Integrated Electrochemical Aptasensor Array toward Monitoring Anticancer Drugs in Sweat.

In the realm of clinical practice, the concurrent utilization of anticancer medications can enhance their overall therapeutic efficacy. However, it is crucial to acknowledge that the interactions among these anticancer drugs can potentially yield detrimental consequences on their intended outcomes. Consequently, the assessment of both anticancer potency and potential toxic side effects is greatly refined when multiple anticancer drugs are simultaneously detected and evaluated. Here, we designed a wearable electrochemical aptasensor array for monitoring multiple anticancer drugs in sweat. The integrated sensor array consists of three working electrodes modified with three different aptamers (Apt1, Apt2, and Apt3), a Au counter electrode, and a Ag/AgCl reference electrode. Molecular docking simulations were performed to show the binding affinities between three anticancer drugs and their corresponding aptamers. Various eigenvalues were derived from the square-wave voltammetry electrochemical signals, and these data sets were subjected to rigorous analysis through multivariate data analysis techniques. This analytical approach demonstrated exceptional performance by achieving flawless 100% accuracy in the precise identification of nine anticancer drugs consistently at uniform concentrations. Furthermore, the integrated wearable sensor array exhibited impressive capabilities, correctly recognizing all nine anticancer drugs with 100% accuracy and successfully distinguishing between these drugs in artificial sweat samples. The proposed sensor array presents good stability for 15 days. Flexibility tests showed stable device performance after 500 twisting cycles. This innovative wearable sensing array represents a novel approach for achieving real-time monitoring and precise adjustment of drug dosages. It offers invaluable insights for tailoring the treatment of anticancer drugs to individual patients, predicting both drug efficacy and potential adverse reactions within the field of clinical medicine.

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.

Wearable sweat chloride sensors: materials, fabrication and their applications.

Chloride is a crucial anion required for multiple functions in the human body including maintaining acid-base balance, fluid balance, electrical neutrality and supporting muscles and nerve cells. Low-chloride levels can cause nausea, diarrhoea, etc. Chloride levels are measured in different body fluids such as urine, serum, sweat and saliva. Sweat chloride measurements are used for multiple applications including disease diagnosis, sports monitoring, and geriatric care. For instance, a sweat chloride test is performed for cystic fibrosis screening. Further, sweat also offers continuous non-invasive access to body fluids for real-time monitoring of chloride that could be used for sports and geriatric care. This review focuses on wearable chloride sensors that are used for periodic and continuous chloride monitoring. The multiple sections in the paper discuss the clinical significance of chloride, detection methods, sensor fabrication methods and their application in cystic fibrosis screening, sports and geriatric care. Finally, the last section discusses the limitation of current sensors and future directions for wearable chloride sensors.

Longitudinal assessment of sweat-based TNF-alpha in inflammatory bowel disease using a wearable device.

Wearable devices can non-invasively monitor patients with chronic diseases. Sweat is an easily accessible biofluid for continuous sampling of analytes, including inflammatory markers and cytokines. We evaluated a sweat sensing wearable device in subjects with and without inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract. Participants with an IBD related hospital admission and a C-reactive protein level above 5 mg/L wore a sweat sensing wearable device for up to 5 days. Tumor necrosis factor-alpha (TNF-α) levels were continually assessed in the sweat via the sensor, and daily in the blood. A second cohort of healthy subjects without chronic diseases wore the device for up to 48 h. Twenty-eight subjects were enrolled. In the 16 subjects with IBD, a moderate linear relationship between serum and sweat TNF-α levels was observed (R2 = 0.72). Subjects with IBD were found to have a mean sweat TNF-α level of 2.11 pg/mL, compared to a mean value of 0.19 pg/mL in 12 healthy controls (p < 0.0001). Sweat TNF-α measurements differentiated subjects with active IBD from healthy subjects with an AUC of 0.962 (95% CI 0.894-1.000). A sweat sensing wearable device can longitudinally measure key sweat-based markers of IBD. TNF-α levels in the sweat of subjects with IBD correlate with serum values, suggesting feasibility in non-invasive disease monitoring.

