Optical Fiber Biosensors for Protein Detection: A Review
Round 1
Reviewer 1 Report
In this manuscript, the authors reviewed the major mechanism and progress of protein detection based on optical fiber-based biosensors. The sensing mechanisms, recent progress, pro and cons for each fiber sensing mechanism have been summarized and discussed in the manuscript. It is definitely a great review both researchers in this fields to get a full picture of the state of the art and outside researchers to get a general idea of optical fiber-based protein sensors. The figures and tables are prepared in high quality for the readers to understand the differences and combinations of technologies and how they are evolving anc compared with each other. I have a few comments or suggestions that hope the authors can address:
1. The authors discussed the challenges of optical fiber-based protein sensors on commercialization and mass production. This has been the longstanding challenges for the optical fiber based biosensors. I am wondering if the authors can also summarize the progress made during the recent years to push the technology towards commercialization . It would be very helpful for the readers to understand the potential future impact of the technology.
2. Please check the typos and formatting. (e.g. "safty" Line[14]).
Author Response
Response to Reviewer 1 Comments
Point 1: The authors discussed the challenges of optical fiber-based protein sensors on commercialization and mass production. This has been the longstanding challenges for the optical fiber based biosensors. I am wondering if the authors can also summarize the progress made during the recent years to push the technology towards commercialization . It would be very helpful for the readers to understand the potential future impact of the technology.
Response 1: Thank you for your professional advice. In the updated manuscript, we have added the following prospects for the commercialization of optical fiber biosensors.
“The open challenge is to devolope the the miniaturized interrogators and improve its performance. However, there have been some achievements that may promote the commercialization of optical fiber biosensors. On the one hand, the cost of optical fiber fabrication can be reduced by designing optical fiber structures that are easy to be standardized, such as ball resonators interrograted optical backscatter reflectometer. Moreover, Yang et al. demonstrated a cost-effectively mass-produce tech-nology, which plays a positive role in the promotion of marketization. As for the optical interrogation, On the other hand, with the development of Internet of Things technology, the sensing platform of integrated biochip makes the optical fiber biosensor more accessible. It can be predicted that after the above two challenges are further overcome, the optical fiber biosensor will usher in explosive applications.”
Point 2: Please check the typos and formatting. (e.g. "safty" Line[14]).
Response 2: We were really sorry for our careless mistakes. We have corrected it in our resubmitted manuscript. Thank you for your reminder.
Author Response File: 
Author Response.docx
Reviewer 2 Report
This manuscript reviews the development of sensors based on optical fiber components applied to biosensing, especially for protein detection. In general, this manuscript is well-written and organized.
Here are some suggestions:
- Fix the grammar issue in line 22.
- Include citations in the caption of figure 5. Also, this figure size should be increased if possible. For example, it is difficult to read the scale in the inset of figure 5d.
- Text between lines 368-370 was duplicated in lines 403-405. Equation 3 is the same as equation 5.
- Subsection 3.1 starts in line 132, and under session 2 (line 92).
- It looks like there is a mistake in line 761 regarding the session identification.
- Figure 17 is not cited in the manuscript.
Author Response
Response to Reviewer 3 Comments
Point 1: Fix the grammar issue in line 22.
Response 1: Thank you for your reminder. We have fixed it in the revised version.
where the propagation distance L is twice that of the latter.Point 2: Include citations in the caption of figure 5. Also, this figure size should be increased if possible. For example, it is difficult to read the scale in the inset of figure 5d.
Response 2: Thanks for your reminder. We include citations of all figures that need to be added. And we adjusted the size of figure 5, especially the inset of figure 5d, as much as possible in the revised manuscript. While it is still hard to read the scale. Although the scales are difficult to read, this figure is intended to show that the diameter of the metal ball is in a normal distribution, which can clearly read from the figure. Moreover, I added a note to the caption of figure 5.
Point 3: Text between lines 368-370 was duplicated in lines 403-405. Equation 3 is the same as equation 5.
Response 3: Thank you for your careful attention to this problem. We have added the correct content to the corresponding section. And the equation 5 is different from the equation 3, where the propagation distance L is twice that of the latter.
Point 4: Subsection 3.1 starts in line 132, and under session 2 (line 92).
Response 4: Thank you very much for reminding us of this big mistake. We have corrected all the wrong labels.
Point 5: It looks like there is a mistake in line 761 regarding the session identification.
Response 5: Thanks again for your reminder. But I think there are not mistakes in this section. The third part of the manuscript summarizes the biosensor structures based on the different sensing mechanisms. And we put challenges and prospects in the last part.
Point 6: Figure 17 is not cited in the manuscript.
Response 6: Thank you. Figuire 17 is made by ourselves, and it does not belong to any other paper as far as we know.
