One-step synthesized 2D heteroatom doped graphene for high throughput electrochemical biosensing: A combined experimental and computational studies

Journal Pre-proof One-step synthesized 2D heteroatom doped graphene for high throughput electrochemical biosensing: A combined experimental and computational studies

Francis Opoku, Adeniyi Olugbenga Osikoya, Ezekiel Dixon Dikio, Penny Poomani Govender PII:

S0925-9635(19)30643-0

DOI:

https://doi.org/10.1016/j.diamond.2019.107592

Reference:

DIAMAT 107592

To appear in:

Diamond & Related Materials

Received date:

31 August 2019

Revised date:

14 October 2019

Accepted date:

20 October 2019

Please cite this article as: F. Opoku, A.O. Osikoya, E.D. Dikio, et al., One-step synthesized 2D heteroatom doped graphene for high throughput electrochemical biosensing: A combined experimental and computational studies, Diamond & Related Materials (2018), https://doi.org/10.1016/j.diamond.2019.107592

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© 2018 Published by Elsevier.

Journal Pre-proof One-step synthesized 2D heteroatom doped graphene for high throughput electrochemical biosensing: A combined experimental and computational studies Francis Opokua,*, Adeniyi Olugbenga Osikoyaa, Ezekiel Dixon Dikiob, and Penny Poomani Govender a,* a

Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011,

Applied Chemistry and Nanoscience Laboratory, Department of Chemistry, Vaal University

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Doornfontein Campus, Johannesburg 2028, South Africa.

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of Technology, P.O. Box X021, Vanderbijlpark 1900, South Africa *Corresponding authors.

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E-mail addresses: [email protected]; [email protected]

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Journal Pre-proof Abstract In this study, through the chemical vapor deposition method, we nanofabricated heteroatom graphene (HGr) and dispersed it into poly (3, 4-ethylene dioxythiophene)/poly (styrene sulfonate) to obtain a nanostructured interface material for bioelectronic applications. With Xray photoelectron spectroscopy, the existence of chlorine, nitrogen, and oxygen as dopants in the lattice of the as-synthesized HGr framework is verified, while structural assessment is

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performed by Raman spectroscopy. X-ray diffraction spectroscopy disclosed that the

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synthesized material contained sp2 hybridized carbons. The electrobiocatalytic activity of the conjugate interface material is examined by chronoamperometry using glucose as a sample

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analyte. The electrobiocatalytic test shows a sensitivity of 381.29 µA mM-1 cm-2, linear

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response of 1.393 to 8.752 mM and detection limit of 0.05 mM towards glucose sensing.

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Density Functional Theory (DFT) method is used to study glucose adsorption on Cl-, O-, and N-doped HGr. DFT findings indicated that the existence of Cl as a dopant on the graphene

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nanosheet greatly favored glucose adsorption on the doped graphene. The adsorption of the

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glucose molecule is accomplished through the transfer of electrons from the doped graphene to the glucose molecule, which improves the sensing response. The combined computational and experimental studies have shown that the introduced dopants improve the HGr electrobiocatalytic activity.

Keywords: 2D heteroatom graphene; glucose; Density Functional Theory; bioelectrode; electrochemical biosensing; x-ray photoelectron spectroscopy. 1. Introduction Recently, the focus on device design and manufacturing has been on slender, flexible, and miniaturized systems with performance greater and better than their bulky predecessors [1]. These have been achieved with 2-dimensional (2D) materials including graphene [2, 3]. 2

Journal Pre-proof Studies have shown that graphene has excellent potential for several applications, including energy storage, supercapacitors, bioelectronics, solar systems, and biofuel cells [4, 5]. The outstanding heat and mechanical characteristics and the elevated surface area of graphene (about 2630 m2

g-1) contribute to its versatility in device fabrications [6, 7]. It has been

established in the literature that the synthesis routes for graphene materials determine some of its properties [8]. It has been indicated that the mechanical cleavage synthesis technique produces great pristine graphene nanosheets but has the restriction of low output and

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hydrophobicity. The chemical methods, on the other hand, can produce high yield and

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hydrophilic graphene derivative (graphene oxide (GO)) but mostly with lots of disruption in the

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sp2 hybridization of the resultant product, leading to reduced conductivity in chemically

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produced graphene derivatives [9]. This has necessitated the development of graphene-metal nanoparticles to improve electron transport properties. The chemical vapor deposition (CVD)

