Soft, skin-interfaced microfluidic systems with integrated immunoassays, fluorometric sensors, and impedance measurement capabilities

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Significance

Skin-interfaced, wireless devices for clinical-grade monitoring of physiological parameters are of growing interest for uses that range from healthcare to sports performance. This paper introduces a multifunctional skin-mounted microfluidic platform for capture and biomarker analysis of microliter volumes of sweat, a biofluid that can be collected noninvasively, with potential relevance in biophysical sensing. The focus is on colorimetric and digital assessments of a collection of parameters related to stress, including concentrations of vitamin C, cortisol, and glucose, along with quantitative measurements of sweat rate and galvanic skin response. The results represent important additions to a portfolio of emerging capabilities in skin-interfaced technologies for physiological monitoring, with particular relevance to conditions that follow from unhealthy levels of physical and mental stress.

Abstract

Soft microfluidic systems that capture, store, and perform biomarker analysis of microliter volumes of sweat, in situ, as it emerges from the surface of the skin, represent an emerging class of wearable technology with powerful capabilities that complement those of traditional biophysical sensing devices. Recent work establishes applications in the real-time characterization of sweat dynamics and sweat chemistry in the context of sports performance and healthcare diagnostics. This paper presents a collection of advances in biochemical sensors and microfluidic designs that support multimodal operation in the monitoring of physiological signatures directly correlated to physical and mental stresses. These wireless, battery-free, skin-interfaced devices combine lateral flow immunoassays for cortisol, fluorometric assays for glucose and ascorbic acid (vitamin C), and digital tracking of skin galvanic responses. Systematic benchtop evaluations and field studies on human subjects highlight the key features of this platform for the continuous, noninvasive monitoring of biochemical and biophysical correlates of the stress state.

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Kevin W Eliceiri, Caroline A Schneider, Wayne S Rasband (2018)

For the past twenty five years the NIH family of imaging software, NIH Image and ImageJ have been pioneers as open tools for scientific image analysis. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.

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

Wei Gao, Sam Emaminejad, Hnin Nyein … (2016)

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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The Dynamics of Capillary Flow

Edward W. Washburn (1921)

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Author and article information

Journal

Journal ID (nlm-ta): Proc Natl Acad Sci U S A

Journal ID (iso-abbrev): Proc Natl Acad Sci U S A

Journal ID (hwp): pnas

Journal ID (pmc): pnas

Journal ID (publisher-id): PNAS

Title: Proceedings of the National Academy of Sciences of the United States of America

Publisher: National Academy of Sciences

ISSN (Print): 0027-8424

ISSN (Electronic): 1091-6490

Publication date (Print): 10 November 2020

Publication date (Electronic): 26 October 2020

Publication date PMC-release: 26 October 2020

Volume: 117

Issue: 45

Pages: 27906-27915

Affiliations

[1] ^aQuerrey Simpson Institute for Bioelectronics, Northwestern University , Evanston, IL 60208;

[2] ^bDepartment of Materials Science and Engineering, University of Illinois at Urbana–Champaign , Urbana, IL 61801;

[3] ^cMaterials Research Laboratory, University of Illinois at Urbana–Champaign , Urbana, IL 61801;

[4] ^dDepartment of Medicine, Konkuk University , Seoul 05029, Republic of Korea;

[5] ^eDepartment of Materials Science and Engineering, Northwestern University , Evanston, IL 60208;

[6] ^fNano Hybrid Technology Research Center, Electrical Materials Research Division, Korea Electrotechnology Research Institute , Changwon 51543, Republic of Korea;

[7] ^gAccident Tolerant Fuels Technology Development Division, Korea Atomic Energy Research Institute , Daejeon 34057, Republic of Korea;

[8] ^hInstitut Charles Sadron UPR22, CNRS, Université de Strasbourg , F-67000 Strasbourg, France;

[9] ⁱCenter for Electronic Materials, Korea Institute of Science and Technology , Seoul 02792, Republic of Korea;

[10] ^jMaterials Sciences Research Center, Japan Atomic Energy Agency , Tokai, Ibaraki 319-1195, Japan;

[11] ^kDepartment of Mechanical Engineering, Korea Advanced Institute of Science and Technology , Daejeon 34141, Republic of Korea;

[12] ^lResearch and Development Division , Epicore Biosystems, Inc., Cambridge, MA 02139;

[13] ^mDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana–Champaign , Urbana, IL 61801;

[14] ⁿSchool of Mechanical Engineering, Yonsei University , Seoul 03722, Republic of Korea;

[15] ^oDepartment of Biomedical Engineering, Northwestern University , Evanston, IL 60208;

[16] ^pSchool of Biomedical Engineering, Korea University , Seoul 02841, Republic of Korea;

[17] ^qDepartment of Materials Science and Engineering, Querrey Simpson Institute and Feinberg Medical School, Northwestern University , Evanston, IL 60208;

[18] ^rDepartment of Biomedical Engineering, Querrey Simpson Institute and Feinberg Medical School, Northwestern University , Evanston, IL 60208;

[19] ^sDepartment of Neurological Surgery, Querrey Simpson Institute and Feinberg Medical School, Northwestern University , Evanston, IL 60208;

[20] ^tDepartment of Chemistry, Querrey Simpson Institute and Feinberg Medical School, Northwestern University , Evanston, IL 60208;

[21] ^uDepartment of Mechanical Engineering, Querrey Simpson Institute and Feinberg Medical School, Northwestern University , Evanston, IL 60208;

[22] ^vDepartment of Electrical Engineering and Computer Science, Querrey Simpson Institute and Feinberg Medical School, Northwestern University , Evanston, IL 60208

Author notes

³To whom correspondence may be addressed. Email: rooz@ 123456northwestern.edu , jahyunkoo@ 123456korea.ac.kr , pbraun@ 123456illinois.edu , or jrogers@ 123456northwestern.edu .

Edited by Klavs F. Jensen, Massachusetts Institute of Technology, Cambridge, MA, and approved September 25, 2020 (received for review June 18, 2020)

Author contributions: S.K., B.L., J.T.R., S.H.S., R.G., J.K., P.V.B., and J.A.R. designed research; S.K., J.T.R., S.H.S., S.-U.L., A.H.-F., J.S., H.J., Y.S.O., G.L., M.-H.S., S.S.K., S.J., G.P., S.H., I.P., H.-I.J., and J.K. performed research; S.K., B.L., J.T.R., J.S., Y.S., H.J., Y.S.O., A.J.A., S.P.L., J.B.M., G.L., M.-H.S., S.S.K., I.P., H.-I.J., R.G., J.K., P.V.B., and J.A.R. contributed new reagents/analytic tools; S.K., B.L., S.H.S., S.-U.L., A.H.-F., J.S., Y.S., Y.S.O., A.J.A., S.P.L., J.B.M., G.L., M.-H.S., S.S.K., S.J., G.P., S.H., I.P., H.-I.J., R.G., J.K., P.V.B., and J.A.R. analyzed data; and S.K., B.L., J.T.R., S.H.S., A.H.-F., Y.S., Y.S.O., A.J.A., S.P.L., J.B.M., S.J., R.G., J.K., P.V.B., and J.A.R. wrote the paper.

¹S.K., B.L., J.T.R., and S.H.S. contributed equally to this work.

²Present address: Phil and Penny Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR 97403.