Multifunctional Wearable Sensing Devices Based on Functionalized

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Multifunctional Wearable Sensing Devices Based on Functionalized Graphene films for Simultaneous Monitoring of Physiological Signals and VOC Biomarkers Hua Xu, Jian Xin Xiang, Yi Fei Lu, Ming Kun Zhang, Jia Jia Li, Bingbing Gao, Yuanjin Zhao, and Zhongze Gu ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b00073 • Publication Date (Web): 19 Mar 2018 Downloaded from http://pubs.acs.org on March 22, 2018

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ACS Applied Materials & Interfaces

Multifunctional Wearable Sensing Devices Based on Functionalized Graphene films for Simultaneous Monitoring of Physiological Signals and VOC Biomarkers Hua Xu†,‡*, Jian Xin Xiang†, Yi Fei Lu†, Ming Kun Zhang†, Jia Jia Li†, Bing Bing Gao†, Yuan Jin Zhao†and Zhong Ze Gu†,‡,* †

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering,

Southeast University, Si Pai Lou 2, Nanjing 210096 (China) ‡

Research Institute of Biomaterials and Medical Devices, Jiang Su Industrial Technology

Research Institute, Jiang Ning, Nanjing 211100 (China) E-mail: [email protected]; [email protected].

KEYWORDS: multifunctional wearable sensing device, functionalized graphene film, physiological signal, VOC biomarkers, signal interference

ACS Paragon Plus Environment

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ABSTRACT

In this study, a multifunctional wearable sensing device based on two different graphene films is fabricated and can achieve simultaneous detection of physiological signals and VOC biomarkers without mutual signal interference. The wearable device was designed with two sensing components: on the upper layer of the device, four kinds of porphyrin-modified reduced graphene oxide (rGO) films were prepared and used for a sensor array that could sufficiently react with VOC vapors to achieve highly sensitive detection. A porous rGO film was designed on the under layer of the device and used as a strain-sensing matrix, which could be closely attached to the skin to achieve a highly sensitive detection of the physiological signal. A polyimide film between the two sensing components was used not only as a flexible substrate, but also as a protective layer to avoid the porous rGO film’s response to VOC molecules. Investigation of detection ability showed that the porous rGO strain-sensing matrix can achieve a higher gauge factor (282.28) than the unstructured rGO counterpart (8.96) and is more desirable for the detection of physiological motion. In contrast, the porphyrin-modified rGO sensor array displayed a superior response to VOC vapors and eight different VOC biomarkers could be detected and discriminated using the as-prepared sensor array together with a pattern recognition approach. The multifunctional sensing devices displayed excellent ability for detection of a variety of human physiological signals, such as pulse and respiration rate. Simultaneous analysis of simulated diabetic breath samples, simulated nephrotic breath samples, and of breath samples exhaled by healthy individuals using our wearable device exhibited clear identification and discrimination. Our study provides new insights into fabrication and design of multifunctional sensing devices without signal interference and the application of the proposed devices are promising in preventive medicine and healthcare.


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INTRODUCTION

The areas of personalized healthcare and early diagnosis, in combination with disease’s prevention, have gained increasing attention and are considered to be cost-efficient approaches to achieving better health outcomes. Effective healthcare and early diagnosis rely on uninterrupted monitoring and acquiring of an individual’s health data. Wearable devices that can be directly mounted on the skin have attracted considerable attention for this purpose because of their ease of obtaining the wearer’s health parameter in real time, continuously and noninvasively. Various wearable devices based on different materials and structures have been rapidly developed for monitoring different health parameters.1-8 However, a single health parameter is insufficient for a full evaluation of the health condition of the wearer or for the diagnosis or prediction of a disease. Thus, there is a need for the development of multifunctional wearable devices for monitoring of multiple health signals, in particular for simultaneous monitoring of multiphysiological indices and biomarkers. Numerous experimental data have also verified that the amount and/or species of volatile organic compounds (VOCs) in the exhaled breath are closely related to some metabolic diseases. Continuous detection of the specific VOCs provides a promising approach for noninvasive and easy-to-perform monitoring of diseased and other states.9–14 To date, various nanomaterials have been extensively used for fabrication of wearable sensors or sensor arrays for volatile biomarker monitoring because their high special surface area provides fast response, high sensitivity, and quick recovery times.15–25 Among them, some flexible sensors have been reported to be responsive to VOC biomarkers as well as to other stimuli (such as strain, temperature, and relative humidity, etc.),19–25 and have been used to achieve multiparametric detection in a single sensing platform. Although these flexible sensing platforms have an obvious advantage in the


