Hydrothermal Synthesis of Nitrogen-Doped and Excitation-Dependent Carbon Quantum Dots for Selective Detection of Fe3+ in Blood Plasma
, Taha Tavaci 4, Asli Yilmaz 1,* and Mehmet Yilmaz 2,3,*
Round 1
Reviewer 1 Report
In this article, the authors prepared and tested N-doped CQDs for Fe3+ sensing and antibacterial activity. In general, the article can be reconsidered for publication after a major revision.
1) There are a lot of studies dealing with Fe3+ sensing in blood, cells, etc. Please clearly state what is the unique point in your manuscript.
2) Experimental methodology is not reproducible. The authors used a variable mass ratio, but what was the total mass of reagents dissolved in 10 mL of water? What was the purity of reagents?
3) Quantum yield is excitation-dependent. At which excitation wavelength the QY is equal to 48%?
4) CQDs can be also sensitive to Cu and Cr elements. Check the corresponding elements for selectivity!
5) I don't see any statistical analysis (Fig. 5d, Fig. 6b) How many samples were tested per specific concentration? Add corresponding error bars!
6) What are LOD and LOL for Fe3+ sensing for these CQDs?
7) Introduction part can be improved with highly relevant studies such as doi: 10.1016/j.sbsr.2019.100271 and doi: 10.1016/j.cplett.2018.05.048.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
In the paper entitled “Hydrothermal Synthesis of Nitroen-Doped and Excitation-Dependent Carbon Quantum Dots for Selective Detection of Fe3+ in Blood Plasma” the authors report the synthesis and characterization of fluorescent CQDs usig a novel method using urea and lactic acid as precursors. A detailed analysis about the influence of the synthetic parameters on the characteristics and properties of the prepared nanostructures was carried out. As well, the stability, cytotoxicity, antibacterial activity and sensing capability of the synthesized CQDs were also analyzed.
In general, I found the work suitable for its publication in Coatings after minor revisions. Following I expose some specific and general suggestions that could improve the paper and which I would like the authors to address before consider resubmission.
Line 39: put commas in the sentence and change “has” by “have”.
Line 88-89: I do not consider it necessary to introduce abbreviations when they are not going to be used during the manuscript (AAS or ICPMS, for instance).
Line 102: Introduce preposition: “The effect OF…”. In general I suggest a revision of the English style. Although the authors use short sentences as appropriate, many of them are not well-constructed.
I suggest to introduce a brief critical discussion about other nanoparticulated systems used for iron sensing in plasma already reported in literature in the introduction. Moreover, since you highlighted the novelty of using urea and lactic acid as precursors, I suggest to detail the advantages of this strategy (biocompatibility, cheaper method, etc.)
In order to avoid the introduction going on too long after addressing my previous comment, I think the enumeration of techniques used to characterize the CQDs can be removed, as well as the short description of top-down fabrication strategies.
Experimental section: Report centrifugation speeds in RCF (not RPM) to make your protocols reproducible for the scientific community.
Experimental section: What were the concentrations of urea and lactic acid used to prepare the CQDs? You provided the ratio between both compounds (1:1, 1:3 or 3:1) and the volume os solvent (10 mL), but not the concentration. Indicate the concentrations of the precursors for each condition in the form of mg/mL, molarity or similar.
Lines 138, 147, 195, 333, etc.: I suggest removing the articles “The” from the titles of all these sub-sections.
Why MRC5 and A549 cell lines were selected for citotoxicity studies?
In the first part of results and discussion section I missed some references to support the interpretation of the different UV-Vis spectra (for instance in lines 200-204, 228-233, etc.).
Which was the preursors ratio used in the study about the influence of synthesis time in the fromation of CQDs? In the text it was indicated 1:1 ratio (line 197), but in Figure 1 legend the indicated ratio was 1:3.
I suggest to merge Figures 1, 2 and 3 in only one Panel about synthesis optimization. It is easier for the readers to see all the information in a single larger panel (similar to Figure 2 about further characterization of CQDs, which is very attractive and explanatory).
Increase the size of the titles and the numbers of the axes in the graphs; they are difficult to see being so small. Apply in all the figures of the manucript.
Provide the values of CQDs core diameter, the interlayer spacing, etc. in the form of average value ± standard deviation.
In my opinion the Figure S1 is highly-relevant in the scope of the developed strategy and should be incorporated in one of the panels of the manuscript and not in Supporting Information.
The letters “b” and “c” to identify the associated sub-figures are not placed in figure 4. Moreover, I suggest to replace the TEM image by other with higher magnification. Or at least incorporate a high-magnification TEM image in Supporting Material.
"Zoom in" to high percentages or change figure 5a to a dot plot to better see the differences between the fluorescence intensitty of the CQDs in the presence of the different analyzed metallic elements.
Following my previous comment about Figures 1, 2 and 3, I also suggest merging Figures 5 and 6 on one side, and Figures 7 and 8 on the other. The current Figures 5 and 6 both explain the experiments of iron sensing, while cytotoxicity and antibacterial assays could also be combined in only one panel.
Can you speculate why the viability degree was markedly higher in the A545 cell line than in the MRC5 one?
Critical comment: what about nitrogen doping? You highlighted the positive effect of N-doping in the abstract and the introduction of the manuscript (even in the title), but then you didn´t explian in detail where the nitrogen atoms incorporated in the structure of the designed CQDs come from!!! I supposse the origin of nitrogen doping is the use of ureal as precursor, but you should specify this point with much more detail and clarity. And even, following one of my previous comments, you should highlight that it is another advantage of using urea as precursor to preparare the CQDs.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
A revised manuscript can be accepted for publication.
