6
Sensors and Actuators B 246 (2017) 455–460 Contents lists available at ScienceDirect Sensors and Actuators B: Chemical jo ur nal home page: www.elsevier.com/locate/snb Smart bandage with wireless connectivity for optical monitoring of pH Petar Kassal a , Marko Zubak a , Gregor Scheipl b , Gerhard J. Mohr b , Matthew D. Steinberg c , Ivana Murkovi ´ c Steinberg a,a Faculty of Chemical Engineering & Technology, University of Zagreb, Maruli´ cev Trg 19, HR-10000 Zagreb, Croatia b Joanneum Research Forschungsgesellschaft mbH Materials, Franz-Pichler-Straße 30, Weiz A-8160, Austria c GoSense Wireless Ltd.,Moorfield Road, Duxford, Cambridge CB22 4PP, UK a r t i c l e i n f o Article history: Received 16 November 2016 Received in revised form 14 February 2017 Accepted 15 February 2017 Available online 20 February 2017 Keywords: Smart bandage Wound monitoring Optical pH sensor Wireless chemical sensor Radio-frequency identification a b s t r a c t Wound care technologies need to adapt in order to cope with the growing socio-economic burden of chronic wounds. Non-invasive analytical systems which monitor important wound status biomarkers such as pH of wound fluid, are needed. In this work, a wireless smart bandage for optical determination of pH, as an indicator of wound status, is demonstrated and characterised. The bandage is constructed by immobilising cellulose particles, covalently modified with a pH indicator dye, within a biocompatible hydrogel. Thin layers of the pH sensitive hydrogel are cast onto a conventional dressing and interfaced to a wireless platform via a miniaturised optoelectronic probe. The smart bandage can detect pH changes in the physiologically relevant range with high accuracy and precision, and communicate this information with an external readout unit using radio-frequency identification (RFID). The new system could provide insight into temporal changes in wound status in a convenient and non-invasive manner, and prompt an appropriate response from a healthcare provider. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Wound management is a significant socio-economic burden for modern society. Two percent of the population in the developed world will suffer a chronic wound during their lifetime [1]. The United States spends $25bn a year on chronic wound care [2], and comparable amounts are spent in other major economies [3,4]. Early identification of non-healing wounds and wound infection is thus of paramount importance in preventing deterioration of a patient’s condition, hospitalisation of the patient, or even limb or life-threatening consequences [4,5]. There is a clear need for smart wound care dressings dressings equipped with physical and or (bio)chemical sensors or indicators that can determine and com- municate wound status in a clinically relevant and cost effective manner [6]. Smart dressings should be simple, effective and provide actionable data, thus enabling truly non-invasive wound assess- ment that will guide treatment decisions [6]. A strategy typically adopted by healthcare providers in managing chronic wounds is to attempt to reduce the total cost of patient treatment by focusing Abbreviations: RFID, radio-frequency identification; NFC, near field communi- cation. Corresponding author. E-mail address: [email protected] (I. Murkovi ´ c Steinberg). on reducing the incidence of complications (infection), the num- ber and duration of patient hospitalisations, and on reducing the total time to heal. Nurse time and community/home visits thus tend to dominate the real cost of patient treatment when compared to the baseline material costs incurred (dressings, bandages, antisep- tics) which account for only a small percentage of the overall cost [7]. Therefore smart dressings may generate significant savings if they reduce the frequency of nursing home visits, reduce the sever- ity of infections by facilitating early detection and treatment and, by implication, reduce the frequency and duration of patient hospitalisations. The pH of wound fluid is known to affect wound healing and is recognised as an important biomarker of wound status [4,8]. Gen- erally after an acute cutaneous wound has occurred, acidosis of the underlying tissue regulated at around pH 7.4 follows. This is a natural response to injury that aims to prevent infection and bac- terial growth [9]. Colonising bacteria seek to increase the pH to create a more favourable microenvironment, and thus an increase in wound fluid pH may indicate infection [9,10]. The pH of chronic wounds is more complex, but seems to oscillate between pH 7–8 as the wound fails to heal [9]. Different electrochemical methods have been used to determine the pH of wound fluids [11,12]. Examples of such include potentio- metric sensing with screen-printed electrodes [13] and monitoring the pH-dependent oxidation current of endogenous biomarkers http://dx.doi.org/10.1016/j.snb.2017.02.095 0925-4005/© 2017 Elsevier B.V. All rights reserved.