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development of a compact, multifunctional wearable sensing device, they usually give a combined response signal of VOC biomarkers and other stimuli and it is difficult to uncouple these combined signals, which limits their practical application. A different approach for a multifunctional wearable sensing device is based on parallel integration of multiple different sensors on a single platform, where each sensor is response to a defined stimulus.19 Since each sensor unit in such multi-sensing device is dedicated to sensing a defined stimulus, which efficiently solve the combined signal issues of multifunctional sensing platform based on single sensors.26-28 Courbat reported a multifunctional sensing platform for simultaneous monitoring of VOCs vapors, temperature and CO through parallel integration of three different sensors on a polyimide (PI) film, including a polymer-based capacitive sensor, a Pt thermometer and metal oxide-based chemiresistive sensor.29 However, the sensing platform still suffers from signal interference because the VOCs vapors and CO at elevated temperature have an increased probability of interaction with adjacent sensing films and introduced interference to other sensing units of the platform.30 Furthermore, signal interference originating from mechanical deformation is a concern in most of flexible sensing device because a strain/pressure event at a specific sensing unit often induced misleading signals in neighboring units.19,31 In addition, the multi-sensing platform based on different sensing materials and processes usually required numerous fabrication steps, which leading to a complicated structure, sophisticated fabrication and high production cost. All these issues have limited the development and application of the multifunctional wearable sensing devices for simultaneous monitoring of VOC biomarkers and physiological signal and calls for a breakthrough in material design and fabrication. Reduced graphene oxide (rGO) has been used as new sensing elements in developing


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flexible wearable electronic devices because of their unique electrical, mechanical, and thermal properties.15-16, 32-34 Although a number of rGO-based flexible gas and strain sensors have been developed, their sensitivity still need to be improved for accurately detecting target analytes over interferents. In particular, modification of rGO with various compounds has been performed to improve their gas selectivity and sensitivity.32 Porphyrins are an attractive sensing material for non-covalent functionalization of graphenen with aromatic porphyrinic cores that interact strongly with π-conjugated graphene sheet. Furthermore, porphyrin are able to specifically bind with VOCs vapors through metal coordination, hydrogen bonding, and π-π interactions to achieve highly sensitive sensing detection.35-37 In this study, we developed a simple, cost-efficient approach for manufacturing of multifunctional wearable sensing devices based on two different graphene films that can achieve simultaneous detection of physiological signals and VOC biomarkers without mutual signal interference. A gas sensor array composed of four different porphyrin-modified rGO films was designed on the upper layer of the device for highly sensitive detection of VOC biomarkers (Figure 1). A strain-sensing matrix based on porous rGO films that could be closely attached to the skin to achieve highly sensitive detection of physiological signals, was designed on the underlayer of the device. A PI film was designed between two sensing components and used not only as a flexible substrate, but also as a protective layer on the surface of the porous rGO strainsensing matrix to avoid the porous rGO film’s response to VOC molecules. The devices displayed excellent ability for detection of human physiological signals, such as pulse and respiration rate. Simultaneous analysis of exhaled breath using these devices showed that the simulated exhaled breath of diabetic patients and nephrotic patients, and the exhaled breath of healthy individuals could clearly be identified and distinguished. Compared with existing


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multifunctional healthcare devices, our devices hold obvious advantages in the detection of VOC biomarkers and physiological signals without mutual signal interference, as well as easy to massproduce, simple, and low-cost characteristics.