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method provides an opportunity to synthesize scalable pristine graphene and the synthesis

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parameters can be adjusted to achieve the synthesis of either monolayer, few-layer or multilayer graphene. Also, the CVD technique can be used to synthesize doped graphene sheets,

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while maintaining its sp2 hybridization [10, 11]. Because of its exceptional electronic features and biocompatibility, the use of graphene material in biodevice manufacturing has attracted tremendous attention [12, 13]. However, the efficiency of such biodevice is restricted owing to the disturbance of the sp2 hybridization in most frequently used graphene type (graphene oxide, (GO)), which ultimately results in slow electron transfer rate owing to poor conductivity [14]. Several studies have used doped graphene in bioelectronics systems with great electrobiocatalytic reaction to enhance the electrobiocatalytic operations of graphene-based bioelectronics systems [15]. Zhang et al. and Shao et al. [16, 17] used nitrogen-doped graphene structure in fabricating efficient enzyme biosensor and achieved an extremely conductive graphene-enzyme framework with effective 3

Journal Pre-proof electrobiocatalytic activity resulting in a sensitivity of 226.24 µAm M-1 m-2 for glucose sensing. Studies have shown better electrocatalytic efficiency, durability, and selectivity of nitrogendoped graphene towards oxygen and hydrogen peroxide reduction than undoped graphene [16]. In this study, highly active few-layered heteroatom graphene material is fabricated and structured with PEDOT: PSS to obtain an efficient interfacial electrode material for electrochemical biosensing and bioelectronics applications. DFT calculations are used to

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confirm experimental observations by evaluating the adsorption behavior, adsorption energies,

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and detailed adsorption mechanism of glucose molecule on X-doped HGr (X = N, Cl, and O) in order to determine the most effective dopant site for glucose sensing [18]. The charge density

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difference distribution, electron transfer, and density of states (DOS) are further explored,

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followed by an assessment of the changes in the bond length of X-doped HGr after exposure to

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D-glucose molecule. Based on the theoretical and experimental methods, we can offer a clear

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atomistic insight into the sensing mechanism of D-glucose molecule. 2. Experimental and computational details

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2.1 Materials and chemicals

Potassium ferrocyanide (K4Fe(CN)6) (≥ 99%, Labchem), Glucose oxidase from Aspergillus niger (100 U mg-1, Sigma Aldrich), potassium chloride (KCl) (≥ 99 %, Labchem), dipotassium hydrogen phosphate (K2HPO4) (≥ 99%, Sigma Aldrich), potassium dihydrogen phosphate monobasic (KH2PO4) (99.99%, Sigma Aldrich), ferrocene dicarboxylic acid (C12H10FeO4) (97%, Sigma Aldrich), and phosphate buffer saline tablets (1X, VWR). Poly (3, 4ethylenedioxythiophene)-poly (styrene sulfonate) [PEDOT: PSS] (≥ 99 %, Sigma Aldrich). These reagents are used without further purification. Dichloromethane (CH2Cl2, 99%, Labchem); Nitrobenzene (C6H5NO2, 99.5%, Labchem); ethanol (C2H5OH, 99 %, Labchem);

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Journal Pre-proof nitrogen (N2, 99.99 %, Afrox); argon (Ar, 99.999 %, Afrox); Millipore water system (18.2 MΩ cm) is used to prepare all aqueous solutions in the study. 2.2 Synthesis of heteroatom graphene (HGr) Few layers heteroatom graphene is fabricated through the CVD method using a copper strip with dimensions (1 mm thickness and 2.0 x 6.0 cm) as substrate. The mixture of nitrogen (N2) and argon (Ar) gases are used as purge and carrier (with flow rates of 250 cm3 min-1 and 350

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cm3 min-1, respectively), whereas dichloromethane and nitrobenzene mixture in a 1:1 ratio is

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utilized as carbon and dopant sources. Ar (50 cm3 min-1) is used to purge the quartz chamber

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for 30 min; then the heating of the CVD system through the programmed temperature controller. At the attainment of the synthesis temperature (850oC), the argon gas flow is

) through the mixture of dichloromethane and nitrobenzene for 2 min and finished by

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1

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increased to 350 cm3 min-1. The synthesis experiment started by bubbling N2 gas (250 cm3 min-

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discontinuing N2 flow. The reaction product is cooled to 500oC under Ar flow at 350 cm3 min-1 and subsequently to room temperature under Ar at 50 cm3 min-1.

