Article

Correlation Between Sweat Glucose and Blood Glucose in Subjects with Diabetes

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Abstract

Sweat contains glucose that can accurately reflect blood glucose. However, skin surface glucose can confound these measurements. A perfusion method was used to rapidly harvest sweat from forearm sites on human subjects. The sweat samples were analyzed for glucose by high-performance liquid chromatography methods and compared with the results obtained with a blood glucose meter. The results of 23 different studies of seven individual subjects with diabetes show a strong correlation between sweat glucose and blood glucose. Sweat glucose, when properly harvested to prevent contamination from other sources on the skin's surface, can accurately reflect blood glucose levels.

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... It can monitor sweat glucose for duration of an entire exercise (20~100 min) with a typical sweat glucose concentration range from 0 to 100 μM and the sensitivity is 2.1 nA µM −1 . For longer glucose monitoring, skin ISF is an ideal sample source, because it is formed by capillary filtration of blood and its glucose concentration is almost the same as that in blood 48 . Microneedle-based electrochemical biosensors have been developed to monitor dermal glucose in skin ISF with minimal invasion. ...
... During drinking, alcohol is absorbed within 5 to 10 min, showing peaks in the blood 30 to 90 min after drinking and lasting for 12 h 70,71 . Alcohol in sweat lasts up to 24 h and for 24 to 48 h in saliva 48 . About 10% of alcohol leaves the body through the urine, which lasts for three to five days 48,72,73 . ...
... Alcohol in sweat lasts up to 24 h and for 24 to 48 h in saliva 48 . About 10% of alcohol leaves the body through the urine, which lasts for three to five days 48,72,73 . Some commercial sensors mentioned above have been able to monitor alcohol for months and are suitable for long-term alcohol monitoring (Fig. 2). ...
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Physiological monitoring can provide detailed information about health conditions, and therefore presents great potentials for personalized healthcare. Flexible miniaturized sensors (FMS) for physiological monitoring have garnered significant attention because of their wide applications in collecting health-related information, evaluating and managing the state of human wellness in long term. In this review, we focus on the time scale of human physiological monitoring, the needs and advances in miniaturized technologies for long-term monitoring in typical applications. We also discuss the rational sample sources of FMS to select proper strategies for specific monitoring cases. Further, existing challenges and promising prospects are also presented.
... The association between SG and BG is also explicitly demonstrated [27,28]. Since sweat reaction occurs quickly and the sweat gland is highly vascularized, glucose levels inside the body can be estimated from sweat samples [29]. The concentration of glucose in human sweat is from 0.06-0.2 ...
... mM and corresponds to 3.3-17.3 mM in BG [29,30]. However, significant challenges remain in obtaining accurate sweat glucose data, such as changes in environmental parameters such as temperature, contamination from skin, sporadic sampling without iontophoretic incitement, low production rate, and the mixing of old samples with the new samples. ...
Article
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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.
... Metabolites such as glucose and lactate are present in sweat and have proven to be correlated to their blood levels. 340,341 Abnormal health conditions can change the sweat composition by affecting the concentration of its components or by the occurrence of new ones. Although the segregating mechanisms at play are still poorly understood, it has been hypothesized that analytes contained in sweat passively or actively diffuse from the neighboring blood or ISF at levels ranging from traces (e.g., proteins, pM − nM), to intermediate (e.g., glucose, μM), and to high concentrations (e.g., urea and lactate, mM). ...
... 342,343 Several studies presented that sweat glucose is correlated to blood glucose, as such it can be used for diabetes screening and management, while abnormally high sweat urea concentration can suggest kidney failure. 341 Similarly, sweat lactate is speculated to be informative of the physiological status (e.g., physical stress and aerobic/anaerobic transitions). 344,345 These observations have made sweat an accessible and ideal biofluid for noninvasive biosensing compared to the more conventional blood. ...
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Electrochemical detection of metabolites is essential for early diagnosis and continuous monitoring of a variety of health conditions. This review focuses on organic electronic material-based metabolite sensors and highlights their potential to tackle critical challenges associated with metabolite detection. We provide an overview of the distinct classes of organic electronic materials and biorecognition units used in metabolite sensors, explain the different detection strategies developed to date, and identify the advantages and drawbacks of each technology. We then benchmark state-of-the-art organic electronic metabolite sensors by categorizing them based on their application area (in vitro, body-interfaced, in vivo, and cell-interfaced). Finally, we share our perspective on using organic bioelectronic materials for metabolite sensing and address the current challenges for the devices and progress to come.
... It should be noted that very large differences exist in reported concentration ranges in the literature, which makes the choice of analyte concentration for this study somewhat arbitrary. The glucose level in sweat has been shown to correlate with blood, however, the presence of glucose is much lower than in blood, but with very large variations in reported values between different studies (from 0.1 mM up to around 2 mM) [38,39]. Sweat electrolyte concentration can vary widely between individuals, with concentration values of sodium and chloride reported below 10 mM and above 100 mM, with chloride being used for diagnosis of cystic fibrosis [9,10]. ...
... As shown in Section 3.1, a voltammetric e-tongue can be used to separate complex physiological fluids of different compositions, which could be used for example to determine attributes of the fluids or to monitor changes in the fluids. Sweat is of particular interest as it can be monitored non-invasively, contains a wealth of physiologically and metabolically important biomarkers, and shows a large variability in composition [5,36,39,48]. To allow for sweat monitoring directly on the skin, a wearable e-tongue prototype was designed, shown in Figure 5. Au, Pt, and Pd were plated on a flexible circuit board and used as working electrodes, with an Ag counter/reference electrode. ...
Article
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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.
... In general, it is usually easier detect some substance in sweat in areas of the skin with higher amounts of eccrine glands like palms and sole of foot, as they allow the analysis of larger volumes. The correlations of chemical molecular levels in blood and sweat have been reported, such as glucose [45], lactate [46], ethanol [13], ammonia and urea [47]. These studies concluded that, to some extent, blood analysis can be replaced by sweat analysis. ...
... However, the final composition of sweat is influenced by several factors such as extracellular concentrations solute, residual sweat, sweat flow rate, sweat gland metabolism in each area of skin, skin contamination and sample evaporation. Thus, despite all the non-invasive advantages, the diagnosis of human sweat on the skin surface of an individual may have some inconveniences such as low sample volumes, contamination of the The correlations of chemical molecular levels in blood and sweat have been re-ported, such as glucose [45], lactate [46], ethanol [13], ammonia and urea [47]. These studies concluded that, to some extent, blood analysis can be replaced by sweat analysis. ...
Article
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The continued focus on improving the quality of human life has encouraged the development of increasingly efficient, durable, and cost-effective products in healthcare. Over the last decade, there has been substantial development in the field of technical and interactive textiles that combine expertise in electronics, biology, chemistry, and physics. Most recently, the creation of textile biosensors capable of quantifying biometric data in biological fluids is being studied, to detect a specific disease or the physical condition of an individual. The ultimate goal is to provide access to medical diagnosis anytime and anywhere. Presently, alcohol is considered the most commonly used addictive substance worldwide, being one of the main causes of death in road accidents. Thus, it is important to think of solutions capable of minimizing this public health problem. Alcohol biosensors constitute an excellent tool to aid at improving road safety. Hence, this review explores concepts about alcohol biomarkers, the composition of human sweat and the correlation between alcohol and blood. Different components and requirements of a biosensor are reviewed, along with the electrochemical techniques to evaluate its performance, in addition to construction techniques of textile-based biosensors. Special attention is given to the determination of biomarkers that must be low cost and fast, so the use of biomimetic materials to recognize and detect the target analyte is turning into an attractive option to improve electrochemical behavior.
... We assume that in order to expand the upper limit of the linear detection range, it is necessary to increase the immobilizing capacity of enzyme onto a WE. * Low LOD and linear detection range (LDR) of glucose (summarized in table 9) is a necessary and sufficient for detection glucose in urine samples (the normal concentration of glucose in urine sample is between 0 and 0.8 mM [76]) and in perspiration (sweat glucose levels can accurately reflect blood glucose levels, with a correlation whereby 0.3 mM glucose in sweat corresponds to 16.7 mM glucose in the blood [80]). Zahed [28] and Yoon [78] et al., reported applications of LIGbased sensors for detection glucose in sweet. ...
