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      An epidermal wearable microfluidic patch for simultaneous sampling, storage, and analysis of biofluids with counterion monitoring

      1 , 2 , 1
      Lab on a Chip
      Royal Society of Chemistry (RSC)

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          Abstract

          An epidermal, wearable bio-fluidic patch is demonstrated that facilitates simultaneous on-demand extraction, sampling, and storage of sweat and interstitial fluid (ISF) together with monitoring of their corresponding counterions.

          Abstract

          Simultaneous access to different biofluids enables an accurate analysis of multiple analytes, leading to a precision diagnosis and appropriate medication. Additionally, establishing a relationship between various markers in different biofluids and their correlation to biomarkers in blood allows the development of an algorithmic approach, which aids non-invasive diagnosis through single parameter monitoring. However, the main bottleneck that exists in multiple biofluid analyses for its clinical implementation is the requirement of an advanced microfluidic coupled device design, which empowers simultaneous collection and monitoring. To tackle this challenge, an epidermal wearable bio-fluidic patch that facilitates simultaneous on-demand extraction, sampling, and storage of sweat and interstitial fluid (ISF) together with monitoring of their corresponding counterions is presented. The clean room free development of a biofluidic patch is realized through 3D integration of laser patterned optimized microfluidic structures, a low-cost screen-printed stimulation module, and a potentiometric chloride (Cl ) and calcium (Ca 2+) ion sensing module for adequate dual biofluid sampling and analysis. The developed Cl and Ca 2+ ion-selective sensors exhibit good repeatability, selectivity, acceptable stability, and sensitivity. The proof-of-concept demonstration of the fabricated patch for simultaneous dual-sampling, storage, and monitoring of the sweat Cl and ISF Ca 2+ on a healthy volunteer during different periods of the day leverages its potential in real-time personalized healthcare clinical usages. Furthermore, the patch's electronic interface and use of wireless transmission facilitates a point-of-care non-invasive lab-on-skin application for monitoring the health status of individuals.

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          Most cited references57

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          Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis.

          Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.
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            Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform.

            Perspiration-based wearable biosensors facilitate continuous monitoring of individuals' health states with real-time and molecular-level insight. The inherent inaccessibility of sweat in sedentary individuals in large volume (≥10 µL) for on-demand and in situ analysis has limited our ability to capitalize on this noninvasive and rich source of information. A wearable and miniaturized iontophoresis interface is an excellent solution to overcome this barrier. The iontophoresis process involves delivery of stimulating agonists to the sweat glands with the aid of an electrical current. The challenge remains in devising an iontophoresis interface that can extract sufficient amount of sweat for robust sensing, without electrode corrosion and burning/causing discomfort in subjects. Here, we overcame this challenge through realizing an electrochemically enhanced iontophoresis interface, integrated in a wearable sweat analysis platform. This interface can be programmed to induce sweat with various secretion profiles for real-time analysis, a capability which can be exploited to advance our knowledge of the sweat gland physiology and the secretion process. To demonstrate the clinical value of our platform, human subject studies were performed in the context of the cystic fibrosis diagnosis and preliminary investigation of the blood/sweat glucose correlation. With our platform, we detected the elevated sweat electrolyte content of cystic fibrosis patients compared with that of healthy control subjects. Furthermore, our results indicate that oral glucose consumption in the fasting state is followed by increased glucose levels in both sweat and blood. Our solution opens the possibility for a broad range of noninvasive diagnostic and general population health monitoring applications.
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              A Wearable Electrochemical Platform for Noninvasive Simultaneous Monitoring of Ca(2+) and pH.

              Homeostasis of ionized calcium in biofluids is critical for human biological functions and organ systems. Measurement of ionized calcium for clinical applications is not easily accessible due to its strict procedures and dependence on pH. pH balance in body fluids greatly affects metabolic reactions and biological transport systems. Here, we demonstrate a wearable electrochemical device for continuous monitoring of ionized calcium and pH of body fluids using a disposable and flexible array of Ca(2+) and pH sensors that interfaces with a flexible printed circuit board. This platform enables real-time quantitative analysis of these sensing elements in body fluids such as sweat, urine, and tears. Accuracy of Ca(2+) concentration and pH measured by the wearable sensors is validated through inductively coupled plasma-mass spectrometry technique and a commercial pH meter, respectively. Our results show that the wearable sensors have high repeatability and selectivity to the target ions. Real-time on-body assessment of sweat is also performed, and our results indicate that calcium concentration increases with decreasing pH. This platform can be used in noninvasive continuous analysis of ionized calcium and pH in body fluids for disease diagnosis such as primary hyperparathyroidism and kidney stones.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                LCAHAM
                Lab on a Chip
                Lab Chip
                Royal Society of Chemistry (RSC)
                1473-0197
                1473-0189
                May 03 2022
                2022
                : 22
                : 9
                : 1793-1804
                Affiliations
                [1 ]Soft Transducers Laboratory, École Polytechnique Fédérale de Lausanne (EPFL), 2000 Neuchatel, Switzerland
                [2 ]Micro & Nano systems Centre, Tyndall National Institute, T12 R5CP Cork, Ireland
                Article
                10.1039/D2LC00183G
                4f4f8497-76a2-4676-aeea-0c3c848209c7
                © 2022

                http://rsc.li/journals-terms-of-use

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