Partially Reduced Graphene Oxide (PRGO) Modified Tetrahedral

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Partially Reduced Graphene Oxide (PRGO) Modified Tetrahedral Amorphous Carbon (ta-C) Thin Film Electrodes as a Platform for Nanomolar Detection of Dopamine Niklas Wester, Sami Sainio, Tommi Palomäki, Dennis Nordlund, Vivek Kumar Singh, Leena-Sisko Johansson, Jari Koskinen, and Tomi Laurila J. Phys. Chem. C, Just Accepted Manuscript • DOI: 10.1021/acs.jpcc.6b13019 • Publication Date (Web): 16 Mar 2017 Downloaded from http://pubs.acs.org on March 22, 2017

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The Journal of Physical Chemistry

Partially Reduced Graphene Oxide (PRGO) Modified Tetrahedral Amorphous Carbon (ta-C) Thin Film Electrodes as a Platform for Nanomolar Detection of Dopamine Niklas Westera, Sami Sainiob, Tommi Palomäkib, Dennis Nordlundc, Vivek Kumar Singha, Leena-Sisko Johanssond, Jari Koskinena and Tomi Laurilab* a

Department of Materials Science, School of Chemical Technology, Aalto University, Espoo

02150, Finland b

Department of Electrical Engineering and Automation, School of Electrical Engineering, Aalto

University, Espoo 02150, Finland c

Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo

Park, CA 94025, USA d

Department of Forest Products Technology, Aalto University, Espoo 02150, Finland

*Corresponding author: tel: +358 50 3414375 email: [email protected] (Tomi Laurila) Abstract In this study we present for the first time a tetrahedral amorphous carbon (ta-C) – partially reduced graphene oxide (PRGO) hybrid electrode nanomaterial platform for electrochemical sensing of dopamine (DA). Graphene oxide was synthesized with modified Hummer’s method. Before modification of ta-C by drop casting, partial reduction of the GO was carried to improve electrochemical properties and adhesion to the ta-C thin film. A facile nitric acid treatment that slightly re-oxidized the surface and modified the surface chemistry was subsequently performed to further improve the electrochemical properties of the electrodes. The largest relative increase was seen in carboxyl groups. The HNO3 treatment increased the sensitivity towards DA and AA, and resulted in a cathodic shift in the oxidation of AA. The fabricated hybrid electrodes were characterized with scanning electron microscopy (SEM), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS) and electrochemical impedance spectroscopy (EIS). Compared to the plain ta-C electrode the hybrid electrode was shown to exhibit superior sensitivity and selectivity towards DA in the presence of ascorbic acid (AA) enabling simultaneous sensing of AA and DA close to the physiological concentrations by cyclic voltammetry (CV) and by differential pulse voltammetry (DPV). Two linear ranges of 0-1 µM and 1-100 µM and a detection limit (S/N = 3.3) of 2.6 nM for DA was determined by means of cyclic voltammetry. Hence, the

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current work provides a fully CMOS compatible carbon based hybrid nanomaterial that shows potential for in vivo measurements of DA. 1. Introduction Dopamine is an important electroactive neurotransmitter that plays a key role in both cognitive and behavioral functions1. Abnormal concentrations of dopamine have been implicated in several neurological disorders2-5. It has been estimated that up to 27 % of the adult population in Europe suffer from mental and neurological disorders6. In vivo detection of neurotransmitters could potentially help millions of patients worldwide by providing better understanding of these diseases. To provide a suitable sensor for this purpose, scientists have studied carbon-based sensors for neurotransmitter detection. Carbon electrodes have been widely applied in in vitro detection of neurotransmitters7-9. Conventional carbon electrodes like carbon fibers (CF), highly oriented pyrolytic graphite (HOPG) and glassy carbon (GC) are, however, not compatible with standard silicon processes. In addition they have limited geometries and are susceptible to biofouling7-8. Tetrahedral amorphous carbon (ta-C) is patternable and fully compatible with standard silicon micro processing. In addition, it has several other attractive attributes including stability in wide potential windows10-12 , good biocompatibility and resistance to bacterial adhesion13-16. Facile electron transfer can be achieved with tetrahedral amorphous carbon (ta-C) thin film electrodes11, 17 . Recently such an electrode has been used to detect 1 µM DA11. As the in vivo levels of DA range from 5 to 700 nM depending on the location18-19, the ta-C electrode is not sufficiently sensitive for in vivo detection of DA. Moreover, this electrode cannot selectively detect DA in the presence of ascorbic acid (AA)20-21. However, the ta-C electrode serves as an ideal mediating layer for further modifying with reduced graphene oxide (RGO). In such a way, a hybrid electrode that combines the best properties of both electrode materials can be realized. Owing to its large surface area, exceptional electrical conductivity and favorable electrocatalytic properties graphene has emerged as an interesting electrode material.22 The electrocatalytic properties are commonly attributed to edge plane and basal plane defect sites, although it has been shown that fast electron transfer can also take place at pristine graphite basal planes (see eg. Lai et al.23). The synthesis of graphene oxide by means of chemical oxidation, exfoliation and reduction requires no metallic catalyst particles and enables the fabrication of an all carbon electrode24. In contrast chemical vapor deposition of (CVD) graphene, CNTs and CNFs generally require metal catalysts24-26. Nanomolar detection of DA has been previously reported with graphene27, graphene oxide28, reduced graphene oxide29-30 and nitrogen doped reduced graphene oxide electrodes31. Most of these studies were based on modified glassy carbon or other conventional carbon electrodes. Surface functionalization, in particular the oxygen and nitrogen content, has been shown to influence the electrochemical sensing properties of carbon nanomaterials31-35. Oxygen functionalities of carbon nanomaterials are likely affecting both the sensitivity and the electrocatalytic activity towards neurotransmitters. Proper distribution of the oxygen functional groups may allow one to shift the oxidation potential of the neurotransmitter and interferent, thus


