Sweat Volume Research Articles

Estimation of the Number of Active Sweat Glands Through Discrete Sweat Sensing.

Sweat is a biomarker-rich fluid with potential for continuous patient monitoring via wearable devices. However, biomarker concentrations vary with the sweat rate per gland, posing a challenge for sweat sensing. To address this, we propose an algorithm to compute both the number of active sweat glands and their individual sweat rates. We developed models of sweat glands and a discrete sweat-sensing device to sense sweat volume. Our algorithm estimates the number of active glands by decomposing the signal into patterns generated by the individual sweat glands, allowing for the calculation of individual sweat rates. We assessed the algorithm's accuracy using synthetic datasets for varying physiological parameters (sweat rate and number of active sweat glands) and device layouts. The results show that device layout significantly affects accuracy, with error rates below 0.2% for low and medium sweat rates (below 0.2 nL min-1 per gland). However, the method is not suitable for high sweat rates. The suitable sweat rate range can be adapted to different needs through the choice of device. Based on our findings, we provide recommendations for optimal device layouts to improve accuracy in estimating active sweat glands. This is the first study to focus on estimating the sweat rate per gland, which essential for accurate biomarker concentration estimation and advancing sweat sensing towards clinical applications.

Pharmacologic properties and results of a clinical study of oxybutynin hydrochloride lotion (APOHIDE® Lotion 20%) as a novel treatment for primary palmar hyperhidrosis

APOHIDE® Lotion 20% is a topical agent for treating primary palmar hyperhidrosis that contains the active ingredient oxybutynin hydrochloride. Oxybutynin hydrochloride has anticholinergic effects and inhibits sweating by binding to the M3 receptor, a subtype of the muscarinic acetylcholine receptor, in eccrine sweat glands. The clinical response to oxybutynin hydrochloride treatment also involves N-desethyloxybutynin, an active metabolite of oxybutynin. A clinical study in Japanese patients with primary palmar hyperhidrosis showed superiority of APOHIDE® Lotion 20% over placebo, i.e., there were significantly more responders (i.e., patients with a reduction in sweat volume ≥50% from baseline) in the APOHIDE® Lotion 20% group (APOHIDE® Lotion 20% group: 52.8%, placebo group: 24.3%; treatment difference: 28.5%; P < 0.001, Fisher's exact test). This and other clinical studies reported some adverse events (AEs) associated with the drug's anticholinergic effects and some application site AEs, but most of the AEs were mild. Clinical response did not decrease with long-term (52-week) treatment, and only a few patients (2 of 125) discontinued treatment because of AEs. Taken together, study results indicate that APOHIDE® Lotion 20% may be an effective and safe new treatment option for patients with primary palmar hyperhidrosis.

Molecularly Imprinted Wearable Sensor with Paper Microfluidics for Real-Time Sweat Biomarker Analysis.

The urgent need for real-time and noninvasive monitoring of health-associated biochemical parameters has motivated the development of wearable sweat sensors. Existing electrochemical sensors show promise in real-time analysis of various chemical biomarkers. These sensors often rely on labels and redox probes to generate and amplify the signals for the detection and quantification of analytes with limited sensitivity. In this study, we introduce a molecularly imprinted polymer (MIP)-based biochemical sensor to quantify a molecular biomarker in sweat using electrochemical impedance spectroscopy, which eliminates the need for labels or redox probes. The molecularly imprinted biosensor can achieve sensitive and specific detection of cortisol at concentrations as low as 1 pM, 1000-fold lower than previously reported MIP cortisol sensors. We integrated multimodal electrochemical sensors with an iontophoresis sweat extraction module and paper microfluidics for real-time sweat analysis. Several parameters can be simultaneously quantified, including sweat volume, secretion rate, sodium ion, and cortisol concentration. Paper microfluidic modules not only quantify sweat volume and secretion rate but also facilitate continuous sweat analysis without user intervention. While we focus on cortisol sensing as a proof-of-concept, the molecularly imprinted wearable sensors can be extended to real-time detection of other biochemicals, such as protein biomarkers and therapeutic drugs.

