A non-enzymatic glucose sensor based on CuO-nanostructure modified carbon ceramic electrode

Accepted Manuscript A non-enzymatic glucose sensor based on CuO-nanostructure modified carbon ceramic electrode

Abdur Rahim, Zia Ur Rehman, Sadullah Mir, Nawshad Muhammad, Fozia Rehman, Mian Hasnain Nawaz, Mustansara Yaqub, Saadat Anwar Siddiqi, Aqif Anwar Chaudhry PII: DOI: Reference:

S0167-7322(17)34280-0 doi:10.1016/j.molliq.2017.10.087 MOLLIQ 8049

To appear in:

Journal of Molecular Liquids

Received date: Revised date: Accepted date:

14 September 2017 15 October 2017 18 October 2017

Please cite this article as: Abdur Rahim, Zia Ur Rehman, Sadullah Mir, Nawshad Muhammad, Fozia Rehman, Mian Hasnain Nawaz, Mustansara Yaqub, Saadat Anwar Siddiqi, Aqif Anwar Chaudhry , A non-enzymatic glucose sensor based on CuOnanostructure modified carbon ceramic electrode. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Molliq(2017), doi:10.1016/j.molliq.2017.10.087

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ACCEPTED MANUSCRIPT

A non-enzymatic glucose sensor based on CuO-nanostructure modified carbon ceramic electrode Abdur Rahim*1, Zia Ur Rehman2, Sadullah Mir*2, Nawshad Muhammad1, Fozia Rehman1, Mian Hasnain Nawaz1, Mustansara Yaqub1, Saadat Anwar Siddiqi1, Aqif Anwar Chaudhry1 1

Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of

Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad,

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Information Technology, Lahore, Pakistan.

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Pakistan E-mail: [email protected]

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[email protected]

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Tel:+ 92 3359249230

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ACCEPTED MANUSCRIPT Abstract: Mesoporous silica-graphite composite (SiO2/C-graphite) was synthesized by the sol-gel technique. The surface area (SBET = 98.93 m²/g), pore volume (0.30 cm³/g) and pore size (12.16 nm) were characterized by BET. The novelty of this work lays in the fabrication of material in which ceramic material (SiO2/C-graphite) was decorated with copper oxide (CuO) nanostructure. SEM images revealed material compactness without phase segregation and EDX mapping showed a homogenous structure. Pressed disk electrode fabricated with

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SiO2/C/CuO nanocomposite material was evaluated as an amperometric non-enzymatic glucose sensor in 0.1 M NaOH solution. The linear response range, sensitivity, detection limit, and quantification limit were 0.02–20.0 mmol L-1, 0.06 µmol L-1, 472 µA mmol-1L-1

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cm-2, and 0.76 mmol L-1, respectively. The electrode response time is less than 1 s with the

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addition of 0.02 mmol L-1 glucose. The electrode is chemically stable, exhibits rapid and excellent sensitivity and does not show any interference from coexisting species present in

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the blood samples. The proposed sensor repeatability was assessed as 1.9 % RSD for ten measurements of 13.0 mmol L-1 glucose solution. The sensor tested to ascertain glucose in blood serum showed to be a promising tool for the future evolution of non-enzymatic glucose

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sensors.

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Keywords: CuO, glucose; non-enzymatic; nanocomposite; sol-gel; Carbon Ceramic Material

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ACCEPTED MANUSCRIPT Introduction Glucose detection is of substantial significance in the diabetes mellitus diagnosis [1]. To control this disease early diagnosis, regular monitoring of glucose level and appropriate treatment is necessary. A rapid, accurate, cheap and highly sensitive glucose sensor is required for reliable and accurate glucose determination in the blood of diabetic patients. In the biosensor industry, it is estimated that 85% of sensor research is related to glucose sensors

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[2]. These sensors are also employed in the quantification of glucose concentration in food products and biofuel cells [3]. Conventional glucose sensors are composed of glucose oxidase

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(GOx) enzyme which oxidize glucose into gluconolactone and hydrogen peroxide (H2O2). The glucose concentration is monitored through electrochemical determination of H2O2

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concentration [4]. Enzyme-based sensors have some limitations such as limited stability, susceptibility to humidity, the lower lifetime of the enzyme, high cost and electrode surface

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fouling by interfering species [5]. To overcome these limitations, a viable research direction is an advancement of enzyme-free glucose detection. In non-enzymatic sensors, glucose is

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directly oxidized on the surface of electrode and is detected by monitoring the electrode current.