Figure 1 Schematic of fabricating a multifunctional wearable sensing device.

RESULTS AND DISCUSSION Fabrication of multifunctional wearable healthcare devices Figure 1 showed a schematic of fabricating two different graphene films used for the multifunctional sensing devices. Graphene oxide (GO) dispersion was deposited on glass slide by drop-casting approach and the as-prepared GO film was immersed into ascorbic acid solution to chemical reduction. The obtained rGO film could easily separated from the hydrophilic glass slide and become freestanding because of the hydrophilic group’s removal in the graphene sheets. Next, the porphyrin was coated onto the rGO film via spin-coating technology to obtain the porphyrin-modified rGO film. Four different porphyrins (TPP(NH2)4, CuTPP, ZnTPP and CoTPP) were used for modification of rGO film to achieve different gas selectivity and specificity.35–39 Four kinds of porphyrin-modified rGO film were transferred to the surface of PI substrate to fabricate the flexible porphyrin-modified rGO sensor array (Figure 2 a).


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Figure 2 (a-b) Photograph of the multifunctional sensing device based on two functionalized graphene films. SEM images of rGO film (c-d), porpyirn-modified rGO film (e) and porous rGO film (f-g). (h) Raman spectra of three graphene films. Nanoparticles of ~330 nm diameter were used as the pore template and were added to the GO solution, and the mixture was dropped on the glass slide and then chemically reduced to obtain a free-standing rGO film containing nanoparticles (Figure 1). A subsequent etch was then conducted on the composite film to remove the nanoparticles and a porous rGO film was obtained. Although silica and polystyrene nanoparticles have been used as the porous template for fabrication of the porous graphene foam or framework,40-41 we found that these nanoparticles were not suitable for fabrication of the porous graphene film (Figure S1). Many cracks appeared in the composite film when using silica and polystyrene nanoparticles as the pore template because of their hard structure that would lead to the breakage of the film and would limit the fabrication of large-scale porous graphene film. In this work, the soft nanoparticles P(BA-coMMA) was used as the pore template and large-area porous graphene films without any cracks could be easily fabricated (Figure S1). This is likely due to the intrinsic flexibility of P(BA-co-


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MMA) NPs that can adjust the curvature of the graphene sheet during the drying of the composite film. Two kinds of porous graphene film based on the composite films with 20 wt% and 10 wt% nanoparticles were fabricated by this method, and were denoted as PGF-1 and PGF2, respectively. The as-prepared porous rGO film was transferred and fixed on other side of the PI film to produce the flexible strain sensor (Figure 2b). At last, a PET film was coated onto the porous rGO film to produce the multifunctional wearable sensing devices. Compared with existing multifunctional healthcare devices, our devices hold obvious advantages of simple, low-cost fabrication character. Furthermore, using this method, large-size rGO and porous rGO film can be fabricated by simply increasing the substrate’s size, and thus the mass production of our multifunctional wearable sensor is easily realized. The as-prepared rGO and porous rGO film displayed excellent flexibility and metallic luster (Figure S1). SEM analysis shows that the surface of the rGO film is flat and the cross-section of the film revealed a layered structure (Figure 2c, d). After coating with porphyrin, SEM observation of the rGO film showed no damage to the original structure, and porphyrin covered the film surface uniformly (Figure 2e). The SEM images of PGF-1 and PGF-2 all showed a distinct porous structure of the film surface (Figure 2f). Furthermore, in comparison with the thick layered structure of the rGO film, the cross-sectional SEM images of PGF-1 and PGF-2 exhibited a cellular network assembled from layer of graphene sheet and the pores originated from the removal of nanoparticles between the graphene sheets (Figure 2g). It has been reported that detection sensitivity can be significantly enhanced by empolying a microstructured graphene film for the strain sensor due to the increased spatial deformation.33-34 Thus an excellent