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In this review, laser‐induced graphene (LIG) ‐based electrodes are discussed by covering such essential areas, as a characterization of LIG material properties necessary for electroanalysis, including data on LIG sheet resistance, wettability, spatial resolution, as well as correlations of "process" ‐ "properties" ‐ "electroanalytical characteristics", electrochemical characteristics of LIG‐electrodes. Moreover, typical and innovative LIG‐based electrodes designs for electroanalytical applications, including combined multi‐analyte multimodal wearable sensors, interdigitated electrodes, are shown. The essential data related to LIG in electroanalysis are summarized in tables. The authors also discussed recent LIG‐based electroanalytical applications. Close attention has been paid to LIG glucose sensors and biosensors.
... Alternatively, glucose screening using external body fluids that can be non-invasively collected, such as tears, saliva, sweat, or urine, has been studied in humans Moyer et al., 2012;Yamaguchi et al., 1998). Several previous studies have attempted to demonstrate the correlation between BG and tear glucose (TG) levels in humans and to develop non-invasive TG sensors, such as contact lenses (Badugu et al., 2004;Park et al., 2018) and flexible spring-like devices placed under the lower eyelid (Kownacka et al., 2018). ...
Article
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Background: No previous studies have quantified tear glucose (TG) levels in dogs or compared changes in TG and blood glucose (BG) concentrations. Objective: To quantify TG concentration and evaluate its correlation with BG level in dogs. Methods: Twenty repetitive tests were performed in alternate eyes of four dogs, with a minimum washout period of 1 week. Tears and blood were collected at 30-min intervals with successive glucose injections (1 g/kg) every 30 min. Cross-correlations of BG and TG levels were assessed. The delay and association between TG and corresponding BG levels were analysed for each dog; samples were collected at 5-min intervals. The tears were collected using microcapillary tubes. Collected tears and blood were analysed for glucose concentration using a colorimetric assay and commercially available glucometer, respectively. Results: The average baseline BG and TG levels were 4.76 ± 0.58 and 0.39 ± 0.04 mmol/L, respectively. Even with highly fluctuating BG levels, a significant cross-correlation coefficient (r = 0.86, p < 0.05) was observed between changes of BG and TG levels. The delay time between BG and TG levels was 10 min. On average, BG levels were 16.34 times higher than TG levels. There was strong correlation between BG and TG levels (rs = 0.80, p < 0.01). Significant differences in TG concentrations between normoglycaemia, mild hyperglycaemia, and severe hyperglycaemia were found (p < 0.05). Conclusions: Canine TG concentrations have not been quantified previously. Our findings suggest preliminary data for future research on TG levels in dogs and show TG measurement could be used to screen for diabetes mellitus in dogs.
... As shown in Figure 4a, the detected glucose concentrations in artificial sweats were close to the standard concentrations both in sweat from healthy people (0.06−0.2 mM, within the green region in Figure 4a) and people with hyperglycemia (>0.2 mM, above the green region) or hypoglycaemia (<0.06 mM, below the green region). 43,44 In addition, a high linear correlation coefficient (R 2 = 0.9951) was obtained between the standard concentrations and the measured concentrations (Figure 4b). Therefore, abnormalities in the glucose concentration of a person can be precisely determined. ...
Article
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In situ analysis of sweat provides a simple, convenient, cost-effective, and noninvasive approach for the early diagnosis of physical illness in humans and is particularly useful in family care. In this study, a flexible and skin-attachable colorimetric sweat sensor for multiplexed analysis is developed using a simple, cost-effective, and convenient method. The obtained sweat sensor can be used to simultaneously detect glucose, lactate, urea, and pH value in sweat, as well as sweat loss and skin temperature. Only 2.5 μL of sweat is enough for the whole test, and the sweat loss and chemical-sensing results can be read out conveniently by naked eyes or a smartphone. In addition, body temperature can also be detected with an additional electrical circuit. Our sweat sensor provides a new, cost-effective, and convenient approach for in vitro diagnosis of multiple components in sweat, and the easy fabrication and cost-effectiveness make our sensor commercializable in the near future.
... The research results show that the time delay of ISF, sweat, tears and saliva is 15-20 min, 8-10 min, at least 15 min and about 1000 s, respectively. 15,60,[63][64][65] Along with noninvasive devices, wearable meters have been used in the area of CGM, and although the idea of wearable meters to monitor BG levels noninvasively has been proposed a while back most of them are still in their infancy; for example, the GlucoWatch (Cygnus, California, USA), which is based on the reverse iontophoresis, was withdrawn from the market because of the long warmup time, skin irritation and poor instant detection. However, wearable meters still show great prospects and certain research under development has recently achieved encouraging results (Fig. 5). ...
Article
Blood glucose (BG) concentration of the human body serves as an important index for diagnosis of diabetes, and its detection methods need to be more efficient due to high mortality rates for diabetes. Typical household BG meters are invasive products based on electrochemistry and rely on finger pricks to procure blood, which might result in skin damage and bacterial infections. Moreover, such BG meters can only detect the BG concentration at a certain time while ignoring the BG level at other times. Recently, to achieve microinvasive, noninvasive and continuous glucose monitoring (CGM) by detecting body fluid, such as sweat or tears, the research direction has been gradually developing toward wearable devices. This review discusses the glucose detection mechanism of various electrochemical and optical glucose sensors, and briefly analyzes their advantages and challenges. Additionally, wearable products based on various principles that have appeared on the market are also summarized. Furthermore, based on the analysis, this review proposes a design concept for future research directions.
... Of all body fluids, sweat has attracted attention for glucose monitoring in a completely non-invasive manner. Potts et al. showed that sweat glucose strongly correlates with blood glucose 18 . This and other complementary works in the field have established the value of measuring sweat glucose as a truly non-invasive strategy for monitoring glycemic control in humans [19][20][21][22] . ...
Article
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Diabetes is a chronic endocrine disease that occurs due to an imbalance in glucose levels and altering carbohydrate metabolism. It is a leading cause of morbidity, resulting in a reduced quality of life even in developed societies, primarily affected by a sedentary lifestyle and often leading to mortality. Keeping track of blood glucose levels noninvasively has been made possible due to diverse breakthroughs in wearable sensor technology coupled with holistic digital healthcare. Efficient glucose management has been revolutionized by the development of continuous glucose monitoring sensors and wearable, non/minimally invasive devices that measure glucose concentration by exploiting different physical principles, e.g., glucose oxidase, fluorescence, or skin dielectric properties, and provide real-time measurements every 1–5 min. This paper presents a highly novel and completely non-invasive sweat sensor platform technology that can measure and report glucose concentrations from passively expressed human eccrine sweat using electrochemical impedance spectroscopy and affinity capture probe functionalized sensor surfaces. The sensor samples 1–5 µL of sweat from the wearer every 1–5 min and reports sweat glucose from a machine learning algorithm that samples the analytical reference values from the electrochemical sweat sensor. These values are then converted to continuous time-varying signals using the interpolation methodology. Supervised machine learning, the decision tree regression algorithm, shows the goodness of fit R ² of 0.94 was achieved with an RMSE value of 0.1 mg/dL. The output of the model was tested on three human subject datasets. The results were able to capture the glucose progression trend correctly. Sweet sensor platform technology demonstrates a dynamic response over the physiological sweat glucose range of 1–4 mg/dL measured from 3 human subjects. The technology described in the manuscript shows promise for real-time biomarkers such as glucose reporting from passively expressed human eccrine sweat.
... Many current laboratory-based methods, such as colorimetry [22], spectrophotometry [23], immunoassays [24], chromatography [25], and mass spectrometry [26], can be used to evaluate biological markers in biofluids. However, these approaches are generally coupled with sample processing, skilled lab workers, or miniaturization difficulties. ...