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By captivating the advantages of excellent sensitivity, selectivity and stability

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nanomaterial-based non-enzymatic glucose sensors have attracted immense interest. Nanoscale metals, metal oxides, metal oxide doped composites, organic and inorganic composite materials have been used as electrode material. Metals such as Au [6], Ag [7], Cu [8], Pt [9], Ni [10] and their alloys [11-13] based sensors were investigated for glucose direct

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electro-oxidation. Nevertheless, metal based sensors have limitations of high cost, poor selectivity, low sensitivity and fouling of electrode by chloride ions and other intermediates

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present in blood [14]. Conversely, enzyme free glucose sensors based on nano-scale metal oxide are inexpensive, highly stable, selective and sensitive. For example, metal oxides such as MnO2 [15], CuO [16], Cu2O [17], Ag2O [18] and NiO [19] have been commonly used for the advancement of non-enzymatic glucose sensors. Among these metal oxides, copper oxide has numerous advantages for example natural abundance, low production cost, good catalytic and electrochemical properties. Due to these features copper oxide is one of the best materials for sensing. According to the literature, glucose sensors based on copper oxide nanostructures have excellent stability, selectivity, selectivity, and sensitivity [20-22].

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ACCEPTED MANUSCRIPT Nanocomposite materials also exhibit admirable sensing properties. For example, carbon ceramic composites (CCC) are a new class of material possessing high stability, sensitivity and selectivity. Carbon ceramic electrodes (CCEs) are porous, rigid, modifiable and have surface renewability properties which exhibit excellent sensing properties [23]. Doping of metal and metal oxide nanoparticles in composites enhance its sensing properties. These composites have been used for the sensing of different analytes such as NADH [24],

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Oxalic acid [25], Nitrite [26, 27], Dopamine [28-30], Ascorbic acid [30], Dissolved Oxygen [31], Hydroquinone and Catechol [32].

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In the present work, we address the synthesis of a new silica-graphite based nanocomposite and its application for the enzyme-free detection of glucose. Mesoporous

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silica-graphite matrix was synthesized by using the conventional sol-gel method. The high specific surface area and pore volume presented by the silica-graphite that allow

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incorporation of CuO on the surface and ensure the fast diffusion of the target analyte to the active site dispersed throughout the porous structure. To enhance the electrical conductance

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and sensitivity, the synthesized material was decorated with copper oxide nanoparticles. Pressed disks of obtained material SiO2/C/CuO was used to fabricate electrodes for electrochemical oxidation of glucose. We analyzed the performance of this chemical sensor

Material and methods

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for glucose detection in human blood serum.

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Chemicals and reagents

All the chemicals and reagents employed were of analytical grade purity: Ethanol (99.8 %),

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Tetraethyl orthosilicate (TEOS synthetic grade 99 %), Nitric acid (65 %), Hydrofluoric Acid (38-40%) and Copper nitrate were purchased from Merck chemicals. Graphite powder (99 % <45µm), Maltose (99 %), Sucrose (99 %), Sodium hydroxide (99 %), Dopamine (99.99 %) and Fructose (99 %) were obtained from Sigma-Aldrich. Daejung chemicals supplied ethylene glycol (99 %) and Ascorbic acid (above 99 %). Sodium hydroxide (Analytical grade) was purchased from Fischer chemicals. BDH chemicals supplied glucose-D (99.9 %) and Uric acid (98 %).

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ACCEPTED MANUSCRIPT Characterization techniques The prepared samples morphology was analyzed through scanning electron microscope (Tescan Vega-3) operated at 0-20 kV, furnished with a high resolution backscattering and a secondary electron detector. Energy Dispersive X-ray spectroscopy (EDX) was used for the determination of elemental constitution of the specimens. The surface area, pore size and pore volume of SiO2/C-graphite material was measured by BET surface area and porosity

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analyzer (Micromemitics TriStar II 3020).

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Finally, the sensing capabilities of the material were determined by potentiostat machine (Gamry Reference-3000). Cyclic voltammetry technique was applied to measure the

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oxidation potential of the sensor against glucose. By using the amperometric technique, the response of the sensor was recorded at different concentrations of glucose. The sensing

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properties of the materials were examined through electrochemical methods. In electrochemical cell a three-electrode system was used, consisting of Pt wire as a counter

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electrode, saturated calomel electrode (SCE) as a reference electrode, and synthesized material based electrodes as working electrode. The working electrodes were fabricated from pressed disks by pressing the synthesized materials of SiO2/C-graphite, SiO2/C/Cu, and

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SiO2/C/CuO.