Designing of multifunctional graphene quantum dot-polyvinyl alcohol-polyglycerol luminescent film for fluorescence detection of pH in sweat.

BACKGROUND: Wound infection, skin disease, renal failure, cancer, cystic fibrosis, and other pathologies may induce obvious pH changes in sweat. Thus, tracking skin pH changes can help monitor human health in a convenient manner. Owing to their biocompatibility, easy preparation, and sensitive response to pH changes, graphene quantum dots (GQDs) have received increased attention in the optical detection of pH changes. However, their poor luminescent efficiency under visible light excitation and lack of functional diversification limit their application in skin pH monitoring. Therefore, the development of GQDs with excellent ultraviolet protection ability and antibacterial and luminescence performance is essential. RESULTS: Folic acid-, histidine-, and serine-functionalized boron-doped graphene quantum dots (FHSB-GQDs) were designed and synthesized via thermal treatment. The resulting FHSB-GQDs exhibit strong yellow fluorescence emission under excitation with 490-nm visible light and sensitive pH responsiveness. The peak fluorescence intensity linearly decreases with increasing pH from 4 to 9. Furthermore, the FHSB-GQDs were integrated with polyvinyl alcohol and polyglycerol to form a luminescent film via hydrogen bond interactions. The film exhibits high transparency, mechanical flexibility, ultraviolet protection ability, and antibacterial activity. The presence of polyvinyl alcohol and polyglycerol restricts the free movement of the FHSB-GQDs and improves fluorescence behavior. The film was successfully applied in an intelligent pH-sensing system for monitoring pH changes in human sweat. SIGNIFICANCE: The graphene quantum dot-polyvinyl alcohol-polyglycerol luminescent film offers excellent transparency, mechanical flexibility, ultraviolet protection ability, antibacterial activity, and luminescence performance. It was successfully applied in an intelligent pH sensing system for the detection of pH changes in human sweat. This study provides a new strategy for the design and construction of wearable sensing systems for health monitoring, facial masks, and medical dressings.

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

OBJECTIVE: To 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). DESIGN: Prospective, population-based study. SETTING: Public Statewide Newborn Screening Programme where the incidence rate of CF is ≈1:11 000. PATIENTS: Subjects with positive two-tiered immunoreactive trypsinogen. INTERVENTIONS: Sweat induction and collection were performed in the same facility; one sweat sample was obtained per individual. MAIN OUTCOME MEASURES: The QNS rate and its predictors; analysis corresponded to the day of sweat collection. RESULTS: Among the 975 participants, QNS rates for 10 and 15 µL were 3.6% (95% CI 2.5% to 4.9%) and 8.3% (95% CI 6.6% to 10.2%). Infants weighing >3056 and >3845 g and with gestational age higher than 37 weeks had a greater likelihood (5.5 and 6.7, and 2.7 and 5.8 times more, respectively) of avoiding QNS than their peers. CONCLUSION: QNS rates fulfilled the requirements, but predictors differed from those recommended by the Cystic Fibrosis Foundations guidelines.

Wearable biosensors for human sweat glucose detection based on carbon black nanoparticles.

Wearable glucose biosensors enable noninvasive glucose monitoring, thereby enhancing blood glucose management. In this work, we present a wearable biosensor based on carbon black nanoparticles (CBNPs) for glucose detection in human sweat. The biosensor consists of CBNPs, Prussian blue (PB), glucose oxidase, chitosan, and Nafion. The fabricated biosensor has a linear range of 5 µM to 1250 µM, sensitivity of 14.64 µA mM-1 cm-2, and a low detection potential (-0.05 V, vs. Ag/AgCl). The detection limit for glucose was calculated as 4.83 µM. This reusable biosensor has good selectivity and stability and exhibits a good response to glucose in real sweat. These results demonstrate the potential of our CBNP-based biosensor for monitoring blood glucose in human sweat.