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2.3 Fabrication of the heteroatom graphene-enzyme hybrid structure The high throughput 2D heteroatom HGr-GOx interface biostructure is fabricated by dispersing 1.0 mg of the as-synthesized HGr in 1% PEDOT: PSS (1 mL). The mixture is sonicated for 2h and then subjected to centrifugations/resuspension to separate the HGr agglomerates. Glucose oxidase solution (10 mg mL-1) is prepared in 0.1 M PBS (pH 7.4) and incubated (at 25oC) for 3h with gentle shaking. HGr-GOx conjugation is achieved by mixing the dispersed HGr (500 µL) with the enzyme solution (500 µL), followed by incubation at 25oC for 3h. 2.4 Electrocatalytic Properties Study

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Journal Pre-proof The fabrication of bioelectrodes is achieved by carefully pre-cleaning and polishing glassy carbon electrodes (GCE) using 0.05, 0.3, and 1.0-micron alumina slurry, respectively. The previously prepared HGr-GOx bioconjugate solution is homogenized by sonication for 1 min, then it is drop-cast (20 µL) on the pre-cleaned electrode and allowed to dry for 8h in the fume cupboard. 2.5 Characterization

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The morphological characterization of the as-synthesized HGr is performed with scanning

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electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force

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microscopy (AFM). The samples for TEM characterization are prepared by dispersing 1mg of

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HGr in 10 mL of distilled water, followed by sonication (30s) to ensure uniform dispersion of HGr. The dispersed HGr (5 µL) is drop cast on 3µm copper grid for TEM observation. The

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TEM is obtained via monochromated beam (60 kV), with over 200 meV FWHM energy

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resolution and a final resolution of about 1Å. The SEM characterization is done using Jeol XL30 with a voltage of 1-30 keV and an image resolution of 2 nm. Raman characterization is

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done using HR800 Raman spectrometer. 2.6 Computational details

In this study, each simulated system consists of a 7 × 4 graphene supercell (64 C atoms) with a doped atom substituting one C atom and subsequently D-glucose molecule adsorbed onto it. The corresponding dopant concentration is about 1.562 %, which is similar to other studies. The same supercells have been used in other studies [19-22]. The dopant concentrations are retained within 5%, which is in agreement with fabricated doped graphene [23, 24]. The geometry optimization and electronic property are carried out using the plane-wave DFT calculations as implemented in the Cambridge Serial Total Energy Package code [25] of Material Studio 2016 [26]. The Perdew-Burke-Ernzerhof function of the generalized gradient 6

Journal Pre-proof approximation [27] is used to evaluate the exchange-correlation energy, while the ultrasoft pseudopotential is used to account for the core-valence electron interactions [28]. The valence electron configurations of C (2s2 2p2), N (2s2 2p3), O (2s2 2p4), Cl (3s2 3p5), and H (1s1) are used during the pseudo-atomic calculations. The Brillouin-zone integration is sampled by the Monkhorst-Pack scheme [29] with 8 × 2 × 1 k-point grids for geometrical optimization. Also, a plane-wave basis set with cut-off energy of 500 eV is employed in the present study. For the density of states calculation, we use a 16 x 4 x 1 Monkhorst-Pack grid and Gaussian smearing

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of 0.05 eV. The Tkatchenko and Scheffler [30] scheme is adopted to consider the weak van der

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Waals interactions in HGr sheets. A layer thickness of 20 Å along the Z-axis direction is

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enough to avoid interaction of periodic images. For self-consistent electron minimization, the

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Broyden-Fletcher-Goldfarb-Shanno scheme [31] with a convergence criterion of 0.05 GPa, 0.001 Å, 0.03 eV/Å, and 10-6 eV/atom for maximum stress, displacement, force, and energy,

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respectively. The adsorption energy (Eads) is defined as:

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𝐸ads = 𝐸(substrate+D−glucose) − 𝐸substrate − 𝐸D−glucose

(1)

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where 𝐸(substrate+D−glucose) are the total energies of N-, O-, and Cl-doped HGr sheets adsorbed with D-glucose, 𝐸substrate is the total energy of isolated N-, O-, and Cl-doped HGr sheets and 𝐸free D−glucose is the D-glucose molecule, respectively. Based on this definition, a more negative Eads corresponds to a more stable adsorption system. We have explored the charge transfer using Hirshfeld charge analysis [32]. 3. Result and discussion The CVD arrangement for the HGr fabrication shown in the Supporting information (Fig. S1), while Fig. S2 (supporting information) is a representative equation of the reaction. Figure 1(a & b) is the TEM characterization result for the synthesized HGr. HRTEM image showed that

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Journal Pre-proof the synthesized material is crystalline with five graphitic layers, which indicates few-layer

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HGr.