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Synthesis of mesoporous SiO2/C-graphite material The mesoporous SiO2/C-graphite matrix was synthesized through the sol-gel process. A 50 mL solution of TEOS (tetraethyl orthosilicate) and ethanol was prepared in 1:1 (v/v)

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proportion. Then 4.0 mL deionized H2O and 0.1 mL concentrated nitric acid was added to the solution and heated to reflux temperature for 3 hours at 300 rpm under constant magnetic

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stirring. After cooling to room temperature, 3.3 g graphite powder was added into the solution. The amount of graphite was 50 wt %, calculated from the expected weight of SiO2. Subsequently, 4.0 mL deionized water and 0.5 mL hydrofluoric acid were added into the solution and sonicated for 30 min for gelation of the material. After gelation, the material was dried at 298 K for 15 days. After that, the material was ground in an agate mortar and washed with ethanol many times to eliminate impurities. Finally, this powder was dried in an oven at 373 K for 3 hours [25].

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ACCEPTED MANUSCRIPT In situ synthesis of CuO nanoparticles on mesoporous SiO2/C matrix Copper oxide nanoparticles were synthesized in situ on mesoporous SiO2/C-graphite to form SiO2/C/CuO composite material by modifying a reported method [33]. For this purpose, 0.35 g copper nitrate was dissolved in 50 mL ethylene glycol and 0.1 M sodium hydroxide solution was added dropwise to maintain pH 9 of the solution. Then 5 g SiO2/C powder was added to the solution and stirred for 30 min at 298 K. The solution was then heated at 463 K

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for 3 hours. After cooling, the solution was filtered and dried at 423 K. Finally, the sample

SiO2/C/CuO nanocomposites.

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Preparation of working electrode and Instruments

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was annealed in the ambient environment at 573 K for 30 min yielding mesoporous

For the preparation of working electrodes of SiO2/C, SiO2/C/Cu and SiO2/C/CuO composite

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materials, pellets of each material were prepared with UTM (Universal Testing Machine) by pressing 60 mg of each sample under the force of 6000 N. The resultant pellets (of diameter 6

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mm, thickness 2 mm, surface area of top 28.27 mm2) were glued with cyanoacrylate ester glue to the end of Pyrex glass tube (diameter 6 mm, length 15.4 cm). A small quantity of graphite powder and copper wire were inserted in a glass tube for electrical contact with a

Results and discussion

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pellet.

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Characterization of mesoporous SiO2/C and SiO2/C/CuO composite materials BET surface area and porosity analyzer investigated the surface area, pore volume and pore

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size of the SiO2/C-graphite matrix. Figure 1 shows adsorption-desorption isotherm of nitrogen. The isotherm shows hysteresis adsorption that is typical for mesoporous materials. The shape of isotherm is similar to H3-type hysteresis loop which shows slit-like pores [34]. The surface area (SBET) and pore volume (pv) of material are 98.93 m²/g and 0.30 cm³/g respectively. The inset figure shows pore size distribution of material, which is maximum at 12.16 nm confirming the mesoporosity (2-50 nm) of material. The morphology of the matrix was characterized by Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDX). SEM images of matrices show granular and flakes structure of surface as shown in Figure 2A and B of 6

ACCEPTED MANUSCRIPT SiO2/C and SiO2/C/CuO material, respectively. These images also illustrated the compactness of materials and gaps between the flakes on the surface. EDX colors mapping of SiO2/C/CuO portrays the homogeneous dispersion of particles, which is associated to the compactness of material (Figure 3A-D). Also, the surface EDX image (Figure 3D), shows that copper is dispersed homogeneously on the sample matrix surface. Figure 3E demonstrates the quantitative elemental composition obtained from the EDX spectrum and the amount of

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copper (in weight and atom %) are 6.02 and 5.23 respectively, such quantity is adequate for electrocatalysis [35].