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allowing selectivity for DA with common interferents such as AA, uric acid (UA) and serotonin (HT5)31, 34-35. In this paper, we present a ta-C – partially reduced graphene oxide (PRGO) hybrid electrode and demonstrate its applicability as electrochemical sensor for detecting dopamine. This electrode is capable of selective detection of DA in the presence of the common interferent AA. We show that graphene oxide can be partially reduced by only a 10 min immersion in liquor ammonia solution at room temperature to substantially improve the electrochemical properties. Ammonia is a less hazardous alternative to the common reducing agent hydrazine that has previously been used to achieve highly reduced GO36. After reduction a filtered cathodic arc deposited ultrathin ta-C electrode was modified with reduced graphene oxide by drop casting and functionalized by a rapid immersion in 10 M HNO3. The fabricated hybrid electrodes were characterized with scanning electron microscopy (SEM), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS). The electrochemical properties of the fabricated hybrid electrodes were evaluated with both outer and inner sphere redox probes. The analytical performance was studied by in vitro measurements of DA. High electrochemically active surface area and high sensitivity towards DA was found. 2. Experimental 2.1 Preparation of partially reduced graphene oxide GO was prepared from synthetic graphite powder by modified Hummer’s method37-38. The centrifuged and washed GO solution was dried after which it was dispersed in water by ultrasonication. A more detailed description of the GO synthesis can be found in the Supporting Information. The reduction of the GO was carried out with ammonia. 1 ml of liquor ammonia solution (NH4OH) was added to 10 ml of GO solution and stirred for 10 min. The PRGO was then collected by filtration and washed for multiple times with deionized (DI) water. Finally, the PRGO was dispersed in DI water to achieve a concentration of 10 mg ml-1. 2.2 Electrode fabrication The electrodes were deposited on highly conductive, p-type, boron-doped (100) Si wafers with 0.001-0.002 Ωcm resistivity (Ultrasil, USA). A 20 nm Ti adhesion layer was deposited by means of direct current magnetron sputtering, after which a 7 nm tetrahedral amorphous carbon top layer was deposited with filtered cathodic vacuum arc (FCVA). The deposition process is described in greater detail in refs11 and17. The obtained plain ta-C electrodes were then modified with PRGO. The pre-diced ta-C samples were placed on a copper clad FR4 – PCB laminate sheet and covered with PTFE film (Saint-Gobain Performance Plastics CHR 2255-2). A hole 3 mm in diameter was punched in the film before placing it on the electrode surface. The electrode surface was then modified by drop casting 10 ml of the PRGO solution. The PRGO solution was subsequently dried in a vacuum oven at 60 °C. The drop casting and drying procedure was repeated 3 times. Some electrodes were then pretreated by submersion in 10 M nitric acid for 5 min. GO modified electrode were also prepared as reference, by repeating the same drops casting procedure once.



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2.3 Characterization Visible Raman spectroscopy of the fabricated electrodes was carried out with LabRAM HR (Jobin Yvon Horiba). The system was equipped with an argon laser (λ = 514 nm, power of 10 mW) and BX41 (Olympus) microscope with 100x objective lens resulting in a spot size of less than 1 µm. The GO, PRGO and HNO3 treated PRGO samples were also subjected to Fourier transform infrared spectroscopy (FT-IR) analysis (Nicolet Manga-IR 750 spectrometer). For the FT-IR analysis separate samples of GO and PRGO were prepared on undoped (100) silicon as described above. Both untreated and nitric acid treated PRGO samples were analyzed. The morphology of the PRGO electrodes was assessed by scanning electron microscopy (Hitachi S4700 and JEOL JSM-6330F). Before imaging the Teflon film used in drop casting was removed. Planar images were first obtained after which cross-sectional samples were prepared by dicing of the wafer. The surface chemistry of the electrodes was evaluated with X-ray photoelectron spectroscopy (AXIS Ultra, Kratos Analytical), using monochromatic Al Kα irradiation at 100 W and under neutralization. Samples were pre-evacuated overnight. High resolution spectra of C 1s, O 1s and N 1s regions were recorded along with survey data on 2-4 locations for each sample. The analysis area was 400 x 800 µm2. XPS analysis depth was less than 10 nm. 100 % cellulose filter paper (Whatman) was measured with the sample batch and used as an in-situ reference39. The high resolution data was fitted with CasaXPS software, assuming Gaussian line shapes. The binding energies were charge corrected with the help of the above mentioned cellulose reference using 286.7 eV for carbon atoms which are singly bonded to one oxygen atom, and 285.0 eV for aliphatic carbon, which in this case are unresolvable from graphitic carbon atoms40. The XAS study was carried out on beamline 10-1 at Stanford Synchrotron Radiation Lightsource (SSRL). The samples were mounted on an aluminum stick using double-sided carbon tape. Three different incidence angles (grazing angle of 20°, 54° and 90°) were used to evaluate any anisotropy. The beamline monochromator was operated at 0.2 eV resolution, providing ~1011 ph/s in a 1mm2 beam spot. The whole dataset was aligned in energy with 0.05 eV precision using the i0 dip in the incoming flux, monitored by an Au evaporated mesh. All spectra have been background-subtracted, normalized, analyzed and the peaks fitted with IGOR Pro version 6.36 software. Spectra were calibrated by placing the π* sp2 at 285.3 eV. With this calibration all the functional groups are well in agreement with the values often reported in literature41-51. 2.4 Electrochemistry The electrochemical properties of the electrodes were assessed by means of cyclic voltammetry. The common Ru(NH3)63+/2+, FcMeOH+/0 and Fe(CN)64-/3- redox probes were used. Cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) were carried out with a Gamry Reference 600 potentiostat. A conventional three electrode setup with a Ag/AgCl reference electrode (+0.199 V vs SHE, Radiometer Analytical) and a graphite rod counter was used. For the CV measurements 1 mM concentrations of hexaammineruthenium(III) chloride (Sigma-Aldrich) and iron(III) ferrocyanide (SigmaAldrich) in 1 M KCl were used. Ferrocenemethanol (Sigma-Aldrich) was dissolved in 0.15 M H2SO4 (Merck Suprapur) to achieve the same concentration. For the EIS measurements a 5 mM