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Page 1: Sensors and Actuators B: Chemical - unizg.hrSmart... · Kassal et al. / Sensors and Actuators B 246 (2017) 455–460 457 Fig. 2. Cross-section of the optoelectronic probe in relation

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Sensors and Actuators B 246 (2017) 455–460

Contents lists available at ScienceDirect

Sensors and Actuators B: Chemical

jo ur nal home page: www.elsev ier .com/ locate /snb

mart bandage with wireless connectivity for optical monitoring of pH

etar Kassala, Marko Zubaka, Gregor Scheiplb, Gerhard J. Mohrb, Matthew D. Steinbergc,vana Murkovic Steinberga,∗

Faculty of Chemical Engineering & Technology, University of Zagreb, Marulicev Trg 19, HR-10000 Zagreb, CroatiaJoanneum Research Forschungsgesellschaft mbH – Materials, Franz-Pichler-Straße 30, Weiz A-8160, AustriaGoSense Wireless Ltd.,Moorfield Road, Duxford, Cambridge CB22 4PP, UK

r t i c l e i n f o

rticle history:eceived 16 November 2016eceived in revised form 14 February 2017ccepted 15 February 2017vailable online 20 February 2017

eywords:

a b s t r a c t

Wound care technologies need to adapt in order to cope with the growing socio-economic burden ofchronic wounds. Non-invasive analytical systems which monitor important wound status biomarkerssuch as pH of wound fluid, are needed. In this work, a wireless smart bandage for optical determinationof pH, as an indicator of wound status, is demonstrated and characterised. The bandage is constructedby immobilising cellulose particles, covalently modified with a pH indicator dye, within a biocompatiblehydrogel. Thin layers of the pH sensitive hydrogel are cast onto a conventional dressing and interfaced to

mart bandageound monitoring

ptical pH sensorireless chemical sensor

adio-frequency identification

a wireless platform via a miniaturised optoelectronic probe. The smart bandage can detect pH changes inthe physiologically relevant range with high accuracy and precision, and communicate this informationwith an external readout unit using radio-frequency identification (RFID). The new system could provideinsight into temporal changes in wound status in a convenient and non-invasive manner, and prompt anappropriate response from a healthcare provider.

© 2017 Elsevier B.V. All rights reserved.

. Introduction

Wound management is a significant socio-economic burden forodern society. Two percent of the population in the developedorld will suffer a chronic wound during their lifetime [1]. Thenited States spends $25bn a year on chronic wound care [2], andomparable amounts are spent in other major economies [3,4].arly identification of non-healing wounds and wound infections thus of paramount importance in preventing deterioration of aatient’s condition, hospitalisation of the patient, or even limb or

ife-threatening consequences [4,5]. There is a clear need for smartound care dressings – dressings equipped with physical and or

bio)chemical sensors or indicators – that can determine and com-unicate wound status in a clinically relevant and cost effectiveanner [6]. Smart dressings should be simple, effective and provide

ctionable data, thus enabling truly non-invasive wound assess-

ent that will guide treatment decisions [6]. A strategy typically

dopted by healthcare providers in managing chronic wounds is tottempt to reduce the total cost of patient treatment by focusing

Abbreviations: RFID, radio-frequency identification; NFC, near field communi-ation.∗ Corresponding author.

