Flexible Electrochemical Transducer Platform for Neurotransmitters

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Article Cite This: ACS Omega 2018, 3, 3489−3500

Flexible Electrochemical Transducer Platform for Neurotransmitters Aravindan Aashish,†,§ Neethu Kalloor Sadanandhan,† Krishna Priya Ganesan,∥ Unnikrishnan Nair Saraswathy Hareesh,‡,§ Sankaran Muthusamy,∥ and Sudha J. Devaki*,†,§ †

Chemical Sciences and Technology Division, ‡Materials Science and Technology Division, and §Academy of Scientific and Innovative Research (CSIR-NIIST Campus), CSIR-National Institute for Interdisciplinary Science and Technology, Trivandrum 695019, India ∥ ISRO Satellite Centre, Old Airport Road, Vimanapura Post, Bengaluru 560017, Karnataka, India S Supporting Information *

ABSTRACT: We have designed a flexible electrochemical transducer film based on PEDOT−titania−poly(dimethylsiloxane) (PTS) for the simultaneous detection of neurotransmitters. PTS films were characterized using various techniques such as transmission electron microscopy, scanning electron microscopy, atomic force microscopy, four probe electrical conductivity, ac-impedance, and thermomechanical stability. The electrocatalytic behavior of the flexible PTS film toward the oxidation of neurotransmitters was investigated using cyclic voltammetry and differential pulse voltammetry. The fabricated transducer measured a limit of detection of 100 nm ± 5 with a response time of 15 s and a sensitivity of 63 μA mM−1 cm−2. The fabricated transducer film demonstrated for the simultaneous determination of epinephrine, dopamine, ascorbic acid, and uric acid with no interference between the analyte molecules. Further, transducer performance is validated by performing with real samples. The results suggested that the fabricated flexible PTS transducer with superior electrocatalytic activity, stability, and low response time can be explored for the sensing of neurotransmitters and hence can be exploited at in vitro and in vivo conditions for the early detection of the various diseases.

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INTRODUCTION Design and development of flexible, stretchable, and biocompatible electrochemical sensor platforms in rolled-up forms are receiving overwhelming importance for the live monitoring of the transitory release of biomarkers by living tissues/cells which can be applied for futuristic medical diagnostics.1−3 The advancement of real-time and selective detection of various analytes faces many challenges using conventional analytical techniques such as fluorescence, chromatography which remains limited because of their high cost, tedious operation, dependence on the pretreatment of extraction or derivatization, and postprocessing steps leading to additional costs to the entire process.4,5 In this respect, electrochemical sensors are widely recognized for its simple instrumentation, simple analysis of the data, accurate reproducibility, and specificity for various chemically and biologically relevant analytes and are exclusively placed to facilitate the miniaturization of a clinical laboratory.6−9 Transducers endowed with high electrical stability, sensitive electrochemical performance, and excellent cellular compatibility are receiving tremendous importance for the assembly of highly efficient, sustainable, light weight, and flexible electrochemical sensors.10−12 Recent advancements in the field of hybrid conductive polymer nanotechnology processes have paved a great attention to the development of high-performance organic electronic devices because of its © 2018 American Chemical Society

synergistic properties arising from the molecular-level mixing of these two components.13,14 In these systems, an intimate contact is established between polymer-inorganic nanoparticles which may help to increase the interfacial area resulting in an enhancement in the charge concentration, mobility, and also the electrical conductivity. In addition, self-organization, ordered structure, crystallinity, well-defined morphologies, and interactions between the semiconducting polymer nanoparticle in the nanolevel also play pivotal role in the properties of these hybrid nanocomposites.15,16 In this respect, hybrid conductive nanocomposite originated from the hierarchical networks of organic−inorganic nanoparticles deposited on flexible films having biocompatible features along with the channels of electron-transfer mediators and electron collectors is receiving keen research interest.17−19 Nanostructured conductive polymers gifted with tunable size, shape, spatial arrangement with large surface area, shortened pathways for charge/mass/ion transport, and also exhibiting exciting features such as flexibility, lightweight, and processability are making itself available for use in various applications.20 There is a wider interest in the use of Received: December 23, 2017 Accepted: March 14, 2018 Published: March 26, 2018 3489

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ACS Omega nanostructured conducting polymers in the field of electrochemistry for improved performance of electrochemical detection of various biologically and environmentally important analytes. Because the recognition element attachment and target molecules can cause perturbations in the chain conformation of conducting polymer films, a binding event can be converted to an electrical signal which can be further amplified for readable measurement.21 Electropolymerization has also been applied for the modification and detection of various analytes because it can enhance the selectivity, sensitivity, homogeneity, strong adherence to the electrode surface, and excellent chemical stability.22,23 Among the range of nanostructured conducting polymers such as polyaniline, polypyrrole, and poly(3,4-ethylenedioxythiophene), PEDOT has been a viable candidate as a functional material for a wide range of applications because of its tunable structural, optical, and electronic properties such as side chain functionalization, optical transparency, low band gap, electrical conductivity, flexibility, ease of preparation, thermal stability, and also widely known for its bioconjugation.24−26 Our group has developed biotemplate-aided PEDOT nanospindles, which were used as an electrochemical transducer for the detection of various analytes. The high current response toward electrocatalytic oxidation is attributed to the shape of the PEDOT nanospindles which facilitate the smooth transfer of charge carriers from end to end.27 The literature shows that the development of hybrid conductive nanocomposite can enhance the electrocatalytic performance toward various analytes by contributing through shortened electron-transfer pathways and by enhancing charge concentration and mobilities.28,29 Among the semiconductor metal oxides, nanotitania receives prime importance because of its high chemical, thermal, and optical stability, nontoxicity, low cost, and corrosion resistance.30 In recent times, hierarchical titania nanostructures have been synthesized and investigated as active materials in various applications. These structures are proficient enough in contrast to other nanodimensions by providing enhancement in ions/ charge transport through the scattering effect. Because of their largely owned micron-sized structure which includes nanoscale primary units, such as nanorods, nanoparticles, and nanosheets, helps to increase the final properties of the material in the nanocomposites.31−33 These metal oxides can be easily synthesized and can present the vision of very low cost and highly performing materials for device applications. There is currently a significant usage in the hybrid nanocomposites/ films as the electrode materials in electrochemical transducers for improved performance of electrochemical detection of various biologically and environmentally relevant analytes. For instance, metal nanoparticles (Ag, Au etc.), conducting polymers (PEDOT, PANI, and PPy) and its composites are frequently deposited onto the conventional electrodes to improve the electrochemical responses by promoting the electron/ion transport through its highly conductive nanostructured pathways, as well as facilitate the immobilization of analyte molecules and other biologically relevant molecules. The induction of these hybrid systems can potentially enhance the catalytic property, selectivity, and sensitivity of the electrochemical sensor device.34−36 Flexible electrochemical devices are of great interest because of excellent properties such as lightweight, flexibility, and portability which even are wearable and implantable and are expected to bring revolution in the arena of electrochemical sensors.37 There are several polymer candidates such as

