Sweat Samples Research Articles

Wearable Potentiometric Sensor Based on Na0.44MnO2 for Non-invasive Monitoring of Sodium Ions in Sweat.

Here, we present a wearable potentiometric ion sensor for real-time monitoring of sodium ions (Na+) in human sweat samples using Na0.44MnO2 as the sensing material. Na0.44MnO2 is an attractive material for developing wearable electrochemical sensors due to its good Na+ incorporation ability, electrical conductivity, stability, and low fabrication cost. In the first step, the analytical performance of the electrode prepared using Na0.44MnO2 is presented. Then, a miniaturized potentiometric cell integrated into a wearable substrate is developed, which reveals a Nernstian response (58 mV dec-1). We achieved the detection of Na+ in the linear ranges of 0.21-24.54 mmol L-1, which is well within the physiological range of Na+. Finally, for on-body sweat analysis, the potentiometric sensor is fully integrated into a headband textile. This platform can be employed for non-invasive analysis of Na+ in human sweat for healthcare and disease diagnosis.

Design and fabrication of novel flexible sensor based on 2D Ni-MOF nanosheets as a preliminary step toward wearable sensor for onsite Ni (II) ions detection in biological and environmental samples

Herein, for the first time, an innovative and sensitive flexible sensor for efficient potentiometric monitoring of Ni (II) ions has been designed and developed. The developed flexible sensor is constructed from highly porous activated flexible carbon cloth decorated with nitrogen and spherical porous carbon nanoparticles derived from low-cost cotton doped with polypyrrole nanoparticles via simple carbonization-activation process followed by dip-coating in membrane cocktail containing 2D Ni-MOF nanosheets as an electroactive material. The developed flexible sensor affords rapid, accurate and stable response for the Ni (II) ions monitoring at its trace level in the biological fluids including human saliva and sweat samples in addition to tap water as an environmental sample without any preconditioning steps over pH range of 2–8 with detection limit of 2.7 × 10−6. Additionally, the flexible sensor shows good antibacterial properties against both of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria presenting safe handling for human skin as a flexible sensor for wearable system applications. This study presents a forward step for the fabrication of a wearable sensor for rapid onsite monitoring of Ni (II) ions in biological and environmental samples.

Colorimetric and Electrochemical Screening for Early Detection of Diabetes Mellitus and Diabetic Retinopathy-Application of Sensor Arrays and Machine Learning.

In this review, a selection of works on the sensing of biomarkers related to diabetes mellitus (DM) and diabetic retinopathy (DR) are presented, with the scope of helping and encouraging researchers to design sensor-array machine-learning (ML)-supported devices for robust, fast, and cost-effective early detection of these devastating diseases. First, we highlight the social relevance of developing systematic screening programs for such diseases and how sensor-arrays and ML approaches could ease their early diagnosis. Then, we present diverse works related to the colorimetric and electrochemical sensing of biomarkers related to DM and DR with non-invasive sampling (e.g., urine, saliva, breath, tears, and sweat samples), with a special mention to some already-existing sensor arrays and ML approaches. We finally highlight the great potential of the latter approaches for the fast and reliable early diagnosis of DM and DR.

Comprehensive Review on Wearable Sweat-Glucose Sensors for Continuous Glucose Monitoring.

The incidence of diabetes is increasing at an alarming rate, and regular glucose monitoring is critical in order to manage diabetes. Currently, glucose in the body is measured by an invasive method of blood sugar testing. Blood glucose (BG) monitoring devices measure the amount of sugar in a small sample of blood, usually drawn from pricking the fingertip, and placed on a disposable test strip. Therefore, there is a need for non-invasive continuous glucose monitoring, which is possible using a sweat sensor-based approach. As sweat sensors have garnered much interest in recent years, this study attempts to summarize recent developments in non-invasive continuous glucose monitoring using sweat sensors based on different approaches with an emphasis on the devices that can potentially be integrated into a wearable platform. Numerous research entities have been developing wearable sensors for continuous blood glucose monitoring, however, there are no commercially viable, non-invasive glucose monitors on the market at the moment. This review article provides the state-of-the-art in sweat glucose monitoring, particularly keeping in sight the prospect of its commercialization. The challenges relating to sweat collection, sweat sample degradation, person to person sweat amount variation, various detection methods, and their glucose detection sensitivity, and also the commercial viability are thoroughly covered.