E-mail address: [email protected] (I. Murkovic Steinberg).

ttp://dx.doi.org/10.1016/j.snb.2017.02.095925-4005/© 2017 Elsevier B.V. All rights reserved.

on reducing the incidence of complications (infection), the num-ber and duration of patient hospitalisations, and on reducing thetotal time to heal. Nurse time and community/home visits thus tendto dominate the real cost of patient treatment when compared tothe baseline material costs incurred (dressings, bandages, antisep-tics) which account for only a small percentage of the overall cost[7]. Therefore smart dressings may generate significant savings ifthey reduce the frequency of nursing home visits, reduce the sever-ity of infections – by facilitating early detection and treatment –and, by implication, reduce the frequency and duration of patienthospitalisations.

The pH of wound fluid is known to affect wound healing and isrecognised as an important biomarker of wound status [4,8]. Gen-erally after an acute cutaneous wound has occurred, acidosis of theunderlying tissue – regulated at around pH 7.4 – follows. This is anatural response to injury that aims to prevent infection and bac-terial growth [9]. Colonising bacteria seek to increase the pH tocreate a more favourable microenvironment, and thus an increasein wound fluid pH may indicate infection [9,10]. The pH of chronicwounds is more complex, but seems to oscillate between pH 7–8as the wound fails to heal [9].

Different electrochemical methods have been used to determinethe pH of wound fluids [11,12]. Examples of such include potentio-metric sensing with screen-printed electrodes [13] and monitoringthe pH-dependent oxidation current of endogenous biomarkers

Page 2: Sensors and Actuators B: Chemical - unizg.hrSmart... · Kassal et al. / Sensors and Actuators B 246 (2017) 455–460 457 Fig. 2. Cross-section of the optoelectronic probe in relation

456 P. Kassal et al. / Sensors and Actua

Fig. 1. Schematic showing operation of the wireless smart bandage. The pH-inducedcolour change of cellulose particles with covalently linked GJM 534 is measured ands

–eaptbiflueewIolmaspucalcca

nobwwlTsdtaDwc

components by automated pick and place followed by reflow solderˇ

ent by contactless readout to a remote unit.

such as uric acid – during voltammetric scans [14]. Wirelesslectrochemical platforms which enable potentiometric [15] andmperometric [16] sensing have been developed in parallel to sup-ort these electrochemical measurement methodologies, althougho the best of our knowledge a fully wireless electrochemical smartandage for pH sensing has not yet been devised. Optical chem-

cal sensors that sense pH through the change in absorbance oruorescence of an (immobilised) indicator dye are simple to man-facture in high volume, are easily miniaturised, do not suffer fromlectromagnetic interference and do not require a separate ref-rence electrode [17]. Optical sensors are therefore attractive foround pH sensing and in the imaging and mapping of wounds.

n the simplest case optical readout is by naked eye of the colourf an indicator dye [18]. In practice however this simple approachimits the level of quantification of the wound. By addition of instru-

entation the optical quantification and accuracy can be improved,lthough this in turn can impact the price and complexity, and inome cases may impair the mobility of the patient [19,20]. Smarthones and mobile computing devices, such as tablets, are nearbiquitous in the developed world, and combine high-resolutionameras with powerful computational ability [21]. As such, theyre popularly used as instruments for mobile diagnostics. Nonethe-ess, accurate determination of true colour even with high-qualityonsumer products is non-trivial and requires complex image pro-essing, as well as auxiliary (often ‘phone-specific) coupling devicesnd/or light sources [22,23].

In this paper we provide a viable solution to the challenge set forext generation wound dressings – a quantitative optical indicatorf wound pH status with non-contact electronic readout. This haseen achieved by immobilising a pH indicator dye on a commercialound dressing, and integrating the pH sensing film thus formedith a novel radio-frequency identification (RFID)-based contact-

ess readout platform via a low-cost optoelectronic interface, Fig. 1.he proposed dye immobilisation technique enables low-cost andcalable fabrication (e.g. by screen printing) of pH sensitive films onifferent kinds of materials commonly used in dressings. The elec-ronics autonomously measures and stores quantitative pH data,nd upon request, transfers it wirelessly by RFID to a computer.evelopment of an appropriate Android application in the future

ould allow the electronics to directly communicate by near field

ommunication (NFC) with a Smartphone or tablet.

