Reprinted from Lab on a Chip - University of Peng - New...Reprinted from Lab on a Chip Lab on a Chip...

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  • Reprinted from Lab on a Chip

    Lab on a Chip

    PAPER

    Cite this: Lab Chip, 2016, 16, 4415

    Received 8th August 2016,Accepted 7th October 2016

    DOI: 10.1039/c6lc01013j

    www.rsc.org/loc

    A new oil/membrane approach for integratedsweat sampling and sensing: sample volumesreduced from L's to nL's and reduction of analytecontamination from skin

    R. Peng,ab Z. Sonner,b A. Hauke,b E. Wilder,c J. Kasting,c T. Gaillard,d D. Swaille,e

    F. Sherman,e X. Mao,e J. Hagen,f R. Murdockf and J. Heikenfeld*b

    Wearable sweat biosensensing technology has dominantly relied on techniques which place planar-

    sensors or fluid-capture materials directly onto the skin surface. This on-skin approach can result in sam-

    ple volumes in the L regime, due to the roughness of skin and/or due to the presence of hair. Not only

    does this increase the required sampling time to 10's of minutes or more, but it also increases the time that

    sweat spends on skin and therefore increases the amount of analyte contamination coming from the skin

    surface. Reported here is a first demonstration of a new paradigm in sweat sampling and sensing, where

    sample volumes are reduced from the L's to nL's regime, and where analyte contamination from skin is

    reduced or even eliminated. A micro-porous membrane is constructed such that it is porous to sweat only.

    To complete a working device, first placed onto skin is a cosmetic-grade oil, secondly this membrane, and

    thirdly the sensors. As a result, spreading of sweat is isolated to only regions above the sweat glands before

    it reaches the sensors. Best case sampling intervals are on the order of several minutes, and the majority of

    hydrophilic (low oil solubility) contaminants from the skin surface are blocked. In vitro validation of this

    new approach is performed with an improved artificial skin including human hair. In vivo tests show strik-

    ingly consistent results, and reveal that the oil/membrane is robust enough to even allow horizontal sliding

    of a sensor.

    Introduction

    Recently, it has become clear that eccrine sweat provides a po-tentially attractive source of ion, molecule, and proteinanalytes.1,2 Consequently, there has been a significant in-crease in technology38 to detect sweat analytes as theyemerge onto skin. These new wearable approaches place aplanar sensor or sweat-collecting material directly on skin.Placing sensors onto skin quickly resolves3 the historical chal-lenges in sweat biosensing, such as very large sample vol-

    umes, evaporation, lack of sampling devices, and need for atrained staff.9 However, the current focus of mostresearchers18 is primarily for continuous monitoring, not forone time sampling which is arguably already well-served bydrawing blood. This creates challenges beyond those encoun-tered historically for sweat,3 especially because current ap-proaches in placing sensors or sampling materials againstskin limit sampling rates to 10's of minutes or even 100's ofminutes for lower sweat rates.1,3 We are not aware of any re-ports which address this critical challenge with sample vol-umes and sampling rates. Slow sampling rates also mean thatsweat spends more time sitting on the skin surface, whichwill only increase analyte contamination coming from theskin surface.10 Reducing skin contamination has beenachieved for clinical (one-time) sampling,10 but is a clear chal-lenge that remains unresolved for wearable and continuoussensing of analytes in sweat.3

    Reported here is demonstration of a novel oil/membraneapproach for sweat sampling and sensing. This report repre-sents the beginning of a new paradigm where sample vol-umes are reduced from the L's to nL's regime, and whereanalyte contamination from skin is reduced or even

    Lab Chip, 2016, 16, 44154423 | 4415This journal is The Royal Society of Chemistry 2016

    a School of Optical-Elect. and Comp. Engin., Univ. of Shanghai for Sci. and Tech,

    PR ChinabNovel Devices Lab, Dept. of Electrical Engin. and Computing Sys., Univ.

