Tin, Titanium, Tantalum, Vanadium and Niobium Oxide Based Sensors to Detect Colorectal Cancer Exhalations in Blood Samples

Round 1

Reviewer 1 Report

The research presented in this work is valuable, however, it cannot be considered for publication in its current form. The paper is difiicult to follow and, therefore, the results are unclear.

Some suggestions for the resubmission:

• Introduction should contain only the context and motivation of the work, including related works (I would avoid subsections here)
• Materials and methods section should be included before the results section (some of the information in the intro subsection can be moved here)
• Results section must be carefully checked, there are some concepts that are not defined (e.g.: normalized response)
• Conclusions are missing

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript " Tin, Titanium, Tantalum, Vanadium and Niobium oxide based sensors to detect colorectal cancer exhalations in blood samples"describes the detection of volatile organic compounds (VOCs) as indicators for the detection of Colorectal cancer biomarkes  using a device designed and patented by the authors for it in samples of different kind as i.e blood, biopsy, saliva, breath, ...., in this work they try to explain the Results obtained when blood samples are analyzed. This  work is undoubtedly very interesting, although its reading is complex and some more data should be included in order to contribute to the advancement of science in this relevant aspect, such as cheap non-invasive analysis .To improve understanding of the text, the authors have to introduce the following changes:
1. They must rewrite the text from the beginning, showing that this study is carried out with equipment designed and patented by them and establish what studies have been carried out so far with this equipment and what achievements have been achieved and what problems it presents.
2. If the patent has already been applied to blood samples, what is new that the authors intend to contribute with this work?
3. section 4: Materials and Methods should go before section 2: Results.
4. The authors should indicate how much blood they use to carry out the study.
5. Clearly indicate which VOC compounds are detected in this study.
6. The authors are based on different chemoresistive gas sensors, published in previous papers (sensors 2014, 14, 18982-92), clearly indicate  any modification has been included.
7. There are references that the authors must include:
Sensors and Actuators B, 271 (2018) 203-214.
Proceedings 2019, 14, 34; doi: 10: 10.3390 / proceedings2019014034
and comment on their relationship to the subject of the work.
8. When statistical treatment is applied to the results of the analysis, they must make it clear, how many samples analyzed, replicas of each sample ,.
9. How long does it take to get the test result?
10. What would be the approximate cost of the analysis.
11. Make a comparison of results with a reference method or with the methods currently proposed. 

After these modifications the work could be considered for its publication in this journal

 

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

Dear authors.

In your paper you describe four sensors evaluated for discriminate blood samples coming from subjects with and without colorectal cancer. The study is interesting and the device and sensors used seem promising. But I have some concerns that force me to mark this for a mayor revision.

I feel that the evaluation of the discriminating power lacks rigor and could add more value to readers. I think the equation 3 is incorrect because it doesn't take into account the variability of the measurements. You should use a more standard statistical analysis to evaluate this discrimination power. Perhaps a t student test and you could even calculate the statistical power, although the power is usually skipped so I feel it is not necessary. (https://en.wikipedia.org/wiki/Power_of_a_test).

Also, you should frame the accuracy, sensitivity and specificity of the method comparing it to other diagnosing methods currently used. Also, could be interesting to read an evaluation of the usability/usefulness of these values in the health practice.

Finally, there is no analysis of other factors that could be correlated to the result of the test. For example sex or age. How are those correlated to the results of the sensors. Also, are CRC patients well distributed among age and sex?

   

Other small comments are as follows:

Line 54. References to all these techniques would be useful.

Line 86: You are mixing typical sensors description with the concrete building of your sensors. I think it could be better to re-emplace "typical" for "the sensors used in this study"... Or split the paragraph in two, description of typical and the concrete sensors used in this study.

Also might be useful say at the end that you will further describe the building of the sensors in section 4.

Line 89: What thickness do you consider thick?

Line 91: Missing word "deposited" between "contacts" and "with"?

Line 106: I'm not native English speaker, but the usage of "flanked" seems a bit odd in this context, please check.

122: I doubt a 1.2 micron filter can eliminate volatile compounds, but it is probably more suited to remove particulate matter above 2.5 microns (PM2.5)

125: "carry" instead of "entrap" 

129: I think there is some strange wording here: "independent of the..." 

Equation 1: Have you tried to use Response=(Vg-Vo)/Vo ? It could increase the relative response of some sensors.

137: Please introduce LSS4 acronym, maybe in line 128?

139: Since you are using a classic headspace volatile extraction method, I think is better to use "headspace" word instead of "exhalation".

Figure 3: I think there are some quantization steps in the plot. Could this affect the results of the analysis or the discrimination power?

Figure 4: Not all the sensors are in a steady state at the time of calculating the response. I think that instead of calling "stead state" you should use "end of exposition". And then explain why did you use that exposition time (5 minutes?)

Line 225: There are very few details of the fabrication process of the sensors and their properties. Could you describe in a bit more of detail or include a reference? I would like to know thickness of the oxide layers, synthesis method of the oxides particles (of provider), times of the firing process...

Line 238: There is, also, very few data about the samples. I would like to know the amount of blood used? The volume of the head space on the vials?  Flow rate of carrier gas thought the vials with the blood? How much time the blood sample was let rest in the sample chamber generating head space?

I hope all these comments helps you to make the paper better.

Warm regards!

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Authors have significantly improved their manuscript. However, they should enlarge conclusions section, highlighting the main advances of their work before its publication.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

I consider that the manuscript in present form can be accepted for publication in this journal.

Author Response

We are grateful to the reviewer to have accepted the revised version of our manuscript as it is. 

Reviewer 3 Report

Dear authors

Thank you for all the good and detailed responses to all the points. I still have some minor points to address, but the paper is ready to be published. Thank you again.

1 - Please include the details of the determination of the steady state in the paper, perhaps before line 124 or perhaps in Figure 1 text...     

e.g.: "Steady state (when voltage did not change more than 2/3 mV in 30 seconds)... "

2 - Equation 2 vs line 129 Rg or Rt ?

3 - Line 217: Maybe is fired?

4 - Please include some sentence about co-factors (Age or sex), perhaps in conclusions when describing future work

e.g.: (...where some other cofactors (like sex or age) will be considered...).

5 - I still think is better to say that the filter stops particulate matter or aerosols. Usually volatile compounds are referred to gaseous substances (usually organic) while other things like microorganisms are particulate matter ( https://www.sciencedirect.com/science/article/pii/S0045653518315534?via%3Dihub )

Thank you very much for the work in the responses

Best regards

 

Author Response

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Author Response File: Author Response.pdf