Printable and Integrated System with Long-Term Stability for Versatile and Multimodal Perspiration Tracking.

Real-time and continuous monitoring of physiological status via noninvasive sweat sensing shows promise for personalized healthcare and fitness management. However, the largely varied perspiration rates in different body statuses introduce challenges for effective sweat collection and accurate sensing. Herein, a fully printable strategy was developed to realize fully integrated patches for wireless sensing of sweat biomarker levels and perspiration rates with desirable stability and versatility. The printable calcium sensors with modified ion-selective membranes displayed an ultrawide linear range of 0.1-100 mM and a long-term stability with minimized drift down to 0.083 mV/h for around 40 h. Moreover, the microfluidic channels in versatile configurations were capable of a minimum sweat rate monitoring of 0.5 µL/min and a large sweat storage volume of up to 200 µL. The as-proposed fully printable sensing platforms provide high compatibility for sensor integration to achieve versatile perspiration tracking and comprehensive health monitoring.

Patterned Gold Nanoparticle Superlattice Film for Wearable Sweat Sensors.

Nanoparticle superlattices are beneficial in terms of providing strong and uniform signals in analysis owing to their closely packed uniform structures. However, nanoparticle superlattices are prone to cracking during physical activities because of stress concentrations, which hinders their detection performance and limits their analytical applications. In this work, template printing methods were used in this study to prepare a patterned gold nanoparticle (AuNP) superlattice film. By adjustment of the size of the AuNP superlattice domain below the critical size of fracture, the mechanical stability of the AuNP superlattice domain is improved. Thus, long-term sustainable high-performance signal output is achieved. The patterned AuNP superlattice film was used to construct a wearable sweat sensor based on surface-enhanced Raman scattering (SERS). The designed sensor showed promise for long-term reliable use in actual scenarios in terms of recommending water replenishment, monitoring hydration states, and tracking the intensity of activity.

Skin Development and Disease: A Molecular Perspective.

Skin, the largest organ in the human body, is a crucial protective barrier that plays essential roles in thermoregulation, sensation, and immune defence. This complex organ undergoes intricate processes of development. Skin development initiates during the embryonic stage, orchestrated by molecular cues that control epidermal specification, commitment, stratification, terminal differentiation, and appendage growth. Key signalling pathways are integral in coordinating the development of the epidermis, hair follicles, and sweat glands. The complex interplay among these pathways is vital for the appropriate formation and functionality of the skin. Disruptions in multiple molecular pathways can give rise to a spectrum of skin diseases, from congenital skin disorders to cancers. By delving into the molecular mechanisms implicated in developmental processes, as well as in the pathogenesis of diseases, this narrative review aims to present a comprehensive understanding of these aspects. Such knowledge paves the way for developing innovative targeted therapies and personalised treatment approaches for various skin conditions.

Ontogeny of Skin Stem Cells and Molecular Underpinnings.

Skin stem cells (SCs) play a pivotal role in supporting tissue homeostasis. Several types of SCs are responsible for maintaining and regenerating skin tissue. These include bulge SCs and others residing in the interfollicular epidermis, infundibulum, isthmus, sebaceous glands, and sweat glands. The emergence of skin SCs commences during embryogenesis, where multipotent SCs arise from various precursor populations. These early events set the foundation for the diverse pool of SCs that will reside in the adult skin, ready to respond to tissue repair and regeneration demands. A network of molecular cues regulates skin SC behavior, balancing quiescence, self-renewal, and differentiation. The disruption of this delicate equilibrium can lead to SC exhaustion, impaired wound healing, and pathological conditions such as skin cancer. The present review explores the intricate mechanisms governing the development, activation, and differentiation of skin SCs, shedding light on the molecular signaling pathways that drive their fate decisions and skin homeostasis. Unraveling the complexities of these molecular drivers not only enhances our fundamental knowledge of skin biology but also holds promise for developing novel strategies to modulate skin SC fate for regenerative medicine applications, ultimately benefiting patients with skin disorders and injuries.