Author Response File: Author Response.docx
Reviewer 3 Report
Review article:
Optical Fiber Biosensors for Protein Detection: A Review
The authors present a review about Optical Fiber Biosensors for Protein Detection
This is a well-written and structured manuscript. In this manuscript there are the potentialities to publications in Photonics but the paper has needed some important specification and reviews.
In general, in the review an important point to be included is the Lab-on-Fiber concept in order to open the view toward an optrode medical device.
In the FBG-based fiber biosensors section, the authors can be consider an interesting and recently review of Presti, Fiber bragg gratings for medical applications and future challenges: A review 2022.
In the LPG-based fiber biosensors section:
- The equation 13 have be change in line with the theory lambda resonance is equals to (ncore - ncladding) * Delta.
- At line [591] (TiOx) thin-film, poly(methylmethacrylate)-co-methacrylic acid (PMMA-co-MA) about the poly(methylmethacrylate)-co-methacrylic acid (PMMA-co-MA) an interesting papers, that have to adding, in this field is Zuppolini, Label-free fiber optic optrode for the detection of class C β-lactamases expressed by drug resistant bacteria, 2017 were also a design and development of the automated system for simultaneous multi-target clinical analyses is shows. In line with this argument the authors have be stressed the concept based on the Reflection Long Period Grating that is an interesting solution when it is necessary to use a probe to introduce in an eppendorf.
- In the section Scattering-based Fiber Biosensors the authors have be include the works that introduce the SERS substrate performance toward the Optical fiber SERS probe. In particular, Pisco et al. shown a Self-assembled periodic patterns on the optical fiber tip by microsphere arrays in 2015 and subsequent publications shown the way to realize the concept that, starting from the microsphere arrays, it is possible to adapt the SERS nanostructure sizes according to the biological targets. Two interesting and recent paper of Meng et al. Fabrication of a three-dimensional (3D) SERS fiber probe and application of in situ detection in 2022 and Kim at al. presents Fiber‐optic SERS probes fabricated using two‐photon polymerization for rapid detection of bacteria, 2020 shown the possibility to realize a SERS optrode and in order to introduce the optofluidic Hunter at al. shown Optofluidic label-free SERS platform for rapid bacteria detection in serum, 2019
Author Response
Response 1: We sincerely appreciate the valuable comment and add the following introduction in the line [52].
“the impressive performances of on-chip nano-photonic biosensors have been com-bined with those novel optical fiber, resulting in a complete research field called ‘Lab-on-Fiber’.”
Point 2: In the FBG-based fiber biosensors section, the authors can be consider an interesting and recently review of Presti, Fiber bragg gratings for medical applications and future challenges: A review 2022.
Response 2: We think this is an excellent suggestion. We have studied this review and specifically stated it in the summary as fellow.
“It is worth mentioning that the inherent biocompatibility of FBG makes it a powerful tool in medical biosensors.”
Point 3: The equation 13 have be change in line with the theory lambda resonance is equals to (ncore - ncladding) * Delta.
Response 3: Thank you for your reminder. We have correted the equation 13.
Point 4: At line [591] (TiOx) thin-film, poly(methylmethacrylate)-co-methacrylic acid (PMMA-co-MA) about the poly(methylmethacrylate)-co-methacrylic acid (PMMA-co-MA) an interesting papers, that have to adding, in this field is Zuppolini, Label-free fiber optic optrode for the detection of class C β-lactamases expressed by drug resistant bacteria, 2017 were also a design and development of the automated system for simultaneous multi-target clinical analyses is shows. In line with this argument the authors have be stressed the concept based on the Reflection Long Period Grating that is an interesting solution when it is necessary to use a probe to introduce in an eppendorf.
Response 4: This is a very valuable literature. We have added the concept based on the Reflection Long Period Grating to the manuscript at line [640].
Point 5: In the section Scattering-based Fiber Biosensors the authors have be include the works that introduce the SERS substrate performance toward the Optical fiber SERS probe. In particular, Pisco et al. shown a Self-assembled periodic patterns on the optical fiber tip by microsphere arrays (2015), Manago at al. shown a Tailoring lab-on-fiber SERS optrodes towards biological targets of different sizes (2021), Kim at al. presents Fiber‐optic SERS probes fabricated using two‐photon polymerization for rapid detection of bacteria, 2020 and in order to introduce the optofluidic Hunter at al. shown Optofluidic label-free SERS platform for rapid bacteria detection in serum, 2019.
Response 5: We sincerely appreciate the valuable comments. We have checked the literature carefully and added those references about SERS into the section Scattering-based Fiber Biosensors part in the revised manuscript.
Round 2
Reviewer 3 Report
The authors inserted the comments highlighted by the reviewer. The paper can be published in this present form.
Author Response
Thank you so much for taking the time to review my work.