polyethylene terephthalate, polyethylene naphthalate, polycarbonate, polystyrene, polydimethyl siloxane (PDMS), and so forth, reported to be used as flexible substrates for various applications.38 Among these, PDMS belongs to the group of polymeric organosilicon compounds that are commonly referred to as silicones and are widely used in functional devices, medicine, and cosmetics. PDMS offers a high degree of deformability and conformability on diverse surfaces with varied textures and geometries, portraying themselves as practically viable candidates for use as active flexible electrode materials. Incorporating hybrid nanocomposites onto flexible PDMS substrates through a simple solution blending process provides opportunities for many bendable substrates, in particular, as electrodes in sensors. Advantages of flexible PDMS electrodes including its lightweight, controllability in thickness, high portability, and resistance to mechanical impact tension, torsion, and bending are well-suited for the fabrication of biochip, medical product, and minimally invasive implantable device applications.39−41 Liu et al., developed a flexible Au nanotubes/PDMS electrode for the real-time monitoring of nitric oxide release from mechanically sensitive human umbilical vein endothelial cells.42 However, sensitivity and mechanical stability of the developed sensor was not much efficient in detecting very weak signals from cells triggered by stretch strains. In another report, same group overcame the problem by relying on a hierarchical percolation network of carbon nanotube and Au nanotubes, which prevailed over important constraints. Its hybrid structure enabled the performance of the sensor with excellent and reproducible properties for real-time monitoring of very weak transient chemical signals.43 Epinephrine commonly known as adrenaline is present in the central nervous systems and belongs to the family of neurotransmitters. It has been estimated that the physiological concentration of epinephrine in human adult is 10 ng/L.44a,b It was discovered in the year 1901 and later developed by Stolz and Dalkin in 1904. The main function of epinephrine (EP) is to act as a messenger in scheming the routine functions of the nervous system and its inadequacy can lead to an altercation of the blood pressure level, heart beats and will deplete the regular metabolic activities in the human body. It is also widely recognized as a type of hormone, which is responsible for a cycle of events in the nervous system and the occurrence is universally called as “fight or flight” response. Hence its determination is important for diagnosis of various diseases and mental disorders and is been used as a pharmaceutical drug to treat these disorders.45−47 Therefore, it is highly recommended and is of great significance for the perceptible quantification of EP at physiological pH in human body fluids. Our group has actively involved in the transducer performance of various neurotransmitters such as dopamine, serotonin using electrochemically prepared PANI and PEDOT with metal nanoclusters such as Au, Ag, and so on, using modified commercial glassy carbon electrode.48,49 In the present work, we have fabricated flexible transducer for sensing neurotransmitters based on conducting polymer nanocomposite for the first time. There are several reports based on electrodes modified with conducting polymer and its composites for the determination of EP. A report by Hong Zhou et al., discussed about the molecularly imprinted polypyrrole-modified glassy carbon electrodes (GCE) for the electrochemical sensing of EP. Here, they have measured a linear range detection of EP from 10−3 to 10−7 M.50 In another report by Tsele et al., an electrode 3490

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Scheme 1. Schematic Representation Illustrating the Preparation of Titania, PEDOT, PT, and poly(dimethylsiloxane) (PTS) Films

and resulting in the formation of hierarchical titania complex. The residue containing titanium tetra hydroxide was calcined at 450 °C to obtain nanotitania. Particle size and zeta potential of the titania was measured to be 40−60 nm ± 5 nm and +15 mV, respectively, and the Brunauer, Emmett, and Teller (BET) surface area calculated as 122.7 m2/g by BET method. The prepared nanotitania exhibited a mixed phase of anatase and rutile, and the formation of mixed anatase and rutile crystalline phase of titania was prepared and well-characterized from our group.53,54 Nanospindles of poly(3,4-ethylenedioxythiophene) was prepared by a liquid crystalline biotemplate approach as reported earlier from our group.27 Here, we are using 3pentadecylphenol-4-sulfonic acid (PDPSA) as biosurfactant. 3PDPSA forms an adduct with the monomer EDOT by an acid−base reaction which can easily form columnar liquid crystalline phase. Formation of liquid crystalline phase was confirmed by polarized light microscopy. PEDOT−PDPSA was prepared by oxidative chemical polymerization of EDOT using ammonium persulfate as an oxidative initiator at ice cold conditions (Scheme 1b). This liquid crystalline phase can form self-template during the polymerization. Interestingly, we have observed that the formed polymer (PEDOT) mimics ordering of the mother template in the nanometer regime. Formation of nanospindles was further confirmed by microscopic analysis [scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM)] and are discussed more in detail in the morphology part. PEDOT−titania (PT) hybrid nanocomposites were prepared by the same procedure as the preparation of PEDOT. However, the polymerization of liquid crystalline template of EDOT− PDPSA was conducted in the dispersion of titania (Scheme 1b). The structure of PEDOT, titania, and the interaction between the PEDOT and titania was confirmed by FTIR spectra. The Fourier-transform infrared spectroscopy (FTIR) spectra of titania, PEDOT, and PT3 nanocomposites are shown in Figure S1a−c. The structural FTIR spectral bands of titania at 400−700 cm−1 are related to the Ti−O and Ti−O−Ti stretching modes which confirms the formation titania