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Ru(NH3)63+/2+ in 1 M KCl was used. An AC signal with an amplitude of 15 mV in the frequency range of 100 kHz to 10 mHz was utilized. The formal potential as determined with CV for Ru(NH3)63+/2+ was used as DC potential. The EIS data was fitted with a Randles circuit with a charge transfer resistance (Rct), a Warburg element (W) and a constant phase element (CPE). Dopamine measurements were carried out with different dopamine concentrations in phosphate buffered saline (PBS) solution with and without 1 mM AA. The electrodes were rinsed in PBS between every measurement and the solution was stirred by bubbling nitrogen after injection of analyte. To prevent oxidation all solutions were prepared on the day of the measurement and solutions were deaerated for at least 15 min prior to measurement. The cell was kept at nitrogen overpressure during measurements and all measurements were carried out at room temperature. 3. Results 3.1 Structural and surface properties 3.1.1 SEM From the planar view of Fig. 1a it is evident that much of the PRGO has agglomerated in solution or upon drying and has formed particles several µm in size. Fig 1 b) shows the edge of a graphene nanoflake at larger magnifications. The cross-sectional micrographs (Fig. 1c and d) show that all of the surfaces of the electrode seen in the cross-section is covered with a layer of PRGO. A typical agglomerate can also be seen in the cross sectional micrographs. The SEM micrographs show that the PRGO layer is fairly continuous.



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Figure 1. Planar a) and b) as well as cross-sectional c) and d) scanning electron micrographs of the PRGO electrode.

Figure 2. The a) Raman spectra and b) FT-IR spectra of the GO, PRGO and HNO3 treated PRGO electrodes. The ta-C Raman spectrum was acquired with 488 nm and other samples with 514 nm wavelength. Table 1. Assigned FT-IR peaks to oxygen containing functionalities. Group or functionality Adsorbed OH groups C=O C=C C–O (epoxide) C–O (alkoxy)

Assignment regions (cm-1) 3400–2400 1735 1587, 1425 1230, 854, 810 1060

3.1.2 Raman The self-normalized Raman spectra of the ta-C, GO, PRGO and HNO3 treated PRGO electrodes are shown in Fig. 2a. The GO sample showed an ID/IG ratio of 1.74. No change in the ID/IG was observed after partial reduction, whereas the HNO3 treatment resulted in a small decrease to 1.64. The plain ta-C electrodes have been analyzed and are discussed elsewhere11, 17. Compared to the Raman spectra of graphite52-53 the G peaks in these samples are slightly blue shifted and centered around 1600 cm-1. For the modified ta-C electrodes the high-intensity D peak is centered around 1350 cm-1. In addition all samples also show peaks around 1150 and 1700 cm-1 (see Fig. 2a, peak A and B). Peak A could be related to trans-polyacetylene54 and Peak B is likely due to Stony-Walls defects and C2 defects54-55. These peaks arise from imperfect carbon rings and appear to be distinct to GO and do not appear in highly reduced GO54. 3.1.3 FT-IR Fig. 2b shows the FT-IR spectra of GO, PRGO and HNO3 treated PRGO samples. Table 1 shows the peaks assigned to different functional groups that can be observed in all samples and


