Dear Dr. Miki,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Peter R. Corridon

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: The manuscript entitled "Design of Polyether Sulfone Flat-sheet Membranes for Multi-Layered Hemodiafiltration Devices" focuses on the design, development and utilization of poylethersulfone-based membranes and devices for hemodiafiltration applications. Generally, the article is well presented, however still some improvements are required to publish it in PLOS ONE. Following minor issues need to be addressed before acceptance.

1) What is novelty of this study?

2) Line 27: What is difference between in vitro and ex vivo experiments?

3) Figure 3: How can membranes of different geometrical shapes be compared to assess their pressures withstanding performance? Cylindrical shaped membranes can more efficiently withstand comparatively higher pressures than their flat shaped counterparts due to support from all directions in case of cylinders.

4) Whole manuscript: There are many language errors specially involving numerous unnecessarily hyphenated words. Please remove hyphens throughout manuscript.

5) Was there any chance of blood contamination on applying this device?

6) Discussion section needs to be further elaborated with references if available.

7) Performance results on humans may be different due to presence of many components in blood stream. What results are expected for humans’ blood?

8) Prolonged filtration tests can help to assess fouling tendency of membranes.

Reviewer #2: Comments on the manuscript entitled: Design of Polyether Sulfone Flat-sheet Membranes for Multi-Layered Hemodiafiltration Devices, PONE-D-24-51471

The following questions can be considered:

1. The abstract should contain answers to the following questions: What problem did you study and why is it important? What methods did you use? What were your main results? And what conclusions can you draw from your results? Please include in your abstract more specific and quantitative results when it suits broader audiences.

2. To make the reader know you work clearly and quickly, the main objects of this study at the last paragraph in "Introduction" was suggested to be stated point by point.

3. The section on membrane preparation is vaguely written. Were the membranes prepared by the phase inversion method? In this case, after preparing the wet film, the wet film should be immediately immersed in deionized water. Whereas in the experimental section it is stated that the wet film was immersed in water for 24 hours. It is necessary to rewrite this section and write the details step by step.

4. What was the area of the membranes made by spin coating?

5. The volume of solution used to prepare the membranes should be stated.

6. Why wasn't PVP used instead of Polyethene glycol?

7. What was the thickness of fabricated membranes? How the authors measured this value? Details should be given in the experimental section.

8. For SEM images of the cross-section of membranes, the preparation method should be detailed. Were the membranes cut by a cutter?

9. During membrane testing, which side of the membrane was in contact with the dialysis solution: the support or the skin side?

10. What was the method of measuring rejection? Details of the method with calibration curve must be given in the manuscript.

11. In what time period was the amount of filtrate was measured to calculate the membrane flux? Details should be added in the experimental section.

12. The mechanical properties of the constructed membrane should be measured and the stress-strain curve should be given

13. The roughness (Ra, Rv, Rq) of the membrane surface is key factor in fouling and can be calculated by AFM and added to the discussion section. The following paper is recommended: 10.1039/D0NJ03231J;

14. Fouling is the key factor for membrane characterization. Flux measurement with time in necessary and calculation of fouling factors should be done.

15. Comparison of the performance of the fabricated membrane with similar one reported in the literature should be done.

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: Yes:  Muhammad Sarfraz

Reviewer #2: No

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Design of Polyether Sulfone Flat-sheet Membranes for Multi-Layered Hemodiafiltration Devices

PONE-D-24-51471R1

Dear Dr. Miki,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Muhammad Shakaib, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: N/A

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Dear authors,

Thank you for addressing all comments. Revised article can now be accepted for publication in PLOS ONE.

Reviewer #2: The authors replied all comments properly and manuscript can be considered for publication in the PLOS One.

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: Yes:  Muhammad Sarfraz

Reviewer #2: No

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