material of MWCNT functionalized with polyaniline doped with metal oxide nanoparticles of titania and ruthenium oxide have been developed and modified the gold electrode with their active material. They have found a linear detection limit in the range of micromolar concentration.51 Further Ghanbari et al., developed an electrochemical sensor using a polypyrrole-based nanocomposite heterostructured electrode modified with glassy carbon electrode for the sensing of EP. They also found a linear detection limit in the micromolar range.52 All of these developed electrodes show good response toward the EP through modification of conventional electrodes such as Au and GCE. Even though there are numerous reports available for the transducer performance of EP. In all of the cases, the developed materials are modified with conventional electrodes such as glassy carbon, platinum, gold, indium tin oxide, and fluorine tin oxide electrodes. It is noteworthy to mention that all of these electrodes are manufactured using highly sophisticated instrumentation, with precursor materials of very high cost and the fabrication is seemingly a time-consuming process. Furthermore, all of these possess the limitations of high rigidity, brittleness, difficult for large area production, less fatigue resistance, and damping characteristics, thus possessing some significant shortcomings for use in flexible electronics. Hence, in this aspect, the developed flexible electrode meet the requirements to be used as flexible electrode in this device. Herein, we report fabrication and property evaluation PEDOT−titania−PDMS nanocomposite films and further assessing its electrocatalytic oxidation of EP. The fabricated flexi electrodes also offered distinct voltammograms for simultaneous determination of EP with other interfering analytes.

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RESULTS AND DISCUSSION Titania was prepared by one-pot hydrothermal method from titanium butoxide using HCl, as shown the Scheme 1a. Here, the rate of hydrolysis of titanium butoxide was carried out under acidic conditions (pH = 1) for the formation of welldefined titania nanostructures. The slow hydrolysis of titanium precursor leads to the formation of titanium(IV) complex ions 3491

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Figure 1. TEM (a,b), SEM (c), and AFM (d) images of titania; SAED pattern is shown in the inset of (b); TEM (e) and AFM (f) images of PEDOT, SEM (g), AFM (h), and TEM (i,j) images of PT3 nanocomposite; and inset of (j) SAED pattern of PT3. SEM (k) and 3D AFM (l) images of PTS3 inset of (l) shows the height profile of PTS3 film.

onset of the free carrier tail is shifted to higher wavelengths at 826 nm, revealing the presence of the metallic state. PT3 and PTS3 exhibiting free carrier tail with a polaron band revealed the presence of a high density of charge carriers because of PEDOT and titania interactions. This is further supported during the measurement of electrical conductivity. TEM, SEM, and AFM microscopic analyses were carried out for getting an insight in to the morphology of the prepared titania, PEDOT, PT3, and PTS3. TEM images of titania exhibited dandelion flowerlike hierarchical structures, consisting of large number of tiny titania nanorods protruding from the center with an average diameter of 10−15 nm (Figure 1a and inset). The presence of anatase and rutile was confirmed by the presence of fringes in the high-resolution transmission electron microscopy (HRTEM) pattern (Figure 1b), which showed a lattice spacing of 0.32 nm corresponding to the rutile phase of (110) plane and 0.35 nm which corresponds to the anatase phase of (101) plane, suggesting the nanorod growth direction along the [001].56 The corresponding selected area electron diffraction (SAED) pattern is shown in the inset of Figure 1b confirming the crystalline nature of the hierarchical titania, which supports the fast electron transport for enhancing the better electrocatalytic properties. The SEM picture of the same is given in Figure 1c. AFM images of the same (Figure 1d) also confirmed the formation of hierarchical titania architectures. The TEM pictures of PEDOT exhibited nanospindles of 20−40 nm width and 100−200 nm lengths (Figure 1e). SEM images of PEDOT showing the formation of nanospindles are shown in Figure S3. AFM of PEDOT (Figure 1f) further supports the observations made from SEM and TEM. Furthermore, SEM analyses of PT3 showed the formation of self-assembled PEDOT nanospindles on titania nanorods to form hierarchical nanosheet-like features (Figure 1g). The TEM images of the PT3 nanocomposite confirm the self-assembly process of hierarchical nanosheets coupled with PEDOT nanospindles (Figure 1i). HRTEM and SAED pattern of the PT3 nanocomposite confirm the preservation of crystalline phase of titania in PT3 nanocomposite (Figure 1j and inset). The self-assembled structures

nanoparticles and are shown in Figure S1a. Figure S1b shows the FTIR spectra of PEDOT showing the bands at 1518, 1483, and 1339 cm−1 which are ascribed to the stretching modes of CC and C−C in the thiophene ring, respectively. Further, the vibration modes of the C−S bond in the thiophene ring were established from the bands at 978, 842, and 691 cm−1. The stretching modes of the ethylenedioxy group and ethylenedioxy ring deformation mode were confirmed from the spectral bands at 1213, 1093, and 920 cm−1 correspondingly. The doping of the PEDOT is confirmed from the band at 1622 cm−1. The formation of PEDOT was confirmed from the vanishing of the 890 cm−1 band which is related to the C−H bending mode of EDOT monomer. The bands at about 1200, 1145, and 1085 cm−1 are assigned to the stretching modes of C−O−C bonds in the ethylenedioxy groups, and the band around 920 cm−1 is due to the ethylenedioxy ring deformation mode. The stretching of the quinoidal structure in the thiophene ring was confirmed from the vibration bands at 1514 and 1332 cm−1 which are ascribed to the stretching modes of CC and C−C in the thiophene rings, respectively. It can be observed from the FTIR spectra (Figure S1c) that PT3 showed a shift in the characteristic bands of titania and PEDOT suggest its various interactions established between titania and PEDOT in the PT nanocomposite. Hence, the structural observations made from FTIR imply the effective interface between the PEDOT and titania existing in PT nanocomposites, and the results are strengthened by the observation made by other researchers.55 The photophysical properties of the TiO2, PEDOT, PT3, and PTS3 were studied by UV−visible absorption spectroscopy in ethanol and are shown in Figure S2a−d. Titania nanoparticles showed absorption maximum at 330 nm, and the UV− visible spectra of PEDOT exhibited bands at 380 nm because of π−π* and PTs exhibited a broad strong absorption band at 800−900 nm which is attributed to the polaron−π* transition. This indicates that PEDOT is in a bipolaronic state as well as the formation of a sufficient number of charge carriers in the nanocomposites. The UV−visible spectra of hybrid composites PT3 and the PTS3 film showed the π−π* band as well as the 3492