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are typical to GO56-57. The reduction of GO results in lower intensity in all peaks related to oxygen containing functionalities as seen also in58-59. The broad peak in the 3400-2400 cm-1 region related to hydroxyl groups, is also significantly reduced in intensity after the reduction of GO. A widely accepted hypothesis assigns the band around 1600 cm-1 to C=C stretching modes of aromatic systems, whose intensity is reinforced by chemisorbed oxygen. Moreover, Fuente et al.60 showed that the bands around 1600 and 1380-1480 cm-1 region in acidic carbon surfaces can be ascribed to vicinal hydroxyl groups that induce IR absorption by carbon ring vibrations. This combination of C=O and two C=C peaks has been observed in GO57 and HNO3 oxidized activated carbon61. The HNO3 treatment slightly broadens the band related to adsorbed hydroxyl groups. It also slightly increases the intensity of the peaks around 1735 and 1587 cm-1 related to carbonyl functionalities and stretch of aromatic C=C, respectively. It should be noted that H-C=C, C-O-C and C-OH groups result in several widely distributed peaks in the 1000-1400 cm-1 region. Thus unequivocal interpretation of changes in the relative abundance of C-O bonds in epoxide and alkoxy groups is difficult. Nevertheless the HNO3 does not seem to be related to a significant increase in these functionalities. Whereas the HNO3 treatment clearly results in an increase in the intensity of the bands related to carbonyl functionalities. The high wavenumber observed for the carbonyl band suggests that it is related to carboxylic acids or lactones60. The broad O–H stretch band further indicates the presence of carboxylic groups. 3.1.4 XPS Surface chemical characterization was carried out with X-ray photoelectron spectroscopy. The survey spectra of the GO, PRGO and PRGO HNO3 samples are presented in the Fig. S1 and Table S2 (SI). According to XPS (see SI Fig S1) all sample surfaces consisted mainly of carbon and oxygen, as expected. In addition, both PRGO samples had a high surface loading of silicon, which was present as SiO2 (30 to 45 at. %). Since no silica particles were observed in SEM, the source of silica could be the silicon adhesive from the Teflon films used in electrode fabrication. All the samples also contained some nitrogen and trace amounts of boron. The latter could originate from the dicing of the boron-doped Si. Further traces of Al, F, Na, Ca, S and Mn were observed on GO and PRGO samples prior to HNO3 treatment. Of these, Na, S and Mn likely originated from the modified Hummer’s process, while fluorine came from the Teflon film as with silica. These traces were no longer observed after the HNO3 treatment, indicating that the treatment cleans the surface of the electrodes. XPS high resolution data for C 1s and N 1s are shown in Fig. 3 and the results of C 1s spectra deconvolution are summarized in Table 2. Effect of the GO reduction into PRGO is clearly seen in the C 1s spectra as a drastic decrease in carbon atoms bound to oxygen (Fig. 3a and Table 2). This is also reflected in lower surface oxygen content (after the subtraction of the oxygen in silica from total surface oxygen), which is consistent with decrease in intensity of oxygen containing functionalities in the FT-IR spectra. Accordingly, the ratio of oxidized vs nonoxidized carbon atoms COx/CC decreased from 1.2 for the GO sample to 0.5 (Table 2). The N 1s peaks also changed as a result of the reduction treatment and the total nitrogen content increased from 0.6 to 1.3 at %. Increase of nitrogen content has been observed when reducing GO with



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nitrogen containing reducing agents, such as ammonia36 and hydrazine44, 52.The nitric acid treatment resulted in a slight re-oxidation of the sample as seen by the increase of COx/CC to 0.7, and reduced the nitrogen content to 0.5 at %. The re-oxidation effect of the HNO3 treatments seen in XPS is consistent with FT-IR results.

Figure 3. High resolution x-ray photoelectron spectra of a) C 1s and b) N 1s. Table 2. Data from peak fitting of high resolution C 1s spectra. Sample

COx/CC

GO PRGO PRGO HNO3

1.2 0.5 0.7

CC (284.7 eV) 45.5 67.7 59.9

C-O (286.7 eV) 48.5 24.1 30.4

C=O (288.4 eV) 6.0 8.2 9.7

3.1.5 XAS The differences in the PRGO and the nitric acid treated PRGO samples were further studied by means of C 1s XAS. X-ray absorption probes the local electronic structure and is sensitive to chemical shifts, bond type and orbital character43, and has been successfully applied in many graphene oxide systems27, 44-46. XAS can complement XPS in extracting chemical functionalities and it is particularly powerful when used in conjunction with XPS and FT-IR. Fig. 4 shows the C 1s spectra for the PRGO and the HNO3 treated PRGO samples. The spectral features are interpreted through peak fitting using the vast amount of experimental information from earlier studies41-51. In particular, sp2-like carbon as well as a number of functionalized carbon groups (ketone/aldehyde, C-H and carboxyl groups) are individually treated in the analysis presented in Table 3.


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Figure 4. (a) PRGO and (b) PRGO HNO3 – C 1s spectra shown for energy range of 280 - 310 eV. Peaks fitted to the spectra are (reading from the left) π* sp2, ketone/aldehyde, C-H, carboxyl, Rydberg states and σ* sp2. Peaks post the IP at 290.6 eV, except for the σ* sp2 are used to numerically serve the fit. Table 3. Energies (eV), peak attributions and intensities (in arbitrary units) along with the calculated relative intensities of the oxygen and hydrogen functional groups, related to the π* sp2 intensity. PRGO PRGO (HNO3) (untreated) Intensity (Arbitrary Units)

Energy (eV)

Peak attribution

285.3 286.8 287.7 288.9 290.2 291.9

π* sp2 ketone/aldehyde C-H carboxyl Rydberg σ* sp2

1.014 0.447 0.582 1.289

0.862 0.421 0.534 1.354

-

-

0.558

0.584

[ketone/aldehyde]/ sp2 [C-H] / sp2 [carboxyl] / sp2 [σ* sp2] / π* sp2

44 % 57 % 127 % 55 %

49 % 62 % 157 % 68 %

From comparison of the two spectra we observe a lowering of the π* sp2 peak intensity and slight increase of the carboxyl groups in the nitric acid treated sample. This is confirmed by peak fitting analysis that showed that the HNO3 treatment (i) increased ketone/aldehyde, C-H, carboxyl groups and (ii) reduce π* sp2. These observations are in good agreement with the results from the XPS and FT-IR, where HNO3 treated PRGO sample showed an increase in the amount of oxygen functionalization. The normalized functional group increase is most significant for the