Sweat Pore-Inspired Functional Nanofiber Fabrics for Sweat Management and Simultaneous Detection.

Functional fabric with directional sweat transport and simultaneous sweat detection is highly desirable in daily life due to its crucial role in ensuring exercise comfort and promoting health. Herein, the inspiration is drawn from both the perspiration function of sweat pores and the backflow prevention feature of the surrounding solid skin to develop bioinspired hydrophobic nanofiber fabric. When combined with commercial cotton, this fabric enables rapid discharge of sweat through the sweat pore-like channels at an ultrafast speed of 240 g s-1 m-2, while effectively preventing backflow around these channels to ensure highly efficient personal drying. The performance of the bioinspired nanofiber fabric surpasses that of five commercially available moisture-wicking fabrics by effectively guiding liquid transport while minimizing residual moisture accumulation on the inner side. Furthermore, a colorimetric analysis system is integrated into the bioinspired nanofiber fabric, which facilitates convenient sampling of sweat samples and detection of biomarkers in sweat such as chloride ion, calcium ion, and pH level. This innovative design based on the concept of sweat pores opens up new possibilities for developing intelligent fabrics, electronic skins, and point-of-care devices.

Hybrid Printing of Fully Integrated Microfluidic Devices for Biosensing.

The advent of 3D printing has facilitated the rapid fabrication of microfluidic devices that are accessible and cost-effective. However, it remains a challenge to fabricate sophisticated microfluidic devices with integrated structural and functional components due to limited material options of existing printing methods and their stringent requirement on feedstock material properties. Here, a multi-materials multi-scale hybrid printing method that enables seamless integration of a broad range of structural and functional materials into complex devices is reported. A fully printed and assembly-free microfluidic biosensor with embedded fluidic channels and functionalized electrodes at sub-100 µm spatial resolution for the amperometric sensing of lactate in sweat is demonstrated. The sensors present a sensitive response with a limit of detection of 442 nm and a linear dynamic range of 1-10 mm, which are performance characteristics relevant to physiological levels of lactate in sweat. The versatile hybrid printing method offers a new pathway toward facile fabrication of next-generation integrated devices for broad applications in point-of-care health monitoring and sensing.

A Fully Elastic Wearable Electrochemical Sweat Detection System of Tree-Bionic Microfluidic Structure for Real-Time Monitoring.

Fresh sweat contains a diverse range of physiological indicators that can effectively reflect changes in the body. However, existing wearable sweat detection systems face challenges in efficiently collecting and detecting fresh sweat in real-time. Additionally, they often lack the necessary deformation capabilities, resulting in discomfort for the wearer. Here, a fully elastic wearable electrochemical sweat detection system is developed that integrates a sweat-collecting microfluidic chip, a multi-parameter electrochemical sensor, a micro-heater, and a sweat detection elastic circuit board system. The unique tree-bionic structure of the microfluidic chip significantly enhances the efficiency of fresh sweat collection and discharge, enabling real-time detection by the electrochemical sensors. The sweat multi-parameter electrochemical sensor offers high-precision and high-sensitivity measurements of sodium ions, potassium ions, lactate, and glucose. The electronic system is built on an elastic circuit board that matches perfectly to wrinkled skin, ensuring improved wearing comfort and enabling multi-channel data sampling, processing, and wireless transmission. This state-of-the-art system represents a significant advancement in the field of elastic wearable sweat detection and holds promising potential for extending its capabilities to the detection of other sweat markers or various wearable applications.

Development of Physiologically Relevant Skin Organoids from Human Induced Pluripotent Stem Cells.