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sensitivity would be anticipated employing the porous graphene film for strain or physiological signal detection. The contact angle of the GO film was ~33° (Figure S2), whereas the contact angles of the rGO and porous rGO films showed an obvious increase at ~75° and ~81° as a result of the hydrophilic group’s removal from the graphene sheets. XPS analysis displayed that the C 1s peaks at 286.9 eV decreased significantly and C/O atomic ratio increased from 0.76 for the GO film to 1.46 and 1.37 for the rGO and the porous rGO films, respectively (Figure S3). Simultaneously, the D peak in the Raman spectra exhibited increase and the ID/IG ratio increased from 0.92 for GO film to 1.13 and 1.10 for the rGO and porous rGO films, respectively (Figure 2h). These results indicated that hydrophilic groups of GO were efficiently removed and the conductive graphene films was formed. I–V characteristics of the rGO and porous rGO films showed a distinct decrease in the resistance compared with the GO film, which is ascribed to the reduction of the graphene film (Figure S4). Furthermore, the resistance of the porphyrinmodified rGO film showed no obvious change compared with the rGO film, and VOC vapors can be detected by the resistance feature. Detection of strain using porous rGO film The strain–response performance of the rGO and porous rGO (PGF-1 and PGF-2) films was tested by monitoring the variations in their normalized resistance change (∆R/R0). When strains were applied on the sensor by bending and stretching the film in a convex fashion from 30 to 25 mm (Figure 3a), the ∆R/R0 of three sensors increased by 8%, 17%, and 58%, respectively. The increased ∆R/R0 of the sensors can be attributed to the variations of the contact conditions between the graphene sheets in the stacked film, which is in accord with the previous research.33-


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In comparison with the rGO strain sensor, the PGF-1 and PGF-2 strain sensor with porous

microstructure exhibited an enhanced resistance change under the same bending–stretching condition, which indicated that the porous rGO films have a higher response to strain deformation and are more suitable for highly sensitive strain sensing. This also confirms recently reported results that using a microstructured rGO film for the strain sensor could achieve enhanced detection sensitivity over the unstructured counterpart, because of the increase in spatial deformation.33-34 Furthermore, under the same bending–stretching condition, the PGF-2 strain sensor with 20 wt% nanoparticles as pore template obtained a sevenfold improvement in resistance change, whereas the PGF-1 strain sensor with 10 wt% nanoparticles as pore template only achieved a twofold improvement in resistance change. This result indicated that the rGO film with more porous microstructure for the strain sensor could achieve higher detection sensitivity. However, the GO film with > 20 wt% nanoparticles as pore template could not obtain a complete rGO film without any breakage after reduction and removal of the nanoparticles because small number of graphene sheets could not form a continuous uniform film on the nanoparticle. Therefore, the PGF-2 film with 20 wt% nanoparticles as pore template was chosen for highly sensitive strain sensing in this work.


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Figure 3 (a) Response curves of rGO, PGF-1 and PGF-2 sensors under applied repeating strain. (b) Relative resistance change of rGO, PGF-1 and PGF-2 sensors under various bending chord lengths. c) Relative resistance change of rGO, PGF-1 and PGF-2 sensors under different strains. To investigate the strain sensing performance of the sensor, we applied seven different strains on the sensors by modulating the chord length of the sensor from 40 to 37, then to 34, 31, 28, 25, 22, and 19 mm. Under the bending–stretching strain, the normalized resistance of the three sensors rose with rise in the bending–stretching strain (Figure 3b). This result indicates that the sensor hold the capacity of quantitative analysis of the applied strain. Furthermore, compared with that of the rGO sensor, the resistance change of the sensor based on the PGF-2 film displayed 8–16 times increase under different bending–stretching condition. The gauge factor (GF) is a typical parameter that represents the strain sensor’s sensitivity and can be come from the ratio (∆R/R0)/(∆ε), where ∆ε is the strain. For strain between 0.25% and 0.75%, the GF values of the rGO, PGF-1, and PGF-2 strain sensors were 8.96, 122.08, and 282.28 (Figure 3c). This result shows that the PGF-2 strain sensor is indeed much more sensitive and is desirable for monitoring of weak physiological motion, such as human breath and pulse motion, whereas the rGO strain sensor would produce a negligible response to these motions because of its inferior sensitivity, which could solve the interference of the physiological signals on the VOC response signal of the rGO film. Multiple bending tests involving more than 1,000 cycles of 0.25% strain were repeatedly applied on the PGF-2 strain sensors and relaxed. The resistance values of the sensor were evaluated under each bend and relaxation state and the results showed almost identical change (Figure S5), which confirms that our PGF-2 strain sensor had excellent mechanical robustness and reliability for practical application.