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Non-enzymatic electrooxidation of glucose on SiO2/C/CuO electrode

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To study the electrochemical measurements for non-enzymatic glucose sensing, a simplified analysis was conducted in the potential range from -0.2 to 0.8 V versus SCE, which is more

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appropriate for amperometric detection of glucose. Figure 4A represents the cyclic voltammograms for the SiO2/C, SiO2/C/Cu and SiO2/C/CuO electrodes in the absence of

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glucose in 0.1 M NaOH supporting electrolyte solution and did not show any redox peak. Figure 4B depicts the cyclic voltammograms for the SiO2/C, SiO2/C/Cu, and SiO2/C/CuO electrodes in the presence of 2 mmol L-1 glucose in 0.1 M NaOH as supporting electrolyte

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solution. As can be seen from the Figure 4B, SiO2/C/CuO based electrode oxidizes glucose

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and shows an oxidation peak at 0.6 V. When compared with the SiO2/C and SiO2/C/Cu electrodes, no oxidation peak of glucose is observed. Furthermore, it is clear that electrodecontaining CuO give a better response to glucose oxidation due to the double bond between

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the copper and oxygen atoms which facilitates the transfer of electrons from the electrode surface to glucose [36, 37].

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The results were further verified on sequential addition of different glucose concentrations. Figure 4C shows the CVs obtained with SiO2/C/CuO electrode at different glucose concentrations. It is detected that the oxidation peak current at 0.6 V increases with the increase in glucose concentration. It proved that the SiO2/C/CuO electrode was sensing glucose non-enzymatically at the surface of electrode. Based on the above discussion the most appropriate and possible mechanism for glucose oxidation on at CuO-nanostructure modified carbon ceramic electrodes in basic medium as shown in equations (1) and (2) according to the previous literature [38, 39]:

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ACCEPTED MANUSCRIPT 𝐶𝑢𝑂 + 𝑂𝐻 − − ⅇ− → 𝐶𝑢𝑂(𝑂𝐻)

(1)

𝐶𝑢𝑂(𝑂𝐻) + 𝐺𝑙𝑢𝑐𝑜𝑠𝑒 → 2𝐶𝑢𝑂 + 𝐺𝑙𝑢𝑐𝑜𝑛𝑜𝑙𝑎𝑐𝑡𝑜𝑛𝑒 + 𝐻2 𝑂

(2)

Amperometric detection of glucose at the modified SiO2/C/CuO electrode

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The non-enzymatic response of SiO2/C/CuO electrode for glucose oxidation was furthermore evaluated through amperometry by successively adding different glucose concentrations.

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Figure 5A shows the amperogram after successive addition of 0.2 mmol L-1 aliquots of glucose solution at 0.6 V applied potential in 0.1 M NaOH, after each 50 s interval. This

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curve was attained in the low concentration range of glucose from 0.02 – 0.1 mmol L-1, which shows the response of proposed sensor to detect glucose in solution with very low

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concentration.

The non-enzymatic electrocatalytic response of the sensor was also examined at higher

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glucose concentration to calculate the linear response range. Figure 5B exhibits the amperogram obtained at higher glucose concentration, after adding 1 mmol L-1 glucose solution into 50 mL of 0.1 M NaOH at 100 and 200 seconds’ interval into the electrochemical

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cell, and the sensor exhibit good response. After that consecutive addition of 2 mmol L-1

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glucose afterward every 100 second interval was added and response of the sensor was observed. The sensor response was outstanding up to 20 mmol L-1 glucose concentration, which proved that the proposed sensor has broad linear range. The inset figure 5B exhibits

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the glucose calibration curve at the SiO2/C/CuO electrode. The proposed sensor gave a linear response within the range of 0.02 – 20 mmol L-1 to glucose with 0.998 correlation coefficient.

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The current response was directly correlated to glucose concentration while the regression equation was i(µA) 62.14+ 472 [glucose] / µA mmol-1. The electrode has a high sensitivity of 472 μA mmol-1 cm−2 and a low detection limit 0.06 µmol L-1 (3 standard deviations of the blank divided by the slope of the calibration curve) for glucose sensing. The quantification limit (LOQ) was 0.076 mmol L-1 using 10s /slope; ‘s’ referring to standard deviation (SD) of the mean value for 10 amperograms of the blank; determined as per IUPAC recommendations [40, 41]. The amperometric response time of SiO2/C/CuO after addition of 0.02 mmol L-1 glucose is less than 1 second, which proves that the proposed sensor is very