Quantification of amino acids in small volumes of palm sweat samples

This study investigates the significance of quantifying amino acids in minute sweat volumes using high-performance liquid chromatography with fluorescence detection. Sweat, a valuable biofluid for non-invasive health monitoring, provides real-time insights into physiological changes. Amino acids, which are critical for various physiological processes, are key to protein synthesis and cellular regulation. Therefore, analyzing sweat's amino acid profiles can offer insights into metabolic states, exercise-induced stress, and potential biomarkers for health conditions. For sensitive analysis, amino acids were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), followed by liquid chromatographic separation on an octadecylsilyl column and fluorescence detection. The developed method was validated and applied to human sweat samples, enabling the quantification of 14 amino acids. The most abundant amino acids in the samples were serine, glycine, and alanine, which aligns with prior studies. This method offers a non-invasive and efficient way to screen for diseases by detecting amino acids in sweat, even with minimal sweat volumes. The approach could also be used to analyze other biomolecules in sweat, expanding its potential applications.

A wearable sensor patch for joule-heating sweating and comfortable biofluid monitoring

Extracting sufficient volumes of sweat consistently in various scenarios is necessary for next-generation wearable sweat sensors. Here, we developed a sensor patch for Joule-heating sweating and comfortable biofluid monitoring. The Ti3C2Tx nanosheet provides silk fabrics with good electrical conductivity which can serve as an efficient low-voltage electrothermal platform. This biosensor can induce significant sweating in volunteers within just 5 minutes through mild heat stimulation, allowing real-time assessment of metabolic syndrome risks, including Na+, K+, pH, and uric acid levels. Unlike traditional sweat sensors that rely on iontophoresis or physical movement, our approach offered enhanced comfort and efficiency, particularly in sedentary scenarios. Such integration of Joule-heating sweating and sweat analysis endows its potential as a versatile and user-friendly tool in precision medicine and healthcare monitoring.

Capillary-osmotic wearable patch based on lateral flow assay for sweat potassium analysis

This paper reports a simple, disposable, and wearable patch inspired by lateral flow assay (LFA) that can continuously and non-invasively sample sweat for colorimetric sensing of potassium (K+). K+ is an important biomarker for healthy cardiovascular and neuromuscular functions of the body. Current techniques for K+ sensing in sweat commonly use ion-selective electrodes that require complex fabrication steps, signal drift issues, and active perspiration for continuous operation. Here, the sensor uses passive osmotic-capillary principles to collect sweat from the skin without the need of external power for sampling. A skin-mounted hydrogel patch equilibrated with glucose and glycerin solutions can extract fluid from the skin at rest because of the high osmotic strength of the hydrogel compared to sweat. The gel delivers fluid to a commercial colorimetric assay via a paper strip. The assay contains the reagent dipicrylamine which is selective to K+. On-body human trials prove that these patches function with low sweat volumes (∼2–3 µL) and measure K+ concentration in sweat extracted both during exercise and rest. The sweat potassium concentration is independent of the sweat rate and its magnitude matches that of blood. Such economical patches could open opportunities for at-home or in-field point-of-care (POC) diagnostics.

A self-driven multifunctional microfluidic sweat analysis system for efficient sweat collection and real-time monitoring