Graphene Oxide Functionalized Biosensor for Detection of Stress-Related Biomarkers.

A graphene oxide (GO)-based cortisol biosensor was developed to accurately detect cortisol concentrations from sweat samples at point-of-care (POC) sites. A reference electrode, counter electrode, and working electrode make up the biosensor, and the working electrode was functionalized using multiple layers consisting of GO and antibodies, including Protein A, IgG, and anti-Cab. Sweat samples contact the anti-Cab antibodies to transport electrons to the electrode, resulting in an electrochemical current response. The sensor was tested at each additional functionalization layer and at cortisol concentrations between 0.1 and 150 ng/mL to determine how the current response differed. A potentiostat galvanostat device was used to measure and quantify the electrochemical response in the GO-based biosensor. In both tests, the electrochemical responses were reduced in magnitude with the addition of antibody layers and with increased cortisol concentrations. The proposed cortisol biosensor has increased accuracy with each additional functionalization layer, and the proposed device has the capability to accurately measure cortisol concentrations for diagnostic purposes.

Wearable soft electrochemical microfluidic device integrated with iontophoresis for sweat biosensing

A soft and flexible wearable sweat epidermal microfluidic device capable of simultaneously stimulating, collecting, and electrochemically analyzing sweat is demonstrated. The device represents the first system integrating an iontophoretic pilocarpine delivery system around the inlet channels of epidermal polydimethylsiloxane (PDMS) microfluidic device for sweat collection and analysis. The freshly generated sweat is naturally pumped into the fluidic inlet without the need of exercising. Soft skin-mounted systems, incorporating non-invasive, on-demand sweat sampling/analysis interfaces for tracking target biomarkers, are in urgent need. Existing skin conformal microfluidic-based sensors for continuous monitoring of target sweat biomarkers rely on assays during intense physical exercising. This work demonstrates the first example of combining sweat stimulation, through transdermal pilocarpine delivery, with sample collection through a microfluidic channel for real-time electrochemical monitoring of sweat glucose, in a fully integrated soft and flexible multiplexed device which eliminates the need of exercising. The on-body operational performance and layout of the device were optimized considering the fluid dynamics and evaluated for detecting sweat glucose in several volunteers. Furthermore, the microfluidic monitoring device was integrated with a real-time wireless data transmission system using a flexible electronic board PCB conformal with the body. The new microfluidic platform paves the way to real-time non-invasive monitoring of biomarkers in stimulated sweat samples for diverse healthcare and wellness applications.

Electrochemical determination of glucose in blood serum and sweat samples by the strontium doped Co3O4

• The conventional synthesis routes were investigated for the preparation of Sr doped Co 3 O 4 (Sr-Co 3 O 4 ). • The successful incorporation of Sr in Co 3 O 4 lattice was found for hydrothermal method. • The occupation of Sr in octahedral sites increases the non-stoichiometric oxygen in the Co 3 O 4 lattices. • These defected electronic structures were inspected against the electrocatalytic activity of glucose oxidation. • The Sr-Co 3 O 4 is applied in real-time monitoring of glucose in blood serum and sweat samples which received good recoveries. This work reports the noninvasive electrochemical determination of glucose by strontium doped cobaltic cobalt oxide nanostructures (Sr-Co 3 O 4 ). The Sr-Co 3 O 4 is prepared by three conventional methods namely hydrothermal, magnetic stirring, and ultrasound. Among all, the hydrothermal method effectively incorporated the Sr in the Co 3 O 4 lattice. The Sr percentage and Co oxidation states were investigated by x-ray photoelectron spectroscopy. The Sr has a more ionic radius than cobalt, therefore, it is occupied in the octahedral site. As a result, the non-stoichiometric oxygen content was increased in the Co 3 O 4 lattices, which are the main contributor to the electrochemical determination of glucose. The results revealed that hydrothermally synthesized Sr-Co 3 O 4 (HSC) exhibited improved electrocatalytic activity such as low peak potential (0.55 V) and high current (116 µA) towards glucose oxidation than the other electrocatalysts. The HSC/GCE revealed a good sensitivity (9.01 ± 0.15 µA mM −1 cm −2 ) and low LoD (31 ± 3 nM). Also, high selectivity was observed towards glucose detection in the presence of co-interfering species. Moreover, the Sr-Co 3 O 4 is applied in real-time monitoring of glucose in blood serum and sweat samples which received good recoveries.

