Citrus/urea nitrogen-doped carbon quantum dots as nanosensors for vanillin determination in infant formula and food products via factorial experimental design fluorimetry and smartphone

Vanillin is a flavouring agent that is prohibited for use in infant food products with ages lower than 6 months. Excessive vanillin usage could lead to eating disorders, nausea, headache, and vomiting. Therefore, it is essential to control the contents of vanillin in food samples, especially in infant formula. Here, we developed a highly sensitive nanosensor for vanillin based on using green synthesized highly fluorescent (QY = 29.5%) N-doped carbon quantum dots (N-CQDs) as a turn-off fluorescent nanoprobe. The N-doped CQDs synthesis was adopted using citrus bulb squeeze extract and the commonly used fertilizer, urea, as substrates. After mixing with vanillin, the fluorescence of the N-CQDs was largely quenched in a vanillin concentration-dependent manner. The sensing conditions were optimized by quality-by-design using a two-level full factorial design (22 FFD). The N-doped CQDs could detect vanillin in the range 0.1-12.0 mu g/ml with a limit of detection of 0.013 mu g/ml. Next, a smartphone imaging-based assay combined with a UV chamber was adopted and applied for vanillin determination. This simple detection technique showed sensitivity similar to that of the conventional fluorimetric method. Both conventional and smartphone-based methods were successfully applied for the determination of vanillin in infant milk formula and biscuits and could detect real vanillin concentrations in the analyzed samples with high % recoveries (94.5% to 105.5%). At last, the biocompatibility of the newly synthesized N-CQDs was tested, and it was found to be an excellent candidate for cancer cell imaging. The current study introduces a highly sensitive N-CQDs-based fluorescent nanosensor for the determination of vanillin in infant formula and food samples. A rapid microwave-assisted approach was adopted for the synthesis of N-CQDs in only 5 min using orange bulb extract and urea as cost-effective bio-derived and available substrates. A smartphone imaging-based assay was also adopted and applied for vanillin determination.image