Wearable sweat sensors offer the opportunity for non-invasive and real-time monitoring of metabolite information in sweat, enabling individuals to dynamically monitor their physiology states at the molecular level. However, sweat possesses characteristics such as small volume, volatility, susceptibility to epidermal contamination, and low analyte concentrations, making its reliable collection and detection challenge for wearable sweat sensors. In this work, we develop a self-driven multifunctional microfluidic sweat analysis system (SMMSAS) for efficient sweat collection and detection. The SMMSAS features with a wetting contrast for the sweat, which comprises superhydrophobic inlet, superhydrophilic microchannel enriched with nanofiber, and an absorbent test paper. Such a feature enables the spontaneous sweat transports in the form of dropwise due to the exertion of “Laplace force-capillary force-capillary force” on sweat, thereby facilitating the real-time sweat detection. SMMSAS integrated with the functions of impedance and colorimetry analysis is able to simultaneously record the multiple information in sweat, including sweat volume, sweating rate, total electrolyte concentration, glucose concentration, and pH value, all of which are important to reflect the physiological state of the human body. We also demonstrate the capability of SMMSAS in real-time monitoring the sweating conditions of the human body, which is attributed to its fast responsiveness (∼ 100 ms) for the wide range sweating rate (0.5−15 μL/min) and various total electrolyte concentration (0−80 mM), paving the way for next-generation personalized healthcare.

Altered Sweat Composition Due to Changes in Tight Junction Expression of Sweat Glands in Cholinergic Urticaria Patients.

In cholinergic urticaria (CholU), small, itchy wheals are induced by exercise or passive warming and reduced sweating has been reported. Despite the described reduced muscarinic receptor expression, sweat duct obstruction, or sweat allergy, the underlying pathomechanisms are not well understood. To gain further insights, we collected skin biopsies before and after pulse-controlled ergometry and sweat after sauna provocation from CholU patients as well as healthy controls. CholU patients displayed partially severely reduced local sweating, yet total sweat volume was unaltered. However, sweat electrolyte composition was altered, with increased K+ concentration in CholU patients. Formalin-fixed, paraffin-embedded biopsies were stained to explore sweat leakage and tight junction protein expression. Dermcidin staining was not found outside the sweat glands. In the secretory coils of sweat glands, the distribution of claudin-3 and -10b as well as occludin was altered, but the zonula occludens-1 location was unchanged. In all, dermcidin and tight junction protein staining suggests an intact barrier with reduced sweat production capability in CholU patients. For future studies, an ex vivo skin model for quantification of sweat secretion was established, in which sweat secretion could be pharmacologically stimulated or blocked. This ex vivo model will be used to further investigate sweat gland function in CholU patients and decipher the underlying pathomechanism(s).

Paper-based microfluidic chip for sweat volume, ECG and EMG monitoring

With the development of wearable devices, the application of non-invasive wearable devices to monitor sweat in real time is the most important for human health. Here, a paper-based microfluidic chip for monitoring of sweat loss during exercise is proposed. Highly absorbent rice paper is selected as the paper-based material, and the capillary action of the paper base is used to actively adsorb sweat, and it can be used repeatedly. As the electrode material, the conductive cloth has good tensile properties and bending resistance, which ensures that the change of resistance is caused by the amount of sweat entering. Other materials of the chip are highly hydrophobic, ensuring that all sweat will be absorbed by the paper base. The sweat volume monitored by the microfluidic chip in real time is 0.5μl-225μl. Compared with rigid electrodes and wet electrodes, the application of flexible electrodes allows the chip to fit well with the skin, the ECG waveform is clearer and has greater amplitude, and the EMG is smoother and has a greater signal-to-noise ratio.

Plant‐Inspired Dual‐Functional Sensor for Monitoring Pulse and Sweat Volume

AbstractWearable health monitoring sensors, when employed to monitor pulse and sweat volume in real‐time during human physical activity, serve as an effective preventative measure against abnormal health conditions, such as elevated heart rate or excessive dehydration. Herein, a dual‐functional sensor based on a sandwich structure composed of polyvinylidene fluoride hexafluoropropylene / conductive carbon black perforated film (named PCp film) and corncob sponge is designed to monitor pulse and sweat volume. The PCp film prepared by the breath figure method serves as a piezoresistive sensor with high sensitivity (0.06 kPa−1), a fast response time (0.9 ms), and high reusability for pulse monitoring. Furthermore, the PCp film has excellent water permeability (27.3 L m−2 h−1); thus, the sweat permeating through the PCp film can be absorbed by the corncob sponge. The sandwich‐structured capacitive sensor is also highly sensitive (6.021 pF nL−1) to the absorbed sweat and is highly reusable. In addition, the dual‐functional sensor is successfully integrated into a sports bracelet system to display real‐time pulse and sweat‐volume data of the wearer. This approach provides a dependable foundation for the advancement of multifunctional sensors in the field of sports monitoring.