Biofluids manipulation methods for liquid biopsy in minimally-invasive assays

The Liquid Biopsy (LB) is an opportunity for non-invasive diagnosis and prognosis of various diseases. To date, it isn't possible to consider that tissue biopsy can represent a pathology entirety. Then, body fluids are rich in a large number and variety of biomarkers and they can provide information about several diseases.•Recently, other biological fluids, easy to be collected are rising for their significant content of biomarkers and for the possibility to collect and manipulate them without the intervention of medical staff.•The management of biological fluids requires suitable storage methods. Temperature, storage time and physical stresses due to sample handling can lead to chemical and physical changes that may induce sample degradation and incorrect analysis.•The reliability of a diagnostic or screening test depends on its sensitivity and specificity. As the liquid biopsy is a 'snapshot' of a pathophysiological condition, it is crucial that its components do not degrade due to the improper handling of the body fluid.In this review, some handling methods of Saliva, Urine, Stool, Seminal Fluid, Tears and Sweat samples will be described, as well as protocols to facilitate the analysis of metabolites, nucleic acids, proteins and Extracellular Vesicles (EVs) from those unusual body fluids.

Detection of Infectious Respiratory Disease Through Sweat From Axillary Using an E-Nose With Stacked Deep Neural Network

Several methods have been used to detect infectious respiratory diseases, for example, by taking samples from blood, saliva, and phlegm. Although these methods generated high accuracy, they raised more problems that increased the risk of spreading and required more time to detect. Therefore, an accurate, quick, and low-cost device is required to help detect infectious respiratory diseases. This study proposes a new approach for detecting infectious respiratory diseases using an electronic nose (E-nose) through sweat samples from the human axilla. E-nose became safer by taking samples through the axillary because infectious respiratory diseases are not transmitted through sweat. This study proposes two new feature extraction techniques called stable value and highest slope. This study also proposes a stacked Deep Neural Network (DNN) for effective infectious respiratory disease detection. In the proposed stacked DNN, five fine-tuned DNN models obtained from hyperparameter tuning are stacked then the output of each DNN model became the input of the meta-model in the form of a fully connected layer. The proposed feature extraction method outperformed the existing feature extraction and was able to separate data between classes better. Furthermore, the proposed stacked DNN model generated an accuracy of 0.934 in the testing data, outperforming DNN single models and other state-of-the-art machine learning algorithms.

Patch-Type Wearable Enzymatic Lactate Biofuel Cell With Carbon Cloth Bioelectrodes for Energy Harvesting From Human Sweat

Enzyme-powered biofuel cells (EBFCs) are one of the most possible power sources for wearable microelectronic devices because of their small size and specificity of enzymes. The optimum realization of these energy sources becomes possible by fabricating biocompatible, flexible, and environment-friendly electrode materials with high active sites. Nanomaterials, with enhanced surface area, fulfill the above necessities and are used in a variety of applications. In this work, a novel membraneless enzymatic biofuel cell utilizing carbon nanotubes coated carbon cloth (CC) as bioelectrodes is presented. The bioelectrodes were integrated onto an article substrate to develop an economical and disposable patch-type wearable EBFC (W-EBFC). Such W-EBFC is designed which can deliver a power density of 132 and <inline-formula> <tex-math notation="LaTeX">$104 \mu \text{W}$ </tex-math></inline-formula>/cm², with a stable voltage in 8-mM lactate concentration and real samples of human sweat, respectively. The results reflect that CC-based bioelectrodes-based biofuel cells have enormous potential to be a good energy source for wearable biomedical applications.

Wearable healthcare smart electrochemical biosensors based on co-assembled prussian blue-graphene film for glucose sensing.