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Detection of VOC biomarkers using porphyrin-modified rGO array The gas-sensing performance of the porphyrin-modified rGO sensor was investigated using its normalized resistance change, which was defined as R (%) = (Rg – R0)/R0 × 100%, where R0 and Rg represent the resistance values of the sensor upon exposure of air and VOC vapor, respectively. The normalized resistance of four porphyrin-modified rGO sensors exhibited an obvious increase when exposed to ammonia (Figure 4a). This may be ascribed to the easy interaction of ammonia and porphyrin molecules by metal coordination or hydrogen bonding, and electron transfer from ammonia to porphyrin-modified rGO occurred, which led to an increase in sensor resistance.35-37 It is notable that the resistance change of each porphyrinmodified rGO sensor was different despite exposure to identical ammonia. This result indicated that porphyrin can adjust to the vapor response of rGO film and different porphyrin-modified rGO films have different responses to the same vapor, which is very important for a crossreactive sensor array. Furthermore, the resistance increases of the sensor reached maximum after exposure to ammonia for ~260 s and 95% of the resistance value of the sensor can revert to the value when the used ZnTPP-rGO film, CoTPP-rGO film, TPPNH4-rGO film and CuTPP-rGO film were exposed to air for ~ 12, 15, 23 and 35 min respectively, which indicated the rapid response and good reversibility of our porphyrin-modified rGO sensor.


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Figure 4 (a) Response curves of four porphyrin-modified rGO films exposed to 10 ppm ammonia vapor. (b) Response curves of CuTPP-modified rGO films upon exposure to four different concentrations of ammonia (25ppm, 50ppm, 75ppm, 100ppm) under static and cyclic bending tests, respectively. (c) The gas response with respect to the ammonia concentration. (d) The response radar plots of the porphyrin-modified rGO sensor array to VOC vapors at 298K. Channels a–d separately represents ZnTPP, TPPNH4, CuTPP, CoTPP modified rGO film, respectively. (e) Hierarchical clustering analysis (HCA) and (f) Principal component analysis (PCA) of eight VOC vapors. To investigate the influence of bending on the sensor’s gas response, the vapor detection was performed by bending the porphyrin-modified rGO film from 30 to 20 mm in a ~40° convex


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fashion. Four different concentrations (25, 50, 75, and 100 ppm) of ammonia-sensing test were carried out for this bent sensor. The response of the sensor was found to be 18.5%, 31.5%, 42.1%, and 68.2%, respectively (Figure 4b-c), which was similar to the response in the flat condition (17.2%, 29.1%, 39.1%, and 62.9%, respectively). The resistance values displayed negligible difference, which indicates the excellent suitability of the sensor for flexible sensing application. To check the capacity of our flexible sensor array for discrimination of different vapors, eight VOC vapors with diverse chemical functionalities were tested. The normalized resistance change values (R (%)) of different rGO sensors were obtained for the vapor and are represented as a radar plot. As shown in Figure 4d, each vapor has a unique radar plot, which can use as functional fingerprint to discriminate one vapor from others. The different R(%) changes of the sensing units resulted from the special interaction between porphyrin and different VOC vapors, which induced charge transfer to graphene and results in changes in electrical conductivity of graphene film.42 Moreover, using our sensor array, a wide range of VOC vapor could be distinguished, not only the vapors from the different chemical categories but also the vapors from the same chemical family (Figure 4d). The above results indicated that our flexible sensor array have high sensitivity in distinguishing different VOC vapors. To investigate the reproducibility and practicability of our flexible sensing array to detect each VOC vapor, PCA and HCA methods were used for analysis of the triplicate test results of the aforementioned eight vapors. As shown in Figure 4e, the result of HCA show that all vapors were accurately classified in triplicate trials, in accordance with the electronic and structural characteristics of different vapor. Figure 4f showed a two-dimensional (2D) PCA plot of the above eight VOC vapors. The first two principal components that hold 96.80% of the total