Article
Wearable electrochemical sensors that can detect chemical analytes non-invasively are a fast developing next-generation digital-health technology. Because of their excellent performance, intrinsic compactness, and low cost, electrochemical-based sensors are capable of detecting biomarkers through a non-invasive approach for the continuous monitoring of real-time health status, which holds a lot of potential as wearable sensors for a tremendous promise for a plethora of applications. These wearable electrochemical sensors have been incorporated into various materials systems and even directly on the epidermis for different monitoring purposes because of their unique potential to process chemical analytes in a minimal/non-invasive and non-obtrusive manner. With ongoing innovation and a focus on critical challenges, such minimal/non-invasive electrochemical biosensors are anticipated to open up a new exciting path in the field of wearable wireless sensing devices and body-sensor networks, and thus find abundant use in a wide range of personal healthcare monitoring as well as in sport and military applications. Hence, this review article examines current advancements and discoveries in the field of wearable biosensors, with a focus on a subset of these devices that can conduct very sensitive electrochemical analysis. Recent insights into novel sampling strategies, various electrochemical sensing mechanisms and power management techniques have been discussed in detail in this review article. Finally, present unmet challenges and opportunities in wearable electrochemical biosensors are explored to motivate future technological breakthroughs.
... This lag time is related to the time it takes for glucose to diffuse from blood vessels through the capillary walls to the interstitial fluid, which is approximately 15−20 min, 4,30 after which glucose reaches the skin surface via sweat glands. Despite this delay, sweat glucose levels can be correlated with the real blood glucose levels, 31 and therefore, our MPA sensing patch is a highly promising platform to be used as a wearable patch (Figure 5b) for noninvasive continuous glucose monitoring in sweat. ...
... Therefore, non-invasive glucose monitoring has been widely studied. [95][96][97] The Zahed team developed a glucose sensor for sweat monitoring. 98 Graphene electrodes integrated on a PI substrate were modified with glucose oxidase, fabricating a glucose sensor with high sensitivity and stability. ...
Article
In recent years, real-time health management has received increasing attention, benefiting from the rapid development of flexible and wearable devices. Conventionally, flexible and wearable devices are used for collecting health data such as electrophysiological signals, blood pressure, heart rate, etc. The monitoring of chemical factors has shown growing significance, providing the basis for the screening, diagnosis, and treatment of many diseases. Nowadays, in order to understand the health status of the human body more comprehensively and accurately, researchers in the community have started putting effort into developing wearable devices for monitoring chemical factors. Progressively, more flexible chemical sensors with wearable real-time health-monitoring functionality have been developed thanks to advances relating to wireless communications and flexible electronics. In this review, we describe the variety of chemical molecules and information that can currently be monitored, including pH levels, glucose, lactate, uric acid, ion levels, cytokines, nutrients, and other biomarkers. This review analyzes the pros and cons of the most advanced wearable chemical sensors in terms of wearability. At the end of this review, we discuss the current challenges and development trends relating to flexible and wearable chemical sensors from the aspects of materials, electrode designs, and soft-hard interface connections.
... 24,25,28,37 However, simplicity of preparation, utilization of low-cost materials, and preparation technologies provide great opportunity in the large-scale manufacturing of this type of sensors for adequate glucose detection levels, which requires distinguishing analyte levels from 100 to 10 mM according to reports of the Diabetes Association. 94 Glucose detection in blood, sweat, and urine requires high selectivity in sensing, due to the presence of other endogenous compounds such as urea, uric acid, acetic acid, and other sugars (sucrose, fructose), which constrain the functionality of the enzyme-free sensors. 11 As is shown in Figure 6C, the fabricated electrodes showed no response to other analytes. ...
Article
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Low-cost enzyme-free glucose sensors with partial flexibility adaptable for wearable Internet of Things devices that can be envisioned as personalized point-of-care devices were produced by electroplating copper on locally carbonized flexible meta-polyaramid (Nomex) sheets using laser radiation. Freestanding films were annealed in nitrogen and nitrogen/air working environments, leading to the formation of Cu microspheroids and CuO urchins dispersed on the substrate film. The aggregation mechanism, crystallographic properties, surface chemistry, and electrochemical properties of the films were studied using scanning electron microscopy, X-ray diffractometry, transmission electron microscopy, X-ray photoelectron spectroscopy, and cyclic voltammetry. Cu microspheroids and CuO urchins attained activity for glucose detection and showed improvement of amperometric sensitivity to 0.25 and 0.32 mA cm–2 mM–1, respectively. The CuO urchin film retained its chemical composition after amperometric testing, and, by rinsing, allowed multiple repetitions with reproducible results. This study opens the possibility for the fabrication of durable composite biosensors with tailored shape, capable of implementation in flexible carriers, and microfluidic systems.
... Applying variations with the salted water represents salt contained in sweat, so various amounts of salt were used to indicate the difference in the amount of salt contained in sweat [13]. Sugar water substrate represents glucose contained in sweat. ...
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Recently, usage of fabrics as wearable device, along with their applications are increasing, one example being the detection of bio-analyzes such as blood or sweat. One method used to observe the properties of the material of a fabric is to use the Refcletance Spectroscopy, in which excitation of monochromatic light with a specific wavelength is given to a fabrics. Intensity value is then processed using the PCA method in order to obtain the pattern of the difference between each substrate. The proposed transducer optic system consists of 405nm blueviolet laser as the light source, biconvex lens, Adafruit AS7262 light detector, and Arduino. This system can only detect the difference in substrate content from the occurring light scatter. This system can be applied to various kinds of fabric wearable material with differing scatter intensity values depending on the kind of fabrics. Softer kind of fabric is proposed as material for the wearable device because it gives a high scatter intensity value and constant values in every repetation which results in better data reading.Keywords: clustering, optical, reflectance, spectroscopy, transducer, wearable.
... 但是器件在实际场景的性能不稳定, 无法满足运动员的需求[109] .加州大学洛杉矶的 Yichao Zhao 等人 [110] 研发了一种集成多功能的智能手表, 该手表具有汗液采样、电 化学传感、葡萄糖检测等功能, 能实现在高强度的运动条件进行物质检测. ...
... blood glucose level can also be monitored via sweats as blood vessels around sweat glands are highly developed 82 . Contact lenses are one of the most representative non-invasive approaches to monitor glucose level via tears. ...
Article
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Diabetes is a chronic metabolic disease characterized by high glucose concentration in blood. Conventional management of diabetes requires skin pricking and subcutaneous injection, causing physical pain and physiological issues to diabetic individuals. Hydrogels possess unique advantages such as lightweight, stretchability, biocompatibility, and biodegradability, offering the opportunities to be integrated as flexible devices for diabetes management. This review highlights the development of hydrogels as flexible materials for diabetes applications in glucose monitoring, insulin delivery, wound care, and cell transplantation in recent years. Challenges and prospects in the development of hydrogel-based flexible devices for personalized management of diabetes are discussed as well.
... The amperometric response of the glucose sensor was evaluated by CA after the addition of diluted glucose drops (concentrations: 0.00 mM, 0.20 mM, 0.40 mM, 0.60 mM, 0.80 mM, and 1.00 mM) to the artificial sweat, as shown in Fig. 4(a). This artificial sweat glucose concentration may cover the normal range of human sweat (Gao et al., 2018;Lee et al., 2018;Moyer et al., 2012). Fig. 4(b) shows a graph of the linear regression analysis according to the amperometric response to variations in glucose (n = 5, n is number of samples). ...
Article
Recent advances in wearable patches have included various sensors to monitor either physiological signs, such as the heart rate and respiration rate, or metabolites. Nevertheless, most of these have focused only on a single physiological measurement at a time, which significantly inhibits the calibration of various biological signals and diagnostic facilities. In this study, a novel multifunctional hybrid skin patch was developed for the electrochemical analysis of sweat glucose levels and simultaneous monitoring of electrocardiograms (ECGs). Furthermore, pH and temperature sensors were co-integrated onto the same patch for the calibration of the glucose biosensor to prevent inevitable inhibition and weakening of enzyme activity due to changes in the sweat pH and temperature levels. The fabricated electrochemical glucose biosensor exhibited excellent linearity (R² = 0.9986) and sensitivity (29.10 μA mM⁻¹ cm⁻²), covering the normal range of human sweat. The potentiometric pH sensor displayed a good response with an excellent sensitivity of −77.81 mV/pH and high linearity (R² = 0.991), indicating that it can distinguish variations in the typical pH range for human sweat. Furthermore, the P, QRS complex, and T peaks in the measured ECG waveforms could be clearly distinguished, indicating the reliability of the fabricated flexible dry electrodes for continuous monitoring. The fabricated skin patch overcomes the inconvenience of the mandatory attachment of multiple patches on the human body by fully integrating all the electrochemical and electrophysiological sensors on a single patch, thus facilitating advanced glycemic control and continuous ECG monitoring for smart management of chronic diseases and healthcare applications.