Wearable film-based smart biosensors have been developed for real-time biomolecules detection. Particularly, interfacial co-assembly of reduced graphene oxide-prussian blue (PB-RGO) film through electrostatic interaction has been systematically studied by controllable pH values, achieving optimal PB-RGO nanofilms at oil/water (O/W) phase interface driven by minimization of interfacial free energy for wearable biosensors. As a result, as-prepared wearable biosensors of PB-RGO film could be easily woven into fabrics, exhibiting excellent glucose sensing performance in amperometric detection with a sensitivity of 27.78 µA mM-1cm-2 and a detection limit of 7.94μM, as well as impressive mechanical robustness of continuously undergoing thousands of bending or twist. Moreover, integrated wearable smartsensing system could realize remotely real-time detection of biomarkers in actual samples of beverages or human sweat via cellphones. Prospectively, interfacial co-assembly engineering driven by pH-induced electrostatic interaction would provide a simple and efficient approach for acquiring functional graphene composites films, and further fabricate wearable smartsensing devices in health monitoring fields.

Highly sensitive and selective non-enzymatic measurement of glucose using arraying of two separate sweat sensors at physiological pH

A big challenge of non-enzymatic sensors is their lack of enough selectivity towards the analytes such as glucose, which must be addressed. In this study, a new system of arraying two different electrochemical sensors is designed to achieve glucose-selective and -sensitive non-enzymatic sweat-based sensors. Two kinds of sensors have been fabricated using (i) the controlled electrodeposition of cobalt/copper as the glucose-sensing electrode and (ii) the functionalized MWCNT/Fe3O4 electrode to eliminate the interference of other existing chemicals in the sweat. The controlled electrodeposition of Co/Cu led to the nanowire-shaped growth of cobalt and nanoparticle formation of copper on the carbon working electrode, confirmed by the SEM. Also, the functionalization of MWCNT with long-chain amine groups and Fe3O4 electrocatalysts has been monitored. Chronoamperometry test results of Co/Cu sensor showed a linear behavior in response to the glucose with a high sensitivity of 1909.86 µA.mM−1.cm−2 and less than 5% error for the chemicals interferences in the sweat with an exception for the uric acid. The second sensor for minimizing the uric acid interference has been fabricated based on F-MWCNT/Fe3O4, which showed a high sensitivity of 629.75 µA.mM−1.cm−2 towards the uric acid and no sensitivity response to the glucose. The arrayed sensors minimized the error imposed by the uric acid interference and the need for an alkaline medium for measuring the glucose in real sweat samples. The analyzed data of real sweat samples at physiological pH by Clarke's error grid method showed a “zone A” deviation (clinical accuracy zone), comparable with the blood glucose levels measured by the commercial glucometers.

Osmotically Enabled Wearable Patch for Sweat Harvesting and Lactate Quantification.

Lactate is an essential biomarker for determining the health of the muscles and oxidative stress levels in the human body. However, most of the currently available sweat lactate monitoring devices require external power, cannot measure lactate under low sweat rates (such as in humans at rest), and do not provide adequate information about the relationship between sweat and blood lactate levels. Here, we discuss the on-skin operation of our recently developed wearable sweat sampling patch. The patch combines osmosis (using hydrogel discs) and capillary action (using paper microfluidic channel) for long-term sweat withdrawal and management. When subjects are at rest, the hydrogel disc can withdraw fluid from the skin via osmosis and deliver it to the paper. The lactate amount in the fluid is determined using a colorimetric assay. During active sweating (e.g., exercise), the paper can harvest sweat even in the absence of the hydrogel patch. The captured fluid contains lactate, which we quantify using a colorimetric assay. The measurements show the that the total number of moles of lactate in sweat is correlated to sweat rate. Lactate concentrations in sweat and blood correlate well only during high-intensity exercise. Hence, sweat appears to be a suitable biofluid for lactate quantification. Overall, this wearable patch holds the potential of providing a comprehensive analysis of sweat lactate trends in the human body.