Fig. 1. (a, b) HRTEM images of the as-synthesized heteroatom graphene, (c) Tapping mode AFM image of the HGr, and (d) SEM image for the as-synthesized HGr. The tapping mode AFM image of the synthesized material (Fig. 1c) showed thin material with a wide aspect ratio. The material also appears to be crumpled in the middle with some spots all over the surface. These spots can be defects, which have been introduced due to the doping of the material with heteroatoms. The SEM result for the heteroatom graphene (Fig. 1d) showed flat and thin material with a very high aspect ratio, and with similar spots scattered all over the plane of the material, thus confirming the outcomes of the AFM.

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Journal Pre-proof Raman spectrum for the as-synthesized HGr (Fig. 2a) displayed two prominent peaks, the G-

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and D-band at 1570 and 1360 cm-1, respectively.

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Fig. 2. (a) Raman spectra (b) XRD spectra and (c) AFM height profile spectra.

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The D-band is caused by lattice defects, as well as edges with armchair chirality in pristine graphene samples, whereas the G-band can be attributed to E2g (the doubly degenerate zone center) [33, 34]. The shift in the G-band as observed in Fig. 2a may be ascribed to the existence of dopant in the graphene plane. The XRD spectrum for the as-fabricated HGr is shown in Fig. 2b. It is observed that the spectra had four incidental at 37.8o, 44o, 64.6o, and 77.6o, corresponding, respectively, to Miller indices of 021, 101, 203, and 110 (PDF2 reference software) and can be attributed to sp2 graphitic carbon peaks with the bond angle of 120o [35]. The d-spacing and inter-atomic distances are calculated as 11 and 87, and as 2.399540, 2.031700, 1.451650, 1.230800 Å [36, 37], respectively, (with Cu K1 1.54056 Å as fixed slit intensity). The shape of the XRD spectra 9

Journal Pre-proof peaks indicates that there is a crystalline structure in the synthetic material [38]. Fig. 2c is the AFM height profile chart for the synthesized HGr and it shows 1.6 nm as maximum height over the measured area of the as-prepared sample.

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The result of the XPS observations for the fabricated HGr is presented in Fig. 3(a–d).

Fig. 3. XPS spectrum for the as-synthesized HGr showing a) C-1s, b) O-1s, c) Cl-2p, and d) N1s B.E. range spectra. The binding energy (B.E.) range for C-1s orbital (Fig. 3a) is deconvoluted into seven peaks at 290.7, 288.8, 287.2, and 286.3 eV and this is attributed to C=O, C-O, C-O-N, C-Cl groups, respectively, while 285.3, 283.5 and 284.50 eV are attributed to C-1s atoms with sp3 hybridization, C-CH3 groups, and sp2 hybridized C-1s atoms, respectively [39-41]. The B.E. range for O-1s orbital (Fig. 3b) is also deconvoluted into three peaks at 531.57, 533.42, and

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Journal Pre-proof 529.92 eV. The O-1s peaks are ascribed to C=O, -C-O, and -O-Aromatic groups, respectively [42]. For Cl-2p orbital (Fig. 3c), the B.E. range is deconvoluted into three peaks at 198.21, 199.95, and 201.87 eV, which are attributed to anionic and covalently attached chlorine group, respectively [43]. The B.E. range for N-1s orbital presented in Fig. 3d is also deconvoluted into two peaks incidental at 400.17 and 399.01 eV, which are ascribed to substituted nitrogen group and pyridine nitrogen group, respectively [44]. Summary of the percentage composition of the

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constituent groups is given in Table 1.