... In our study, the mean glucose value appeared to be positively associated with COVID-19 severity, as previously reported 18 . COVID-19 severity-related glucose metabolism disorders profoundly affect the morphological structure and physiological functions of erythrocytes, resulting in insufficient microcirculation perfusion, hypoxia, and oxidative stress, promoting the occurrence of critical COVID-19 patient complications and lowering patients' quality of life 19 . Given the importance of erythrocytes in the pathological development of complications, erythrocyte count correlated with the occurrence and progression of these complications. ...
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Objective: It is known that the severity of COVID-19 is linked to the prognosis of patients; therefore, an early identification is required for patients who are likely to develop severe or critical COVID-19 disease. The purpose of this study is to propose a statistical method for identifying the severity of COVID-19 disease by using clinical and biochemical laboratory markers. Patients and methods: A total of 48 clinically and laboratory-confirmed cases of COVID-19 were obtained from King Fahad Hospital, Medina (KFHM) between 27th April 2020 to 25th May 2020. The patients' demographics and severity of COVID-19 disease were assessed using 39 clinical and biochemical features. After excluding the demographics, 35 predicting features were included in the analysis (diabetes, chronic disease, viral and bacterial co-infections, PCR cycle number, ICU admission, clot formation, cardiac enzymes elevation, hematology profile, sugar levels in the blood, as well as liver and kidney tests, etc.). Logistic regression, stepwise logistic regression, L-2 logistic regression, L-2 stepwise logistic regression, and L-2 best subset logistic regression were applied to model the features. The consistency index was used with kernel Support-Vector Machines (SVM) for the identification of associated markers. Results: L-2 best subset logistic regression technique outperformed all other fitted models for modeling COVID-19 disease severity by achieving an accuracy of 88% over the test data. Consistency index over L-2 best subset logistic regression identified 14 associated markers that can best predict the COVID-19 severity among COVID-19 patients. Conclusions: By combining a variety of laboratory markers with L-2 best subset logistic regression, the current study has proposed a highly accurate and clinically interpretable model of predicting COVID-19 severity.
... For instance, the cortisol content in scalp hair correlates with long-term cumulative cortisol exposure 7 . Sweat can also be used as an indicator of internal physiological changes 8 , and attempts have been made to use it for monitoring patients' conditions; for instance, the tracking of blood glucose levels by measuring glucose in sweat samples of patients with diabetes 9 . Although metabolites, proteins, and DNA are relatively easy to collect from the sweat and hair samples 10,11 , it is difficult to collect measurable levels of mRNAs from skin in a non-or low-invasive manner. ...
Article
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Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed increased expression of inflammation-related genes and decreased expression of terminal differentiation-related genes, consistent with the results of previous reports. Further, we found that lipid synthesis-related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.
... Although "The role of sweat in clinical analysis is poor ." [41], there are reports that pleads for correlation of concentration of some biomarkers between sweat and other body fluids [42]. From this point of view it is considered that ". this sample deserves a prominent place that can be achieved after development of appropriate research" [41]. ...
Article
Electrospun polymeric fibers present an emerging alternative for the development of flexible electronics, enabling applications in wearable sensors and biosensors for continuous monitoring, and actuators for tissue engineering. The possibility to prepare sub-micrometric polymeric scaffolds, their processing for increasing the conductivity, their modification with different materials, conductive polymers and biomolecules in order to obtain functional flexible electrodes, allows the development of innovative devices for healthcare, and biomedical applications. In this review, the impact of metallized electrospun polymeric fibers in electrochemical (bio)sensors and actuators is discussed. A relation between their structure and functionality is provided, alongside with an overview of the different methods to obtain functional conductive fibers.
... A study used different non-invasive sensors (sweat, temperature, and ECG) in patients with type 1 diabetes and showed that measurement of sweating in combination with the ECG signal predicted the development of hypoglycemia (Elvebakk et al., 2018). Sweat also contain glucose at orders of magnitude lower in concentration (10-200 μM) compared to blood glucose (Bariya et al., 2018), but require careful considerations to avoid contamination when collected from the skin surface (Moyer et al., 2012). ...
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Diabetes mellitus is characterized by elevated blood glucose levels, however patients with diabetes may also develop hypoglycemia due to treatment. There is an increasing demand for non-invasive blood glucose monitoring and trends detection amongst people with diabetes and healthy individuals, especially athletes. Wearable devices and non-invasive sensors for blood glucose monitoring have witnessed considerable advances. This review is an update on recent contributions utilizing novel sensing technologies over the past five years which include electrocardiogram, electromagnetic, bioimpedance, photoplethysmography, and acceleration measures as well as bodily fluid glucose sensors to monitor glucose and trend detection. We also review methods that use machine learning algorithms to predict blood glucose trends, especially for high risk events such as hypoglycemia. Convolutional and recurrent neural networks, support vector machines, and decision trees are examples of such machine learning algorithms. Finally, we address the key limitations and challenges of these studies and provide recommendations for future work.
... In addition, continuous noninvasive glucose detection (e.g., indirect detection in sweat, tears, or saliva) has the advantage over conventional glucometers that require blood sampling by painful and frequent fingerpricking [2][3][4]. At this stage, the question of a correlation between a person's blood and sweat/tears/saliva glucose levels may arise, but thanks to recent findings, one can say that such a correlation can be found for every human's metabolism, or that the device for realtime glucose monitoring can, at least, warn the user of critical glucose levels and the occurrence of hyperglycemia and hypoglycemia [5,6]. Glucose levels in non-invasive body fluids (e.g., sweat) are known to be in the range of 17-100 μM; therefore, transducers capable of detecting such a small amount of glucose content are required [7,8]. ...
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Noninvasive, continuous glucose detection can provide some insights into daily fluctuations in blood glucose levels, which can help us balance diet, exercise, and medication. Since current commercially available glucose sensors can barely provide real-time glucose monitoring and usually imply different invasive sampling, there is an extraordinary need to develop new harmless methods for detecting glucose in non-invasive body fluids. Therefore, it is crucial to design (bio)sen-sors that can detect very low levels of glucose (down to tens of µ M) normally found in sweat or tears. Apart from the selection of materials with high catalytic activity for glucose oxidation, it is also important to pay considerable attention to the electrode functionalization process, as it significantly contributes to the overall detection efficiency. In this study, the (ZnO tetrapods) ZnO TPs-based electrodes were functionalized with Nafion and chitosan polymers to compare their glucose detection efficiency. Cyclic voltammetry (CV) measurements have shown that chitosan-modified ZnO TPs require a lower applied potential for glucose oxidation, which may be due to the larger size of chitosan micelles (compared to Nafion micelles), and thus easier penetration of glucose through the chitosan membrane. However, despite this, both ZnO TPs modified with chitosan and Nafion membranes, provided quite similar glucose detection parameters (sensitivities, 7.5 µ A mM −1 cm −1 and 19.2 µ A mM −1 cm −1 , and limits of detection, 24.4 µ M and 22.2 µ M, respectively). Our results show that both electrodes have a high potential for accurate real-time sweat/tears glucose detection.
... Sweat contains a wealth of biomarkers related to the metabolites of the human body, including electrolytes (e.g., sodium and potassium), metabolites (e.g., lactate and glucose), and small quantities of hormones and peptides [5][6][7]. The presence of, or variation in, the concentrations of certain biomarkers provides important information on the physiological state [8]. ...
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Wearable sweat sensors are a rapidly rising research area owing to their convenience for personal healthcare and disease diagnosis in a real-time and noninvasive manner. However, the fast and scalable fabrication of flexible electrodes remains a major challenge. Here, we develop a wearable epidermal sensor for multiplexed sweat analysis based on the laser-induced graphene (LIG) technique. This simple and mask-free technique allows the direct manufacturing of graphene electrode patterns on commercial polyimide foils. The resulting LIG devices can simultaneously monitor the pH, Na+, and K+ levels in sweat with the sensitivities of 51.5 mV/decade (pH), 45.4 mV/decade (Na+), and 43.3 mV/decade (K+), respectively. Good reproducibility, stability, and selectivity are also observed. On-body testing of the LIG-based sensor integrated with a flexible printed circuit board during stationary cycling demonstrates its capability for real-time sweat analysis. The concentrations of ions can be remotely and wirelessly transmitted to a custom-developed smartphone application during the period in which the sensor user performs physical activities. Owing to the unique advantages of LIG technique, including facile fabrication, mass production, and versatile, more physiological signals (glucose, uric acid, tyrosine, etc.) could be easily expanded into the LIG-based wearable sensors to reflect the health status or clinical needs of individuals.
