Recent Progress and Perspectives on Non-Invasive Glucose Sensors

Round 1

Reviewer 1 Report

The use of terms 'type I' and 'type II' should be replaced by 'type 1' and 'type 2'.

Ear complications of diabetes are not widely recognised, I would replace with nerves (neuropathy)

Author Response

We would like to thank the reviewers for their comments on our work and their suggestions for how to improve the manuscript. We have responded to each of the reviewer comments below and where we have made a revision of the manuscript, these changes are highlighted with ‘track changes’. If you have any questions regarding our rebuttal or revisions, please do not hesitate to contact us.

Reviewer 1

Thank you for your comments on our work and suggestions for improvement. We have responded to your comments in the section below.

Reviewer #1: The use of terms 'type l' and 'type Il' should be replaced by 'type 1' and 'type 2'.

Thank you for highlighting this. We agree that ‘type 1’ and ‘type 2’ are the more appropriate names and have updated the manuscript to replace any use of ‘type I’ and ‘type II’ with ‘type 1’ and ‘type 2’.

Reviewer #1: Ear complications of diabetes are not widely recognised. I would replace with nerves (neuropathy).

Thank you for your suggestion here. We have amended the text to replace ‘ears’ with ‘nerves (neuropathy)’ and, consequently, have replaced reference no.8 with a review article on the subject.

Reviewer 2 Report

In this manuscript, the authors introduce analyses of glucose via various spectroscopies, namely, mid/near-infrared absorption, Raman scattering, optical coherence tomography, optical rotation, and photoacoustic spectroscopy. These techniques are explained in terms of the basic theory and the application for quantitative detection of glucose with and without figures, respectively. This tutorial review will be useful for the study on non-invasive sensor of blood glucose which applied to diabetes mellitus. 

In p.3, however, the explanation for scattering (Fig.1) can be applied to also fluorescence. Moreover, it is written as "... subsequently re-emits a photon". This seems to explain fluorescence. For scattering, "immediately re-emits" may be suitable. In the case of absorption, the excited state often returns to the ground state via relaxation without re-emission. The authors should revise the explanation to avoid the misunderstanding. 

Consequently, this manuscript is publishable after the revisions as above-mentioned and as follows. 

The latter of p.1: Both "beta" and "β" are used. The word can be unified. 

The bottom of p.6: It is written as "peaks at 9260 and 1660nm (1080 and 1035 cm^-1)". The latter is incorrect, because it does not correspond to 1035 cm^-1 in 8-10 μm region. 

The middle of p.8: "PLS" should be spelled out not in the middle of p.9, but here. 

The latter of p.11: It is written as "This method obtained an R value of 0.85 ... R of 0.99". The corresponding reference, which may be not ref. 87 but ref. 86, should be cited here. From the figure 5 and 1 (or 3?) in ref. 86, the values of 0.85 and 0.99, respectively, may be square of R (R²). 

Ref. 73: The page numbers are missing. 

Ref. 86: The article number is duplicated. 

Ref. 87: The page numbers 1-9 is incorrect, and the article number 047001 may be correct. 

Author Response

We would like to thank the reviewers for their comments on our work and their suggestions for how to improve the manuscript. We have responded to each of the reviewer comments below and where we have made a revision of the manuscript, these changes are highlighted with ‘track changes’. If you have any questions regarding our rebuttal or revisions, please do not hesitate to contact us.

Reviewer 2

Thank you for your comments on our work and suggestions for improvement. We have responded to your comments in the section below.

Reviewer #2: In this manuscript, the authors introduce analyses of glucose via various spectroscopies, namely, mid/near-infrared absorption, Raman scattering, optical coherence tomography, optical rotation, and photoacoustic spectroscopy. These techniques are explained in terms of the basic theory and the application for quantitative detection of glucose with and without figures, respectively. This tutorial review will be useful for the study on non-invasive sensor of blood glucose which applied to diabetes

mellitus.

Thank you for your comments and we are glad to hear that our review will be useful for the study of non-invasive glucose sensing.

Reviewer #2: In p.3, however, the explanation for scattering (Fig.1) can be applied to also fluorescence. Moreover, it is written as "... subsequently re-emits a photon". This seems to explain fluorescence. For scattering, "immediately re-emits" may be suitable.

Thank you for your comment and for highlighting that the explanation of scattering could be misunderstood and applied to fluorescence. We have revised the manuscript to clarify the difference between Raman scattering and fluorescence in three ways. Firstly, we have followed your suggestion and replaced "... subsequently re-emits a photon" with "immediately re-emits a photon" to emphasise the timescale difference between fluorescence and Raman scattering. Secondly, we have added the following sentence after “immediately re-emits a photon”.

This should not be confused with fluorescence, where the electron is excited to a real excited state and then a photon is emitted after a short time during relaxation.   

Thirdly, in the description of scattering we have added the word ‘virtual’ into “raising the electrons to an excited state” to give “raising the electrons to a ‘virtual’ excited state” to clarify another difference between scattering and fluorescence.

Reviewer #2: In the case of absorption, the excited state often returns to the ground state via relaxation without re-emission.

Thank you for highlighting this important point. We have included a sentence to state this in the section below (highlighted yellow).

Absorption occurs when a molecule absorbs a photon, resulting in an excitation of one the energy states of that molecule, usually corresponding to a rotational or vibra-tional degree of freedom related to molecular bond structure. The electron may subsequently return to the ground state during relaxation.

Reviewer #2: The latter of p.1: Both "beta" and "β" are used. The word can be unified.

Thank you for highlighting this. We have changed all instances on “beta” to “β” in the text.

Reviewer #2: The bottom of p.6: It is written as "peaks at 9260 and 1660nm (1080 and 1035 cm-1)". The latter is incorrect, because it does not correspond to 1035 cm- in 8-10 um region.

Thank you for identifying this error. 1660nm is indeed incorrect and was a typing error, it has been replaced by the correct value of 9660nm.

Reviewer #2: The middle of p.8: "PLS" should be spelled out not in the middle of p.9, but here.

Thank you for highlighting this and we agree that the term should be defined in full when it is first used. The use of ‘PLS’ on page 8 has been changed to ‘Partial Least Squares (PLS)’.

Reviewer #2: The latter of p.11: It is written as "This method obtained an R value of 0.85 ... R of 0.99". The corresponding reference, which may be not ref. 87 but ref. 86, should be cited here. From the figure 5 and 1 (or 3?) in ref. 86, the values of 0.85 and 0.99, respectively, may be square of R (R2).

Thank you for highlighting that the reference should be cited in the text here and we agree that it is unclear whether reference 87 or 86 is being referred to in this sentence. Reference 86 has now been cited in this sentence. These values should also be the square of R and have been corrected.

Reviewer #2: Ref. 73: The page numbers are missing.

Thank you for identifying this. The page number (1251) has been added.

Reviewer #2: Ref. 86: The article number is duplicated.

Thank you for identifying this. We have removed the duplicate number.

Reviewer #2: Ref. 86: Ref. 87: The page numbers 1-9 is incorrect, and the article number 047001 may be correct.

Thank you for identifying this. We agree that 047001 is the correct article number and have added this, removing the incorrect page numbers.