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carboxyl groups, and much less significant for the ketone/aldehyde and C-H groups (~30% and ~4% increase in relative intensities, respectively). 3.1.6 Summary of characterization In summary, the SEM micrographs show that the ta-C surface is completely covered with a continuous layer of PRGO with varying thickness. Agglomerated PRGO sheets were also observed on the electrode. The modification also changed the bonding of the surface carbon atoms, reflected by the dramatic change in the Raman spectra following modification compared to the plain ta-C. The results from FT-IR spectroscopy and XPS characterization show that (i) oxygen content was decreased upon partial reduction of the GO and (ii) slight re-oxidation was observed as a result of HNO3 treatment. The reduction further resulted in removal of adsorbed water. The reduction treatment did not cause any change in the ID/IG ratio. The COx/CC ratio increased from 0.5 to 0.7 with the HNO3 treatment. The FT-IR spectra showed increase in the intensity of the peaks related to carbonyl functionalities and stretch of aromatic C=C, respectively. After HNO3 treatment XAS measurements confirmed that the acid treatment resulted in an increase in the amount of ketone/aldehyde, C-H, and carboxyl groups, while the overall intensity of π* sp2 was reduced. The acid treatment also appears to cause the carbonyl functionalities to be more concentrated especially in carboxylic groups based on the XAS. Furthermore, the XPS analysis also showed the HNO3 treatment removed the traces of Al, F, Na, Ca, S and Mn observed on the GO and PRGO samples, indicating that the acid treatment cleans the surface of the electrode. 3.2 Electrochemical properties 3.2.1 Electron transfer The electrochemical properties of the fabricated electrodes were characterized with outer and inner sphere redox probes. The peak potential separation values, peak current ratios and apparent heterogeneous electron transfer rate constants for the different redox probes are shown in Table 4. Rate constants were calculated as proposed by Nicholson62. Diffusion coefficient of 5.47x10-6 63 , 2.17x10-5 64 and 7.17x10-6 cm2/s64 were used for Ru(NH3)63+/2+, FcMeOH+/0 and Fe(CN)64-/3-, respectively. We find that the PRGO electrodes show slightly slower electron transfer kinetics compared to the plain ta-C electrode with the outer sphere systems of FcMeOH+/0 and Ru(NH3)63+/2+. The ∆Ep value of the PRGO electrode increased slightly after HNO3 treatment with Ru(NH3)63+/2+ probe whereas a slight improvement was observed with the same treatment with FcMeOH+/0. However, as the differences between treated and non-treated electrodes were only slightly larger than the standard deviation between the three measured electrodes of each type, it is likely that the observed differences are caused by electrode to electrode variations. It should be noted that when the system becomes more reversible the Nicholson method is more sensitive to small changes in ∆Ep and errors in the determined peak potentials62. When the ∆Ep value increases from 60 mV to 70 mV the rate constant calculated by the Nicholson method (Ru(NH3)63+/2+, scan rate of 100 mV/s) decreases from 0.199 to 0.020.


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With the surface sensitive Fe(CN)64-/3- probe, the HNO3 treatment resulted in an improvement compared to the non-treated PRGO electrode. One plain ta-C electrode was also measured for reference. The peak potential separation ∆Ep of the HNO3 treated PRGO electrode was 120.9 mV, while values of 131 and 156.7 mV were obtained for the plain ta-C and PRGO electrodes, respectively, indicating faster kinetics for the HNO3 treated electrode. This redox probe has been proposed to be affected by edge plane/defect sites in graphitic materials65. Compton’s66 group has shown that the heterogeneous rate constant at the surface of pyrolytic graphite basal and edge planes is affected by the degree of oxidation. The ∆Ep obtained for the HNO3 treated PRGO is close to that of an oxidized edge plane in66. The PRGO modification and HNO3 treatment was also associated with an increase in oxidation current by a factor of 2.1 and 2.7, respectively, caused by the likely increase in surface area. Table 4. Cyclic voltammetric and EIS measurement data as well as calculated apparent electron transfer rate constants for Fe(CN)64-/3-, FcMeOH and Ru(NH3)63+/2+. All CV measurements carried out in 1 mM concentration and with a scan rate of 100 mV/s. Parameter

ta-C

∆Ep (mV) Ipa/Ipc Ipa (µA cm-2) k° (cm s-1) a

131 1.12 72 0.003


59.1 ± 0.9 1.048 ± 0.005 214.8 ± 4.2 0.402


Rs (Ω) Rct (Ω) Cdl (µF/cm2) k° (cm s-1) a a

ta-C + PRGO

ta-C + PRGO HNO3

CV – 1 mM Fe(CN)64-/3156.7 ± 16.8 120.9 ± 19.4 1.01 ± 0.09 0.94 ± 0.01 150.1 ± 6.7 195.5 ± 2.9 0.002 0.003 CV – 1 mM FcMeOH 74.7 ± 3.0 72.7 ± 1.0 1.058 ± 0.004 1.080 ± 0.013 227.3 ± 8.2 230.8 ± 14.4 0.036 0.034

57.1 ± 2.9 0.98 ± 0.01 236.2 ± 4.6 0.245

CV – 1 mM Ru(NH3)63+/2+ 70.4 ± 2.6 mV 73.5 ± 2.7 mV 0.80 ± 0.01 0.73 ± 0.03 226.0 ± 9.2 211.1 ± 7.0 0.018 0.014