Wearable electrochemical patch based on iron nano-catalysts incorporated laser-induced graphene for sweat metabolites detection.

The development of wearable devices shows great application potential in health management. In this work, we propose the fabrication of a novel wearable electrochemical patch and prove its application in sweat metabolites detection. The patch is developed based on iron nano-catalysts incorporated laser-induced graphene (FeNCs/LIG), which is a newly integrated sensing electrode with unique three-dimensional nanostructure and good electrocatalytic activity. It shows desirable sensing performances for sweat metabolites including tyrosine (Tyr) and uric acid (UA) molecules. The detection limit of Tyr and UA can reach 5.11 µM and 1.37 µM, respectively. Besides, density functional theory calculation deeply reveals that the Fe active sites of FeNCs play an important role in molecule adsorption and electron transference, thus promoting sensing performance. To realize wearable application, a dual-channel hydrogel chip is designed and assembled with FeNCs/LIG. The developed patch is successfully utilized to accurately determination of Tyr and UA in sweat. This work is expected to provide a new non-invasive strategy for evaluating amino acid intake and metabolic level.

Lead-containing radiation-attenuating sterile gloves in simulated use: Lead transfer to sweat as an unknown risk to users.

BACKGROUND: Lead protective gloves are widely used to attenuate scattered radiations during fluoroscopic-guided medical procedures, thereby reducing hand exposure to radiation. AIMS: To determine whether lead-containing gloves present a risk of metal leaching onto the operator's skin, particularly due to the presence of sweat. METHODS: Artificial sweat of varying acidity was introduced into two types of commercial gloves containing lead. The level of lead in the sweat was then assessed after different exposure times. Electron microscopy was used to observe the morphology of the glove layers. RESULTS: Lead was detected in artificial sweat during each contact test on two different types of gloves. The concentration of lead increased with the acidity of the sweat, and the contact time. Gloves with a protective lining transferred less lead into sweat, but it was still present at significant levels. (i.e. few milligrams of lead per glove after one hour contact). CONCLUSIONS: Fluoroscopy operators should be aware of the risk of leaching of lead ions when using lead gloves under intensive conditions, although the potential harmfulness of lead ions leached into the glove remains essentially unknown.

Is It Worth the Sweat? Prehabilitation in Uro-oncology: A Mini Review.

In several surgical specialities, exercise as part of a prehabilitation program enhances recovery. However, for uro-oncological patients, evidence up to 2020 did not demonstrate significant benefits in terms of postoperative complications or hospital length of stay (LOS). We reviewed the literature from 2020 to 2023 and screened 205 reports, of which four full texts were included. Two retrospective cohort studies, despite having potential confounding risks, indicated that preoperative exercise might reduce LOS. One of these studies also suggested a lower likelihood of complications. Present evidence hints at the potential benefits of embedding exercise in prehabilitation for uro-oncological patients, particularly for short-term functional results. However, evidence on a direct effect on postoperative complications and LOS is still inconclusive. Future research should prioritise identification of specific exercises (eg, anaerobic vs aerobic, strength training, endurance, or respiratory exercises) that yield the most cost-effective benefits. PATIENT SUMMARY: Recent studies suggest that exercising before surgery might help people with urological cancers to improve their short-term fitness. More research is needed to see if exercise before surgery shortens hospital stays or reduces complications.

Sweat induction using Pilocarpine microneedle patches for sweat testing in healthy adults.

