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      Wireless, soft electronics for rapid, multisensor measurements of hydration levels in healthy and diseased skin

      research-article
      a , b , c , d , e , a , f , g , h , b , a , e , a , a , i , j , a , k , a , a , c , d , e , a , a , l , a , d , l , a , e , a , a , a , i , m , c , d , e , a , f , 2 , a , d , e , i , n , o , p , q , 2
      Proceedings of the National Academy of Sciences of the United States of America
      National Academy of Sciences
      wireless electronics, flexible electronics, biomedical devices, health monitoring, diagnostics

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          Significance

          Wireless electronics for monitoring of skin hydration in a quantitative fashion have broad relevance to our understanding of dermatological health and skin structure in both clinical and home settings. Here, we present a miniaturized, long-range automated system that adheres gently to the skin to yield quantitative recordings of skin water content for both epidermis and dermis. This system supports capabilities in characterizing skin barrier, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, with high levels of repeatability and insensitivity to ambient. Benchtop and pilot studies on patients with skin diseases highlight key features of these devices and their potential for broad utility in clinical research and in home settings to guide the management of disorders of the skin.

          Abstract

          Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.

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          Most cited references27

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          Atopic Dermatitis: Global Epidemiology and Risk Factors

          Atopic dermatitis (AD) is a chronic inflammatory skin disease posing a significant burden on health-care resources and patients' quality of life. It is a complex disease with a wide spectrum of clinical presentations and combinations of symptoms. AD affects up to 20% of children and up to 3% of adults; recent data show that its prevalence is still increasing, especially in low-income countries. First manifestations of AD usually appear early in life and often precede other allergic diseases such as asthma or allergic rhinitis. Individuals affected by AD usually have genetically determined risk factors affecting the skin barrier function or the immune system. However, genetic mutations alone might not be enough to cause clinical manifestations of AD, and it is merely the interaction of a dysfunctional epidermal barrier in genetically predisposed individuals with harmful effects of environmental agents which leads to the development of the disease. AD has been described as an allergic skin disease, but today, the contribution of allergic reactions to the initiation of AD is challenged, and it is proposed that allergy is rather a consequence of AD in subjects with a concomitant underlying atopic constitution. Treatment at best achieves symptom control rather than cure; there is thus a strong need to identify alternatives for disease prevention.
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            Transient plane source techniques for thermal conductivity and thermal diffusivity measurements of solid materials

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              Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year

              Background Loss-of-function mutations in the skin barrier protein filaggrin (FLG) are a major risk for atopic dermatitis (AD). The pathogenic sequence of disturbances in skin barrier function before or during the early development of AD is not fully understood. A more detailed understanding of these events is needed to develop a clearer picture of disease pathogenesis. A robust, noninvasive test to identify babies at high risk of AD would be important in planning early intervention and/or prevention studies. Objectives To ascertain whether a noninvasive measurement of skin barrier function at day 2 after birth and at 2 months predicts the development of AD at 1 year. Furthermore, to determine whether increases in transepidermal water loss (TEWL) predate the development of clinical AD. Methods A total of 1903 infants were enrolled in the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study from July 2009 to October 2011. Measurements of TEWL were made at birth (day 2) and at 2 and 6 months. The presence of AD was ascertained at 6 and 12 months, and disease severity was assessed by using the SCORing Atopic Dermatitis clinical tool at 6 months and by using both the SCORing Atopic Dermatitis clinical tool and Nottingham Severity Score at 12 months. A total of 1300 infants were genotyped for FLG mutations. Results At 6 months, 18.7% of the children had AD, and at 12 months, 15.53%. In a logistic regression model, day 2 upper quartile TEWL measurement was significantly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.81; P < .05). Lowest quartile day 2 TEWL was protective against AD at 12 months. An upper quartile 2 month TEWL was also strongly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.84; P < .05). At both ages, this effect was independent of parental atopy, FLG status, or report of an itchy flexural rash at 2 months. Associations were increased when parental atopy status or child FLG mutation status was added into the linear regression model. Conclusions Impairment of skin barrier function at birth and at 2 months precedes clinical AD. In addition to providing important mechanistic insights into disease pathogenesis, these findings have implications for the optimal timing of interventions for the prevention of AD.
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                Author and article information