17.78 ± 3.69 10.06 ± 2.28 10.37 ± 7.04 0.420

EIS – 5 mM Ru(NH3)63+/2+ – 17.25 ± 1.7 – 170.98 ± 19.50 – 2.17 ± 0.12 – 0.009 ± 0.001

α=0.5 for all electrodes



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Figure 5. Nyquist plots for plain ta-C and HNO3 treated PRGO electrode from the EIS measurement in 5 mM Ru(NH3)63+/2+ in 1 M KCl. The electron transfer properties were further characterized in 5 mM Ru(NH3)63+/2+ utilizing EIS. The Nyquist plots of a plain ta-C electrode and a HNO3 treated PRGO electrode are shown in Fig. 5. The increase in ∆Ep values observed in the cyclic voltammograms are consistent with the observed increase in charge transfer resistance Rct. The PRGO modification resulted in an increase of the Rct from 10 Ω for the plain ta-C electrode to 171 Ω for the PRGO modified and HNO3 treated electrode. The double layer capacitance, however decreased from 10.37 µF/cm2 to 2.17 µF/cm2 as a result of the PRGO functionalization. Casero et al.67 obtained a capacitance of 3.21 µF/cm2 for a GO modified GC electrode. They also observed a higher Rct value for GO than for RGO with Fe(CN)64-/3-. 3.2.2 Sensitivities towards dopamine The HNO3 treatment increased the oxidation current of DA (see Fig. S3, SI) and shifted the oxidation potential of AA to lower potential (see Fig. S4, SI). Thus, similar improvement in the electrochemical properties was observed with DA and AA as with Fe(CN)64-/3-. Compared to the plain ta-C electrode the oxidation current increased by a factor of 4.0 as a result of the PRGO modification and HNO3 treatment (see Fig S5, SI). No improvement in the sensitivity towards DA was observed with modification with GO, as compared to plain ta-C. Due to the better sensitivity and selectivity only the HNO3 treated PRGO electrodes were used for electrochemical detection of DA and AA.


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Figure 6. a) cyclic voltammograms and b) linearization of the HNO3 treated PRGO electrode in PBS with DA concentrations ranging from 0-100 µM. The inset shows magnified DA oxidation peaks for the HNO3 treated PRGO electrode in the concentration range of 0-5 µM. Scan rate 50 mV/s. Fig. 6a shows the cyclic voltammograms of the HNO3 treated PRGO electrode in the concentration range of 0-100 µM. The measurements were carried out with 3 electrodes to assess the repeatability of the measurements. As seen in Fig 6b two linear ranges for the oxidation current as function of DA concentration were obtained. The linear relations between the oxidation peak current in the concentration ranges of 0-1 µM and 1-100 µM were as follows: IDA (µA) = 0.343CDA (µM) + 1.462 (R = 0.9977) and IDA (µA) = 0.079CDA (µM) + 2.042 (R = 0.9947), respectively. The ta-C PRGO hybrid electrode showed high sensitivity towards DA. It should be noted that no background subtraction has been carried out and all the data is shown in the as measured state. The electrochemical reactions of DA on ta-C electrodes have been studied in detail earlier in11, 68. The DA detection limit of the ta-C electrode used in this and earlier works was found to be around 1 µM. With the plain ta-C electrode there is barely any peak at 10 µM concentration21, whereas the hybrid electrode produces distinct peaks down to 250 nM concentration and increasing current above the PBS baseline was consistently observed down to 50 nM concentrations. Thus, the results presented in this work demonstrate that it is possible to achieve detection of DA within the required in vivo concentration range with simple CV scans. The limit of detection (LOD) and limit of quantification (LOQ) were calculated as 3.3ൈσ/S and 10ൈσ/S, where σ is the standard deviation in the blank signal and S the sensitivity. Based on this method and a calculated sensitivity of 339 µA/mM (4792 µA/(mM cm2)) the theoretical LOD is 2.6±1.4 nM and LOQ is 7.9±4.1 nM. These values are among the best reported in literature for the detection of dopamine both for graphene and other carbon as well as carbon- metal nanoparticle composite electrodes. Table 5 shows a summary of detection limits for carbon based



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electrodes. It is the opinion of the authors that the most significant result of this work is the ability to detect DA in the physiological concentration range with CV, which is generally less sensitive and selective than DPV, but can be used for much faster and simpler measurements. Thus, the HNO3 treated PRGO electrode shows great potential for biodetection applications. Table 5.Comparison of analytical performance of different graphitic based electrodes in the presence of the common interferents ascorbic acid (AA), serotonin (5-HT) and uric acid (UA). Electrode material PGEa

Peak Lowest Detection separation measured DA limit AA-DA concentration DA (µM) (mV) (µM) DPV 195 1 0.11

EPPGb

CV DPV

190

40 0.2

0.09

3D graphene nanoflake NGc/GC

CV DPV

181

100 1

– 0.17 – 0.25

AA (µM)

5-HT (µM)

UA (µM)

25500 40 0.560 1000 1000

–

2.5-30

69

40 0.1100 –

–

70

100 100

27

CV DPV

200

1000 0.2

ERGO/GC

CV DPV

224 240

500 0.5

– 0.5

CNF

DPV

320

0.1

0.05

1000

DLC/CNT CV Pt/MWCNT CV /GC DPV

168 190 166

0.5 500 0.061

0.00126 – 0.048

1000 500 24.5765 100 04000 – 1000 1000

GO/GC DPV NAd 1 NDPV 228 0.5 PCNPse/GC ta-C/PRGO CV – 0.05 CV 153 1 DPV 176 0.1 a Pyrolytic graphite electrode b Edge plane pyrolytic graphite c Nitrogen doped graphene d total shut out of AA at physiological pH e nitrogen doped porous carbon nanopolyhedra