% Concentration

Reference

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Position

C 1s sp2

284.50

75.61

[44]

C 1s sp3

285.30

6.34

[45]

C 1s Cl

286.30

1.62

[43]

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Name

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Table 1. Summary of XPS results

C-O-N

1.35

288.83

2.02

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C-O

287.20

290.65

1.16

283.46

1.52

400.17

0.10

[44]

399.01

0.25

[42]

531.57

5.40

[43]

O 1s (-C-O)

533.42

1.84

O 1s (-O-Aromatic)

529.92

1.56

Cl 2p (anionic chlorine)

198.21

0.62

Cl 2p (Covalent chlorine)

199.95

0.51

Cl 2p (Covalent chlorine)

201.87

0.10

C-Me N 1s (Graphitic) N 1s (Pyridinic) O 1s (C=O)

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C=O

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Journal Pre-proof The performance of the synthesized HGr as electrochemical interface material in electrochemical biosensing applications is assessed using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) and the results are displayed in Fig. 4(a-c).

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The detailed CV scan results are also presented in Fig. S3 (Supporting information).

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Fig. 4. (a) CV measurement, (b) scan rates, and (c) electrochemical impedance spectroscopy of bare and modified electrodes.

The cyclic voltammetry measurements of our bare and modified electrodes showed narrow anodic and cathodic peak-to-peak potential separation (∆𝐸𝑝 ). It is observed that the electrodes containing heteroatom graphene-based assembly displayed narrow ∆𝐸𝑝 of 85 mV and anodic peak current (𝐼𝑝𝑎 ) to cathodic peak current

(𝐼𝑝𝑐 ) [𝐼𝑝𝑎 : 𝐼𝑝𝑐 ] ratio of 1 Fig. 4a, thus,

demonstrating the reversibility of the redox couple and a fast electron transfer kinetics at the interface [46]. Similarly, for the bare glassy carbon (GC) electrode, GC-PEDOT: PSS, and GCPEDOT: PSS-HGr-GOx modified electrodes, the ∆𝐸𝑝 value is calculated to be ~100 mV, while 𝐼𝑝𝑎 : 𝐼𝑝𝑐 ratio is also ~I for all the electrodes, indicating reversibility of the redox and a rapid

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Journal Pre-proof electron transfer at the interface. Fig. 4b shows that the 𝐼𝑝𝑎 and 𝐼𝑝𝑐 increases lineally with the square root of the scan rates from 10 to 400 mV/s. This agrees with Randle Sevcik equation (Eq. 1) and it also indicates a diffusion-controlled electrode process. 𝑖𝑝 = 𝑘 𝑥 105 𝑛3⁄2 𝐴√𝐷𝜐 𝐶

(1)

Here k = 2.65 x 105 (mol-1 V-1/2), whereas C is the concentration (mol dm-3), n is the amount of electrons transferred, A is the electrode surface area (cm2), D is the diffusion coefficient (cm2 s-

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) and 𝜐 = scan rate (V s-1).

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Electrochemical impedance spectroscopy (EIS) is used to further characterize the modified electrodes. Fig. 4c shows the Nyquist plot for all modified and bare GC electrodes; the inset is

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the circuit equivalent diagram. We observed that the Nyquist plots display two regions for all

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the electrodes, the semi-circular part of the plots corresponds to the kinetically controlled impedance region (which also represents the resistance of the charge transfer in the cell), while

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the linear region indicates the presence of diffusion-controlled impedance in the

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electrochemical cell. The charge transfer resistance (𝑅𝑐𝑡 ) in the cell under consideration can be evaluated by measuring the diameter of the semi-circular region [47]. The PEDOT: PSS/HGr modified electrode had an 𝑅𝑐𝑡 value of about 750 Ω, while the electrode modified with PEDOT: PSS had an 𝑅𝑐𝑡 value of about 1600 Ω in 1.0 mM ferrocene carboxylic acid solution in 0.1 M PBS (Fig. 4c). This can be due to the multi-atom doping of the graphene (the introduction of multiple active sites on the material basal plane), which enhances the electron transfer process at the interface, thus resulting in a lower 𝑅𝑐𝑡 value in the HGr modified system. However, the 𝑅𝑐𝑡 value increased to about 1800 Ω when the enzyme is immobilized on the electrode system (PEDOT: PSS/HGr/GOx). This may be attributed to the relatively insulating effect of the enzyme (protein) and increased kinetics at the interface [48],

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Journal Pre-proof thus resulting in a higher electron transfer resistance. R The equivalent circuit of Randle is used to fit the cell resistance (Fig 4c Inset). The circuit equivalent diagram demonstrates that impedance is caused by mass transfer of ionic species in solution (which is the solution resistance (𝑅𝑠 )), kinetics at the electrode surface (𝑅𝑐𝑡 ), and electric double layer capacitance (C). The

electrobiocatalytic

activity

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the

fabricated

HGr

is

evaluated

using

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chronoamperometric method as electrode material in glucose electrochemical biosensing. At a

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constant voltage of 500 mV, we present the current-time chronoamperometric reaction to consecutive glucose addition using 10 mM ferrocene carboxylic acid as a mediator (in 0.1 M

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PBS) and 0.1 M KCl as supporting electrolyte (Fig. 5a).