An adaptive thermal management method via bionic sweat pores on electronic devices

Maintaining proper operation temperature is a basial need for electronic devices. However, the current thermal management strategy for electronic devices generally provides a fixed cooling capacity, which cannot be adjusted adaptively based on the working condition. In this study, we report a novel adaptive thermal management method enabling electronic devices to sweat dynamically, similar to human, for adaptive cooling. The proposed method involves the design of adaptive-switching bionic sweat pores, which facilitate the sweating process and sweat evaporation on the surface of electronic devices. To ensure long-term operation, a liquid circulation system is applied as the source of bionic sweat. We conducted experimental research using a test vehicle to evaluate the performance and influencing factors of the method. The results demonstrate that the bionic sweating behavior can provide an additional cooling capacity equivalent to 80% of the original fixed cooling capacity. Furthermore, optimizing factors such as the hydrophily of the evaporation surface, sweating volume, and phase change state of the bionic sweat can enhance the additional cooling capacity. Theoretical analysis further indicates that a maximum additional cooling capacity of up to 208 W/cm2 can be achieved when the bionic sweat was in boiling state.

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.

Abnormal quantitative sudomotor axon reflex test results in patients with tinnitus as a possible indicator of small fiber neuropathy.

A few cases of small fiber neuropathy (SFN) and tinnitus (TN) associated with coronavirus disease 2019 have been reported. However, the relationship between SFN and TN has not been studied. This study investigated a possible relationship between SFN and patients with TN (PwTNs) using autonomic function tests (AFTs) including quantitative sudomotor axon reflex tests (QSART). We performed QSARTs and other AFTs such as the Sympathetic skin response (SSR), Valsalva ratio (VR), and heart rate variability (HRV). The QSART results, obtained at seven hospitals using same protocols, were compared between PwTNs and healthy controls. We confirmed the abnormalities in SSR, VR, and HRV in PwTNs, although those parasympathetic AFTs were not performed in healthy controls. Additionally, we checked Tinnitus handicap inventory (THI) scores for PwTNs and ~50% of PwTNs had low-grade disability, whereas 9.3% had high-grade disability. Data from 57 PwTNs and 122 healthy controls were analyzed. The sweat volumes of QSART in the older age group tended to be higher in the PwTNs than in age-matched healthy controls, and significant differences between the PwTN and control groups were observed in the feet in both sexes (p < 0.001) and in the arms in women (p = 0.013). In the younger age group, the sweat volumes in the feet of men were higher in PwTNs than in healthy controls (p = 0.017). No association was observed between THI and QSART scores. In this study, the sweat volumes in QSARTs were higher in PwTNs than in healthy controls. However, abnormal SSR, HRV, and VR results were not commonly observed in PwTNs. Although the results should be interpreted with caution because of limitations in study, PwTNs might also have SFN apart from dysautonomia. This is the first study to perform QSART with other parasympathetic AFTs in PwTNs. However, larger and more rigorously controlled studies will be needed to reveal the relationship between SFN and TN in the future.

Rate and predictors of insufficient sweat volume in very young infants after pilocarpine gel iontophoresis: prospective, population-based study

ObjectiveTo verify the rate and predictors of ‘quantity not sufficient’ (QNS) among Brazilian infants younger than 3 months with positive newborn screening (NBS) for cystic fibrosis (CF).DesignProspective, population-based study.SettingPublic Statewide...