tors B 246 (2017) 455–460

2. Materials & methods

2.1. Chemicals and reagents

The pH indicator dye 4-[4-(2-hydroxyethanesulfonyl)-phenylazo]-2,6-dimethoxyphenol (GJM-534) [24,25] was fromJoanneum Research Forschungsgesellschaft mbH (Austria). Sig-macell Cellulose Type 20 particles were from Aldrich (Austria).Hydromed D4 polyurethane-based hydrogel was from Cardiotech(USA). Wide range pH buffer solutions were prepared by weighingboric acid (Sigma–Aldrich,St. Louis, MO,USA), citric acid andsodium hydroxide (Kemika d.d., Zagreb, Croatia), dissolving themin deionised water and mixing with phosphoric acid (Kemikad.d., Zagreb, Croatia). pH was adjusted with 0.1 M solution ofhydrochloric acid (Carlo Erba Reagenti, Arese, Italy).

2.2. Preparation of coloured cellulose particles and sensor layers

In a typical immobilisation procedure, 100 mg of GJM-534 wastreated with 1.0 g of concentrated sulfuric acid for 30 min at roomtemperature [18]. This converted the hydroxyethylsulfonyl groupof the indicator dye into the sulfonate. Then, the mixture waspoured into 200 ml of distilled water containing 50.0 g of Sigma-cell cellulose particles and neutralized with 1.6 ml of a 30% sodiumhydroxide solution. Then, 25.0 g of sodium carbonate in 100 ml ofwater and 5.2 ml of a 30% sodium hydroxide solution were added.Upon addition of sodium hydroxide and sodium carbonate, the dyesulfonates were converted into vinylsulfonyl derivatives and cou-pled via Michael addition to the hydroxyl groups of cellulose. After60 min, the particles were filtrated using a Buchner funnel and werewashed repeatedly with distilled water and acetone to removesalts and unbound dyes. The dry pigments were then dispersedinto the 10% polymer solution of Hydromed D4 in aqueous ethanol(ethanol/water = 9:1) and stirred overnight. The well stirred dis-persion was pipetted onto the top side of a 2 mm thick adhesivesurgical dressing (Vivapore, Tosama d.o.o., Domzale, Slovenia) andspread using a knife-coating blade to form a thin opaque pH sensi-tive layer with dimensions 15 mm × 15 mm. A structurally relateddye (fluorine atom instead of methoxy group) was immobilised tothe present type of cellulose particles and the resulting sensor par-ticles were evaluated with respect to their cytotoxicity according toISO 10993-5. Neither the undiluted eluate nor direct contact withthe MRC-5 cells caused any decrease in cell viability [26].

2.3. Wireless RFID platform

Optical measurements were performed with a wireless sen-sor platform designed specifically for optical chemical sensing.The platform is a small, lightweight and fully programmableautonomous mobile analytical instrument. The overall dimen-sions of the platform are 60 mm × 60 mm × 10 mm. The systemis powered from a standard 3 V CR 2032 lithium coin cell andcommunicates with mobile devices via a set of custom ISO15693RFID/NFC commands. The device is built around a commercial inte-grated circuit (MLX90129, Melexis BV, Belgium) which providesthe wireless communication functions (RFID and NFC), as well asa programmable data logger function and integrated temperaturesensor. Electronic circuits were designed using a schematic cap-ture and printed circuit board (PCB) layout suite with autorouter(EASY-PC Professional v14.0 with Tracerouter, Number One Sys-tems Ltd., Gloucester, UK). Printed circuit boards were fabricatedfrom standard FR4 materials and populated with surface mount

(L-Tek Elektronika d.o.o., Sentjernej, Slovenia). The wireless plat-form is interfaced to a miniaturized optoelectronic probe consistingof a wide viewing angle (120◦) surface mount LED (LM1-EPG1-

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P. Kassal et al. / Sensors and Actuators B 246 (2017) 455–460 457

e pH sensitive film, illustrating the optical component configuration.