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peak at around 25.5° (d = 3.5 Å) which is attributed to the crystalline nature of PEDOT with highly ordered π−π interaction in the PEDOT chains. XRD results suggests the molecular arrangement or interchain stacking of PEDOT chains in the hybrid nanocomposite (PT3) which became more ordered, and also the reduced interchain hopping distance resulting in efficient charge transport, which can be attributed to the measured hike in the electrical conductivity of the PT3 and PTS3 films, which is discussed in the electrical conductivity section. The electrical conductivity of the as-prepared nanocomposites (PT) and films (PTS) was measured using four-probe conductivity meter. Electrical conductivity of PT nanocomposites studied with increasing concentration of titania in PEDOT is shown in Figure S4 of the Supporting Information. It was observed that by the incorporation of increasing amount of titania from 1, 2.5, 5, and 7.5 (wt %) within the PEDOT matrix, electrical conductivity increased gradually from 40.9, 42.1, 78.1, and 54.3 S/cm, respectively, and it was also observed that at a particular composition (PT3), the electrical conductivity was observed to be maximum (78.1 S/cm) beyond which the conductivity reduced, which can be because of the agglomeration of titania in the matrix. Electrical conductivity variation of PTS films with varying amount of PT in the PDMS matrix is shown in Figure S5. Maximum conductivity was measured for PTS3 flexible film with a conductivity of 1.421 S/cm. Hence, PTS3-based flexible films were used as the electrode material in transducer for the evaluation of electrocatalytic oxidation of epinephrine. The enhancement in the conductivity can be attributed to the welldispersed PT particles within the polymeric network. Beyond the percolation concentration, particles tend to aggregate which is the reason for reduced conductivity. The surface resistivity measurement is one of the key properties of films for many device applications. The surface resistivity of PTS3 was measured in the range 2.48 × 108 Ω/sq. The excellent electrical conductivity and low surface resistivity PTS3 film suggest its application toward as-conductive electrodes in device applications.57 Figure S6 shows the electrical I−V characteristics of PDMS and PTS films measured at room temperature using Keithley high resistivity electrometer 6517B. Because of the comparatively insulating/amorphous nature of PDMS, the film exhibits only a low conductivity(3 mS/cm). By incorporating PT3 in the PDMS matrix, the electrical conductivity increased significantly. The surface resistivity of the PTS films are measured primarily in the parallel direction with respect to the electrodes, and the I−V characteristics are symmetrical and near-linear and PTS3 film exhibiting highest conductivity (1.421 S/cm). The PTS3 film exhibited highest conductivity compared to the other nanocomposite films which is mainly because of the well-dispersed-ordered percolated structure in the PDMS matrix. Thus, the presence of highly ordered hierarchical self-assembled PEDOT and titania structures of PT3 in PDMS is expected to enhance the charge-transfer process through its smooth nanostructured pathways. Electrochemical impedance spectroscopy is a steady-state technique to probe the electron transfer and the mechanism of the charge conduction process at the electrode/electrolyte interface. Electrochemical impedance measurements were carried out in a mixture of 5 mMK3[Fe(CN)6], 5 mM K4[Fe(CN)6] in 0.1 M KCl at a frequency range of 0.1 Hz to 10 kHz at a particular open-circuit potential. Nyquist plot of the

of PT3 were further confirmed from AFM analysis (Figure 1h). The height profile of the PT3 nanocomposite showed an average height of 6 ± 3 nm upon drop-casting on cleaned mica (inset of Figure 1h). The surface morphology of films is a very important factor for device applications because a nonuniformity on the surface can cause crash or curb with the upper layers and can cause serious problems on the performance of the devices. The surface morphology of PTS3 film (PT3 nanocomposite blended with PDMS) was studied through SEM and AFM analyses. SEM image of the PTS3 composite film showed particles that are dispersed uniformly within the matrix which substantiate the excellent contact of the particles within the films (Figure 1k). AFM was also used to characterize the surface and also to estimate the grain size and surface roughness and are shown in Figure 1l. The surfaces of the thin films were observed as smooth, and the root mean square surface roughness of the films was observed to be 5−10 nm for PTS3 film with an average thickness of 1 mm. It is important to note the particles are at uniform height (4 ± 2 nm, Figure 1l and inset). This PTS3-based film was further demonstrated for their electrochemical applications. The crystalline phase and composition of titania, PEDOT, hybrid PT3 nanocomposite, and PTS3 film were studied using X-ray diffraction and are shown in Figure 2a−d, respectively.

Figure 2. XRD profiles of (a) TiO2, (b) PT3, (c) PTS3 film, and (d) PEDOT.

The prepared hierarchical titania nanostructures (Figure 2a) exhibited mixed phase of anatase (A) and rutile (R). The diffraction peaks at around 25°, 27°, 35.8°, 38.8°, 42.8°, 44.3°, 48.4°, 53.9°, and 57.8° corresponds to the diffraction peak of A(101), R(110), R(101), A(004), R(200), R(111), R(210), R(211), and R(220) planes of titania, respectively, confirming the mixed anatase-rutile form and are well-crystallized (JCPDS files # 21-1272, JCPDS no. # 21-1276). The mass fraction of anatase/rutile phase of nanotitania was calculated from the relative X-ray powder diffraction (XRD) diffraction intensities corresponding to the A(101) and R(110) peaks. XRD measurement revealed that 70% of rutile and 30% of anatase phase of titania were present in the prepared titania sample. The average crystallite size of ∼30−50 nm was estimated from the full width at half maximum using the Scherrer equation.54 The as-prepared PT3 nanocomposites retained its highly crystalline nature in the nanocomposite form (Figure 2b). The PTS3 film too exhibited crystalline nature with less intense peak (Figure 2c). Figure 2d shows the XRD profile of PEDOT, which showed peaks at 2θ = 6.2°, 12.2°, and 18.2°, and a broad 3493

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Figure 3. Electrochemical impedance profile [A] PT nanocomposites (a) PT1, (b) PT2, (c) PT3, and (d) PT4 and [B] PTS films (a) PTS1, (b) PTS2, and (c) PTS3.