3D Printed Skin-Wash Sampler for Sweat Sampling in Cystic Fibrosis Diagnosis Using Capillary Electrophoretic Ion Ratio Analysis

Sweat chloride analysis is one of the important approaches in cystic fibrosis diagnosis. The commonly used Macroduct method to acquire sweat samples is semi-invasive, time consuming and expensive. Furthermore, this method often fails to collect a sufficient amount of sweat in newborns due to the insufficient sweating rate. In this work, we present a novel, simple, 3D-printed sampling device that is used to collect sweat specimens completely noninvasively in less than one minute. The device has a flow-through channel adjacent to the skin surface, through which 500 µL of deionized water is flushed and the spontaneously formed sweat on the skin in the channel area is washed into a plastic vial. The developed skin-wash procedure is a single step operation, is completely noninvasive and it always produces a sweat specimen. The ions from the skin-wash are subsequently analyzed by capillary electrophoresis with contactless conductivity detection and selected ion ratio (Cl−/K+) or ((Cl− + Na+)/K+) is used as a cut-off value to diagnose cystic fibrosis patients with sensitivity and specificity comparable to the conventional Macroduct method.

Sweat metabolomics before and after intravenous antibiotics for pulmonary exacerbation in people with cystic fibrosis

BackgroundPeople with cystic fibrosis (PWCF) suffer from acute unpredictable reductions in pulmonary function associated with a pulmonary exacerbation (PEx) that may require hospitalization. PEx symptoms vary between PWCF without universal diagnostic criteria for diagnosis and response to treatment. Research questionWe characterized sweat metabolomes before and after intravenous (IV) antibiotics in PWCF hospitalized for PEx to determine feasibility and define biological alterations by IV antibiotics for PEx. Study design and methodsPWCF with PEx requiring hospitalization for IV antibiotics were recruited from clinic. Sweat samples were collected using the Macroduct® Sweat Collection System at admission prior to initiation of IV antibiotics and after completion prior to discharge. Samples were analyzed for metabolite changes using ultra-high-performance liquid chromatography/tandem accurate mass spectrometry. ResultsTwenty-six of 29 hospitalized PWCF completed the entire study. A total of 326 compounds of known identity were detected in sweat samples. Of detected metabolites, 147 were significantly different between pre-initiation and post-completion of IV antibiotics for PEx (average treatment 14 days). Global sweat metabolomes changed from before and after IV antibiotic treatment. We discovered specific metabolite profiles predictive of PEx status as well as enriched biologic pathways associated with PEx. However, metabolomic changes were similar in PWCF who failed to return to baseline pulmonary function and those who did not. InterpretationOur findings demonstrate the feasibility of non-invasive sweat metabolomic profiling in PWCF and the potential for sweat metabolomics as a prospective diagnostic and research tool to further advance our understanding of PEx in PWCF.

Analysis of Stimulants in Sweat and Urine Using Disposable Pipette Extraction and Gas Chromatography Coupled to Mass Spectrometry in the Context of Doping Control.

Urine is initially collected from athletes to screen for the presence of illicit drugs. Sweat is an alternative sample matrix that provides advantages over urine including reduced opportunity for sample adulteration, longer detection-time window and non-invasive collection. Sweat is suitable for analysis of the parent drug and metabolites. In this study, a method was developed and validated to determine the presence of 13 amphetamine- and cocaine-related substances and their metabolites in sweat and urine using disposable pipette extraction (DPX) by gas chromatography coupled to mass spectrometry. The DPX extraction was performed using 0.1 M HCl and dichloromethane:isopropanol:ammonium hydroxide (78:20:2, v/v/v) followed by derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide at 90°C for 20 min. DPX extraction efficiencies ranged between 65.0% and 96.0% in urine and 68.0% and 101.0% in sweat. Method accuracy was from 90.0% to 104.0% in urine and from 89.0% to 105.0% in sweat. Intra-assay precision in urine and in sweat were <15.6% and <17.8%, respectively, and inter-assay precision ranged from 4.70% to 15.3% in urine and from 4.05% to 15.4% in sweat. Calibration curves presented a correlation coefficient -0.99 for all analytes in both matrices. The validated method was applied to urine and sweat samples collected from 40 professional athletes who knowingly took one or more of the target illicit drugs. Thirteen of 40 athletes were positive for at least one drug. All the drugs detected in the urine were also detected in sweat samples indicating that sweat is a viable matrix for screening or confirmatory drug testing.