Discretised microfluidics for noninvasive health monitoring using sweat sensing.

Using sweat instead of blood for monitoring chemical biomarker concentrations of hospitalised patients offers several advantages for both the patients and healthcare workers. Unlike blood, sweat can be noninvasively and continuously sampled without direct involvement of a professional, and sweat contains a rich composition of biomarkers. However, patients in resting state have extremely low sweat rates and they produce correspondingly small sweat volumes, which makes sweat sensing of hospitalised patients highly challenging. We propose a unique solution that enables the use of sweat as a viable biofluid for noninvasive health monitoring, by actively transporting the sweat in a discretised manner. Our device uses electrowetting-on-dielectrics (EWOD) to create and move sweat droplets with a volume of around 1 nanolitre from a sweat gland to sensors integrated in the device. We present the first wearable device with integrated EWOD, and we show that it can collect and transport sweat on-body, while measuring sweat rate, under conditions typical for individuals at rest.

Soft Epidermal Paperfluidics for Sweat Analysis by Ratiometric Raman Spectroscopy.

The expanding interest in digital biomarker analysis focused on non-invasive human bodily fluids, such as sweat, highlights the pressing need for easily manufactured and highly efficient soft lab-on-skin solutions. Here, we report, for the first time, the integration of microfluidic paper-based devices (μPAD) and non-enhanced Raman-scattering-enabled optical biochemical sensing (Raman biosensing). Their integration merges the enormous benefits of μPAD, with high potential for commercialization and use in resource-limited settings, with biorecognition-element-free (but highly selective) optical Raman biosensing. The introduced thin (0.36 mm), ultra-lightweight (0.19 g), and compact footprint (3 cm2) opto-paperfluidic sweat patch is flexible, stretchable, and conforms, irritation-free, to hairless or minimally haired body regions to enable swift sweat collection. As a great advantage, this new bio-chemical sensory system excels through its absence of onboard biorecognition elements (bioreceptor-free) and omission of plasmonic nanomaterials. The proposed easy fabrication process is adaptable to mass production by following a fully sustainable and cost-effective process utilizing only basic tools by avoiding typically employed printing or laser patterning. Furthermore, efficient collection and transportation of precise sweat volumes, driven exclusively by the wicking properties of porous materials, shows high efficiency in liquid transportation and reduces biosensing latency by a factor of 5 compared to state-of-the-art epidermal microfluidics. The proposed unit enables electronic chip-free and imaging-less visual sweat loss quantification as well as optical biochemical analysis when coupled with Raman spectroscopy. We investigated the multimodal quantification of sweat urea and lactate levels ex vivo (with syntactic sweat including +30 sweat analytes on porcine skin) and achieved a linear dynamic range from 0 to 100 mmol/L during fully dynamic continuous flow characterization.

Skin-Interfaced Bifluidic Paper-Based Device for Quantitative Sweat Analysis.

The erratic, intermittent, and unpredictable nature of sweat production, resulting from physiological or psychological fluctuations, poses intricacies to consistently and accurately sample and evaluate sweat biomarkers. Skin-interfaced microfluidic devices that rely on colorimetric mechanisms for semi-quantitative detection are particularly susceptible to these inaccuracies due to variations in sweat secretion rate or instantaneous volume. This work introduces a skin-interfaced colorimetric bifluidic sweat device with two synchronous channels to quantify sweat rate and biomarkers in real-time, even during uncertain sweat activities. In the proposed bifluidic-distance metric approach, with one channel to measure sweat rate and quantify collected sweat volume, the other channel can provide an accurate analysis of the biomarkers based on the collected sweat volume. The closed channel design also reduces evaporation and resists contamination from the external environment. The feasibility of the device is highlighted in a proof-of-the-concept demonstration to analyze sweat chloride for evaluating hydration status and sweat glucose for assessing glucose levels. The low-cost yet highly accurate device provides opportunities for clinical sweat analysis and disease screening in remote and low-resource settings. The developed device platform can be facilely adapted for the other biomarkers when corresponding colorimetric reagents are exploited.