Figure 4. (a) CV profile of PTS3 film for 50 successive scans (scan rate 50 mV/s, pH 7.4). (b) plot of Ipa vs square root of the scan rate of PTS3 film.

in the PTS3 film to the interphase which results in the high electronic conductivity of the film. Mechanical stability of the prepared PTS films was measured using universal testing machine (Instron 3345) as per ASTM D 412 and ASTM D624-86, respectively. Two specimens from each film were tested according to the standard testing method (Figure S7a−d). The tensile strength of the film increased from 2.15, 6.5, 12.5, and 16.18 ± 1.26 MPa for virgin PDMS, titania−PDMS (TP), PEDOT−PDMS (PP), and PTS3, respectively, which represents the good compatibility, reinforcement, and interfacial interaction between the PDMS and PT, PP, and TP which may be responsible for the improved strength of the composites blends than that of the PDMS film. Thermal stability of titania, PEDOT, PT3, PDMS, and PTS3 films were studies using thermogravimetric analysis and are shown in Figure S8a,b. The TG profile of titania (Figure S8a) exhibited almost stable profile. PEDOT exhibited a three-step decomposition starting at 150 °C because of the removal of moisture and volatile matter followed by second-stage degradation at 330 °C which is attributed to the loss of small fragments from sulfonate-anchored PEDOT and almost total degradation at 450−500 °C. PT3 exhibited higher thermal stability starting at 350 °C, which is due to the removal of volatile molecules during the scission of the covalent bonding between titania onto the PEDOT chain. The observed enhancement in the thermal stability can also be related to a better dispersion of nanoparticles. It was observed that with the incorporation of titania into the polymer matrix leads to a less weight loss compared to bare PEDOT (Figure S8b,c). Thermal stability of the PDMS and PTS3 films is shown in Figure S8d,e. Results suggest that the thermal stability of composite film

PT and PTS electrodes at a particular open-circuit potential is shown in Figure 3A,B. The plot of PT nanocomposites (Figure 3A(a−d)) was almost vertical, with phase angles close to ∼90° in the low-frequency region (inset of Figure 3A). This suggested that the PT electrodes displayed a diffusioncontrolled Warburg capacitive behavior. The absence of a semicircular feature in the plot indicated that the electrochemical behavior was not affected by charge-transfer limitations.58 The charge-transfer resistance (Rct) of the PT1, PT2, PT3, and PT4 electrodes was measured as 45, 32, 9, and 19 Ω, respectively, which can significantly enhance the iontransfer kinetics at the electrode surface and expected to improve its electrochemical performance. The Nyquist plot of the flexible PTS1-, PTS2-, and PTS3-based films are shown in Figure 3B. The semicircle observed in the high-frequency region of flexible films suggested that there is high resistance compared to PT nanocomposites which is arising from the insulative nature of PDMS, and thus there will be small amount of charge-transfer hindrance between the electrode and the current collector. PTS1, PTS3, and PTS4 exhibited an Rct of 120, 65, and 95 Ω, respectively. The comparable electrontransfer conductance of PTS films compared to that of conventional electrodes shows the high conductivity of the flexible electrode, and this response is attributed to the good contact produced during the electrode preparation and suggests its applicability toward its usage as electrodes in various devices. The equivalent circuit of the plot containing the solution resistance (RS), capacitance (Cdl), the charge-transfer resistance (Rct), and Warburg impedance (W) is shown in the inset of Figure 3B shows which symbolizes the efficient distribution of the charged species arising from PEDOT and titania interface 3494

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ACS Omega PTS3 system increased as compared with the PDMS film. The onset degradation temperature has delayed from 340 to 380 °C for PTS3 film compared to PDMS, which suggested the higher thermal stability of the PTS3 film. All of these results suggest that the incorporation of PT nanocomposite has a profound impact on the thermal stability of the PTS film which is expected to be utilized for various applications in electronic devices. The electrochemical behavior of flexible PTS3 film was studied by cyclic voltammetry (CV). The CV response for the one electrode reduction in 5 mM K3Fe(CN)6 in 1 M KCl with a scanning rate of 50 mV s−1 is shown in Figure 4a. The PTS3 electrode exhibited two broad redox peaks at +0.6 and −0.7 V, indicating the presence of PEDOT and titania in the film. The electrochemical stability of the modified flexi electrode was studied for 50 successive scans using CV at a scan rate of 50 mV s−1. There was a minimal decrease in current response of the PTS3 film from the first cycle compared after 50 cycles. The percentage of the current drop obtained was less than 5%. Thus, the anodic peak currents remained almost stable, indicating excellent electrode stability during repeated CV scans and are not undergoing serious surface fouling.59 The effective electroactive surface area of the modified electrode was studied by varying the scan rate and thereby analyzing the variation in the anodic peak current by CV for the one-electrode reduction of K3[Fe(CN)6] (5 mM in 1 M KCl). Figure 4b shows the peak current versus square root of the scan rate plots of the PTS3 film electrode. The plot of the oxidation peak current versus scan rate (ν) showed a linear relationship, indicating that the oxidation peak current increased linearly with the increasing scan rate. The anodic peak current have a linear dependence against the square root of scan rate with the correlation coefficient of 0.9901. From the plot of peak current Ip versus the square root of scan rate, the electroactive surface area was calculated using Randles−Sevcik equation (eq 1). Ipa = 2.68 × 10−5n1/2AC0D1/2ν1/2

Figure 5. CV profile PT5 film in the presence of epinephrine solution in phosphate buffer solution (scan rate 50 mV/s, pH 7.4).