Flat Disc-Shaped Sampling Probe and Online Re-extraction Apparatus for Mass Spectrometric Analysis of Skin Metabolites: A Proof of Concept.

Sweat analysis provides an alternative and noninvasive way of clinical diagnostics. However, sampling and transferring sweat-derived samples to analytical instruments is challenging. In this report, we demonstrate a method utilizing a flat disc-shaped sampling probe, and a compatible re-extraction apparatus coupled online with extractive electrospray ionization (EESI) mass spectrometry (MS). The probe enables sampling of metabolites from a skin area of ∼2.2 cm2. The subsequent online re-extraction and analysis by EESI-MS further mitigates matrix effects caused by sweat components, thus eliminating sample preparation steps. The total analysis time is only 6 min. We have optimized the key parameters of the system, including flow rate of the nebulizing gas in ESI, pressure of the nebulizing gas in pneumatic sample nebulizer, flow rate of the solvent in ESI, and composition of extractant. The standard solutions (0.1 mL) were supplemented with 0.04 M sodium chloride to mimic the matrix effect normally observed in sweat samples. The method has been characterized with four chemical standards (positive-ion mode of histidine, leucine, urocanic acid; negative-ion mode of lactic acid). The limits of detection range from 1.09 to 95.9 nmol. We have further demonstrated the suitability of the method for analysis of sweat. An attempt was made to identify some of the recorded signals by product-ion scan and accurate/exact mass matching.

Wearable Electronic Tongue for Non-Invasive Assessment of Human Sweat.

Sweat is a promising biofluid in allowing for non-invasive sampling. Here, we investigate the use of a voltammetric electronic tongue, combining different metal electrodes, for the purpose of non-invasive sample assessment, specifically focusing on sweat. A wearable electronic tongue is presented by incorporating metal electrodes on a flexible circuit board and used to non-invasively monitor sweat on the body. The data obtained from the measurements were treated by multivariate data processing. Using principal component analysis to analyze the data collected by the wearable electronic tongue enabled differentiation of sweat samples of different chemical composition, and when combined with 1H-NMR sample differentiation could be attributed to changing analyte concentrations.

A Wearable Patch for Prolonged Sweat Lactate Harvesting and Sensing.

Operating at low sweat rates, such as those experienced by humans at rest, is still an unmet need for state-of-the-art wearable sweat harvesting and testing devices for lactate. Here, we report the on-skin performance of a non-invasive wearable sweat sampling patch that can harvest sweat at rest, during exercise, and post-exercise. The patch simultaneously uses osmosis and evaporation for long-term (several hours) sampling of sweat. Osmotic sweat withdrawal is achieved by skin-interfacing a hydrogel containing a concentrated solute. The gel interfaces with a paper strip that transports the fluid via wicking and evaporation. Proof of concept results show that the patch was able to sample sweat during resting and post-exercise conditions, where the lactate concentration was successfully quantified. The patch detected the increase in sweat lactate levels during medium level exercise. Blood lactate remained invariant with exercise as expected. We also developed a continuous sensing version of the patch by including enzymatic electrochemical sensors. Such a battery-free, passive, wearable sweat sampling patch can potentially provide useful information about the human metabolic activity.

Canine Olfactory Detection of SARS-COV2-Infected Patients: A One Health Approach.

The aim of the present study is to apply the canine olfactory sensitivity to detect COVID-19-positive axillary sweat samples as a One Health approach in Latin America. One hundred volunteers with COVID-like symptoms were invited to participate, and both axillary sweat samples for dog detection and nasopharynx/oropharynx swabs for qPCR were collected. Two dogs, previously trained, detected 97.4% of the samples positive for COVID-19, including a false-negative qPCR-test, and the positive predictive value was 100% and the negative predictive value was 98.2%. Therefore, we can conclude that canine olfactory sensitivity can detect a person infected with COVID-19 through axillary sweat successfully and could be used as an alternative to screen them without invasive testing.