The development of skin organs for studying developmental pathways, modeling diseases, or regenerative medicine purposes is a major endeavor in the field. Human induced pluripotent stem cells (hiPSCs) are successfully used to derive skin cells, but the field is still far from meeting the goal of creating skin containing appendages, such as hair follicles and sweat glands. Here, the goal is to generate skin organoids (SKOs) from human skin fibroblast or placental CD34+ cell-derived hiPSCs. With all three hiPSC lines, complex SKOs with stratified skin layers and pigmented hair follicles are generated with different efficacies. In addition, the hiPSC-derived SKOs develop sebaceous glands, touch-receptive Merkel cells, and more importantly eccrine sweat glands. Together, physiologically relevant skin organoids are developed by direct induction of embryoid body formation, along with simultaneous inactivation of transforming growth factor beta signaling, activation of fibroblast growth factor signaling, and inhibition of bone morphogenetic protein signaling pathways. The skin organoids created in this study can be used as valuable platforms for further research into human skin development, disease modeling, or reconstructive surgeries.

3D Wetting Gradient Janus Sports Bras for Efficient Sweat Removal: A Strategy to Improve Women's Sports Comfort and Health.

Developing Janus fabrics with excellent one-way sweat transport capacity is an attractive way for providing comfort sensation and protecting the health during exercise. In this work, a 3D wetting gradient Janus fabric (3DWGJF) is first proposed to address the issue of excessive sweat accumulation in women's breasts, followed by integration with a sponge pad to form a 3D wetting gradient Janus sports bra (3DWGJSB). The 3D wetting gradient enables the prepared fabric to control the horizontal migration of sweat in one-way mode (x/y directions) and then unidirectionally penetrate downward (z direction), finally keeping the water content on the inner side of 3DWGJF (skin side) at ≈0%. In addition, the prepared 3DWGJF has good water vapor transmittance rate (WVTR: 0.0409 g cm-2 h-1) and an excellent water evaporation rate (0.4704 g h-1). Due to the high adhesion of transfer prints to the fabrics and their excellent mechanical properties, the 3DWGJF is remarkably durable and capable of withstanding over 500 laundering cycles and 400 abrasion cycles. This work may inspire the design and fabrication of next-generation moisture management fabrics with an effective sweat-removal function for women's health.

Tailored Polypyrrole Nanofibers as Ion-to-Electron Transduction Membranes for Wearable K+ Sensors.

Conductive polymers are recognized as ideal candidates for the development of noninvasive and wearable sensors for real-time monitoring of potassium ions (K+) in sweat to ensure the health of life. However, the low ion-to-electron transduction efficiency and limited active surface area hamper the development of high-performance sensors for low-concentration K+ detection in the sweat. Herein, a wearable K+ sensor is developed by tailoring the nanostructure of polypyrrole (PPy), serving as an ion-to-electron transduction layer, for accurately and stably tracing the K+ fluctuation in human sweat. The PPy nanostructures can be tailored from nanospheres to nanofibers by controlling the supramolecular assembly process during PPy polymerization. Resultantly, the ion-to-electron transduction efficiency (17-fold increase in conductivity) and active surface area (1.3-fold enhancement) are significantly enhanced, accompanied by minimized water layer formation. The optimal PPy nanofibers-based K+ sensor achieved a high sensitivity of 62 mV decade-1, good selectivity, and solid stability. After being integrated with a temperature sensor, the manufactured wearable sensor realized accurate monitoring of K+ fluctuation in the human sweat.

Micropatterned Polymer Nanoarrays with Distinct Superwettability for a Highly Efficient Sweat Collection and Sensing Patch.