Fig. 5. (a) Amperometric response current-time curve and (b) calibration curve. The GC/PEDOT: PSS/HGr/GOx bioconjugate electrode showed a rapid response, thereby increasing the molar concentration of glucose by achieving steady-state current in 3 seconds, which demonstrates a well-defined current response. The fast response can be attributed to the high electrocatalytic performance of the as-fabricated bioelectrode system. The calibration curve (Fig. 5b) showed a linear response from 1.393 to 8.752 mM, with the dynamic response of 0.059 to 11.188 mM, while the limit of detection is estimated at 1.41 mM and the sensitivity value is 381.29 µA/mM/cm2. These findings showed that the fabricated 14

Journal Pre-proof PEDOT: PSS HGr/GOx interfaced bioelectrode displayed excellent electrobiocatalytic efficiency towards glucose sensing with a small detection limit. This response can be linked to the biocompatibility of the fabricated HGr, the introduction of various active sites on the graphitic plane and the subsequent enhancement of the electrobiocatalytic properties is due to the presence of the electronegative element dopants. A comparison showing electrochemical

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results from similar studies is presented in Table 2.

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Journal Pre-proof Table 2. Comparison table for glucose sensing 2

Electrode Materials

Limit of detection (µM)

Sensitivity (µA/µM/ cm )

Linear Range

Ref.

MoS2/AuNPs/GOx

0.042 µM

13.80

0.25 µM - 13.2 mM

[49]

BiOCl-G NHS

0.22 mM

127.2

2 -10 mM

[50]

GC/Ch/Gr/GOD

0.02 mM

37.93

0.08 - 12 mM

[51]

AA-rGO/VS-PANI/LuPc2/GOx-MFH

25 µM

15.31

2 - 12 mM

[52]

Nafion-MGF-GOD

0.25 mM

1 - 12 mM

[53]

ERCGr-GOD/GC

0.02 mM

7.0

2 -18 mM

[54]

rGO/PTZ-O/GDH

-

42

0.5 – 12 mM

[55]

GR-CS/GOD/HRP

1.50

10.547

0.005–5.0 mM

[56]

1.13

1 - 8 mM

[57]

40.8 µM

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0.42 µM – 8 mM

[58]

1.41

381.29

1.4 - 8.8 mM

This study

ERGO/SDS/GOD GOx/poly(2,6-DP)/MWNT/GC PEDOT:PSS/HGr/GOx

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Journal Pre-proof To evaluate the repeatability of the chronoamperometric measurement, the experiments are repeated thrice and the average standard deviation is estimated as 2.31%. The standard deviation is plotted as the error bar in Fig. 5b. The durability of the fabricated bioelectrode is also evaluated by observing the response to 5.0 mM glucose concentration in 10 mM ferrocene carboxylic acid over a period of 7 days while storing the fabricated electrode at 4oC in between uses. No appreciable change in the current response is observed over the seven-day period.

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To further support the experimental results, DFT calculations are used to simulate the

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adsorption behavior of D-glucose molecule on X-doped HGr. According to the different binding sites on the D-glucose molecule, all possible initial configurations are considered.

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After geometry optimization, the most favorable adsorption configurations of D-glucose

(b)

(d)

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adsorbed over the X-doped HGr are shown in Fig. 6.