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variance was chose to represent all response data. The results showed a significant discrimination of eight kinds of vapors. It is notable that our flexible sensing array had excellent reproducibility and practicability to detect a very wide range of VOC vapors, which indicates its promising application in the detection and screening of VOC-related disease. Simultaneous detection of physiological signals and VOC-related disease Having established their superior performance, we next examined the application of the asprepared multifunctional wearable healthcare device for simultaneous monitoring of physiological signals and VOC biomarkers in exhaled breath. As vital signs, the detection of respiratory rate and pulse is crucial in a hospital. Our sensing device can be attached on a person’s wrist or chest for real-time recording of pulse and respiratory rate signals, providing a simple, effective, and inexpensive method for vital sign monitoring (Figure 5a). Figure 5b displayed the captured pulse and respiratory signals, where each cycle stands for a pulse or breath. The valleys and peaks represent the shrinking and stretching of the chest, respectively, in breathing. According to the obtained results, the pulse and breath rates were about 76 and 19 in 60 s, respectively. These data were all within a healthy adult’s normal range, demonstrating the potential application of our wearable device in the simple, effective, and real-time detection of vital signs. Furthermore, the porphyrin-modified rGO sensor of our sensing device exhibited a negligible resistance change when the PGF-2 strain sensor detected human pulse rate (Figure S6), which indicated that the porphyrin-modified rGO sensor is not response to the physiological motions and avoid the interference of the physiological signals on the VOC response signal of the rGO film.


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Figure 5 (a) Photograph of the as-prepared multifunctional wearable device mounted on the human wrist for simultaneously monitoring of VOC-related disease and plus signal. (b) The normalized resistance changes of the PGF-2 sensor for monitoring wrist pulses and respiratory rate of a 22-year-old healthy male. (c) PCA analysis of exhaled breath of simulated nephrotics patients, diabetic patients and healthy people. Simultaneous analysis of VOC biomarkers in exhaled breath for clinical disease diagnostics using our multifunctional wearable devices can also be performed because of their superior performance of mutual noninterference. According to previous studies, acetone and ammonia gas have been identified as specific biomarkers for diabetic and nephrotic patients, respectively.13–14 Thus, 10 ppm acetone and ammonia gas were introduced into the exhaled breath of healthy individuals to simulate the exhaled breath of diabetic and nephrotic patients, respectively. Three kinds of exhaled breath (simulated diabetic breath, simulated nephrotic breath, and the breath of healthy individuals) were investigated and each exhaled breath sample was tested five times in five independent experiments. The obtained response data were analyzed by the PCA method and the results are shown in Figure 5c. A distinction between the three breath samples is clearly observed. The exhaled breath samples of five healthy individuals, five simulated diabetic patients, and five simulated nephrotic patients were categorized into three distinguishable


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clusters without any overlap. These results demonstrate that our wearable devices have high potential for diagnosis of VOC-related disease.

CONCLUSION In summary, we have developed a multifunctional wearable sensing device based on two different functionalized graphene films that can perform simultaneous monitoring of VOC biomarkers and physiological signals without mutual signal interference. A gas sensor array composed of four different porphyrin-modified rGO films was designed on the upper layer of the device that could sufficiently react with VOC biomarkers to achieve highly sensitive detection. A strain-sensing matrix based on porous rGO films that could be closely attached to the skin to achieve highly sensitive detection of physiological signals, such as human breath and pulse motions, was designed on the underlayer of the device. A PI film was designed between the two sensing components and used not only as a flexible substrate for the sensor array, but also as a protective layer on the surface of the porous rGO strain-sensing matrix to avoid the porous rGO film’s response to VOC molecules. Investigation of detection ability showed that the use of the porous rGO film for the strain sensor demonstrated enhanced detection sensitivity over the nonporous rGO counterpart. In contrast, the porphyrin-modified rGO sensor array exhibited a superior response to VOC vapor, yet a negligible response to weak human breath and pulse motions. Eight different VOC biomarkers could be detected and discriminated using the asprepared sensor array together with pattern recognition approach. The application of the asprepared sensing devices to detect different human physiological signals, such as pulse and respiration rate, was easily accomplished by directly attaching on different body locations and the result all showed excellent detection capability. Simultaneous detection of simulated diabetic