... Many developments have been reported for the monitoring of glucose in sweat through epidermal patches [12], textiles [13], or wristbands [14]. Despite some reports on sweat to blood glucose correlation [15,16], it is still unclear whether the sweat glucose levels reflect the metabolic status of the wearer. Besides, the extraction of sweat can be also cumbersome when dealing with diabetic patients and might rely on integrated iontophoretic systems [17]. ...
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Monitoring blood glucose levels is a vital indicator of diabetes mellitus management. The mainstream techniques of glucometers are invasive, painful, expensive, intermittent, and time-consuming. The ever-increasing number of global diabetic patients urges the development of alternative non-invasive glucose monitoring techniques. Recent advances in electrochemical biosensors, biomaterials, wearable sensors, biomedical signal processing, and microfabrication technologies have led to significant research and ideas in elevating the patient's life quality. This review provides up-to-date information about the available technologies and compares the advantages and limitations of invasive and non-invasive monitoring techniques. The scope of measuring glucose concentration in other bio-fluids such as interstitial fluid (ISF), tears, saliva, and sweat are also discussed. The high accuracy level of invasive methods in measuring blood glucose concentrations gives them superiority over other methods due to lower average absolute error between the detected glucose concentration and reference values. Whereas minimally invasive, and non-invasive techniques have the advantages of continuous and pain-free monitoring. Various blood glucose monitoring techniques have been evaluated based on their correlation to blood, patient-friendly, time efficiency, cost efficiency, and accuracy. Finally, this review also compares the currently available glucose monitoring devices in the market.
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Wearable sweat sensors have received significant research interest and have become popular as sweat contains considerable health information about physiological and psychological states. However, measured biomarker concentrations vary with sweat rates, which has a significant effect on the accuracy and reliability of sweat biosensors. Wearable sweat loss measuring devices (SLMDs) have recently been proposed to overcome the limitations of biomarker tracking and reduce inter- and intraindividual variability. In addition, they offer substantial potential for monitoring human body homeostasis, because sweat loss plays an indispensable role in thermoregulation and skin hydration. Previous studies have not carried out a comprehensive and systematic review of the principles, importance, and development of wearable SLMDs. This paper reviews wearable SLMDs with a new health perspective from the role of sweat loss to advanced mechanisms and designs. Two types of sweat and their measurement significance for practical applications are highlighted. Then, a comprehensive review of advances in different wearable SLMDs based on hygrometers, absorbent materials, and microfluidics is presented by describing their respective device architectures, present situations, and future directions. Finally, concluding remarks on opportunities for future application fields and challenges for future sweat sensing are presented.
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Covalent organic frameworks (COFs) with uniform porosity, good stability, and desired biocompatibility can function as carriers of immobilized enzymes. However, the obstructed pores or partially obstructed pores have hindered their applicability after loading enzymes. In this study, the hierarchical COFs were prepared as an ideal support to immobilize glucose oxidase (GOD) and obtain GOD@COF. The hierarchical porosity and porous structures of COFs provided sufficient sites to immobilize GOD and increased the rate of diffusion of substrate and product. Moreover, N,Fe-doped carbon dots (N,Fe-CDs) with peroxidase-like activity were introduced to combine with GOD@COF to construct an enzyme-mediated cascade reaction, which is the basis of the sensor GOD@COF/N,Fe-CDs. The sensor has been successfully built and applied to detect glucose. The limit of detection was 0.59 μM for determining glucose with the proposed fluorescence sensor. The practicability was illustrated by detecting glucose in human serum and saliva samples with satisfactory recoveries. The proposed sensor provided a novel strategy that introduced COF-immobilized enzymes for cascade reactions in biosensing and clinical diagnosis.
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Here, we report the use of dendrimer-encapsulated Au nanoparticles (Au DENs) terminated with zwitterionic groups (G4-NH2-PS(Au)) for nonenzymatic perspiration glucose analysis based on water splitting-assisted electrocatalysis (WSE). The Au DENs with controllable sizes are prepared and characterized, and their electrocatalytic activities towards nonenzymatic glucose oxidation are investigated. It is found that the Au DENs with a smaller diameter (1.3 ± 0.5 nm) show higher electrocatalytic activity than larger Au DENs do (1.7 ± 0.7 nm and 2.8 ± 1.4 nm), which leads to a sensitivity of 414 μA mM⁻¹ cm⁻² for glucose detection and a detection limit of 4.9 μM. The Au DENs terminated with zwitterionic groups also exhibit acceptable selectivity, reproducibility, and long-time stability for glucose sensing in artificial perspiration samples. The sensor is then used for wearable perspiration glucose monitoring, and the results show a correlation between perspiration glucose and blood glucose.
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Wearable multimodal sensors could enable the continuous, non-invasive, precise monitoring of vital human signals critical for remote health monitoring and telemedicine. Atomically thin materials with intriguing physical characteristics, rich chemistry, and extreme sensitivity to external stimuli are attractive for implementing high-performance wearable sensors. Despite the increased interest and efforts in 2D materials-based wearable sensors, reducing the manufacturing and integration costs while improving the product performance remains challenging. Previous review articles provided good coverage discussing the material and device aspects of 2D materials-based wearable devices. However, few reviews discussed the status quo, prospects, and opportunities for the scalable nanomanufacturing of 2D materials wearable sensors for health monitoring. To fill this gap, we have reviewed the recent advances in 2D materials-based wearable health sensors. We discussed the structure design, fabrication processing, the mechanisms of 2D materials-based wearable health sensors, and their applications for human health monitoring. More significantly, we have provided a systematic discussion of the state-of-the-art and technological gaps for enabling future design and nanomanufacturing of 2D materials wearable health sensors. Finally, we discussed the challenges and opportunities associated with the scalable nanomanufacturing of 2D wearable health sensors. This article is protected by copyright. All rights reserved.
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The assessment of blood glucose levels is necessary for the diagnosis and management of diabetes. The accurate quantification of serum or plasma glucose relies on enzymatic and nonenzymatic methods utilizing electrochemical biosensors. Current research efforts are focused on enhancing the non-invasive detection of glucose in sweat with accuracy, high sensitivity, and stability. In this work, nanostructured mesoporous carbon coupled with glucose oxidase (GOx) increased the direct electron transfer to the electrode surface. A mixed alloy of CuNi nanoparticle-coated mesoporous carbon (CuNi-MC) was synthesized using a hydrothermal process followed by annealing at 700 °C under the flow of argon gas. The prepared catalyst’s crystal structure and morphology were explored using X-ray diffraction and high-resolution transmission electron microscopy. The electrocatalytic activity of the as-prepared catalyst was investigated using cyclic voltammetry (CV) and amperometry. The findings show an excellent response time of 4 s and linear range detection from 0.005 to 0.45 mM with a high electrode sensitivity of 11.7 ± 0.061 mA mM cm−2 in a selective medium.
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With the development of medical science and the extension of people's life expectancy, medical care and health monitoring in daily life have become a universal, worldwide concern. Accurate quantification of glucose is of great concern in diagnostics because it can indicate diabetes and help avoid related medical complications. Over the years, a variety of analytical methods have been used to sense glucose with good selectivity, good feasibility, sensitive response and low cost. Nevertheless, there is a lack of universal approach which can be applicable for the measurements across a variety of biological fluids (e.g., blood, sweat and urine), as the concentrations of glucose in there fluids vary significantly from low-micromolar to millimolar range. To fill this role, we proposed a glucose biosensor platform to improve the adaptability of glucose biosensor in clinical application. In our study, we coupled an electrochemical etching approach with the manipulation of nanostructured surfaces of gold electrodes to achieve arbitrarily tunable detection range for glucose measurements, with the detection range in blood sample (20 ∼ 1000 μM), sweat (6 ∼ 1000 μM), and urine (1.6 ∼ 100 μM), respectively.