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ACCEPTED MANUSCRIPT rapid for the sensing of glucose. Table 1 shows the comparative analysis of the sensing performance of proposed glucose sensor with reported non-enzymatic glucose sensors. Reproducibility, stability and response time of the SiO2/C/CuO electrode Finally, the stability and reproducibility of the sensor were also assessed. The amperometric current responses of five SiO2/C/CuO electrodes were examined at 0.6 V vs SCE and

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compared. The RSD was 2.5 %, proving that the sensor fabrication procedure was exceedingly reproducible. Ten consecutive glucose oxidation measurements on a single

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SiO2/C/CuO electrode produced an RSD of 1.9 %, demonstrating the high stability of the sensor. The stability of sensor was also assessed by measuring its current response to glucose

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after 180 days stored at the temperature of 298 K. There was no noteworthy change detected in the response (data not shown). When kept in air, the sensitivity of the sensor was

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monitored after every 3 days. The SiO2/C/CuO electrode current response was around 96 % of the original electrode that can be predominantly ascribed to the chemical stability of CuO.

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Moreover, most of the non-enzymatic glucose sensors composed of metallic Cu nanostructures lose their catalytic response simply owing to the poisoning by chloride ion. It happens due to the Cu and Cl− reaction and their complex formation. In this way the Cu

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electrode electrocatalytic activity decreases [42]. In contrast, CuO does not enter into

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complexation with Cl− after all the oxygen electronegativity is higher than that of Cl. Also, the current response of SiO2/C/CuO electrode was evaluated by adding 1.0 M KCl solution in the supporting electrolyte solution. The result obtained demonstrates that the SiO2/C/CuO

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electrode peak current towards glucose oxidation remains virtually unaffected (data not shown), showing no poisoning of the electrode by chloride ion.

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Interference study

For the selectivity evaluation of the proposed sensor (SiO2/C/CuO), interfering electroactive species usually co-existing with glucose in real samples (e.g. human blood) such as uric acid, fructose, maltose, sucrose, ascorbic acid, dopamine and ethanol, can cause problems in the accuracy of glucose determination. Figure 6 shows the electrochemical response of the interfering species. In human blood, the glucose concentration is about 30 folds higher than the interference species. The study of interference was conducted with subsequent addition of 3 mmol L-1 glucose, 3 mmol L-1 maltose, 2 mmol L-1 AA, 3 mmol L-1 sucrose,10 mmol L-1 9

ACCEPTED MANUSCRIPT ethanol, 2 mmol L-1 UA and 3 mmol L-1 DA into 0.1 M NaOH solution after every 200 sec at 0.6 V of applied potential. The sensor response for interfering species were minimal which proves the high selectivity of proposed sensor for electrochemical glucose detection.

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Glucose determination in human blood serum

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For analysis of real sample, glucose was detected in blood samples of diabetic patients. Figure 7 demonstrate the amperometric response to glucose in the blood samples,

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after a successive addition of 100 µL of blood serum sample into 25 ml 0.1 M NaOH solution at 100 sec. The electrode responds well, which shows that the sensor was oxidizing glucose

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electrochemically in a blood sample. It is evident that the proposed sensor is efficient for glucose level monitoring in the blood sample. This study confirms the efficiency and high

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sensitivity of the proposed sensor for glucose sensing in the samples. Table 2 depict the results of glucose determination of five distinct serum samples. The results show similarity

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with that measured by a portable glucometer (One Touch ® Life Scan, Inc, USA).

Conclusion

The proposed hybrid platform based on supported CuO nanostructure highly dispersed on

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mesoporous SiO2/C has revealed glucose oxidase enzyme like properties, here assessed toward the glucose oxidation. The proposed non-enzymatic glucose sensor SiO2/C/CuO 1 -1

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exhibited a wide response range (0.02 to 20 mmol L-1), the high sensitivity of 472 µA mmolL cm-2, and limit of detection 0.06 µmol L-1 of glucose. This sensor showed the durability

of 6 months, repeatability, high stability, and short response time less than 1 s for glucose determination. The sensor was highly specific, selective, and preparatory method was simplistic, reproducible and robust. Compared to enzyme-based biosensors, the nonenzymatic sensor SiO2/C/CuO is cost effective, stable and selective demonstrating high capability for practical application. These features can be ascribed to the material’s conductivity and the copper oxide environment in the porous material which make them highly reactive towards glucose molecule. The proposed biosensor is highly selective for 10

ACCEPTED MANUSCRIPT glucose determination without showing any interference from other co-existing compounds in the human blood. Certainly, this sensor was successfully used for the determination of glucose in human blood serum. The enzyme-like properties of the SiO2/C/CuO shows that this mesoporous platform is potentially useful for the development of biosensing devices.