Wearable sweat sensor offers a promising means for noninvasive real-time health monitoring, but the efficient collection and accurate analysis of sweat remains challenging. One of the obstacles is to precisely modulate the surface wettability of the microfluidics to achieve efficient sweat collection. Here a facile initiated chemical vapor deposition (iCVD) method is presented to grow and pattern polymer nanocone arrays with distinct superwettability on polydimethylsiloxane microfluidics, which facilitate highly efficient sweat transportation and collection. The nanoarray is synthesized by manipulating monomer supersaturation during iCVD to induce controlled nucleation and preferential vertical growth of fluorinated polymer. Subsequent selective vapor deposition of a conformal hydrogel nanolayer results in superhydrophilic nanoarray floor and walls within the microchannel that provide a large capillary force and a superhydrophobic ceiling that drastically reduces flow friction, enabling rapid sweat transport along varied flow directions. A carbon/hydrogel/enzyme nanocomposite electrode is then fabricated by sequential deposition of highly porous carbon nanoparticles and hydrogel nanocoating to achieve sensitive and stable sweat detection. Further encapsulation of the assembled sweatsensing patch with superhydrophobic nanoarray imparts self-cleaning and water-proof capability. Finally, the sweat sensing patch demonstrates selective and sensitive glucose and lactate detection during the on-body test.

Exercise intensity- and body region-specific differences in sweating in middle-aged to older men with and without type 2 diabetes.

Type 2 diabetes (T2D) is associated with reduced whole body sweating during exercise-heat stress. However, it is unclear if this impairment is related to exercise intensity and whether it occurs uniformly across body regions. We evaluated whole body (direct calorimetry) and local (ventilated-capsule technique; chest, back, forearm, thigh) sweat rates in physically active men with type 2 diabetes [T2D; aged 59 (7) yr; V̇o2peak 32.3 (7.6) mL·kg-1·min-1; n = 26; HbA1c 5.1%-9.1%] and without diabetes [Control; aged 61 (5) yr; V̇o2peak 37.5 (5.4) mL·kg-1·min-1; n = 26] during light- (∼40% V̇o2peak), moderate- (∼50% V̇o2peak), and vigorous- (∼65% V̇o2peak) intensity exercise (elicited by fixing metabolic heat production at ∼150, 200, 250 W·m-2, respectively) in 40°C, ∼17% relative humidity. Whole body sweating was ∼11% (T2D: Control mean difference [95% confidence interval]: -37 [-63, -12] g·m-2·h-1) and ∼13% (-50 [-76, -25] g·m-2·h-1) lower in the T2D compared with the Control group during moderate- and vigorous- (P ≤ 0.001) but not light-intensity exercise (-21 [-47, 4] g·m-2·h-1; P = 0.128). Consequently, the diabetes-related reductions in whole body sweat rate were 2.3 [1.6, 3.1] times greater during vigorous relative to light exercise (P < 0.001). Furthermore, these diabetes-related impairments in local sweating were region-specific during vigorous-intensity exercise (group × region interaction: P = 0.024), such that the diabetes-related reduction in local sweat rate at the trunk (chest, back) was 2.4 [1.2, 3.7] times greater than that at the limbs (thigh, arm). In summary, when assessed under hot, dry conditions, diabetes-related impairments in sweating are exercise intensity-dependent and greater at the trunk compared with the limbs.NEW & NOTEWORTHY This study evaluates the influence of exercise intensity on decrements in whole body sweating associated with type 2 diabetes. Furthermore, it investigates whether diabetes-related sweating impairments were exhibited uniformly or heterogeneously across body regions. We found that whole body sweating was attenuated in the type 2 diabetes group relative to control participants during moderate- and vigorous-intensity exercise but not light-intensity exercise; impairments were largely mediated by reduced sweating at the trunk rather than the limbs.

Subclinical effects of botulinum toxin A and microwave thermolysis for axillary hyperhidrosis: A descriptive study with line-field confocal optical coherence tomography and histology.