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and nephrotic breath samples and exhaled breath samples of healthy individuals using our wearable devices revealed clear identification and discrimination. Our study provides new insights into fabrication and design of multifunctional sensing devices without signal interference and the application of the proposed devices are promising in preventive medicine and healthcare.

EXPERIMENTAL SECTION Reagents and instruments. Natural graphite power (325mesh) was purchased from Nanjing XFNANO Material Tech Co.,Ltd. (China); GO was prepared according to modified Hummers method.38-39,43 meso-tetraphenyl porphyrin Zinc (ZnTPP), meso-tetra(4-aminophenyl) porphyrin (TPP(NH2)4), meso-tetraphenyl porphyrin Copper (CuTPP), and meso-tetraphenyl porphyrin Cobalt (CoTPP) were prepared following literature procedures.35-37 P(BA-co-MMA), silica, polystyrene nanoparticles was prepared according to our previously reported method.36 Polyimide film (KAPTON HN film, Dupton) with a thickness of 125um was purchased from KAIZHEN Co., Ltd. PET film with a thickness of 10um was purchased from Cleanwrap Co., Ltd. VOC vapor were produced by the homemade experimental apparatus according to literature (Figure S7).36 All the measurements were carried out at room temperature ( about 25°C). Dry air (purity: 99.99%, Nanjing Special Gas Co. Ltd) was employed as carrier gas at a flow rate of 300 sccm. Saturated VOC vapor samples were prepared by bubbling dry air through their corresponding pure VOC liquid. Mass flow controller (Brooks 5850E) was used to control the delivery of dry air to a chamber containing the VOC liquid. The analyte chamber was submerged in 25°C thermostatic waterbath to maintain the constant temperature of the VOC liquid.


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Therefore the vapor analysts mixed with the air were at a known vapor pressure. VOC vapor with different concentrations can be achieved by mixing dry air with the VOC vapor. The expiratory air of healthy human was collected by balloon and used as exhale breath sample. Ammonia (100 ppm in synthetic air, Nanjing Special Gas Co. Ltd) and acetone (100 ppm in synthetic air, Nanjing Special Gas Co. Ltd) were diluted with a dry air to 10 ppm. Then, 10 ppm ammonia and 10 ppm acetone were mixed with the exhale breath of healthy human to obtain the simulated exhale breath of diabetic patient and nephrotics patient, respectively. Fabrication of multifunctional sensing devices. The GO solution with a concentration of 2 mg/mL was dropped on the slide, and the obtained GO film was placed in a 65℃ oven for 2 h to dry. Different thickness of the GO film can be obtained through repetition of the above process. Then the GO film was reduced by heating in ascorbic acid solution at 90℃. The obtained freestanding rGO film was dried and modified with porpyrin by spin-coating method. Four types of different porphyrin-modified RGO film (ZnTPP, TPP(NH2)4, CuTPP, and CoTPP) were placed on the surface of PI substrate and were fixed with double-sided adhesive film to fabricate the flexible sensor array. The fabrication process of the freestanding porous RGO film was similar to that of the rGO film. Nanoparticles of ~330 nm diameter were added to the GO solution with a concentration of 2 mg/mL, and the mixture solution was dropped on the slide and the GO film was placed in a 65℃ oven for 2 h to dry. Different thickness of the GO film can be obtained by repeating the above step. The as-prepared film was reduced by heating in ascorbic acid solution at 90℃ and the free-standing rGO film containing nanoparticles was obtained. Then the composite film was incubated in toluene or 4.0% HF aqueous solution to remove the nanoparticles. The obtained porous rGO film was washed and dried. Two kinds of porous graphene film based on the