BACKGROUND: The sweat test using pilocarpine iontophoresis remains the gold standard for diagnosing cystic fibrosis, but access and reliability are limited by specialized equipment and insufficient sweat volume collected from infants and young children. These shortcomings lead to delayed diagnosis, limited point-of-care applications, and inadequate monitoring capabilities. METHODS: We created a skin patch with dissolvable microneedles (MNs) containing pilocarpine that eliminates the equipment and complexity of iontophoresis. Upon pressing the patch to skin, the MNs dissolve in skin to release pilocarpine for sweat induction. We conducted a non-randomized pilot trial among healthy adults (clinicaltrials.gov, NCT04732195) with pilocarpine and placebo MN patches on one forearm and iontophoresis on the other forearm, followed by sweat collection using Macroduct collectors. Sweat output and sweat chloride concentration were measured. Subjects were monitored for discomfort and skin erythema. RESULTS: Fifty paired sweat tests were conducted in 16 male and 34 female healthy adults. MN patches delivered similar amounts of pilocarpine into skin (1.1 ± 0.4 mg) and induced equivalent sweat output (41.2 ± 25.0 mg) compared to iontophoresis (1.2 ± 0.7 mg and 43.8 ± 32.3 mg respectively). Subjects tolerated the procedure well, with little or no pain, and only mild transient erythema. Sweat chloride concentration measurements in sweat induced by MN patches (31.2 ± 13.4 mmol/L) were higher compared to iontophoresis (24.0 ± 13.2 mmol/L). Possible physiological, methodological, and artifactual causes of this difference are discussed. CONCLUSIONS: Pilocarpine MN patches present a promising alternative to iontophoresis to enable increased access to sweat testing for in-clinic and point-of-care applications.

Pharmacy compounded pilocarpine: An adequate solution to overcome shortage of pilogel® discs for sweat testing in patients with cystic fibrosis.

To respond to shortage of pilocarpine discs due to CE-licensing problems a pharmacy compounded pilocarpine HCL solution was developed and validated for use in CF diagnosis. The aim of this study was to compare the results from a pharmacy compounded pilocarpine HCL solution versus Pilogel® discs for the measurements of sweat chloride concentrations. Ten pediatric and adult patients with CF underwent a sweat test using both Pilogel® discs and pilocarpine HCL solution. The average difference between both methods was -3.25 mmol/L (95% Limits of Agreement: -7.19 [95% CI: -9.19;-5.19] and 0.69 [95% CI: -1.31;2.69] mmol/L. Passing-Bablok regression showed that zero was enclosed with the 95% CI of the calculated intercept (0.15 [95% CI: -1.70;1.42] mmol/L). These data show a good agreement in chloride concentrations obtained using the two pilocarpine products. Therefore, the pharmacy compounded pilocarpine HCL solution can be used as an alternative for Pilogel® discs during times of shortage.

Unrevealing the connection between real sample analysis and analytical method. The case of cytokines.

Cytokines are compounds that belong to a special class of signaling biomolecules that are responsible for several functions in the human body, being involved in cell growth, inflammatory, and neoplastic processes. Thus, they represent valuable biomarkers for diagnosing and drug therapy monitoring certain medical conditions. Because cytokines are secreted in the human body, they can be detected in both conventional samples, such as blood or urine, but also in samples less used in medical practice such as sweat or saliva. As the importance of cytokines was identified, various analytical methods for their determination in biological fluids were reported. The gold standard in cytokine detection is considered the enzyme-linked immunosorbent assay method and the most recent ones have been considered and compared in this study. It is known that the conventional methods are accompanied by a few disadvantages that new methods of analysis, especially electrochemical sensors, are trying to overcome. Electrochemical sensors proved to be suited for the elaboration of integrated, portable, and wearable sensing devices, which could also facilitate cytokines determination in medical practice.

Gap junction-mediated contraction of myoepithelial cells induces the peristaltic transport of sweat in human eccrine glands.