0BaiPt1saa

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owboemriIstpatriactwlaG

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3

pcpfo

Fig. 3. (A) Chemical structures of the protonated and deprotonated forms of GJM534 (top) and their respective colours (bottom). (B) Absorbance spectra of GJM 534

Fig. 2. Cross-section of the optoelectronic probe in relation to th

1-N2-00001, Cree Inc., Durham, NC, USA) and photodiode (PD,PW34S, Osram Opto Semiconductors GmbH, Germany). The LEDnd the photodiode are positioned 4 mm apart and facing the sens-ng film at a distance of approximately 6 mm, Fig. 2. The LED andD are controlled by the wireless platform during sample acquisi-ions at an adjustable sample rate. The device is equipped with aMb memory adequate for storage of 32000 measurements, a con-tant current source to drive the LED light source, a transimpedancemplifier for the photodetector, and a boost regulator to generate

5 V power supply.

.4. Experimental protocol

In a typical measurement, 2 ml of buffer solution was pipettednto the bottom side of the bandage (the side in contact with aound) to ensure adequate wicking of the bandage and contact

etween the pH sensitive film and sample. An equilibration periodf 3 min was allowed to elapse before starting measurements tonsure absorption of the buffer solution by the dressing. The opticaleasurement was initialised using a USB-powered desktop RFID

eader (Proxima RF Inc, USA) connected to a PC running a graph-cal user interface (DVK90129 sensor kit dashboard, Proxima RFnc, USA). The sample rate of the smart bandage electronics waset to 0.5 samples per second. After initialisation, the optoelec-ronic probe was placed above the pH sensitive film. A hollowlastic cylinder was used to house the optoelectronics, providing

shield from ambient light and helping position it at a fixed dis-ance of 6 mm from the sensing film, Fig. 2. After 20 samples wereecorded, the smart bandage electronics was placed in the vicin-ty of the RFID reader and data transferred wirelessly to the PC fornalysis. Conversion to pH units is performed in the PC using thealibration curve (Eq. (1), Section 3.3). After each measurement,he functionalised dressing was thoroughly rinsed with deionizedater. Results were correlated against pH values obtained with a

aboratory pH meter (Iskra MA5740, Metrel d.d., Slovenia) using combination pH electrode (BlueLine 17 pH, Schott AG, Mainz,ermany).

. Results and discussion

.1. Choice of indicator dye and immobilisation procedure

The pH indicator dye, 4-[4-(2-hydroxyethanesulfonyl)-henylazo]-2,6-dimethoxyphenol (GJM-534) displays a reversible

olour change from yellow to purple in going from acidic to basicH, Fig. 3A [24,25]. The dye contains reactive vinylsulfonyl groupsor covalent immobilisation to cellulose, which enables fabricationf, for example, indicator swabs for monitoring pH of chronic

immobilised on cellulose and exposed to buffers of different pH. The line indicatesthe peak wavelength of the LED used in the smart bandage.

wounds [18]. However, the dye cannot be covalently linked tonon-cellulose based materials, which are also used in wound care.Wound dressings are commonly made using collagen, silicone,chitosan, hyaluronic acid, heparin, gelatine or alginates [27,28].Thus, in order to functionalise different dressing materials theindicator dye was covalently immobilised onto commerciallyavailable cellulose particles (Section 2.2). These coloured particles

were subsequently embedded into a polyurethane-based hydrogelHydromed D4 and coated onto commercial dressings in the form ofthin pH sensitive layers. Hydromed D4 is a biocompatible hydrogel,
Page 4: Sensors and Actuators B: Chemical - unizg.hrSmart... · Kassal et al. / Sensors and Actuators B 246 (2017) 455–460 457 Fig. 2. Cross-section of the optoelectronic probe in relation

458 P. Kassal et al. / Sensors and Actuators B 246 (2017) 455–460

F asic mv

ciefipts

3

pt(moaasFtSwcftcpiffmstmLsia

ig. 4. Colour change of the smart bandage indicator upon exposure to increasing balues of standard buffer solutions (pH 4–12) (bottom).

ommonly used in medicine, and importantly for this application,s highly ion-permeable. Furthermore, it is soluble in aqueousthanol and can be dried at room temperature, which enablesacile fabrication of the sensor. This immobilisation procedures compatible with mass production techniques, such as screenrinting, and could thus offer a scalable and low-cost route tohe mass production of indicator dressings, as has already beenuggested for the production of textile-based sensors [29].