(c)

(f)

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(e)

N-doped

O-doped C

O

N

Cl-doped Cl

H

Fig. 6. The preferred adsorption configurations (conf 3) of the (a-c) top view and (d-f) side view of D-glucose molecule on X-doped HGr surface. All the bond lengths are in Å. The other adsorption configurations of D-glucose molecule adsorbed onto the on X-doped HGr surface are shown in Fig. S4 and S5. The optimized C-C bond length is around 1.418 Å, and 17

Journal Pre-proof the lattice parameter of pristine graphene is a = 2.435 Å. The obtained bond length and lattice constant are consistent with the experimental value of 1.42 Å [59] and a = 2.46 Å [60], respectively, and reported theoretical results [61, 62]. The 7 x 4 supercell shows bond lengths of 1.428, 1.416, and 1.416 Å for C22-C23, C24-C23, and C23-C52, respectively, around the C atom where the dopants will be introduced, see Fig. 7a.

(a)

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(c)

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C24 1.416 C23 1.428 1.416 C22 C52

ELUMO = -1.89 eV

EHOMO = -5.79 eV

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Fig. 7. Optimized structure of (a) 7 x 4 graphene sheets and (b) D-glucose molecule. (c) HOMO and (d) LUMO plots of D-glucose. The lattice constant of 7 x 4 graphene sheets is a = 17.222, b = 9.840 and c = 23.400 Å. To study the electronic property and geometrical parameters of D-glucose molecule, its crystal structure is optimized to a global minimum. The optimized structure of D-glucose is shown in Fig. 7b. The lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) energies are vital factors in evaluating the chemical reactivity of molecules [63]. The LUMO and HOMO plots of D-glucose are provided in Fig. 7c and d, respectively. The LUMO is mostly localized on the carboxylic acid moiety and specifically over the carbon atom C4 and oxygen O2 (Fig. 7c). The negative LUMO energy of -1.89 eV suggests that D18

Journal Pre-proof glucose is a good electron acceptor. However, the HOMO was on the electron-rich C and H atoms, in combination with the electronegative oxygen atoms (Fig. 7d). The bond distances of Cl-C22, Cl-C24, and Cl-C52 measured as 1.74, 2.42, and 1.74 Å, while the corresponding D-glucose/O-doped HGr system as 1.50, 1.48, and 1.50, which are all much larger than those of 7 x 4 graphene sheets. This is because of the larger ionic radius of Cl (1.81 Å) and O (1.40 Å) atom than that of the C atom (0.15 Å) [64]. The calculated N-C22, N-C24,

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and Cl-C52 bond lengths of 1.44, 1.43, and 1.44 Å, respectively, for D-glucose/N-doped HGr

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complex, show that N atom is slightly projected out of the HGr surface after D-glucose adsorption. This is because of the close ionic radius of N (0.16 Å) to that of C atom (0.15 Å)

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[64]. The Eads of D-glucose adsorption on N-, O-, and Cl-doped HGr surface are calculated as -

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1.69, -1.73, and -1.86 eV, respectively. The calculated Eads suggests strong chemisorption

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process (Eads > 1 eV) [18]. The adsorption energies of D-glucose on X-doped HGr are in the order: Cl (-1.86 eV) > O (-1.73 eV) > N (-1.69 eV). The DFT study suggests that the

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adsorption distance between D-glucose molecule and the Cl-doped HGr surface is the smallest

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with a value of 1.746 Å (or 2.850 Å). Therefore, Cl doping forms the most stable performance towards D-glucose molecule detection. In this study, X-doped HGr exhibited an enhanced sensing performance compared with CNT (5,5) and CNT (8,0) as glucose detection [65]. In order to provide further insights into the adsorption mechanism of D-glucose on X-doped HGr, the electronic density of states (DOS), charge transfer and charge density difference are calculated for the systems [66-68]. The interaction between D-glucose and X-doped HGr is characterized by the contour plots of the charge density difference, see Fig. 8(a-c).

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(b)

(c)

(d)

(e)

(f)

N-doped

O

N

Cl

H

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C

Cl-doped

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O-doped

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Fig. 8. Charge density differences plot of the (a-c) top view and (d-f) side view of preferred

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adsorption configurations (conf 3) of D-glucose molecule on X-doped HGr surface. The yellow

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and blue colors represent the electron density loss and gain regions, respectively. The yellow and blue regions correspond to the charge density depletion (loss of electrons) and

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accumulation (gain of electrons), respectively, with an isovalue of 0.0075 e Å-3. As shown in