Eccrine sweat glands play an essential role in regulating body temperature. Sweat is produced in the coiled secretory portion of the gland, which is surrounded by obliquely aligned myoepithelial cells; the sweat is then peristaltically transported to the skin surface. Myoepithelial cells are contractile and have been implicated in sweat transport, but how myoepithelial cells contract and transport sweat remains unexplored. Here, we perform ex vivo live imaging of an isolated human eccrine gland and demonstrate that cholinergic stimulation induces dynamic contractile motion of the coiled secretory duct that is driven by gap junction-mediated contraction of myoepithelial cells. The contraction of the secretory duct occurs segmentally, and it is most prominent in the region surrounded by nerve fibers, followed by distension-contraction sequences of the excretory duct. Overall, our ex vivo live imaging approach provides evidence of the contractile function of myoepithelial cells in peristaltic sweat secretion from human eccrine glands.

Colorimetric sweat analysis using wearable hydrogel patch sensors for detection of chloride and glucose.

Sweat is a promising non-invasive biofluid that can provide valuable insights into the physiological state of the human body. However, a major obstacle to analyzing sweat in real-time is the fabrication of simple, fast-acting, accurate, and low-cost sensing constructs. To address this challenge, we introduced easily-prepared wearable hydrogel sensors that can be placed on the skin and used colorimetric techniques to assess sweat analytes without invasive procedures. Two typical sweat sensors, chloride ion (Cl-) responsive patches for cystic fibrosis (CF) analysis and glucose response patches for diabetic monitoring, were demonstrated for real sample analysis. The Cl- colorimetric sensor, with a detection limit down to 100 µM, shows a good linear response from 1.56 mM to 200 mM Cl-, and the glucose colorimetric sensor, with a detection limit down to 1 µM, exhibits an adequate linear response from 10 µM to 1 mM glucose. These colorimetric hydrogel sensors are also incorporated into a medical dressing to create wearable sensor devices for real-time sweat analysis. The acquired readings closely match the results obtained from the benchmark analyzing instrument, with a small deviation of less than 10%. Therefore, our simple colorimetric hydrogel sensing patches hold great potential to advance real-time sweat testing and contribute to the transitional development of wearable medical devices.

Gas chromatography-flame ionization detector for sweat based COVID-19 screening.

Simple approach for rapid screening of corona virus disease 2019 (COVID-19) has been developed. This applied gas chromatography-flame ionization detector (GC-FID) analyzing the potential compound marker in sweat samples obtained from COVID-19 positive and negative volunteers in Bangkok, Thailand. The samples were collected by using cotton rods for 15 min, heated at 90 °C for 5 min, and the volatile compounds in the headspace (HS) were injected (5.00 mL) at 150 °C and separated within 13.7 min. The marker peak was tentatively identified as p-cymene by the authentic standard injection and comparison with the GC-mass spectrometry (GC-MS) and comprehensive two-dimensional GC (GC × GC)-MS analysis. Possible mechanisms for the presence of p-cymene were proposed. The marker peak area thresholds were then varied and optimized via construction of the receiver operating characteristic (ROC) curve. With the optimum threshold, the established method offered the accuracy, sensitivity and specificity of 96 %. This method was insignificantly affected (p-value >0.05) by genders, body mass indices, ages, and use of deodorants as well as the p-cymene containing food. However, the performance could be affected by the population with personal hygiene or experiencing the microbiomes producing p-cymene.

Reexamining the Minimum Sweat Rate Requirement for Sweat Chloride Testing.