0.27 0.011 0.0026 10 0.25


31

– 51300 5000 5002000

2-45 –

500 0.5-60

29

0.25– 10 – –

–

71

– – – – –

21 – 72 500 0.45550 28 – 73 07000 – This – work –

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3.2.3 Selectivity between DA and AA Fig. 7 shows the cyclic voltammogram of a) the plain ta-C electrode and b) the HNO3 treated PRGO electrode in solutions of 1 mM AA and varying concentrations of DA. The plain ta-C electrode is clearly unable to resolve between the AA and DA and shows overlapping voltammetric response. With the HNO3 treated PRGO electrode a concentration of 1 µM showed an increase in current due to oxidation of DA and a 10 µM concentration produced a separate peak for oxidation of DA. The detection of nanomolar DA concentrations in the physiological range by CV with this electrode still remains challenging. Most of the works in literature (see Table 5) utilize differential pulse voltammetry (DPV) as it is more sensitive and has better resolution compared to CV. Fig. 7c shows the DPV profile of the PRGO HNO3 electrode. This electrode can clearly distinguish between AA and DA, and produces separate oxidation peaks. The current for oxidation of DA in the presence of 1 mM AA scaled linearly with DA concentration in the same concentration ranges as with the CV measurements presented in Fig. 6. The linear relations between the DPV oxidation peak current in the concentration ranges of 0-1 µM and 1-100 µM were IDA (µA) = 0.519CDA (µM) + 3.317 (R = 0.9943) and IDA (µA) = 0.120CDA (µM) + 4.175 (R = 0.9904), respectively.



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Figure 7. Cyclic voltammograms of a) the plain ta-C electrode and b) the PRGO HNO3 electrode as well as c) DPV measurement for the PRGO HNO3 electrode in presence of 1 mM AA in PBS solution with increasing concentrations of DA. CV scan rate 50 mV/s. 3.3.4 Resistance to fouling Finally, the electrode stability and the fouling of the electrode was studied in 1 mM DA solution. Fig. 8a shows 10 consecutive cycles in 1 mM DA solution for the HNO3 treated PRGO electrode. It has been recently shown that ta-C electrodes suffer from fouling, especially when the DA concentration is in the mM range and wide potential windows are applied68. With this hybrid electrode rapid fouling was not observed, contrary to the plain ta-C electrode. Figure 8b shows the ∆Ep as a function of number of cycles for the hybrid electrode, a plain ta-C electrode as well as a glassy carbon electrode. This observed trend for the HNO3 treated PRGO hybrid electrode continued for 25 cycles, after which the ∆Ep reached a value of 287 mV.


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Figure 8. The a) cyclic voltammogram of 10 consecutive cycles for the PRGO HNO3 electrode in 1 mM DA in PBS solution and b) the peak potential separation ∆Ep as function of number of cycles. Scan rate 50 mV/s. 4. Discussion To rationalize the observed differences in the electrochemical behavior between ta-C and PRGO electrodes we will concentrate on the disparities in the surface properties of the two types of materials. It is to be noted that the absence of metallic catalyst particles in our case excludes the possibility of metal particles contributing to the electrochemical properties. Therefore, we may concentrate on differences in (i) the surface functional groups, (ii) the bonding of the carbon at the surface region and (iii) surface topography between the two types of materials. (i) The partial reduction of GO was confirmed with FT-IR and XPS. FT-IR analysis showed a reduced intensity of all peaks related to oxygen containing functional groups. Further it showed a clear reduction in adsorbed water upon partial reduction of GO. The removal of embedded water has been previously shown to improve connectivity between the flakes and thereby reduce contact resistance and improve conductivity54. The HNO3 treatment re-oxidized the PRGO surface as confirmed by XPS. Further XAS measurements showed larger increase in the relative abundance of carboxylic groups as compared to ketones and aldehydes. The XPS and FT-IR spectra confirmed an increase in carbonyl functionalities, while increase in C-O bonds was also observed with XPS. The FT-IR spectra showed increase especially in the intensity of the bands related to C=O functionalities and C=C with chemisorbed oxygen. A detailed study of the surface chemistry of the plain ta-C sample was very recently published by our group20. The surface of the plain ta-C electrode was found to contain an abundance of ketone, aldehyde and carboxylic groups. Moreover, the O/C ratio and relative abundance of these groups seemed to affect the electrochemical oxidation of AA and DA. Especially with AA, the cathodic shift of the oxidation peak was significant with increasing surface ketone/aldehyde groups compared to carboxyl functionalities. Likewise the HNO3 treatment of the PRGO electrode resulted in a cathodic shift of AA, and an increase in oxidation currents of Fe(CN)64-/3-, DA and AA. Thus, the results of this and other works31-34 strongly suggest that the O/C ratio and the relative abundance of different oxygen containing functional groups affect the sensitivity and