conventional modified electrodes.60 The surface of PTS is endowed with a large distribution of reduced and oxidized ions where the reduced form of the film can mediate the electron transfer for oxidation of analyte molecules.61 The increase in the oxidation peak current values can be correlated with the enhanced electrochemical activity of PTS3 toward EP. The hike in the anodic current can be arising from the strong combination of the electron-rich oxygen atom of titania and the presence of conjugated π−π and reducible cation radicals present in PEDOT film. Studies were also performed toward the oxidation of EP as a function of scan rate effect (range 0.01−0.1 V s−1) at a constant concentration of EP (10−6 M) with PTS3 film electrode and are shown in Figure 6a. The plots of peak current versus square root of scan rate showed a linear relationship. The hike in the oxidation peak current with the increasing scan rate and the suggested diffusion-controlled process are shown in Figure 6b. The surface coverage (Γ) of EP on the surface of the PTS3 electrode was calculated from the slope of the plot of peak current (Ip) versus the square root of scan rate using Laviron equation

(1)

where Ipa represents the anodic peak current (A), n is the number of electrons involved, A is the area of the electrode (cm2), D is the diffusion coefficient, C0 is the concentration of K3Fe(CN)6, and ν is the scan rate. For K3Fe(CN)6, n = 1 and D = 7.6 × 10−6 cm/s. The effective electroactive surface area can be calculated from the slope of the plot of Ipa versus ν1/2, and it was found to be 0.298 cm2 for PTS3 film-based flexible electrode. The higher electroactive surface area of flexible electrode compared to that of the conventional electrode can provide more efficient active sites for the oxidation of analyte molecules.49 The PTS3 flexible electrode having highest electrical conductivity and large electrocatalytic surface area was employed for studying the electrochemical oxidation of EP. It has been observed that the CV diagram measured an enhancement in current during the electrocatalytic oxidation of EP at 0.15 V. The electrocatalytic oxidation of PTS3 toward EP was investigated by measuring the enhancement in anodic current response in the presence of the analyte kept in the phosphate buffer solution of pH 7.4. Experiments were performed with EP in the concentration range of 20−1000 μM (10−6 M concentration) and are shown in Figure 5. The comparable oxidation current of 2.5 μA for PTS3 film electrode toward the EP oxidation suggests enhanced electrocatalytic behavior toward oxidation of EP compared with that of

Ip =

n2F 2νA Γ 4RT

where Ip is the peak current in A, n is the number of electrons transferred, F is the Faraday constant (9.65 × 104 C mol−1), ν is the scan rate in V s−1, A is the area of the electrode in cm2, Γ is the surface coverage of the analyte (mol cm−2), R is the ideal gas constant (8.3144621 J K−1 mol−1), and T is the temperature in K. Assuming that n ≈ 1, the calculated surface coverage of EP on PTS3 film electrode was found to be 1.167 × 10−9 mol cm−2, which is consistent with Mphuthi et al.59 and suggesting the formation of self-assembled monolayer of PT3 nanocomposite on the surface of PTS3 electrode, which provides the efficient catalytic sites toward the oxidation of EP. On the basis of the values of EP surface coverage observed, it can be confirmed that the analyte molecules gets efficiently diffused on the PTS3 film electrode, where the analyte molecules gets electrocatalytically oxidized. The Tafel values were also calculated using the equation below, where Ep was plotted against log ν (Figure 6c). Ep =

⎛b⎞ ⎜ ⎟log ν + k ⎝2⎠

The measured potential value for PTS3 electrode for EP was calculated as 44.2 mV. The low Tafel value specifies the 3495

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Figure 6. Cyclic voltammograms of (a) PTS5 film electrode at scan rate (range 10−100 mV/s) in pH 7.4 phosphate buffer solution containing 1 mL of 10−6 M of EP. (b) Plot of peak current vs square root of scan rate plots of PTS5 film electrode, and (c) plot of Ep was plotted against log ν (phosphate buffer pH = 7.4).

Figure 7. (a) DPV profile PTS3 film in presence of epinephrine solution in phosphate buffer solution and (b) plot of EP concentration vs current (scan rate 50 mV/s), phosphate buffer pH = 7.4.

0.15 V with a satisfactory linearity over a range of concentrations from the range of 20−1000 μM in phosphatebuffered solution of pH 7.4, and the calibration plots of current versus concentration obtained are shown in Figure 7b. Results suggested that the oxidation current peaks are directly proportional to the increase in concentration of EP. The hike in the oxidation peak current with increasing scan rate and further confirms the diffusion-controlled process. The detection limit was calculated based on the relationship LOD = 3.3 δ/m, where δ is the relative standard deviation of the intercept of the y-coordinates from the line of best fit, and m the slope of the same line. The detection limit of 100 nM ± 5 was obtained for EP at PTS3 electrode. The measurements with the flexible electrodes were repeated 5 times for analyzing the transducer performance. The mechanism of the oxidation of epinephrine in pH 7.4 phosphate-buffered solution has been be wellexplained by Kim et al. and Dias et al.63,64 The oxidation of epinephrine to epinephrinechrome at the PTS3 electrode could be considered with the start of reduction of epinephrinequinone to leucoepinephrinechrome and then finally to the oxidation of leucoepinephrinechrome to epinephrinechrome. This observed reaction mechanism (Figure S9) is well in accordance with the literature.61 There are several other analyte molecules such as ascorbic acid (AA), dopamine (DA), and uric acid (UA), which are wellknown to get electro-oxidized at potentials nearby the EP oxidation. To show the selectivity of EP, it is very much essential for the selective detection of EP in the presence of all of the nearby oxidizing analytes. Henceforth, DPV was used for the selectivity of the PTS3 film electrode, where the

adsorption of the analyte on the electrode surface caused by the electrode porosity. Tafel slopes are widely acknowledged as an indication for the efficient electrocatalytic performance of the electrode surface.62 The enhancement in peak current as the scan rate increases further suggested that EP was oxidized by the diffusion process. Further, the Tafel slope used for understanding the mechanistic pathway of the oxidation of EP at the electrode surface using equation Below, where the Tafel slope is defined by the transfer coefficient αa α=