BACKGROUND: Guidelines for sweat chloride testing endorse a minimum sweat rate for reporting results. Bilateral sweat collection is recommended, but if both sites fail to meet the minimum rate (quantity not sufficient, QNS), the test should be repeated. In this study, we examine the correlation between sweat rate and sweat chloride concentration ([Cl-]), assess the accuracy of specimens collected at suboptimal rates, and investigate the use of pooled bilateral specimens for chloride measurement. METHODS: Pearson correlation was employed to analyze the relationship between sweat rate and chloride concentration, [Cl-], in 674 macroduct collections. Weighted kappa was evaluated to determine cystic fibrosis (CF) diagnostic classification concordance for 18 tests with paired arms above vs below the minimum sweat rate. Deming regression was applied to compare [Cl-] from pooled bilateral specimens vs neat specimens in 27 collections with residual volume available after clinical testing. RESULTS: Pearson correlation of sweat rate vs [Cl-] was minimal (r = -0.0735) across specimens with varying rates and [Cl-]. There was substantial agreement in CF diagnostic classification between arms for bilateral collections with discordant sweat rates. Regression analysis of [Cl-] in pooled vs nonpooled specimens revealed a slope of 0.984 and an intercept of 0.796. CONCLUSIONS: Negligible correlation of sweat rate and [Cl-] suggests the minimum sweat rate for macroduct collectors may be overly stringent. Reporting of [Cl-] in specimens with ≥10 µL (rate ≥0.3 µL/min) may reduce QNS rates without compromising diagnostic accuracy. Preliminary data suggests pooling of bilateral collections may be a feasible option to achieve the required volume for testing.

Sweat conductivity diagnostic accuracy for cystic fibrosis: a systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis of diagnostic test accuracy studies to summarise the properties of sweat conductivity (SC) to rule in/out cystic fibrosis (CF). DATA SOURCE: We searched PubMed, Embase, Web of Science, Google Scholar, SciELO and LILACS up to 13 March 2023. STUDY SELECTION: We selected prospective and retrospective diagnostic test accuracy studies which compared SC, measured through two well-established and commercially available devices, that is, Nanoduct or Sweat-Chek Analyser, to quantitative measurement of sweat chloride. MAIN OUTCOME MEASURES: Pooled sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood ratio (-LR), and their corresponding 95% CIs. DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies guidelines were followed. Data were extracted by one reviewer and checked by another. The hierarchical summary receiver operating characteristics model was used to estimate diagnostic test accuracy. RESULTS: Ten studies involving 8286 participants were included. The pooled estimates of sensitivity, specificity, +LR and -LR were 0.97 (95% CI 0.94 to 0.98), 0.99 (95% CI 0.98 to 0.99), 171 (95% CI 58 to 500) and 0.02 (95% CI 0.01 to 0.05), respectively. Sensitivity analyses did not reveal a substantial impact of study-level factors on the results, such as study quality, cut-off values for a positive test, study sample size and participant age group. The quality of evidence was considered moderate. CONCLUSION: SC demonstrated excellent diagnostic performance. In addition, its accuracy parameters suggest its role as an alternative to the sweat test for CF diagnosis. PROSPERO REGISTRATION NUMBER: CRD42022284504.

A Wearable Electrochemical Sensor Based on Anti-Fouling and Self-Healing Polypeptide Complex Hydrogels for Sweat Monitoring.

Although continuous monitoring of constituents in complex sweat is crucial for noninvasive physiological evaluation, biofouling on the sweat sensor surface and inadequate flexible self-healing materials restrict its applications. Herein, a fully self-healing and strong anti-biofouling polypeptide complex hydrogel (AuNPs/MoS2/Pep hydrogel) with excellent electrochemical performances was created. The anti-fouling electrochemical sweat sensor was fabricated based on the AuNPs/MoS2/Pep hydrogel to address these issues. It was found that the polypeptide hydrogel was designed to form a network structure and carried abundant hydrophilic groups, resulting in a AuNPs/MoS2/Pep hydrogel with superior anti-biofouling properties in sweat for 30 min and even long-term stability in undiluted human sweat. In addition, SEM, TEM, UV, XPS, and infrared spectrogram demonstrated that the binding force of π-π stacking force between MoS2 and naphthalene groups in the designed peptide endowed the polypeptide complex hydrogel with an excellent self-healing property. Furthermore, the polypeptide complex hydrogel preserved wearable device function of continuously monitoring uric acid (UA) and ascorbic acid (AA) in sweat in situ. This novel fabricated sweat sensor with high anti-biofouling ability, excellent self-healing property, and sensitive and selective analytical capability describes a new opportunity for health monitoring in situ.