                Journal
                Proc Natl Acad Sci U S A
                Proc Natl Acad Sci U S A
                pnas
                pnas
                PNAS
                Proceedings of the National Academy of Sciences of the United States of America
                National Academy of Sciences
                0027-8424
                1091-6490
                02 February 2021
                18 January 2021
                18 January 2021
                : 118
                : 5
                : e2020398118
                Affiliations
                [1] aQuerrey-Simpson Institute for Bioelectronics, Northwestern University , Evanston, IL 60208;
                [2] bSchool of Electrical Engineering, Korea Advanced Institute of Science and Technology , 34141 Daejeon, Republic of Korea;
                [3] cDepartment of Civil and Environmental Engineering, Northwestern University , Evanston, IL 60208;
                [4] dDepartment of Materials Science and Engineering, Northwestern University , Evanston, IL 60208;
                [5] eDepartment of Mechanical Engineering, Northwestern University , Evanston, IL 60208;
                [6] fWearifi Inc. , Evanston, IL 60201;
                [7] gElectrical and Computer Engineering, The University of Texas at Austin , Austin, TX 78712;
                [8] hDepartment of Electrical and Computer Engineering, University of Wisconsin , Madison, WI 53706;
                [9] iDepartment of Biomedical Engineering, Northwestern University , Evanston, IL 60208;
                [10] jSchool of Chemical Engineering, Sungkyunkwan University , 16419 Suwon, Republic of Korea;
                [11] kSchool of Advanced Materials Science and Engineering, Sungkyunkwan University , 16419 Suwon, Republic of Korea;
                [12] lMaruho Co., Ltd. , 531-0071 Osaka, Japan;
                [13] mDepartment of Dermatology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611;
                [14] nDepartment of Neurological Surgery, Northwestern University , Chicago, IL 60611;
                [15] oDepartment of Chemistry, Northwestern University , Evanston, IL 60208;
                [16] pDepartment of Chemical Engineering, Northwestern University , Evanston, IL 60208;
                [17] qDepartment of Electrical Engineering and Computer Science, Northwestern University , Evanston, IL 60208
                Author notes
                2To whom correspondence may be addressed. Email: jkchang@ 123456mywearifi.com or jrogers@ 123456northwestern.edu .

                Contributed by John A. Rogers, December 8, 2020 (sent for review October 16, 2020; reviewed by Tsuyoshi Sekitani and Benjamin C. K. Tee)

                Author contributions: K.K., J.-K.C., and J.A.R. designed research; K.K., H.W., J.L., K.S.C., H. Jang, I.Y., D.W., A.J.C., C.G.G., L.L., J.U.K., J.K., H. Jeong, H.L., Y.P., C.-J.S., J.W.K., D.S.Y., and J.-K.C. performed research; Y.I., S.R.M., A.I., and S.X. provided advice on skin assessment products; K.K., H.W., Y.I., A.I., A.B., S.X., Y.H., J.-K.C., and J.A.R. analyzed data; and K.K., H.W., S.X., J.-K.C., and J.A.R. wrote the paper.

                Reviewers: T.S., Osaka University; and B.C.K.T., National University of Singapore.

                1K.K. and H.W. contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-2373-7799
                https://orcid.org/0000-0003-4542-2867
                https://orcid.org/0000-0002-7797-9881
                https://orcid.org/0000-0002-3044-5110
                https://orcid.org/0000-0002-1808-7824
                https://orcid.org/0000-0002-1702-0986
                https://orcid.org/0000-0002-4629-1830
                https://orcid.org/0000-0002-3056-1250
                Article
                202020398
                10.1073/pnas.2020398118
                7865173
                33468630
                58469449-e3bd-4c00-8ac2-3ec9349b7930
                Copyright © 2021 the Author(s). Published by PNAS.

                This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

                History
                Page count
                Pages: 12
                Categories
                416
                Physical Sciences
                Engineering
                From the Cover

                wireless electronics,flexible electronics,biomedical devices,health monitoring,diagnostics

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