    Cincinnati., USA. E-mail: heikenjc@ucmail.uc.edu, www.noveldevicelab.comcWinkle College of Pharmacy, University of Cincinnati, Cincinnati, OH, 45267,

    USAdCollege of Nursing, University of Cincinnati, Cincinnati, OH, 45267, USAe P&G Corp. Technical and Research Centers, Cincinnati, OH, USAf Air Force Research Laboratory, 711th Human Performance Wing, Wright

    Patterson AFB, OH 45433, USA

    Electronic supplementary information (ESI) available. See DOI: 10.1039/c6lc01013j

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    http://crossmark.crossref.org/dialog/?doi=10.1039/c6lc01013j&domain=pdf&date_stamp=2016-10-28http://dx.doi.org/10.1039/C6LC01013Jhttp://pubs.rsc.org/en/journals/journal/LChttp://pubs.rsc.org/en/journals/journal/LC?issueid=LC016022

  • Reprinted from Lab on a Chip

    4416 | Lab Chip, 2016, 16, 44154423 This journal is The Royal Society of Chemistry 2016

    eliminated. A micro-porous membrane is coated with a dis-solvable polymer such that it is porous to sweat only, andthen is coated with a cosmetic-grade oil and placed onto theskin (Fig. 1). As a result, sweat is then isolated to regions onlyabove the sweat glands before it reaches the sensors. Thisgreatly reduces the sample volume and therefore the sam-pling rate is proportionally increased. Best case sampling in-tervals are on the order of several minutes, and the majorityof hydrophilic (low oil solubility) contaminants from the skinsurface are blocked. Validation includes in vitro demonstra-tion with and without human hair. As part of the in vitro vali-dation, we also present an improved artificial microfluidicskin which is simpler to fabricate and operate than our previ-ously reported approach.11

    In vivo validation is also performed with an electrical-impedance sensor, revealing that the technique is robustenough to even allow sliding of a sensor over the membrane/oil. The results reported here may represent the beginning ofa new regime for sweat biosensing, where even smalleramounts of sweat are sampled due to more sophisticatedinterfacing of technology on skin.

    Background and design

    There are two goals that motivated pursuit of this work. Thefirst was to reduce the required sweat volume (e.g. the totalvolume that must be refilled and replenished between sen-sors and the eccrine ducts).1,3 The second, was to isolateeccrine ducts from the skin surface to reduce possible con-tamination by analytes coming from the skin surface, fromdead cells, or from microbes.3,10 Both of these goals becomemost important for low or intermittent sweat generation rates(increased time for contamination). At very high sweat rates(nL's min1 per gland), the value of the oil/membrane ap-proach reported here is still beneficial but reduced. Practi-cally, continuously obtaining high sweat rates is likely limitedto applications like athletics, or will require chemicalstimulation.3

    We are not aware of any published results in the first goalof reducing the required sweat volume. However, the use ofpetroleum jelly or oil is well known for imaging sweat pro-duction12 as shown in Fig. 2b. Furthermore, placing oil onskin has also in one instance been used clinically by Boysenet al. (no sensors, bag collection of sweat) to reduce analytecontamination from the skin surface.10 Boysen's work clearlyreveals both the potential advantages and limitations of thework presented here. As shown in the summary of Table 1,even after pre-washing and rinsing of the skin, without a layerof oil there is significant contamination for hydrophilic andlarge analytes. Boysen's work concluded that the contamina-tion was due to elution of water-soluble contaminants intosweat from the epidermis. However, for small lipophilicanalytes (e.g. cholesterol) which are highly soluble in oil, theaddition of a layer of oil had no effect on blocking

    Fig. 1 Diagrams of sweat sensing on skin with (a) the conventionalapproach,18 and (b) time-lapse diagrams of the oil/membrane ap-proach of this paper which reduces volume and skin contamination.

    Fig. 2 Use of oil with bromophenol blue pH dye on skin for imagingsweat emerging from ducts (b) even at sweat low sweat generationrates that otherwise are (a) invisible and insensible due toevaporation.12

    Lab on a ChipPaper

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    http://dx.doi.org/10.1039/C6LC01013J

  • Reprinted from Lab on a Chip

    Lab Chip, 2016, 16, 44154423 | 4417This journal is The Royal Society of Chemistry 2016

    contamination from the skin surface. Therefore, the oil/mem-brane approach is unlikely to provide significant advantagesfor small lipophilic analytes such as hormones (e.g. cortisol).

    With additional reference to the scraping column inTable 1, it should be noted Boysen's work further suggeststhat sweat biosensing approaches should not utilize sam-pling materials (e.g. textiles) or sensors that repeatedly slideacross the bare skin (no oil or skin sealant). Such ap-proaches will likely increase the contamination from skinand should be avoided for high-quality biosensing. Lastly,we note that although Boysen showed that at high sweatrates eluted contamination is mitigated over time, at low orintermittent sweat rates significant contaminati