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      Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module

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          Abstract

          A sweat-based glucose monitoring device with transdermal drug delivery is developed for noninvasive diabetes treatment.

          Abstract

          Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging. We present a wearable/disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module. Careful multilayer patch design and miniaturization of sensors increase the efficiency of the sweat collection and sensing process. Multimodal glucose sensing, as well as its real-time correction based on pH, temperature, and humidity measurements, maximizes the accuracy of the sensing. The minimal layout design of the same sensors also enables a strip-type disposable device. Drugs for the feedback transdermal therapy are loaded on two different temperature-responsive phase change nanoparticles. These nanoparticles are embedded in hyaluronic acid hydrogel microneedles, which are additionally coated with phase change materials. This enables multistage, spatially patterned, and precisely controlled drug release in response to the patient’s glucose level. The system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus.

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          Most cited references36

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          An ultra-lightweight design for imperceptible plastic electronics.

          Electronic devices have advanced from their heavy, bulky origins to become smart, mobile appliances. Nevertheless, they remain rigid, which precludes their intimate integration into everyday life. Flexible, textile and stretchable electronics are emerging research areas and may yield mainstream technologies. Rollable and unbreakable backplanes with amorphous silicon field-effect transistors on steel substrates only 3 μm thick have been demonstrated. On polymer substrates, bending radii of 0.1 mm have been achieved in flexible electronic devices. Concurrently, the need for compliant electronics that can not only be flexed but also conform to three-dimensional shapes has emerged. Approaches include the transfer of ultrathin polyimide layers encapsulating silicon CMOS circuits onto pre-stretched elastomers, the use of conductive elastomers integrated with organic field-effect transistors (OFETs) on polyimide islands, and fabrication of OFETs and gold interconnects on elastic substrates to realize pressure, temperature and optical sensors. Here we present a platform that makes electronics both virtually unbreakable and imperceptible. Fabricated directly on ultrathin (1 μm) polymer foils, our electronic circuits are light (3 g m(-2)) and ultraflexible and conform to their ambient, dynamic environment. Organic transistors with an ultra-dense oxide gate dielectric a few nanometres thick formed at room temperature enable sophisticated large-area electronic foils with unprecedented mechanical and environmental stability: they withstand repeated bending to radii of 5 μm and less, can be crumpled like paper, accommodate stretching up to 230% on prestrained elastomers, and can be operated at high temperatures and in aqueous environments. Because manufacturing costs of organic electronics are potentially low, imperceptible electronic foils may be as common in the future as plastic wrap is today. Applications include matrix-addressed tactile sensor foils for health care and monitoring, thin-film heaters, temperature and infrared sensors, displays, and organic solar cells.
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            Transdermal drug delivery.

            Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.
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              Multifunctional wearable devices for diagnosis and therapy of movement disorders.

              Wearable systems that monitor muscle activity, store data and deliver feedback therapy are the next frontier in personalized medicine and healthcare. However, technical challenges, such as the fabrication of high-performance, energy-efficient sensors and memory modules that are in intimate mechanical contact with soft tissues, in conjunction with controlled delivery of therapeutic agents, limit the wide-scale adoption of such systems. Here, we describe materials, mechanics and designs for multifunctional, wearable-on-the-skin systems that address these challenges via monolithic integration of nanomembranes fabricated with a top-down approach, nanoparticles assembled by bottom-up methods, and stretchable electronics on a tissue-like polymeric substrate. Representative examples of such systems include physiological sensors, non-volatile memory and drug-release actuators. Quantitative analyses of the electronics, mechanics, heat-transfer and drug-diffusion characteristics validate the operation of individual components, thereby enabling system-level multifunctionalities.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                March 2017
                08 March 2017
                : 3
                : 3
                : e1601314
                Affiliations
                [1 ]Center for Nanoparticle Research, Institute for Basic Science, Seoul 08826, Republic of Korea.
                [2 ]School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.
                [3 ]Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
                Author notes
                [*]

                These authors contributed equally to this work.

                []Corresponding author. Email: dkim98@ 123456snu.ac.kr (D.-H.K.); thyeon@ 123456snu.ac.kr (T.H.)
                Author information
                http://orcid.org/0000-0002-6404-2846
                http://orcid.org/0000-0002-5232-9284
                http://orcid.org/0000-0003-2468-2061
                http://orcid.org/0000-0002-0412-2270
                Article
                1601314
                10.1126/sciadv.1601314
                5342654
                28345030
                fd29501f-def8-4f4f-b730-8d3568cdaf96
                Copyright © 2017, The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 10 June 2016
                : 02 February 2017
                Funding
                Funded by: Institute for Basic Science;
                Award ID: ID0EEWCI15509
                Award ID: IBS-R006-D1
                Award Recipient :
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Bioengineering
                Custom metadata
                Nova Morabe

                diabetes,sweat glucose monitoring,wearable and disposible electrochemical sensor,transdermal drug delivery,microneedle

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