Sweat Sensor Based on Wearable Janus Textiles for Sweat Collection and Microstructured Optical Fiber for Surface-Enhanced Raman Scattering Analysis.

Wearable sweat sensors provide real-time monitoring of biomarkers, enabling individuals to gain real-time insight into their health status. Current sensors primarily rely on electrochemical mechanisms, limiting their capacity for the concurrent detection of multiple analytes. Surface-enhanced Raman scattering spectroscopy offers an alternative approach by providing molecular fingerprint information to facilitate the identification of intricate analytes. In this study, we combine a wearable Janus fabric for efficient sweat collection and a grapefruit optical fiber embedded with Ag nanoparticles as a sensitive SERS probe. The Janus fabric features a superhydrophobic side in contact with the skin and patterned superhydrophilic regions on the opposite surface, facilitating the unidirectional flow of sweat toward these hydrophilic zones. Grapefruit optical fibers feature sharp tips with the ability to penetrate transparent dressings. Its microchannels extract sweat through capillary force, and nanoliter-scale volumes of sweat are sufficient to completely fill them. The Raman signal of sweat components is greatly enhanced by the plasmonic hot spots and accumulates along the fiber length. We demonstrate sensitive detection of sodium lactate and urea in sweat with a detection limit much lower than the physiological concentration levels. Moreover, the platform shows its capability for multicomponent detection and extends to the analysis of real human sweat.

Design and fabrication of nepenthes alata-inspired sweat collection patch using wettability patterning method

Sweat-based wearable devices are attracting attention for non-invasive monitoring of various biomarkers present in sweat. However, the problem of inadequate sweat volume remains prevalent in sweat testing. To overcome this challenge, we present an integrated flexible platform that incorporates open microfluidic tracks, specifically designed for efficient sweat collection. The construction of these tracks involves employing a simple wettability patterning method using PDMS-TiO2 nanocomposite as a coating surface. Additionally, a thorough characterization study is conducted to analyze the synthesized composite material comprehensively. Furthermore, we propose a novel curvilinear wedge track design, inspired by the teeth structure of Nepenthes alata, to enhance droplet collection, achieving an improvement in collection efficiency in the range 86–94%. The physics of droplet transport is explained through simulations. To demonstrate the feasibility of our approach, we fabricated and tested a patch embedded with a wedge track and a screen printed three-electrode system, showcasing successful sweat collection. The novelty of this work lies in the development of a fabricated patch that minimizes sample volume requirements when integrated with the electrode system. Additionally, its orientation-independent design makes it suitable for wearable applications.

Smart Wearable Nanopaper Patch for Continuous Multiplexed Optical Monitoring of Sweat Parameters.

Notwithstanding the substantial progress in optical wearable sensing devices, developing wearable optical sensors for simultaneous, real-time, and continuous monitoring of multiple biomarkers is still an important, yet unmet, demand. Aiming to address this need, we introduced for the first time a smart wearable optical sensor (SWOS) platform combining a multiplexed sweat sensor sticker with its IoT-enabled readout module. We employed our SWOS system for on-body continuous, real-time, and simultaneous fluorimetric monitoring of sweat volume (physical parameter) and pH (chemical marker). Herein, a variation in moisture (5-45 μL) or pH (4.0-7.0) causes a color/fluorescence change in the copper chloride/fluorescein immobilized within a transparent chitin nanopaper (ChNP) in a selective and reversible manner. Human experiments conducted on athletic volunteers during exercise confirm that our developed SWOS platform can be efficiently exploited for smart perspiration analysis toward personalized health monitoring. Moreover, our system can be further extended for the continuous and real-time multiplexed monitoring of various biomarkers (metabolites, proteins, or drugs) of sweat or other biofluids (for example, analyzing exhaled breath by integrating onto a facemask).