A simple and one-pot synthetic procedure using two different sources has been demonstrated to prepare heteroatoms doped reduced graphene oxide such as nitrogen-doped reduced graphene oxide (N-RGO) and sulfur-doped reduced graphene oxide (S-RGO). The N-RGO has been hydrothermally synthesized using urea as nitrogen precursor, wherein the S-RGO has been synthesized using dimethyl sulfoxide (DMSO) as sulfur precursor. The successful N-doping, S-doping and other physicochemical properties of N-RGO and S-RGO have been confirmed with different spectroscopic and electrochemical techniques. The results indicated that doping into the graphene structure exhibits a high conductivity and a better transfer of charge. Moreover, heteroatoms doped graphene (N-RGO and S-RGO) and graphene-related materials (RGO) have been applied for the individual detection of uric acid (UA). Interestingly, the N-RGO exhibited a lower limit of detection (LOD, S/N = 3) of 2.7 10– 5 M for UA (10–1000 μM) compared with undoped RGO and S-RGO. Furthermore, the simultaneous detection of UA in the presence of Xanthine (XA) has been demonstrated a wide linear range of detection for UA: 10–1000 μM, with unchanged concentration of XA to be 200 μM, and exhibited a low limit of detection of 8.7 10− 5 M ( S∕N = 3) for UA. This modified sensor based on N-RGO has revealed a high selectivity and reproducibility thanks to its large surface area, high catalytic properties, and chemical structure. Indeed, the practical applicability of the proposed sensor has been evaluated in milk samples even in the presence of high concentrations of UA with satisfactory results.

Synthesis of heteroatoms doped reduced graphene oxide for the electrochemical determination of uric acid in commercial milk
    Abstract
        Graphical Abstract
    1 Introduction
    2 Materials and methods
        2.1 Reagent and solution
        2.2 Apparatus
            2.2.1 Fourier-transformed infrared spectroscopy (FTIR)
            2.2.2 Raman spectroscopy (Raman)
            2.2.3 X-ray Photoelectron Spectrometer (XPS)
            2.2.4 Sessile drop method (contact angle measurements)
            2.2.5 Electrochemical measurements
        2.3 Hydrothermal synthesis of N-RGO and S-RGO
        2.4 Electrode modifications
        2.5 Real sample preparation
    3 Results and discussion
        3.1 Chemical and surface characterization of S-RGO and N-RGO
            3.1.1 FTIR spectroscopy
            3.1.2 Raman spectroscopy
            3.1.3 XPS characterization
            3.1.4 Wettability tests
        3.2 Electrochemical characterization
            3.2.1 Cyclic voltammetry analysis
            3.2.2 Electrochemical impedance spectroscopy analysis
        3.3 Uric acid detection
            3.3.1 Individual determination of UA on different electrodes
            3.3.2 Electrochemical activities of UA in presence of XA
            3.3.3 Simultaneous determination of UA at N-RGOSPCE
            3.3.4 Interferences
    4 Sensitivity, repeatability, and reproducibility of the N-RGOSPCE electrochemical biosensor
    5 Determination of UA in real sample (milk sample)
        5.1 Real application in 100-time diluted milk
        5.2 Real application in 10-time diluted milk
        5.3 Comparison
    6 Conclusions
    Acknowledgements 
    References

• Fatma Besbes(Laboratory of Interfaces and Advanced Materials, Faculty of Science of Monastir, University of Monastir, 5019 Monastir, Tunisia)
• Zouhour Hsine(Laboratory of Interfaces and Advanced Materials, Faculty of Science of Monastir, University of Monastir, 5019 Monastir, Tunisia)
• Rym Mlika(Laboratory of Interfaces and Advanced Materials, Faculty of Science of Monastir, University of Monastir, 5019 Monastir, Tunisia)