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composite films with 20 wt% and 10 wt% nanoparticles were fabricated by this method, respectively. Then the porous rGO film was further fixed on the other side of the PI substrate with double-sided adhesive film to fabricate the flexible strain sensor. A PET film was coated onto the porous rGO film to produce the multifunctional wearable sensing devices. Sensing measurement：The performance of the strain sensor was checked by bending the film from 40 to 37, then to 34, 31, 28, 25, 22, and 19 mm. The porous rGO/PI film (40 mm length) was fixed on a Vernier caliper’s main jaws, which assist in stretching and bending the ﬁlm in anticipant size. When one jaws slid against the other, the flat rGO/PI film will bend. The arc chord of the bending rGO/PI film can be measured with the Vernier caliper and the resistance of the bending rGO/PI film can be recorded with the digital source meter Keithley 4200-SCS. Here seven different chord lengths were controlled and the resistance of the rGO/PI film under each bending condition was tested. For detection of VOC vapors, the device was put in a gas sensing chamber connecting with four channels (Figure S7).44 One channel was used for connecting the porphyrin-modified rGO films with the semiconductor characterization system by two platinum wires and another channel was used for connecting a vacuum pressure gauge. The last two channels were employed for the gas mixture of VOC vapor and air in and out, respectively. The VOC vapor was led continuous into the gas sensing chamber by MFC, and the resistance of the porphyrin-modified rGO films was recorded. In all vapor tests, the sensor was first exposed to air to attain the baseline, then to VOC vapor, and then back to air, which finished one cycle. To demonstrate the capability of our device for simultaneous detection of physiological signals and VOC biomarkers in exhaled breath, the sensors were mounted on a person’s wrist or chest with an adhesive tape (VHB 4910, 3M) for real-time recording of pulse and respiratory rate signals. Three kinds of exhaled breath


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(simulated diabetic breath, simulated nephrotic breath, and the breath of healthy individuals) were introduced into the sensor array respectively and the electrical signals of the porphyrinmodified rGO films under different exhaled breath were recorded. Each exhaled breath sample was tested five times in five independent experiments and the results were used for principal component analysis. All experiments were carried out in accordance with the relevant institutional guidelines and regulation and approved by the institutional committees. In addition, all subjects have provided written informed consent for the participation in the study. Data analysis. The statistical multivariate methods, hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to analyze the responses of the sensor array. The PCA and HCA were performed using IBM SPSS statistics 21 and Statistical Program for Social Science 13 software package, respectively. Characterization Methods. SEM (Ultra Plus, Zeiss) was used to investigate the morphology and microstructure. X-ray photoelectron spectroscopy (XPS) was performed on PHI-5700 ESCA system (Perkin-Elmer, USA). Invia Raman Microscope (Renishaw) with 532 nm Ar+ laser was used to record Raman spectra. The contact angle of the GO, rGO and porous rGO film were measured by powereach (JC2000D, POWEREACH, Shanghai). The source measure unit (Keithley 4200SCS, USA) was used to record the electronic property of the sensor. Letv X500 Phone was used to obtain the photographs of the sensor. Supporting Information. Photograph of the GO/nanoparticle film; Contact angle; XPS spectra; I-V curves; Multiple bending tests; Relative resistance changes of the porphyrin-modified rGO film to physiological


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motions; Schematic diagram of the vapor sensing device. This materials is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author E-mail: [email protected]; [email protected]. ACKNOWLEDGMENT The research is primarily funded by NSFC (Grant No. 51573025), Jiangsu Natural Science Foundation (Grant No. BK20151454) and Jiangsu Key R & D Plan (Grant No. BE2016002) and the Fundamental Research Funds for the Central Universities. REFERENCES 1.

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Table of Contents Graphic


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Multifunctional Wearable Sensing Devices Based on Functionalized

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