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Acknowledgement

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Science and Technology, Pakistan for financial support.

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The authors are indebted to the Higher Education Commission (HEC) and Ministry of

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[32] T.C. Canevari, L.T. Arenas, R. Landers, R. Custodio, Y. Gushikem, Simultaneous electroanalytical determination of hydroquinone and catechol in the presence of resorcinol at an SiO2/C electrode spin-coated with a thin film of Nb2O5, Analyst, 138 (2013) 315-324.

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[33] Y.-W. Hsu, T.-K. Hsu, C.-L. Sun, Y.-T. Nien, N.-W. Pu, M.-D. Ger, Synthesis of CuO/graphene nanocomposites for nonenzymatic electrochemical glucose biosensor applications, Electrochimica Acta, 82 (2012) 152-157.

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[34] K.S. Sing, Reporting physisorption data for gas/solid systems with special reference to the determination of surface area and porosity (Recommendations 1984), Pure and applied chemistry, 57 (1985) 603-619.

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[35] A. Rahim, N. Muhammad, U. Nishan, U.S. Khan, F. Rehman, L.T. Kubota, Y. Gushikem, Copper phthalocyanine modified SiO 2/C electrode as a biomimetic electrocatalyst for 4-aminophenol in the development of an amperometric sensor, RSC Advances, 5 (2015) 87043-87050. [36] P. Guan, Y. Li, J. Zhang, W. Li, Non-Enzymatic Glucose Biosensor Based on CuO-Decorated CeO2 Nanoparticles, Nanomaterials, 6 (2016) 159. [37] S. Muralikrishna, K. Sureshkumar, Z. Yan, C. Fernandez, T. Ramakrishnappa, Non-enzymatic amperometric determination of glucose by CuO nanobelt graphene composite modified glassy carbon electrode, Journal of the Brazilian Chemical Society, 26 (2015) 1632-1641. [38] C. Zhou, L. Xu, J. Song, R. Xing, S. Xu, D. Liu, H. Song, Ultrasensitive non-enzymatic glucose sensor based on three-dimensional network of ZnO-CuO hierarchical nanocomposites by electrospinning, Scientific reports, 4 (2014).

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ACCEPTED MANUSCRIPT [39] G. Wang, X. He, L. Wang, A. Gu, Y. Huang, B. Fang, B. Geng, X. Zhang, Non-enzymatic electrochemical sensing of glucose, Microchimica Acta, 180 (2013) 161-186. [40] A.M. Committee, Recommendations for the definition, estimation and use of the detection limit, Analyst, 112 (1987) 199-204. [41] A.A. Alshaheri, M.I.M. Tahir, M.B.A. Rahman, T. Begum, T.A. Saleh, Synthesis, characterisation and catalytic activity of dithiocarbazate Schiff base complexes in oxidation of cyclohexane, Journal of Molecular Liquids, 240 (2017) 486-496.

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[42] L.-C. Jiang, W.-D. Zhang, A highly sensitive nonenzymatic glucose sensor based on CuO nanoparticles-modified carbon nanotube electrode, Biosensors and Bioelectronics, 25 (2010) 14021407.

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[43] J. Wang, W. Bao, L. Zhang, A nonenzymatic glucose sensing platform based on Ni nanowire modified electrode, Analytical Methods, 4 (2012) 4009-4013.

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[44] K.-J. Chen, C.-F. Lee, J. Rick, S.-H. Wang, C.-C. Liu, B.-J. Hwang, Fabrication and application of amperometric glucose biosensor based on a novel PtPd bimetallic nanoparticle decorated multiwalled carbon nanotube catalyst, Biosensors and Bioelectronics, 33 (2012) 75-81. [45] X. Yang, J. Bai, Y. Wang, X. Jiang, X. He, Hydrogen peroxide and glucose biosensor based on silver nanowires synthesized by polyol process, Analyst, 137 (2012) 4362-4367.

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[46] X. Zhang, Q. Liao, S. Liu, W. Xu, Y. Liu, Y. Zhang, CuNiO nanoparticles assembled on graphene as an effective platform for enzyme-free glucose sensing, Analytica Chimica Acta, 858 (2015) 49-54.