1 (2.303RT /F ) b

Assuming the rate-determining step of the redox reaction in EP involves a one-electron process (n = 1), a value of 0.44 is obtained for the charge-transfer coefficient (α). In PTS3, the percolated nanostructures along with low Tafel slope indicates that the fabricated electrode have superior electrocatalytic activity toward the EP. These results suggested that the PTS3 electrode system enhances the adherence and the activity of the electrode surface by providing a well-defined mass transport regime. Further electrocatalytic performance of the transducer PTS3 toward detection of EP was studied using differential pulse voltammetry (DPV) which is an effective and rapid electroanalytical technique that is extensively utilized because of its minimization of background effects and can therefore typically result in higher sensitivity in detecting the analyte molecules. The electrocatalytic oxidation of EP was investigated and is shown in (Figure 7a). Studies were carried out with varying concentrations of EP. Electrocatalytic oxidation occurred at 3496

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pharmaceutical samples (adrenaline injection) via standard addition method. The samples were diluted using 0.1 M phosphate-buffered solution (pH 7.4) before the analysis. Briefly, the adrenaline injection sample was diluted 50 times with 0.1 M phosphate buffer solution and spiked with different concentrations of epinephrine. The recovery values are summarized in Table 1, which shows that the recoveries are

concentration of EP was increased from 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, and 0.14 mL and the concentration of AA, DA, and UA (0.3 mL, 10−3 M) were kept constant. In Figure 8, the flexible

Table 1. Quantitative and Recovery Analysis of Adrenaline Injection Samples

Figure 8. DPV profile of PTS5 film for simultaneous determination of AA, EP, DA, and UA (scan rate 50 mV/s).

sample

added (μM)

found (μM)

recovery (%)

RSD (%)

real epinephrine

20 20 40 40 60 60

19.05 19.25 39.95 39.63 58.85 59.15

95.25 96.25 99.8 99.07 98.08 98.58

3.44 2.70 0.09 0.06 1.37 1.01

in the range of 95−100%. These results clearly indicate that the PTS3 flexi electrode can be employed for the quantification of adrenaline with appropriate recoveries for practical applications.

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PTS3 electrode showed separate oxidations peaks of AA (−0.03 V), EP (0.15 V), DA (0.15 V), and UA (0.3 V) with no significant interference between the analytes, which shows the efficacy of the flexible electrode for the simultaneous determination of interfering analyte molecules. Because the oxidation potential peak of both EP and DA lies in the same range, the potentials were deconvoluted from the area under the electrocatalytic oxidation profile by fitting the DPV scans using the GRAMS 32 software. This profile is shown in the inset of Figure 8, which shows well-resolved oxidation peaks of EP and DA. The efficient electron-transfer mechanism was further evaluated by calculating the electrochemical band gap and is shown in Figure S10 and Table S1. The efficient electron transfer process observed with the present PTS3 electrode system can be explained from the fundamental band alignment. The mixed phase of titania is the core driving force for enhanced transport of charge carriers in the composite electrode. In PTS electrode, upon electrical excitation, the charge carriers will efficiently move from the LUMO of PEDOT (∼−2.4 eV) which is higher than that of the conduction band of titania (∼−4.2 eV), and this will create an energy barrier for the back electron transport. The effective interaction of the PEDOT chains on the surface of hierarchical titania can enhance the amount of charge carriers on the surface of the electrode. PEDOT alone can be considered as neutral soliton (electrochemical band gap of 2.72 eV), where it possesses less mobility of the electrons along the polymer backbone. To provide more charge carriers, titania in the PTS (low electrochemical band gap of 2.23 eV) will provide a pathway for the π electrons in the form of intermediate bands similar to soliton band for efficient transport of charges, and they can become more stable as they can be delocalized over the polymer chain which leads to the formation of solitons and polarons that facilitates the electronic conductivity in PTS electrode system.65 The CV and DPV profiles of PTS3 electrode in the absence of analyte do not show any oxidation peaks corresponding to any particular analyte (Figure S11). The comparison of polymer-based electrodes for the determination of EP is given in Table S2. The analytical performance of the PTS3-film-modified electrode was further applied for the determination of

EXPERIMENTAL SECTION Materials. Titanium tetrabutoxide (Alfa Aesar), ethylenedioxythiophene (EDOT), epinephrine hydrochloride, dopamine hydrochloride, ascorbic acid, uric acid, potassium ferricyanide, 3-pentadecylphenol, and potassium ferrocyanide were purchased from Sigma-Aldrich Chemicals Pvt. Ltd., India; ammonium persulfate (APS, Merck), potassium dihydrogen phosphate (Merck), polydimethyl siloxane-PDMS (Dow Corning, Sylgard 184 silicone elastomer kit), sodium hydroxide, tetrabutyl ammonium hexaflourophosphate (Merck), acetonitrile (Spectrochem Pvt. Ltd.), isopropyl alcohol (Fischer Scientific), distilled water, and ethanol. All of the chemicals were used as received. PDPSA was prepared as reported earlier from our group.50 Preparation of Titania (TiO2) Using Hydrothermal Method. In a typical synthesis process, 0.5 mL (1.4 × 10−3 M) titanium(IV) butoxide was dissolved in equal volume of concentrated HCl (11 N) and distilled water (5 mL each) by magnetic stirring. The clear transparent solution formed was transferred into an autoclave hydrothermal pressure vessel with a total volume of 25 mL. The sealed pressure vessel was then kept in a furnace for 3 h at 140 °C. Later, the autoclave was cooled to room temperature. Then, the product was washed repeatedly with water through centrifugation and dried in a vacuum oven at 60 °C for overnight and finally calcined at 450 °C. Preparation of Polyethylenedioxythiophene−Titania (PT) Composite by Oxidative Chemical Polymerization. PDPSA [2 g (6 × 10−3 mol)] is added to 30:70 ethanol−water mixture (30 mL of ethanol and 70 mL of water) and stirred the solution for 20 min at 60 °C. EDOT [2.5 mL (1.75 × 10−2 mol)] was added upon stirring at room temperature using a magnetic stirrer for 30 min. Titania (0.1 g) (PT1) dispersed in water was added to the above solution. Then, 5 g (2.19 × 10−2 M) of APS in 25 mL of water was added dropwise to the above solution for 30 min. Later, the solution was stirred for 24 h in ice cold conditions. The product was isolated by centrifugation and washed with distilled water repeatedly and dried in an oven at 50 °C under vacuum for 12 h. Other PT nanocomposites were prepared via similar procedure by varying the amount of 3497