Botulinum toxin A (BTX) and microwave thermolysis (MWT) are standard axillary hyperhidrosis treatments, but comparison of their subclinical effects is lacking. Line-field confocal optical coherence tomography (LC-OCT) is a promising non-invasive imaging tool for visualizing tissue-interactions. This study aimed to describe subclinical effects of BTX and MWT for axillary hyperhidrosis with LC-OCT-imaging compared to histology. This study derived from an intra-individual, randomized, controlled trial, treating axillary hyperhidrosis with BTX versus MWT. Subclinical effects based on LC-OCT images from baseline and 6-month follow-up (n = 8 patients) were evaluated and compared to corresponding histological samples. At baseline, LC-OCT visualized eccrine pores at the skin surface and ducts in the upper dermis (500 µm), but not deeper-lying sweat glands. Histology identified entire sweat glands. Six months post-treatment, LC-OCT revealed no detectable morphology changes in any BTX-treated axillae (100%), while recognizing obstructed eccrine pores and atrophy of eccrine ducts in most MWT-treated axillae (75%). Histology corroborated LC-OCT findings, while also showing substantial changes to entire sweat glands. LC-OCT enabled visualization of subclinical alterations of superficial eccrine ducts after MWT and unchanged morphology after BTX. LC-OCT is a promising tool for non-invasive assessment of treatment-specific tissue-interactions that can be complementary to histology.

The effect of female breast surface area on heat-activated sweat gland density and output.

Female development includes significant morphological changes across the breast. Yet, whether differences in breast surface area (BrSA) modify sweat gland density and output remains unclear. The present study investigated the relationship between BrSA and sweat gland density and output in 22 young to middle-aged women (28 ± $\ \pm \ $ 10 years) of varying breast sizes (BrSA range: 147-561 cm2) during a submaximal run in a warm environment (32  ± $ \pm \ $ 0.6°C; 53  ± $ \pm \ $ 1.7% relative humidity). Local sweat gland density and local sweat rate (LSR) above and below the nipple and at the bra triangle were measured. Expired gases were monitored for the estimation of evaporative requirements for heat balance (Ereq, in W/m2). Associations between BrSA and (i) sweat gland density; (ii) LSR; and (iii) sweat output per gland for the breast sites were determined via correlation and regression analyses. Our results indicated that breast sweat gland density decreased linearly as BrSA increased (r = -0.76, P < 0.001), whereas sweat output per gland remained constant irrespective of BrSA (r = 0.29, P = 0.28). This resulted in LSR decreasing linearly as BrSA increased (r = -0.62, P = 0.01). Compared to the bra triangle, the breast had a 64% lower sweat gland density (P < 0.001), 83% lower LSR (P < 0.001) and 53% lower output per gland (P < 0.001). BrSA (R2 = 0.33, P = 0.015) explained a greater proportion of variance in LSR than Ereq (in W/m2) (R2 = 0.07, P = 0.538). These novel findings extend the known relationship between body morphology and sweat gland density and LSR, to the female breast. This knowledge could innovate user-centred design of sports bras by accommodating breast size-specific needs for sweat management, skin wetness perception and comfort.

Shifting focus: Time to look beyond the classic physiological adaptations associated with human heat acclimation.

Planet Earth is warming at an unprecedented rate and our future is now assured to be shaped by the consequences of more frequent hot days and extreme heat. Humans will need to adapt both behaviorally and physiologically to thrive in a hotter climate. From a physiological perspective, countless studies have shown that human heat acclimation increases thermoeffector output (i.e., sweating and skin blood flow) and lowers cardiovascular strain (i.e., heart rate) during heat stress. However, the mechanisms mediating these adaptations remain understudied. Furthermore, several possible benefits of heat acclimation for other systems and functions involved in maintaining health and performance during heat stress remain to be elucidated. This review summarizes recent advances in human heat acclimation, with emphasis on recent studies that (1) advanced our understanding of the mechanisms mediating improved thermoeffector output and (2) investigated adaptations that go beyond those classically associated with heat acclimation. We highlight that these studies have contributed to a better understanding of the integrated physiological responses underlying human heat acclimation while leaving key unanswered questions that will need to be addressed in the future.

Heat Transfer by Sweat Droplet Evaporation.