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selectivity towards DA. The ability of an electrode to detect inner sphere analytes, such as DA and AA, is often attributed to readiness of adsorption to the surface74. The relative increase in carbonyl functionalities upon reduction and HNO3 treatment seems to facilitate adsorption of both AA and DA. Unlike the results for plain ta-C in20 this work the cathodic shift of AA seems to be related to increase especially in carboxyl groups. The catalytic effect towards AA have been attributed to hydrogen bonds between the lactone of AA and carboxyl on RGO29, 75. Moreover, Jacobs et al.34 observed large increase in the sensitivity towards AA and DA with carboxyl acid functionalized single wall carbon nanotubes. Since there was no increase in the sensitivity of the GO modified ta-C electrode and the unreduced GO was easily washed away by the electrolyte, reduction of the GO was found to be necessary. However, owing to the apparently central role of oxygen functionalities in the detection of DA and AA, only partial reduction was carried out. (ii) Tetrahedral amorphous carbon films deposited with FCVA have been previously shown to have layered structure with an sp2 rich surface and sp3 rich bulk76-77. The sp2 bonded carbons at the surface tend to exist as oleofinic chains in ta-C. On the other hand, experimental work and modelling has shown that oxygen containing functional groups tend to cluster allowing for aromatic domains to exist in the GO55. This difference in the bonding of carbon is reflected in large difference in the Raman spectra of GO and ta-C. The absence of significant changes in the Raman spectra upon partial reduction indicates that there is no increase in edge plane like sites upon reduction as seen in44, 52. Whereas HNO3 treatment resulted in a small decrease in the ID/IG ratio. This is confirmed by the XAS measurements that show a clear decease in the surface sp2 π* intensity, suggesting destruction of π-conjugated network44. It is well established that DA shows complex adsorption behavior at carbon electrodes74. Wang et al.78 proposed that π–π electron interaction can take place between the delocalized π electrons in the phenyl structure of DA and the two-dimensional planar hexagonal carbon structure of graphene. The disparity in the nature of the sp2 carbon on the surface of ta-C and PRGO, eg. oleofinic chains versus aromatic domains, likely contributes to the cathodic shift of AA and increase in sensitivities of both AA and DA with PRGO modification. This effect is likely contributing to the large increase in sensitivity and selectivity towards DA compared to the plain ta-C electrode. It may also explain the larger increase in oxidation current for DA compared to Fe(CN)64-/3- of the HNO3 treated PRGO electrode. The further improvement in electrochemical properties and the decrease in the π* sp2 upon HNO3 treatment, however, suggests that the surface O/C ratio also plays a significant role in the electrochemical oxidation of DA and AA. Moreover, no significant change in the rates of heterogeneous electron transfer was observed with outer sphere probes, indicating that changes in with the inner sphere probes are surface chemistry related. (iii) The electrochemically active surface area was 4 times larger for the HNO3 treated PRGO electrode compared to the plain ta-C electrode. The increase in surface area compared to the plain ta-C electrode likely significantly contributes to the increased sensitivity observed with the PRGO electrodes. Likewise, the irregular surface of the PRGO electrodes appears to hinder passivation by polydopamine layer as seen also in21. A possible reason is that the breaking of the


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planar geometry by PRGO may hinder the polymerization reaction of polydopamine to some extent. The rougher surface can also contribute to the observed changes in the kinetics of the outer sphere redox probes if it establishes steric effects that hinder the electronic coupling between the probes and the surface. However, the possible differences in the electronic structure of the two types of electrodes may also have a decisive role. 5. Conclusions In this study we present a partially reduced graphene oxide (PRGO) modified ta-C hybrid electrode as a highly sensitive and selective platform for electrochemical detection of dopamine. This new material successfully combines the properties of the sp3 rich ta-C with those of partially reduced graphene oxide, resulting in electrochemical properties superior to those of the individual components. The low temperature fabrication process for the ta-C electrode is fully CMOS compatible and scalable. The partial reduction of GO was achieved in 10 min with liquor ammonia at room temperature and resulted in a relatively high amount of residual oxygen containing groups. The immersion in nitric acid slightly re-oxidized the surface and modified the surface chemistry. The PRGO modified and nitric acid treated ta-C electrodes showed a low double layer capacitance, facile electron transfer kinetics and high sensitivity as well as selectivity towards dopamine. The HNO3 treatment significantly increased the selectivity and to some degree the sensitivity of the electrode towards DA. The results presented here indicate that oxygen containing functional groups can facilitate the adsorption and electro-oxidation of DA and AA. Furthermore, complete reduction of GO is not required to achieve a highly sensitive and selective electrode for in vitro and in vivo detection of DA. Moreover, nanomolar detection of dopamine was achieved not only with DPV but also with CV. The PRGO modified electrode also showed significantly improved resistance to fouling compared to the plain ta-C electrode. Thus, these results further highlight that it is possible to synthesize an all carbon hybrid nanomaterial, which can detect nanomolar concentrations of DA in the presence of ascorbic acid. These results further highlight the applicability of the hybrid material as an all carbon platform for electrochemical sensing of biomolecules. Supporting Information Available More detailed description of the modified Hummer’s process for preparation of GO. Survey spectra of the GO, PRGO and PRGO HNO3 samples. The effect of HNO3 treatment on the cyclic voltammograms of DA and AA. Cyclic voltammograms of the ta-C, GO and HNO3 treated PRGO electrode in 100 µM DA in PBS. Acknowledgements The authors would like to acknowledge the Finnish Funding Agency for Technology and innovation (HILE project, grant number 211488), and Academy of Finland (HISCON project, grant number 259595, HYNA, grant number 285015 and FIRE, grant number 285526) for financial support. M.Sc. Anne Tanskanen is also acknowledged for performing FT-IR measurements and M.Sc Ajai Iyer is acknowledged for help with Raman spectroscopy.



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TOC Graphic


Partially Reduced Graphene Oxide (PRGO) Modified Tetrahedral

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