PONE-D-20-20639

3D Printing Direct to Industrial Roll-to-Roll Casting for Fast Prototyping of Scalable Microfluidic Systems

PLOS ONE

Dear Dr. Howell,

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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?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

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 requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: PONE-D-20-20639 “3D Printing Direct to Industrial Roll-to-Roll Casting for Fast Prototyping of Scalable Microfluidic Systems” compares the replication performance of an injet 3D printed device cast in PDMS and replicated by roll casting. The manuscript is well positioned and clearly identifies the capability gap of rapid prototyping suing a manufacturing approach that is compatible with mass manufacturing. The manuscript, however, falls short in demonstrating their solution and potential reasons for that are followed-up insufficiency.

It is impressive that 68 passes of roll casting were evaluated, but considering serious deterioration was observed in the second and third pass, I am unsure what the 68 runs add, rather than that the deterioration in the firs three was probably an unexpected outcome. In a manuscript like this, and considering eh rapid prototyping in design and materials of 3D printing, I would have expected a comparison of different materials, and the introduction of one edge in an (non-conclusive) attempt to fix the repeatability issue falls short delivering on the development of design features.

So the comparable mixing performance is a great start, and I truly believe the approach or using 3D printed templates for rollcasting is valid. But, before publishing, I suggest selecting a range of materials of different hardness (and adhesion of the metal) in order to identify one where a batch of can be replicated 10 times. Otherwise, you are as well off using 3 D printing only.

In order to assess if 10 (or 15, perhaps 8?) replication cycles are required, the authors should include a discussion on the labour and manual handling involved in replacing one template with another.

Reviewer #2: This manuscript titled in “3D Printing Direct to Industrial Roll-to-Roll Casting for Fast Prototyping of Scalable Microfluidic Systems” develops and validates a method to create functional microfluidic prototype devices using 3D printed masters in an industrial-scale roll-to-roll continuous casting process. I believe the work will be of interest to many in bridging the gap between microfluidic technology development and translation to the market. Before considering this manuscript for publication, the authors should consider the following points in any revision as follows:

1. The abstract is described abstractly without specific description of the work. It is suggested to modify the conclusion to emphasize the highlights and workload of the article.

2. In the introduction, the authors should introduce the advantage of the technology in this work in more detail.

3. How about the mechanical strength of PDMS?

4. In Fig.2C, three types of microfluidic mixer patterns are prepared. How about their absolute mixing index?

5. The authors should perform the structure of microfluidic channels by SEM.

6. Why both the channel width and depth are 400 μm? Has this been optimized?

7. This manuscript proposes a new method. There are many schematic diagrams and renderings in the manuscript, lacking effective data support and specific experiments to prove the possibility of relevant applications, such as the mixing effect of various fluids.

8. The size of 3D printing is very critical. It is suggested to indicate the scale and important information on the legend.

9. The authors should check the manuscript carefully to avoid the basic mistakes. For example, flexible typesetting of lines 18-21 in page 9, indent the first line by the same distance, space between numbers and units, etc. The above questions are focused on page 9-10.

10. In page 9 and 10, what is the purpose of gold-plated particles mentioned many times by the authors?

11. What is the effect of E-beam in the manuscript?

12. In page 13, the authors test the hydrophilic and hydrophobic surface of the film, but the volume of the droplets added by the authors is 30 microliters, and the authors should use smaller droplets.

13. In Fig. 2D and 2E, the authors should provide a scale-bar for the photo to determine the size of the device?

14. In the manuscript, the authors explore fluid mixing, and the flow rates of the two fluids should be explained.

I will be happy to recommend for publication a revised version of the manuscript in PLOS ONE.

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Reviewer #1: No

Reviewer #2: No

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3D Printing Direct to Industrial Roll-to-Roll Casting for Fast Prototyping of Scalable Microfluidic Systems

PONE-D-20-20639R1

Dear Dr. Howell,

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,

Ivan Kryven

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

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

Reviewer #2: Yes

**********

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have carefully addressed all the issues I raised previously. I recommend it for publication in PLOS ONE.

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7. PLOS authors have the option to publish the peer review history of their article (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 #2: No