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Fig. 8, the distribution of electrons occurred at the interface, as well as at some specific atoms, which suggests that a covalent bond or ionic exist between the D-glucose molecule and Xdoped HGr. It is evident that the D-glucose molecule withdraws electrons from the doped HGr since the D-glucose is surrounded by the blue region at the dopant sites. Moreover, the interaction in D-glucose/Cl-doped HGr system is found to have a more important contribution, which results in the transfer of about -0.20 |e| to the D-glucose molecule. Such a relatively higher charge transfer value is also confirmed by the stronger interaction (more negative adsorption energy) and corresponding electron density difference plot, where a large charge density distribution area is observed across the interface of D-glucose/Cl-doped HGr system. The Hirshfeld charge transfer values of D-glucose adsorption on the N- and O-doped HGr surface are calculated as -0.08 and -0.12, respectively. We observe that all the optimized D20

Journal Pre-proof glucose adsorption on X-doped HGr had a negative charge migration value, which showed that the electrons were transported from the doped HGr surface to the D-glucose [69]. The DOS projected on the doped atoms and D-glucose molecule adsorption on N-, O-, and Cl-

30 20

0 -5 -4 -3 -2 -1

0

1

2

3

30 20 10

30 20 10

0

-5 -4 -3 -2 -1

0

1

2

3

4

5

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Energy (eV)

C 2p Graphene Cl 3p D-glucose

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(c)

5

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Density of States (electrons/eV)

Energy (eV)

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C 2p Graphene O 2p D-glucose

(b)

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40

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C 2p Graphene N 2p D-glucose

(a)

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Density of States (electrons/eV)

Density of States (electrons/eV)

decorated HGr are shown in Fig. 9.

0

-5 -4 -3 -2 -1

0

1

2

3

4

5

Energy (eV)

Fig. 9. PDOS plots of D-glucose molecule adsorbed over the (a) N-, (b) O-, and (c) Cldecorated HGr. The dashed vertical line refers to the Fermi level. For the D-glucose/Cl-doped HGr system (Fig. 9c), the results suggested that there existed strong hybridization between the Cl 3p states and HGr near the Fermi level, which is responsible for the improvement in the adsorption energy of the Cl-doped HGr. However, the DOS analysis of N-doped HGr, as shown in Fig. 9a revealed a small peak for the N 2p states

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Journal Pre-proof around the Fermi level. This explained the smaller adsorption energy than that of O- and Cldecorated HGr. Therefore, we found that Cl 3p states were more reactive near the Fermi level, which increased the adsorption stability of D-glucose molecule. Moreover, the Cl 3p and O 2p peaks overlapped with the D-glucose molecule around -2.0 to -4.5 eV. Thus, the Cl 3d and O 2p orbitals hybridized with D-glucose molecule below and above the Fermi level, which explained their larger adsorption energy than that of N-doped HGr.

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4. Conclusion

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Using carefully designed one-step novel synthesis method, we synthesized multi-atom doped

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graphene. XPS and HRTEM confirmed the presence of oxygen, nitrogen, and chlorine in the

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lattice of the resulting few-layer graphene. CV and EIS verified that the HGr has outstanding electrochemical responses, while chronoamperometry verified that the material has a superior

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electrobiocatalytic properties with a very small LoD of 1.41 mM and sensitivity of 381.29

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µA/mM/cm2, respectively. The effect of N, O and Cl ions on the response of HGr-based Dglucose sensors were further studied using theoretical calculations. The calculated Eads of -1.69,

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-1.73, and -1.86 eV, suggests strong chemisorption for D-glucose adsorption on the doped HGr surface. The combined theoretical and experimental results provide new insights into the mechanism and sensing efficiency of doped HGr sheets towards D-glucose molecule. Conflicts of interest The authors declare no competing financial interest.

Acknowledgement This work was supported by the Faculty of Science, Centre for Nanomaterials and Science Research, Department of Chemical Sciences (formerly Department of Applied Chemistry,

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Journal Pre-proof University of Johannesburg, South Africa), the Research Directorate of Vaal University of Technology, Vanderbijlpark, South Africa, and the National Research Foundation, South Africa (TTK14052167682). We acknowledge the computational support provided by the Centre for High Performance Computing (CHPC), Cape Town. References

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Journal Pre-proof Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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☐The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests:

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Journal Pre-proof Highlights 

A hybrid nanofabricated PEDOT:PSS/HGr showed high sensitivity and low limit of detection.



Cl doping remarkably enhances the chemical activity of HGr sheets towards Dglucose. The electronic properties and charge transfer of the X-doped HGr sheets were

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theoretically studied.

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