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In composite hydrogels, the high electrical performance of poly(3,4-ethylenedioxythiophene) complexed with poly(styrenesulfonate) (PEDOT:PSS) is integrated with complementary structural and electrochemical functions via a rationally designed poly(acrylamide) second network incorporating phenylboronic acid (PBA). Free-standing double-network hydrogels prepared by a simple one-pot radical polymerization exhibit state-of-the-art electrical conductivity (∼20 S cm-1 in phosphate buffered saline) while retaining a degree of hydration similar to that of biological soft tissues. Low resistance contacts to Au electrodes are formed via facile thermo-mechanical annealing and demonstrate stability over a month of continuous immersion, thus enabling hydrogels to serve as channels of organic electrochemical transistors (OECTs). Despite thicknesses of ∼100 μm, gating of hydrogel OECTs is efficient with transconductances gm ∼ 40 mS and on/off ratios of 103 in saturation mode operation, whereas sufficiently high conductivity enables linear mode operation (gm ∼ 1 mS at -10 mV drain bias). This drives a shift of sensing strategy toward detection of electrochemical signals originating within the bulky channel. A kinetic basis for glucose detection via diol esterification on PBA is identified as the coupling of PBA equilibrium to electrocatalyzed O2 reduction occurring on PEDOT in cathodic potentials. Hydrogel OECTs inherently amplify this direct electrochemical signal, demonstrating the viability of a new class of soft, structural biosensors.
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This work reports the noninvasive electrochemical determination of glucose by strontium doped cobaltic cobalt oxide nanostructures (Sr-Co3O4). The Sr-Co3O4 is prepared by three conventional methods namely hydrothermal, magnetic stirring, and ultrasound. Among all, the hydrothermal method effectively incorporated the Sr in the Co3O4 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 Co3O4 lattices, which are the main contributor to the electrochemical determination of glucose. The results revealed that hydrothermally synthesized Sr-Co3O4 (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-Co3O4 is applied in real-time monitoring of glucose in blood serum and sweat samples which received good recoveries.
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In this work, a human sweat-based wearable sensor for real-time glucose monitoring has been fabricated on a cotton substrate after treating it with a two-step polymerization of pyrrole. The pyrrole-treated fabric was coated with solution of copper sulphate pentahydrate to grow Cu layer. The cotton/pyrrole/Cu fabric was treated with the solutions of copper acetate and manganese acetate to form Cu–Mn transition-metal alloy via electrochemical deposition technique. Results indicate that the developed sensor is reliable with glucose detection limit of 125 µM and 378 µM. In addition, the sensor output ranged between 50 and 400 µM glucose with coefficient of correlation, R2 = 0.983, indicating a linear range of output current. The sensor's response is not significantly affected by interferents. The developed sensor is also validated on human sweat with satisfactory results.
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The measurement of blood glucose levels is essential for diagnosing and managing diabetes. Enzymatic and nonenzymatic approaches using electrochemical biosensors are used to measure serum or plasma glucose accurately. Current research aims to develop and improve noninvasive methods of detecting glucose in sweat that are accurate, sensitive, and stable. The carbon nanotube (CNT)-copper oxide (CuO) nanocomposite (NC) improved direct electron transport to the electrode surface in this study. The complex precipitation method was used to make this NC. X-ray diffraction (XRD) and scanning electron microscopy were used to investigate the crystal structure and morphology of the prepared catalyst. Using cyclic voltammetry and amperometry, the electrocatalytic activity of the as-prepared catalyst was evaluated. The electrocatalytic activity in artificial sweat solution was examined at various scan rates and at various glucose concentrations. The detection limit of the CNT-CuO NC catalyst was 3.90 µM, with a sensitivity of 15.3 mA cm ⁻² µM ⁻¹ in a linear range of 5–100 µM. Furthermore, this NC demonstrated a high degree of selectivity for various bio-compounds found in sweat, with no interfering cross-reactions from these species. The CNT-CuO NC, as produced, has good sensitivity, rapid reaction time (2 s), and stability, indicating its potential for glucose sensing. Graphical Abstract
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Recent advances in microelectronics and electrochemical sensing platforms have preceded the development of devices for personal monitoring and managing physiological and metabolic information that exploit sweat as a noninvasive, convenient approach for providing information about underlying health conditions, such as glucose level monitoring. Although most sweat glucose sensors have targeted applications during exercise and other active stimulation induced-sweat, natural sweating offers an attractive alternative with minimal effect on users that can be accessed during routine and sedentary activities without impeding personal lifestyle and preserves the correlation between blood and sweat glucose. Here, we present a noninvasive sweat glucose sensor with convenient hydrogel patches for rapid sampling of natural perspiration without external activities that stimulate sweating. The wearable hydrogel patch rapidly takes up natural sweat from the hand and serves as a medium for electrochemical sensing. A prussian blue-doped poly(3,4-ethylenedioxythiophene nanocomposite (PB-PEDOT NC) electrode provides cost-effective, stable and excellent electrocatalytic activity in sweat glucose measurements. We demonstrated sweat glucose sensor functionality by long-term measurements of glucose in sweat from human subjects consuming food and drinks. By enabling the analysis of sweat glucose during routine and sedentary activities, the sweat glucose sensor shows great promise for clinical-grade glucose management and enlarges the scope of next-generation noninvasive sensing systems.
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Soft, skin-mounted microfluidic devices can collect microliter volumes of eccrine sweat and are capable of in-situ real-time analysis of different biomarkers to assess physiological state and health. Chrono-analysis of sweat...
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Enzyme‐based colorimetric systems are inexpensive, simple, adaptable, and sensitive methods that allow specific quantification of a substrate. In the clinical field, its use has been the basis for the development of equipment and devices that today are key for disease detection. The objective of this project was to demonstrate the flexibility of a previously developed multi‐enzyme system for colorimetric glucose quantification by adapting and optimizing it for the detection and quantification of other clinical relevant biomolecules, such as galactose, uric acid and 1,5‐anhydroglucitol in buffer conditions. The obtained calibration curves for galactose, uric acid and 1,5‐anhydroglucitol show remarkable linearity (R2 ≥0.997), precision (CV ≤2.38%), and sensitivity with detection and quantification limits of 3.96 and 12.01 μM; 0.16 and 0.48 μM; and 0.08 and 0.25 μM, respectively. In addition, it was shown that the three systems are capable of quantifying different concentrations of their respective substrate, showing low variability (CV <3.3%) and remarkable recovery percentages (99.21‐103.39%). The results obtained with the three optimized enzyme‐based colorimetric systems demonstrate the platform flexibility by modifying parameters such as pH buffer, incubation time, enzyme, and concentration of the reducing agent under buffer conditions. All results together demonstrate the great potential of this multi‐enzyme platform for the quantification of different substrates in non‐conventional biofluids. This article is protected by copyright. All rights reserved.
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With the increasing demand of health monitoring and protection, Point-of-Care Testing has developed rapidly due to its convenience and high efficiency. Here, a visual colorimetric nanofiber-based strip with a hierarchically porous structure was prepared for highly sensitive detection of glucose. To facilitate the subsequent testing, the composites with a hybrid nanoflower structure containing glucose oxidase (GOx), horseradish peroxidase (HRP), 3,3’5,5’-tetramethylbenzidine (TMB) and Mn3(PO4)2 were immobilized on a hierarchically porous PVA-co-PE nanofibrous strip. The obtained strip was used to detect glucose, a strong linear correlation (R² = 0.996) was found between the color difference and ln(Cglucose) in the range of 0.25 to 10 mM glucose. The detection limit is 0.14 mM and a discernible color change could be detected with the naked eye at low glucose concentration, indicating that the strip is highly sensitive to glucose. Additionally, a series of interferences substances including NaCl, KCl and urea were also investigated, and the results showed excellent specificity to glucose. Moreover, the strip exhibits good stability in the pH range of 5–7 and maintains excellent glucose detection performance after 60 days. It demonstrates that this strip is a promising candidate for personal diabetes detection.
