## 3 Results and Discussion
### Electrooxidation of Glucose  
The oxidation mechanism of glucose was firstly studied by using cyclic voltammetry. Figure 6 represents the cyclic voltammetry profile of the commercial gold, copper, and copper oxide electrodes. All electrodes were conditioned with cyclic voltammetry with 0.1 M NaOH before use.  
As it can be seen in Figure 6, copper oxide provides a higher amperometric signal when 5 mM glucose is oxidized in basic media. CuO is directly oxidized to CuOOH, a strong oxidizing agent. The Cu (III) species then electrochemically oxidized glucose to gluconolactone, responding to the oxidation peak of glucose's oxidation reaction, as shown in Figure 6. In the case of copper, this metal needs to be oxidized to Cu (III) in two reaction steps. In the case of gold and bare carbon, they do not present significant catalytic activity for glucose oxidation.  
Cyclic voltammetry was also employed to determine glucose in different concentrations using the reported electrodes as the working electrode. Based on the cyclic voltammetry profiles in Figure 6, the glucose oxidation potential is fixed in 0.55 V. Figure S4  
Figure 6: Cyclic voltammetry (1 cycle, \(-\)0.00 to 0.85 V vs. Ag/AgCl) with 5 mM glucose in 0.1 M NaOH with copper, copper oxide gold, and glassy carbon electrode.  
represents cyclic voltammetries for a copper oxide electrode from 1 to 10 mM of glucose. These data were used to determine the calibration curve of the electrode.  
All experiments were replicated three times keeping the same conditions: temperature, pH, cycles voltage, and conditioning process. The calibration curves in Figure 7 show a linear range of up to 5 mM of glucose in all cases. For copper oxide electrode, the linear equation is y (\(\mu\)A) = 108.48 \(\times\) (mM) + 8.59 with a regression coefficient of 0.99. In the case of copper, the equation is y (\(\mu\)A) = 54.65 \(\times\) (mM) + 36.06. The gold commercial electrode does not show a significant sensitivity for glucose.  
The amperometric signal starts to decline because the active surface of the electrode is saturated with glucose. The sensitivity reported in the linear ranges is 904 \(\mu\)A\(\cdot\)mM\({}^{-1}\cdot\)cm\({}^{-2}\). The limit of detection (LOD) was 0.002 mM, it was estimated by using (Equation (10)):  
\[LOD=3.3\cdot\frac{s_{y}}{S} \tag{10}\]  
where \(S_{y}\) is the standard deviation of the regression line and \(S\) is the slope.  
Blood and interstitial fluid normal glucose values go from 4 mM to 11 mM of glucose [27,28]. However, other biological fluids present glucose maximum values lower than 5 mM, this is the case of pleural, ascites, and spinal liquid besides urine and tears [29, 30, 31, 32, 33].  
Table 1 shows results from similar non-enzymatic electrodes. The developed copper oxide electrode provides good linearity and high sensitivity compared to similar electrodes reported in literature.  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Electrode** & **Linear Range (mM)** & **LOD** & **Sensitivity** & **Media** & **Ref** \\  & & **(\mu\)M** & **(\(\mu\)A\(\cdot\)mM\({}^{-1}\cdot\)cm\({}^{-2}\))** & **NaOH** & **Ref** \\ \hline Cu/Graphene & 0.02–2.3 & 1.39 & 379.71 & 0.1 M & [34] \\ Cu\({}_{2}\)O & 0.05–6.0 & 0.13 & 277.1 & 0.1 M & [35] \\ Cu/Polyaniline/Graphene & 0.001–3.7 & 0.27 & 150 & 0.1 M & [36] \\ CuO/NC\({}^{1}\) & 0.001–2.55 & 0.14 & 272.6 & 0.1 M & [37] \\ CuO/GCE & 0.005–5.89 & 0.012 & 1467.32 & 0.1 M & [38] \\ CuO/stainless & 0–3 & N/A & 1017 & 0.1 M & [21] \\ CuO/GCE & 0–5 & 0.002 & 904 & 0.1 M & This work \\ \hline \hline \end{tabular}
\end{table}
Table 1: Copper and copper oxide-based electrodes for glucose sensing.  
Figure 7: Calibration curve of current response vs. glucose concentration for copper oxide, copper, and commercial gold electrode.