A flexible multiplexed immunosensor for point-of-care in situ wound monitoring

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Abstract

An integrated smart microfluidic dressing with a multibiomarker immunosensor can provide in situ wound status profiling on site.

Abstract

Chronic wounds arise from interruption of normal healing due to many potential pathophysiological factors. Monitoring these multivariate factors can provide personalized diagnostic information for wound management, but current sensing technologies use complex laboratory tests or track a limited number of wound parameters. We report a flexible biosensing platform for multiplexed profiling of the wound microenvironment, inflammation, and infection state at the point of care. This platform integrates a sensor array for measuring inflammatory mediators [tumor necrosis factor–α, interleukin-6 (IL-6), IL-8, and transforming growth factor–β1], microbial burden ( Staphylococcus aureus), and physicochemical parameters (temperature and pH) with a microfluidic wound exudate collector and flexible electronics for wireless, smartphone-based data readout. We demonstrate in situ multiplexed monitoring in a mouse wound model and also profile wound exudates from patients with venous leg ulcers. This technology may facilitate more timely and personalized wound management to improve chronic wound healing outcomes.

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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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Wearable and flexible electronics for continuous molecular monitoring

Yiran Yang, Wei Gao (2019)

Wearable/flexible chemical sensors enable continuous molecular monitoring and provide an individual's dynamic health information at the molecular level. Wearable biosensors have received tremendous attention over the past decade owing to their great potential in predictive analytics and treatment toward personalized medicine. Flexible electronics could serve as an ideal platform for personalized wearable devices because of their unique properties such as light weight, low cost, high flexibility and great conformability. Unlike most reported flexible sensors that mainly track physical activities and vital signs, the new generation of wearable and flexible chemical sensors enables real-time, continuous and fast detection of accessible biomarkers from the human body, and allows for the collection of large-scale information about the individual's dynamic health status at the molecular level. In this article, we review and highlight recent advances in wearable and flexible sensors toward continuous and non-invasive molecular analysis in sweat, tears, saliva, interstitial fluid, blood, wound exudate as well as exhaled breath. The flexible platforms, sensing mechanisms, and device and system configurations employed for continuous monitoring are summarized. We also discuss the key challenges and opportunities of the wearable and flexible chemical sensors that lie ahead.

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Author and article information

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): SciAdv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: May 2021

Publication date (Electronic): 21 May 2021

Volume: 7

Issue: 21

Electronic Location Identifier: eabg9614

Affiliations

[1 ]Institute for Health Innovation & Technology (iHealthtech), National University of Singapore, Singapore 117599, Singapore.

[2 ]Integrative Sciences and Engineering Programme, NUS Graduate School, National University of Singapore, Singapore 119077, Singapore.

[3 ]Department of Electrical and Computer Engineering, National University of Singapore, Singapore 117583, Singapore.

[4 ]Department of Biomedical Engineering, National University of Singapore, Singapore 117583, Singapore.

[5 ]Nursing, Singapore General Hospital, Singapore 168753, Singapore.

[6 ]Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore.

[7 ]Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.

[8 ]Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China.

[9 ]Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.

[10 ]Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.

Author notes

[* ]Corresponding author. Email: yujigao2021@ 123456gmail.com (Y.G.); ctlim@ 123456nus.edu.sg (C.T.L.)

Author information

Yuji Gao http://orcid.org/0000-0001-7222-647X

Dat T. Nguyen http://orcid.org/0000-0003-2750-3145

Su Bin Lim http://orcid.org/0000-0003-1752-7039

Leigh Edward Madden http://orcid.org/0000-0003-1111-9288

Lin Jin http://orcid.org/0000-0002-2059-2571

Fazila Abu Bakar Aloweni http://orcid.org/0000-0001-8435-5068

Ibrahim Abdelwahab http://orcid.org/0000-0002-0107-5827

Kian Ping Loh http://orcid.org/0000-0002-1491-743X

Chia-Hung Chen http://orcid.org/0000-0001-5097-3968

David Laurence Becker http://orcid.org/0000-0002-9300-0899

David Leavesley http://orcid.org/0000-0002-1033-5459

John S. Ho http://orcid.org/0000-0002-9458-9033

Chwee Teck Lim http://orcid.org/0000-0003-4019-9782

Article

Publisher ID: abg9614

DOI: 10.1126/sciadv.abg9614

PMC ID: 8139589

PubMed ID: 34020961

SO-VID: 8cf04f40-0664-4c66-9462-ed5877bcbcf0

Copyright © Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 06 February 2021

Date accepted : 31 March 2021

Funding

Funded by: doi http://dx.doi.org/10.13039/501100001352, National University of Singapore;

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A flexible multiplexed immunosensor for point-of-care in situ wound monitoring

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

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Wearable and flexible electronics for continuous molecular monitoring

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