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Latent fingerprints (LFPs) are important trace evidences found at crime scenes that assist forensic experts in human identification, and a growing number of studies show that LFPs have some medical value. Herein, as one of the common nanoenzymes, Fe3O4 nanoparticles (Fe3O4 NPs) was used for LFPs imaging due to its excellent superparamagnetic properties and for recognition of glucose/H2O2 on LFPs because of its horseradish peroxidase-like activity, which makes it possible to diagnose diabetes non-invasively through LFPs. Furthermore, the intelligent qualitative and semi-quantitative analysis of glucose/H2O2 on LFPs was achieved by designing the classifier based on the multi-channel convolutional neural network (MC-CNN) technology. The qualitative accuracy rate is over 97% and the semi-quantitative accuracy rate reaches 90%. This work offers the promise to facilitate cross-disciplinary studies between artificial intelligence methods and fingerprint development technique.
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An electrochemical sensing device based on a cotton‐thread electrode for real‐time and simultaneous detection of sweat glucose and sweat lactate is reported. The cotton thread surfaces are simply modified by cellulose nanofibers/carbon nanotube ink‐Prussian blue/chitosan to enhance liquid adsorption, bioreceptor immobilization, and sensor performance in addition to minimize potential irritation and allergies on the wearer's skin. The modified thread surfaces are characterized by laser scanning confocal microscopy, scanning electron microscopy, and Fourier transform Raman spectroscopy. Amperometry is carried out via hydrogen peroxide detection for electrochemical characterization of the modified thread electrodes. A circuit and digital readout of this wearable sensor are customized designed to be integrated with thread electrodes for real‐time and simultaneous detection of sweat glucose and sweat lactate. The wristwatch sensing device provides a linear range of 0.025–3 × 10−3 m with a detection limit of 0.025 × 10−3 m for glucose and a linear range of 0.25–35 × 10−3 m with a detection limit of 0.25 × 10−3 m for lactate. This device can effectively determine the cut‐off levels of both glucose and lactate, which can distinguish between a normal individual and one with a diabetic condition. This platform opens a new avenue for noninvasive and real‐time detection of other sweat biomarkers. Thread‐based electrochemical sensor for real‐time and simultaneous determination of sweat glucose and lactate is first developed. The modification of thread enhance the liquid adsorption, conductivity, and enzymatic immobilization and thus the sensor performance. The customized potentiostat are integrated with the modified thread electrode for detection of glucose and lactate. The proposed system can determine the cut‐off levels of glucose and lactate, which can distinguish between normal and diabetic patient.
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Currently, chronic kidney disease (CKD) diagnosis requires painful and prolonged procedures for identification. Therefore, it is urgent to develop rapid, non-invasive monitoring strategies that can be used as surrogates to routine blood screening procedures. It is noted that the majority of the typical molecular markers related to the progression and diagnosis of CKD have not been explored sufficiently for the clinical applications. This review extends systematic and critical overview on the microfluidic wearable biosensors for the monitoring of CKD associated targets in peripheral body fluids (e.g., interstitial fluid (ISF), sweat, saliva, and tears). The performance of recently reported wearable devices is also assessed in terms of various quality assurance parameters for the analysis of CKD related metabolites (i.e., limit of detection, measurement range, and analytical method). At last, our discussion is extended to the various challenges and future prospects for their practical adoption and upscaling.
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As a vital biomarker, glucose plays an important role in multiple physiological and pathological processes. Thus, glucose detection has become an important direction in the electrochemical analysis field. In order to realize more convenient, real-time, comfortable and accurate monitoring, smartphone-based portable, wearable and implantable electrochemical glucose monitoring is progressing rapidly. In this review, we firstly introduce technologies integrated in smartphones and the advantages of these technologies in electrochemical glucose detection. Subsequently, this overview illustrates the advances of smartphone-based portable, wearable and implantable electrochemical glucose monitoring systems in diverse biofluids over the last ten years (2012–2022). Specifically, some interesting and innovative technologies are highlighted. In the last section, after discussing the challenges in this field, we offer some future directions, such as application of advanced nanomaterials, novel power sources, simultaneous detection of multiple markers and a closed-loop system.
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Context Intensive diabetes management using frequent blood glucose measurements to guide therapy has been shown to significantly improve short- and long-term outcomes. Development of a device that makes possible frequent, automatic, painless, and accurate measurements of glucose would facilitate intensive management.Objective To determine the accuracy of the GlucoWatch automatic glucose biographer (Cygnus Inc) compared with that of serial blood glucose measurements.Design Multicenter comparative study of the GlucoWatch biographer and the HemoCue blood glucose analyzer (Aktiebolaget Leo) performed between August 29 and October 17, 1998. Participants wore up to 2 biographers during the 15-hour study session and performed 2 fingersticks per hour for comparative blood glucose measurements. The biographers were calibrated with a single HemoCue measurement after a 3-hour warm-up period. Diet and insulin were manipulated to produce a broad glycemic range during the study.Setting Controlled clinical environment at 2 diabetes centers and 3 contract research organizations in the United States.Participants A total of 92 subjects (mean [SD] age, 42.1 [15.1] years; 59.8% women) with type 1 or 2 diabetes requiring treatment with insulin.Main Outcome Measures Mean error, mean absolute error, correlation, slope, and intercept using Deming regression, and clinical significance of differences between biographer readings and blood glucose measurements using the Clarke error grid.Results Results showed close tracking of blood glucose over a range of 2.2 to 22.2 mmol/L (40-400 mg/dL) for up to 12 hours using a single point calibration. The biographer readings lagged behind serial blood glucose values by a mean of 18 minutes. An analysis of 2167 data pairs shows a linear relationship (r = 0.88; slope = 1.03; intercept = −0.33 mmol/L [−6 mg/dL]) between biographer readings and serial glucose measurements. The mean absolute error between the 2 measurements was 15.6% (mean error [SD], −0.07 [1.82] mmol/L [−1 {33} mg/dL]), and 96.8% of the data fell in the therapeutically relevant regions of the error grid analysis.Conclusion These results demonstrate close agreement between GlucoWatch biographer readings and blood glucose measurements using repeated fingerstick blood samples. The automatic, frequent, and noninvasive measurements obtained with the biographer provides more information about glucose levels than the current standard of care. Figures in this Article Self-monitoring of blood glucose (BG) is a critical part of managing diabetes. However, present procedures for obtaining such information are invasive, painful, and provide only periodic measurements. Development of a painless and automatic approach would represent a significant improvement in the quality of life for people with diabetes. In addition, results from the Diabetes Control and Complication Trial Research Group,1 UK Prospective Diabetes Study,2 and Kumamoto trials3 showed that a tight glucose control regimen, which uses frequent glucose measurements to guide the administration of insulin or oral hypoglycemic agents, leads to a substantial decrease in the long-term complications of diabetes; however, there was a 3-fold increase in hypoglycemic events.1 Moreover, as many as 7 BG measurements per day were not sufficient to detect a number of severe hypoglycemic and hyperglycemic events.4 The GlucoWatch automatic glucose biographer (Cygnus Inc, Redwood City, Calif) provides a means to obtain painless, automatic, and noninvasive glucose measurements. The device provides up to 3 readings per hour for as long as 12 hours after a single BG measurement for calibration. A monitoring system that provides automatic and frequent measurements could provide detailed information on glucose patterns and trends that might identify opportunities for improved BG control. Automatic readings also provide the opportunity for an alarm to be sounded in response to values below a user-selected alert level or as a result of rapid declines in the measured glucose values. These alarms could provide a method to reduce the risk of hypoglycemia and make intensive therapy for diabetes safer and acceptable to more patients.
Article
Die bisherigen im Schrifttum vorhandenen Angaben ber den Zuckergehalt auf der Haut, im Hautdialysat und im Schwei sind unzutreffend, und zwar zu hoch. Die Abweichung von den wirklichen Zuckerwerten ist sehr betrchtlich und drfte mit etwa einer Zehnerpotenz anzusetzen sein. Diese Tatsache ergibt sich daraus, da das Verhalten der auf ihren Zuckergehalt zu prfenden Untersuchungsflssigkeiten bei Anwendung verschieden groer Versuchsmengen, bei Behandlung mit Natronlauge und bei Behandlung mit Tierkohle nicht mit dem Verhalten von Zuckerlsungen entsprechender Konzentration bereinstimmt.Demzufolge knnen auch die von verschiedenen Autoren aus vergleichenden Untersuchungen gezogenen Rckschlsse hinsichtlich der Sonderstellung der Diabetiker nicht mehr als zuverlssig angesehen werden.