Sweating regulates the body temperature in extreme environments or during exercise. Here, we investigate the evaporative heat transfer of a sweat droplet at the microscale to unveil how the evaporation complexity of a sweat droplet would affect the body's ability to cool under specific environmental conditions. Our findings reveal that, depending on the relative humidity and temperature levels, sweat droplets experience imperfect evaporation dynamics, whereas water droplets evaporate perfectly at equivalent ambient conditions. At low humidity, the sweat droplet fully evaporates and leaves a solid deposit, while at high humidity, the droplet never reaches a solid deposit and maintains a liquid phase residue for both low and high temperatures. This unprecedented evaporation mechanism of a sweat droplet is attributed to the intricate physicochemical properties of sweat as a biofluid. We suppose that the sweat residue deposited on the surface by evaporation is continuously absorbing the surrounding moisture. This route leads to reduced evaporative heat transfer, increased heat index, and potential impairment of the body's thermoregulation capacity. The insights into the evaporative heat transfer dynamics at the microscale would help us to improve the knowledge of the body's natural cooling mechanism with practical applications in healthcare, materials science, and sports science.

Screening Allergenic Potencies of Skin-Contact Products Using the Human-Derived THP-1 Cell Activation Test.

With the prevalence of allergic contact dermatitis (ACD) from the usage of skin-contact products, like wearable, skin care, and hair care products, screening their skin sensitizing potential is necessary, for the sake of alleviating the consequent public health impact. In the present study, a total of 77 skin-contact products classified by four categories, watch bands (WBs), skin care products (SCPs), hair care products (HCPs), and rubber gloves (RGs), were investigated, using an optimized in vitro assay of human cell line activation test (h-CLAT). Extracting the products using neutral artificial sweat simulated well the practical usage scenarios, and testing the extracts showed that 26 of them were allergy test positive, including nine WBs, six SCPs, two HCPs, and nine RGs. The allergenic response was mainly characterized by the induction of CD54 expression, and diverse paradigms of CD54 and CD86 levels were observed by analyzing dose-response curves, which could also be influenced by the compromised viability of the THP-1 cells. The data implicated the intricate regulation by different contributors to suspicious ingredients in the test samples. Altogether, a promising methodology for testing skin allergy potential was well established for commonly used commodities by neutral artificial sweat extraction coupled with h-CLAT screening. The findings would be of great help in tracing the potential allergens in practical products and improving their qualities.

The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study.

OBJECTIVES: Urea and creatinine concentrations in plasma are used to guide hemodialysis (HD) in patients with end-stage renal disease (ESRD). To support individualized HD treatment in a home situation, there is a clinical need for a non-invasive and continuous alternative to plasma for biomarker monitoring during and between cycles of HD. In this observational study, we therefore established the correlation of urea and creatinine concentrations between sweat, saliva and plasma in a cohort of ESRD patients on HD. METHODS: Forty HD patients were recruited at the Dialysis Department of the Catharina Hospital Eindhoven. Sweat and salivary urea and creatinine concentrations were analyzed at the start and at the end of one HD cycle and compared to the corresponding plasma concentrations. RESULTS: A decrease of urea concentrations during HD was observed in sweat, from 27.86 mmol/L to 12.60 mmol/L, and saliva, from 24.70 mmol/L to 5.64 mmol/L. Urea concentrations in sweat and saliva strongly correlated with the concentrations in plasma (ρ 0.92 [p<0.001] and 0.94 [p<0.001], respectively). Creatinine concentrations also decreased in sweat from 43.39 µmol/L to 19.69 µmol/L, and saliva, from 59.00 µmol/L to 13.70 µmol/L. However, for creatinine, correlation coefficients were lower than for urea for both sweat and saliva compared to plasma (ρ: 0.58 [p<0.001] and 0.77 [p<0.001], respectively). CONCLUSIONS: The results illustrate a proof of principle of urea measurements in sweat and saliva to monitor HD adequacy in a non-invasive and continuous manner. Biosensors enabling urea monitoring in sweat or saliva could fill in a clinical need to enable at-home HD for more patients and thereby decrease patient burden.