.2. Operation of the wireless smart bandage

The wireless smart bandage was assembled by integrating theH sensitive layers with the wireless platform via the optoelec-ronic probe, as depicted in Figs. 1 and 2. The wireless platformSection 2.3) is a small, lightweight, autonomous analytical instru-

ent, designed specifically for performing measurements withptical chemical sensors. Of the many wireless technologies avail-ble, the use of RFID for sensing in wound care is particularlyttractive, primarily because of the intrinsic low power con-umption of RFID, which facilitates extended measurements [30].urthermore, RFID is compatible with NFC, a short-range con-actless technology which is implemented in new generationmartphones. Therefore, with appropriate application software,ound status parameters from this RFID-based smart bandage

an be read directly by a Smartphone for analysis [31]. The plat-orm may also optionally function as a portable data logger withhe capability of storing up to 32000 measurements. The loggingapability is especially advantageous for clinical research as it willrovide insight into temporal pH changes of wound fluid, valuable

nformation to healthcare practitioners. Because the wireless plat-orm contains an integrated temperature sensor this could be usedor both temperature compensation of the pH response as well as

onitoring of wound temperature, providing the system with aecond independent marker of wound infection [32]. The optoelec-ronic probe consists of a LED light source and a photodiode which

easures the light reflected from the pH sensitive film, Fig. 2. The

ED for the optoelectronic probe was chosen based on recordedpectra of GJM-534, Fig. 3B. As can be seen from the figure, uponncrease of pH, the dye exhibits an increased absorption maximumt 534 nm. Accordingly, an LED with a peak wavelength at 527 nm

edium (top). Response of the smart bandage readout electronics to increasing pH

was chosen to closely match this absorption of the deprotonatedform of the dye. The intensity of the reflected light from the LEDwhich is detected by the photodiode is therefore inversely propor-tional to the degree of deprotonation of GJM-534, i.e. the pH. Thesystem can thus measure and store in its memory the pH of thesample fluid. After each measurement, the electronics also recordsthe background light level whilst the LED is disabled. Changes inbackground light level often indicate motion artifact of the detec-tor relative to the dressing, and thus these can be subtracted fromthe analytical signal to provide a degree of artifact compensation.

3.3. pH response

The smart bandage system was characterised in the laboratorywith standard physiological pH buffer solutions. The functionaliseddressing exhibits a colorimetric response to increasing pH of thesurrounding medium and changes colour from yellow to purple(Fig. 4, top). The response of the electronics to this colour changecaused by exposing the indicator dye to buffer solutions, as detectedby the photodiode and converted to digital form by the analogue-to-digital converter of the wireless platform (ADC code), is shown inFig. 4, bottom. The pH was adjusted with standard buffers between5.9 and 10.4, with two reference values at pH 4 and 12 whichensured complete protonation and deprotonation of GJM-534. Theelectronic sample rate was set to 1 sample every 2 s, and 20 mea-surements were taken per buffer solution. Between measurementsdressings were thoroughly rinsed with deionised water to providean accurate calibration graph.

The pH response curve was constructed by taking the average ofthe last 10 measurement points in each buffer solution and plottingthis value against pH of the buffer solution, Fig. 5. It was foundthat subtracting the background light level improved the results,and the compensated data is shown in the figure. The expectedsigmoid relationship was obtained and a Boltzmann curve, whichcan be used as a calibration curve, was fit to the experimental data(R2 = 0.9997):

[ ( )]

pH = 0.57586 ln

25465 − 7722ADC − 7722

− 1 + 7.345 (1)

The p Ka value, obtained from the inflection point of theBoltzmann curve was 7.35. The dynamic range was found to be

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P. Kassal et al. / Sensors and Actuators B 246 (2017) 455–460 459