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[47] A. Sun, J. Zheng, Q. Sheng, A highly sensitive non-enzymatic glucose sensor based on nickel and multi-walled carbon nanotubes nanohybrid films fabricated by one-step co-electrodeposition in ionic liquids, Electrochimica Acta, 65 (2012) 64-69.

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[48] M. Li, X. Bo, Y. Zhang, C. Han, L. Guo, One-pot ionic liquid-assisted synthesis of highly dispersed PtPd nanoparticles/reduced graphene oxide composites for nonenzymatic glucose detection, Biosensors and Bioelectronics, 56 (2014) 223-230.

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Figures and Tables captions Graphical Abstract. Non- enzymatic biosensor based on SiO2/C/CuO for glucose oxidation

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Figure 1. N2 adsorption–desorption isotherms of SiO2/C, Inset figure pore size distribution curve

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Figure. 2. SEM micrographs of SiO2/C (A) and SiO2/C/CuO (B)

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Figure 3. EDX color mapping of Carbon, Oxygen, Silicon and Copper (A-D) for

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SiO2/C/CuO, Quantitative elemental spectra of SiO2/C/CuO (E)

Figure 4: Cyclic voltammograms of working electrodes (SiO2/C, SiO2/C/Cu, and SiO2/C/CuO) obtained in the absence (a), and the presence of 2 mmol L-1 glucose (b). Cyclic glucose (c).

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voltammograms of SiO2/C/CuO electrode obtained in the presence of 0, 1, 2, 3, 4 mmol L-1 Experimental conditions: 50 ml of 0.1 M NaOH solution as supporting

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electrolyte, scan rate 10 mV sec-1.

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Figure 5. (A). Amperogram of SiO2/C/CuO electrode at 0.6V in 0.1 M NaOH solution with successive addition of 0.02 mmol L-1 glucose after every 50 sec. (B) A program of SiO2/C/CuO electrode at 0.6V in 0.1 M NaOH solution with the successive addition of 1

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mmol L-1 glucose at 100, 200 sec and after that addition of 2 mmol L-1 after every 100 sec. Inset is the calibration curve of current vs. concentration of glucose at the SiO2/C/CuO

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Figure 6. Amperometric response of SiO2/C/CuO electrode with successive addition of 3 mmol L-1 glucose, 3 mmol L-1 maltose, 2 mmol L-1 AA, 3 mmol L-1 sucrose,10 mmol L-1 ethanol, 2 mmol L-1 UA and 3 mmol L-1 DA into 0.1 M NaOH solution Figure 7. Amperometric response of SiO2/C/CuO electrode with 100 µL successive addition of blood Serum in 25 ml of 0.1 M NaOH solution at applied potential of 0.6 V

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ACCEPTED MANUSCRIPT Table 1: Comparison of sensing performance of proposed glucose sensor with other reported glucose sensors Table 2. Determination of glucose concentration in the human blood serum sample

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ACCEPTED MANUSCRIPT Table 1: Comparison of sensing performance of proposed glucose sensor with other reported glucose sensors

Ni–MWCNT CS/GA /GOx/Nafion/PtPd– MWCNT GOD–PVPb –Ag nanowire CuNiO-GRc/GCE

3 4 5 6 7

Ni-MWNT/GCE PtPd-IL-RGOd SiO2/C/CuO

Sensitivity (µA mM−1 cm−2) 367

Linear range (µM) 1 - 5000

Ref.

31 N/A 16 0.89

112 22.4 225. 75 67.19

62–14000 2000–20000 50- 16000 3.2-17500

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2 0.06

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100-22000 20–20000

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Chitosan-glutaraldehyde-glucose oxidase (CS/GA /GOx), bPVP, Polyvinylpyrrolidone. c Graphene (GR), d Ionic Liquid-reduced graphene oxide (IL-RGO)

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LOD (µM) 0.89

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Measured by the proposed sensor (mM)

Measured by the glucometer (mM)

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98.90 100.0 99.29

ACCEPTED MANUSCRIPT Highlights

 We synthesized carbon ceramic SiO2/C materials and modified with CuO nano-structure  Non-enzymatic sensor for glucose

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 The sensor showed a highly sensitive and selective response for the assay of glucose in blood serum

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 The sensor did not show any inference from co-existing species present in blood serum

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