Article
In an attempt to devise a method for collecting large volumes of thermally induced sweat with less epidermal contamination and evaporative water loss, we developed an anaerobic sweat collector by using a sheet of polyethylene film placed over a thin layer of Vaseline and paraffin oil on the skin. To test the validity of the new method, sweat samples collected every 5 min from the new collector (sweat A) were compared with those obtained from a second collector using no oil (sweat B) and scraped sweat for concentrations of adenosine 3',5'-cyclic monophosphate (cAMP), protein, glucose, urea, lactic acid, calcium, sodium, potassium, and cholesterol. The concentration of sweat ingredients in scraped sweat was often far greater than could be expected from evaporative water loss alone. When compared with sweat A, sweat B also had higher concentrations of these ingredients in the initial samples, indicating epidermal contamination, which was especially marked in cAMP, protein, urea, cholesterol, and calcium. Concomitant with a rise in plasma glucose following the administration of a glucose bolus, the sweat glucose significantly increased, indicating the plasma as a major source of sweat glucose. We conclude that the new sweat collector is instrumental in collecting large volumes of the cleanest possible human sweat.
Article
We have developed a simple method for detecting high concentrations of chloride in sweat from ambulatory subjects, a measurement useful in the detection of cystic fibrosis. The method is based on the standard approach of stimulating sweat generation through iontophoresis of pilocarpine nitrate into the skin, followed by collection and analysis of the sweat for chloride concentration. The sweat-stimulating reagents are contained in polymeric gel pads, which are used in conjunction with a small battery-powered stimulator. The chloride analysis is subsequently done on the stimulated site by use of a thin test patch that picks up a fixed amount of sweat and changes color if the chloride concentration is higher than a predetermined value. The successful completion of a test is indicated by a fill tab, which changes color when the appropriate amount of sweat has been picked up by the chloride test patch.
Article
To demonstrate that "reverse iontophoresis" can be used to noninvasively obtain information about systemic glucose levels in vivo in humans. The passage of current across the skin in vivo drives ions into the tissue, from the electrode chambers positioned on the skin surface, and simultaneously pulls ions from the body in the opposite direction. Because of the net negative charge on the skin, under normal conditions, the membrane is permselective to cations, and a potential gradient also results, therefore, in electroosmotic convection of solvent in the direction of counterion flow (i.e., from anode to cathode). Thus, it is also possible to enhance the transport of polar, yet uncharged, species using iontophoresis. In an earlier study, the in vitro extraction of glucose, by "reverse iontophoresis" was established, and extension of the approach to an in vivo model was indicated. The idea has therefore been further explored in vivo in humans. Using small, simple, prototypical electrode chambers, attached to the ventral forearm surface, direct current iontophoresis at 0.25 mA/cm2 for periods of up to 1 hour, and a sensitive analytical procedure to measure the quantities of glucose extracted, it has been shown that iontophoretic sampling of glucose is feasible. However, the shorter periods (15 minutes or less) of extraction considered yield results which are "contaminated" (it is believed) by glucose that is a product of lipid metabolism within the skin. While this material is expected to complicate the initial calibration of the approach, the problem is effectively resolved within one hour, by which time the glucose arriving in the electrode chambers on the skin surface is expected to directly reflect the subcutaneous tissue concentration. Based upon these initial observations, further investigation can now be directed towards optimization of electroosmotic flow and sampling time, improved reproducibility and the development of a practical assay methodology.
Article
Intensive diabetes management using frequent blood glucose measurements to guide therapy has been shown to significantly improve short- and long-term outcomes. Development of a device that makes possible frequent, automatic, painless, and accurate measurements of glucose would facilitate intensive management. To determine the accuracy of the GlucoWatch automatic glucose biographer (Cygnus Inc) compared with that of serial blood glucose measurements. Multicenter comparative study of the GlucoWatch biographer and the HemoCue blood glucose analyzer (Aktiebolaget Leo) performed between August 29 and October 17, 1998. Participants wore up to 2 biographers during the 15-hour study session and performed 2 fingersticks per hour for comparative blood glucose measurements. The biographers were calibrated with a single HemoCue measurement after a 3-hour warm-up period. Diet and insulin were manipulated to produce a broad glycemic range during the study. Controlled clinical environment at 2 diabetes centers and 3 contract research organizations in the United States. A total of 92 subjects (mean [SD] age, 42.1 [15.1] years; 59.8% women) with type 1 or 2 diabetes requiring treatment with insulin. Mean error, mean absolute error, correlation, slope, and intercept using Deming regression, and clinical significance of differences between biographer readings and blood glucose measurements using the Clarke error grid. Results showed close tracking of blood glucose over a range of 2.2 to 22.2 mmol/L (40-400 mg/dL) for up to 12 hours using a single point calibration. The biographer readings lagged behind serial blood glucose values by a mean of 18 minutes. An analysis of 2167 data pairs shows a linear relationship (r = 0.88; slope = 1.03; intercept = -0.33 mmol/L [-6 mg/dL]) between biographer readings and serial glucose measurements. The mean absolute error between the 2 measurements was 15.6% (mean error [SD], -0.07 [1.82] mmol/L [-1 [33] mg/dL]), and 96.8% of the data fell in the therapeutically relevant regions of the error grid analysis. These results demonstrate close agreement between GlucoWatch biographer readings and blood glucose measurements using repeated fingerstick blood samples. The automatic, frequent, and noninvasive measurements obtained with the biographer provides more information about glucose levels than the current standard of care.
Article
The content of glucose was assessed in perspiration, which was induced by an introduction of medical preparations (during 5-10 min) into patient's skin by iontophoresis; the choice of the method was to avoid the risk of infection and pain. A high specific chromogenic substrate was used to determine the content of glucose in the perspiration, which improved the sensitivity of the method and made it possible to determine the quantitative content of glucose in just 5 minutes; or alternatively, the half-quantitative content of glucose could be determined, by using the specially designed high-sensitivity strips, in just 1 minute. The correlation between a concentration of perspiration glucose and a degree of glycemia makes it possible to assess the concentration of glucose in blood by avoiding the invasive diagnostics.
Article
Obtaining representative physiological samples for glucose analysis remains a challenge especially when developing less invasive glucose monitoring systems for diabetic patients. In the present study the glucose content of the stratum corneum was compared with the amount of glucose obtained by short aqueous extractions from a site on the dorsal wrist, using high pressure liquid chromatography with pulsed amperometric detection. Ten successive aqueous 1-minute extractions of the site yielded a total of 60 ng cm(-2). The total glucose content of the stratum corneum of the site, determined from 30 successive tape-strippings of the site, was 360 ng cm(-2). After tape-stripping, the transcutaneous aqueous extraction rate was 86 +/- 13 ng cm(-2) min(-1), compared with rates of 80-600 ng cm(-2) min(-1) obtained with suction effusion or microdialysis after tape-stripping. Glucose on the surface of the skin and within the stratum corneum should be considered as sources of extraneous glucose contamination during testing of less invasive glucose monitoring devices.
Article
There are three main issues in non-invasive (NI) glucose measurements: namely, specificity, compartmentalization of glucose values, and calibration. There has been progress in the use of near-infrared and mid-infrared spectroscopy. Recently new glucose measurement methods have been developed, exploiting the effect of glucose on erythrocyte scattering, new photoacoustic phenomenon, optical coherence tomography, thermo-optical studies on human skin, Raman spectroscopy studies, fluorescence measurements, and use of photonic crystals. In addition to optical methods, in vivo electrical impedance results have been reported. Some of these methods measure intrinsic properties of glucose; others deal with its effect on tissue or blood properties. Recent studies on skin from individuals with diabetes and its response to stimuli, skin thermo-optical response, peripheral blood flow, and red blood cell rheology in diabetes shed new light on physical and physiological changes resulting from the disease that can affect NI glucose measurements. There have been advances in understanding compartmentalization of glucose values by targeting certain regions of human tissue. Calibration of NI measurements and devices is still an open question. More studies are needed to understand the specific glucose signals and signals that are due to the effect of glucose on blood and tissue properties. These studies should be performed under normal physiological conditions and in the presence of other co-morbidities.
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