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      Lactate Biosensing for Reliable On-Body Sweat Analysis

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          Abstract

          Wearable lactate sensors for sweat analysis are highly appealing for both the sports and healthcare fields. Electrochemical biosensing is the approach most widely used for lactate determination, and this technology generally demonstrates a linear range of response far below the expected lactate levels in sweat together with a high influence of pH and temperature. In this work, we present a novel analytical strategy based on the restriction of the lactate flux that reaches the enzyme lactate oxidase, which is immobilized in the biosensor core. This is accomplished by means of an outer plasticized polymeric layer containing the quaternary salt tetradodecylammonium tetrakis(4-chlorophenyl) borate (traditionally known as ETH500). Also, this layer prevents the enzyme from being in direct contact with the sample, and hence, any influence with the pH and temperature is dramatically reduced. An expanded limit of detection in the millimolar range (from 1 to 50 mM) is demonstrated with this new biosensor, in addition to an acceptable response time; appropriate repeatability, reproducibility, and reversibility (variations lower than 5% for the sensitivity); good resiliency; excellent selectivity; low drift; negligible influence of the flow rate; and extraordinary correlation (Pearson coefficient of 0.97) with a standardized method for lactate detection such as ion chromatography (through analysis of 22 sweat samples collected from 6 different subjects performing cycling or running). The developed lactate biosensor is suitable for on-body sweat lactate monitoring via a microfluidic epidermal patch additionally containing pH and temperature sensors. This applicability was demonstrated in three different body locations (forehead, thigh, and back) in a total of five on-body tests while cycling, achieving appropriate performance and validation. Moreover, the epidermal patch for lactate sensing is convenient for the analysis of sweat stimulated by iontophoresis in the subjects’ arm, which is of great potential toward healthcare applications.

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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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            Lab-on-Skin: A Review of Flexible and Stretchable Electronics for Wearable Health Monitoring.

            Skin is the largest organ of the human body, and it offers a diagnostic interface rich with vital biological signals from the inner organs, blood vessels, muscles, and dermis/epidermis. Soft, flexible, and stretchable electronic devices provide a novel platform to interface with soft tissues for robotic feedback and control, regenerative medicine, and continuous health monitoring. Here, we introduce the term "lab-on-skin" to describe a set of electronic devices that have physical properties, such as thickness, thermal mass, elastic modulus, and water-vapor permeability, which resemble those of the skin. These devices can conformally laminate on the epidermis to mitigate motion artifacts and mismatches in mechanical properties created by conventional, rigid electronics while simultaneously providing accurate, non-invasive, long-term, and continuous health monitoring. Recent progress in the design and fabrication of soft sensors with more advanced capabilities and enhanced reliability suggest an impending translation of these devices from the research lab to clinical environments. Regarding these advances, the first part of this manuscript reviews materials, design strategies, and powering systems used in soft electronics. Next, the paper provides an overview of applications of these devices in cardiology, dermatology, electrophysiology, and sweat diagnostics, with an emphasis on how these systems may replace conventional clinical tools. The review concludes with an outlook on current challenges and opportunities for future research directions in wearable health monitoring.
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              Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration.

              The present work describes the first example of real-time noninvasive lactate sensing in human perspiration during exercise events using a flexible printed temporary-transfer tattoo electrochemical biosensor that conforms to the wearer's skin. The new skin-worn enzymatic biosensor exhibits chemical selectivity toward lactate with linearity up to 20 mM and demonstrates resiliency against continuous mechanical deformation expected from epidermal wear. The device was applied successfully to human subjects for real-time continuous monitoring of sweat lactate dynamics during prolonged cycling exercise. The resulting temporal lactate profiles reflect changes in the production of sweat lactate upon varying the exercise intensity. Such skin-worn metabolite biosensors could lead to useful insights into physical performance and overall physiological status, hence offering considerable promise for diverse sport, military, and biomedical applications.
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                Author and article information

                Journal
                ACS Sens
                ACS Sens
                se
                ascefj
                ACS Sensors
                American Chemical Society
                2379-3694
                06 July 2021
                23 July 2021
                : 6
                : 7
                : 2763-2771
                Affiliations
                [1]Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology , Teknikringen 30, SE-100 44 Stockholm, Sweden
                Author notes
                Author information
                https://orcid.org/0000-0002-1221-3906
                Article
                10.1021/acssensors.1c01009
                8397467
                34228919
                6170241a-435c-45fd-82c2-2b2318c74db5
                © 2021 The Authors. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 14 May 2021
                : 22 June 2021
                Funding
                Funded by: Kungliga Tekniska Högskolan, doi 10.13039/501100004270;
                Award ID: K-2017-0371
                Funded by: Stiftelsen Olle Engkvist Byggmästare, doi NA;
                Award ID: 204-0214
                Funded by: EIT Digital, doi NA;
                Award ID: 19376-20
                Funded by: Vetenskapsrådet, doi 10.13039/501100004359;
                Award ID: VR-2019-04142
                Funded by: Vetenskapsrådet, doi 10.13039/501100004359;
                Award ID: VR-2017-4887
                Categories
                Article
                Custom metadata
                se1c01009
                se1c01009

                lactate biosensor,diffusion limiting membranes,real-time monitoring,sweat analysis,wearable sensors

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