4 6 8 10 126000

8000

100 00

120 00

140 00

160 00

180 00

20000

22000

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ig. 5. pH response curve of the wireless smart bandage. A Boltzmann curve, whichhe range between pH 6.4 and 8.4, in which the response is quasi-linear.

pproximately 6–9 pH, while between pH 6.4 and 8.4 the responses quasi-linear and is shown in the inset of Fig. 5. In the linearH range a two-point calibration is sufficient to characterise theesponse, which could greatly simplify use in laboratory and clini-al practice. If the Boltzmann curve is used as a calibration function,H can be sensed over the full range. Both cases cover the pH rangef chronic wounds as suggested by Schneider et al. [9].

.4. Correlation with laboratory pH meter and analyticalvaluation

The performance of the smart bandage was correlated against laboratory pH meter. The pH of seven sample buffer solutions,

6.5 7.0 7. 5 8.0 8.5

6.5

7.0

7.5

8.0

8.5

y = x

pH, s

mar

t ban

dage

pH, pH meter

ig. 6. Correlation plot of pH determined with the smart bandage against pH deter-ined with the reference laboratory pH meter. A unity-slope line (y = x) is shown

or reference. Error bars represent one standard deviation around the mean (n = 6).

e used as a calibration function, was fit to the experimental data. The inset shows

with pH ranging from 6.5 to 8.5, was determined by recording theresponse with the smart bandage and calculating pH from the cal-ibration function of Eq. (1). These values were correlated againstvalues obtained with the laboratory pH meter, Fig. 6. Each pointin the correlation plot represents the average of 6 separate opticalmeasurements (n = 6), since between measurements the optoelec-tronic probe was completely removed from the pH sensitive layerand then placed back. The error bars represent one standard devi-ation between measurements. A unity-slope line is shown on thegraph for reference. The actual linear fit has a slope of 0.9985 andan intercept at −0.015 pH units (R2 = 0.9951), demonstrating excel-lent agreement between the smart bandage and the reference pHmeter. The measurement accuracy can be expressed as the dif-ference between pH determined with the smart bandage and pHdetermined with the reference pH meter, while precision can beexpressed as standard deviation around the mean. These valuesare displayed in Table 1. The precision was in all cases better than0.05 pH units and the accuracy was better than 0.08 pH units (n = 6).We can thus confirm that the smart bandage can measure pH both

accurately and precisely in the pH range tested. The precision andaccuracy are improved compared to two previously reported opti-cal pH sensors for wound monitoring [33,34].

Table 1Accuracy and precision of pH measurements conducted with the smart bandage(n = 6) versus a laboratory pH meter as reference standard.

pH, pHmeter

Mean pH,smart bandage

Absoluteerror

Relativeerror (%)

stdev RSD (%)

6.54 6.49 −0.05 −0.82 0.05 0.807.08 7.04 −0.04 −0.50 0.04 0.587.28 7.30 0.02 0.29 0.02 0.267.59 7.62 0.03 0.44 0.02 0.317.75 7.70 −0.05 −0.65 0.02 0.288.04 7.96 −0.08 −0.98 0.03 0.388.48 8.46 −0.02 −0.24 0.01 0.13

Page 6: Sensors and Actuators B: Chemical - unizg.hrSmart... · Kassal et al. / Sensors and Actuators B 246 (2017) 455–460 457 Fig. 2. Cross-section of the optoelectronic probe in relation

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. Conclusions

A novel contactless smart bandage that could be adopted forndicating wound pH in clinical practice has been demonstrated andharacterised in the laboratory. The system is light-weight, mobile,ow-cost and could in the future enable simple non-invasive woundH assessment. The electronics is fully compatible for readouty Smartphone using international wireless standards RFID andFC. The smart bandage can measure pH in the physiologically

elevant range with high precision and accuracy, and displaysxcellent correlation when compared against a reference labora-ory pH meter. Future development of the smart bandage couldnclude fabrication of the electronics onto a flexible circuit, tomprove wearability and patient mobility that would ensure maxi-

um conformity to limb contours. We believe that smart bandages,uch as the one presented in this work, will help change the chronicound care paradigm from one of routine management and time-

ased dressing changes toward more personalised care regimes andnowledge-based treatment.