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platinum as the counter electrode by CV and DPV. All of the measurements were carried out in the physiological pH of the phosphate-buffered solution (pH = 7.4) at room temperature. The measurements toward the detection of EP were repeated 5 times for analyzing the transducer performance. Briefly, the phosphate-buffered solution was prepared by adding 39.5 mL of 0.1 M NaOH to 50 mL of 0.1 M potassium dihydrogen phosphate.

titania from 0.1, to 0.25, 0.5, 0.75 g, and are designated as PT1, PT2, PT3, and PT4, respectively. Preparation of PTS Films. In a typical procedure, 2 g of PDMS, 1 g of PT nanocomposites, and 0.2 g of curing agent were stirred well using a mechanical stirrer in a beaker. Then, the solutions were casted into a Petri dish and kept at 30 °C for 24 h for the formation of PTS films. PTS films casted from different PT compositions are prepared and are designated as PTS1, PTS2, PTS3, and PTS4, respectively. Characterization Techniques. The surface morphology of the samples was studied using various microscopic techniques SEM, TEM, and AFM. Zeiss EVO 18 cryo-SEM with variable pressure working at 20−30 kV was used for the SEM analysis. HRTEM was performed in an FEI Tecnai S Twin microscope with an accelerating voltage of 100 kV. For TEM measurements, the sample solutions were dispersed in the solvent and sonicated well under an ultrasonic vibrator. Then, the sample solutions were allowed to settle for a while and drop-casted on the top solution on a Formvar-coated copper grid using micro pipette and dried at room temperature before observation. AFM images were obtained under ambient conditions to that of TEM, whereas the samples were drop-casted onto a microscopic cover glass using a Bruker Multimode AFM-3COCF (Germany) operating in the tapping mode. FTIR measurements were made with a fully computerized Nicolet impact 400D FTIR spectrophotometer. Samples were mixed thoroughly with potassium bromide before they were compressed into pellets for the measurements. Powder X-ray diffraction studies were performed with an X-ray diffractometer (Philip’s X’pert Pro) with Cu Kα radiation (l = 0.154 nm) with the step size and the scan rate of 0.02° and 10°/min, respectively, by employing an X’celarator detector and a monochromator at the diffraction beam side. Powder samples/films were used by employing a standard sample holder. Cyclic and differential pulse voltammetric (CV, DPV) studies and impedance analysis were carried out using a CHI6211B electrochemical analyzer, in a three-electrode/one-compartment electrochemical cell in which the flexible electrode was used as the working electrode and a platinum wire was used as counter electrode. All of the potentials were recorded using Ag/AgCl as the reference electrode and purged with nitrogen gas before all measurements. The working electrode, PTS3 film of square dimension, was contacted with a copper wire via a conducting copper tape. The active area of the working electrode was 0.25 cm2. Electrical conductivity measurements of the pellets/films (1 mm thickness) were performed with a standard four-probe conductivity meter using a Keithley 6221 programmable current source and a 2128A nanovoltmeter. Surface resistivity measurements of the films were made using Keithley electrometer 6517B. The tensile properties of the films were measured on a universal testing machine (Instron 3345) as per ASTM D 412 and ASTM D624-86, respectively. Particle size as well as the zeta potential measurements were carried out in a Nano ZS Malvern instrument employing a 4 mW He−Ne laser (I = 632.8 nm) and equipped with a thermostat sample chamber. The BET surface area measurement technique was performed using Micrometrics Gemini 2375 Surface Area Analyzer, U.S.A., via nitrogen (N2) adsorption using the multipoint method after degassing the nanocrystalline titania powders in flowing N2 at 200 °C for 2 h. Electrochemical Sensing of Epinephrine. Electrochemical sensing of analytes was studied using flexi PTS3 as the working electrode and Ag/AgCl as the reference electrode and

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CONCLUSIONS In conclusion, we have successfully fabricated a flexible electrochemical transducer based on PEDOT−titania nanocomposite in the PDMS film and demonstrated its application for the selective sensing of epinephrine. The enhanced current response of the PTS3 electrode was attributed to the efficient electron-transfer process between titania and PEDOT and the synergy between the PEDOT−titania nanocomposites. The flexible electrode film exhibited high thermomechanical stability along with excellent electrical conductivity and low acimpedance. The electrodes were found to be electrochemically stable, which showed simultaneous detection of ascorbic acid, dopamine, and uric acid with excellent sensitivity and response time. The high electrical conductivity, electrochemical stability, and electrocatalytic property of the fabricated flexible transducer suggested its application as an electrode for nanodevices and sensors which can be used in high technological areas.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.7b02055. FTIR, UV−vis spectra, SEM of PEDOT, electrical conductivity and cyclic voltammograms of PTS3 and titania, PEDOT and PT3 nanocomposites, and CV of PTS3 in blank (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Phone: +91471-2515316. ORCID

Unnikrishnan Nair Saraswathy Hareesh: 0000-0001-6455-8220 Sudha J. Devaki: 0000-0002-5445-939X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the ISRO India Respond Project (GAP 137039) and the CSIR-NETWORK (MULTIFUN, CSC0101) Project for the financial support. We are thankful to Dr. A. Ajayaghosh, Director, CSIR-NIIST, Trivandrum, for constant encouragement and support. We are also thankful to Dr. Prabhakar Rao, Prithviraj, and Soumya for XRD and SEM; Kiran Mohan for TEM; and Aswin, Vishnu Mohan, and Vibhu Darshan for AFM. We also thank Nijas Shajahan Mohammed who has done the M.Sc. Project in our group.

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DOI: 10.1021/acsomega.7b02055 ACS Omega 2018, 3, 3489−3500

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DOI: 10.1021/acsomega.7b02055 ACS Omega 2018, 3, 3489−3500