cknowledgements

This work was supported in part by the University of Zagreb,nder research grant number 113004 (2014) “Integrated analyt-

cal chemical systems: development and application of chemicalensors and biosensors”, and part of the work was supportedy the femtech project 840000 “PyzoTex”, and by the Researchtudios Austria project 844724 “SmartColourTextiles” of the Aus-rian Research Promotion Agency (FFG). All support is gratefullycknowledged.

eferences

[1] C.K. Sen, G.M. Gordillo, S. Roy, R. Kirsner, L. Lambert, T.K. Hunt, F. Gottrup, G.C.Gurtner, M.T. Longaker, Wound Repair Regen. 17 (2009) 763.

[2] H. Brem, O. Stojadinovic, R.F. Diegelmann, H. Entero, B. Lee, I. Pastar, M.Golinko, H. Rosenberg, M. Tomic-Canic, Mol. Med. 13 (2007) 30.

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Biographies

Petar Kassal is a postdoctoral researcher at the Faculty of Chemical Engineeringand Technology, University of Zagreb, Croatia. He received an M.Sc. in chemicalengineering (2010) and a Ph.D. in applied chemistry (2015) from this institution.His main research interest is the development of novel electrochemical and opticalchemical sensors and biosensors for wearable and wireless applications.

Marko Zubak received his B.Eng. degree from the Faculty of Chemical Engineering& Technology, University of Zagreb in 2015. He is currently pursuing an M.Sc. degreeat the same Faculty and working on wireless wound monitoring as his thesis topic.

Gregor Scheipl studied earth sciences with focus on petrology and geochemistry atthe Karl-Franzens University in Graz. He finished his studies with the applied masterthesis: “Purification and chemical characterization of organic semiconducting mate-rials” in 2005. Since 2008 he is employed as a permanent scientist at JOANNEUMRESEARCH/Materials in Austria. His main interests are fabrication and characteriza-tion of physical sensors as well as ferroelectric polymers, pyro- and piezoelectricityand printing/imprinting techniques.

Dr. Gerhard J. Mohr received his PhD in Chemistry (1996) at Karl-Franzens Uni-versity Graz in the field of optical sensors for anions. Then he moved to the Centrefor Chemical Sensors at ETH Zurich where he was engaged in the synthesis andcharacterisation of new chemosensor dyes and functional polymers. In May 2001,he submitted his habilitation thesis entitled: “Chromogenic and fluorogenic reac-tands: New tools for molecular recognition of neutral analytes” to the Department ofApplied BioSciences of the Swiss Federal Institute of Technology (ETH) and receivedthe Venia Legendi in April 2002. From 2001 until 2008, he was Marie Curie andHeisenberg fellow at Friedrich-Schiller University Jena and from 2009 until 2011he was establishing the Fraunhofer workgroup Sensor Materials in Regensburg,focussing on new functional dyes, fluorescent nanosensors and their combinationwith polytronic systems. Currently, he is senior researcher at Joanneum Research,developing new indicator dyes for polymer layers, textiles and non-wovens andcombining them with information and communication technology.

Matthew D. Steinberg is a co-founder and director of GoSense Wireless Ltd.His research interests are in instrumentation and microsystem technologies, par-ticularly the integration of sensors and low-power communications for mobilemonitoring. He has a B.Eng. in Electronic Engineering from the University of Liv-erpool, and a Ph.D. from the Institute of Biotechnology, University of Cambridge.

Ivana Murkovic Steinberg is Associate Professor of Chemistry at the Faculty ofChemical Engineering & Technology, University of Zagreb. Her current research

tures for integration with wireless sensing systems. She graduated with a B.Eng. inChemical Engineering from the University of Zagreb, and has a Ph.D. in chemistryfrom the Karl-Franzens University of Graz for research on optical sensors for thedetermination of metal ions.