From the journal Digital Discovery Peer review history

05-Jun-2023

Dear Professor Schubert:

Manuscript ID: DD-ART-04-2023-000074
TITLE: Best practice for sampling in automated parallel synthesizers

Thank you for your submission to Digital Discovery, published by the Royal Society of Chemistry. I sent your manuscript to reviewers and I have now received their reports which are copied below.

After careful evaluation of your manuscript and the reviewers’ reports, I will be pleased to accept your manuscript for publication after revisions.

Please revise your manuscript to fully address the reviewers’ comments. When you submit your revised manuscript please include a point by point response to the reviewers’ comments and highlight the changes you have made. Full details of the files you need to submit are listed at the end of this email.

Digital Discovery strongly encourages authors of research articles to include an ‘Author contributions’ section in their manuscript, for publication in the final article. This should appear immediately above the ‘Conflict of interest’ and ‘Acknowledgement’ sections. I strongly recommend you use CRediT (the Contributor Roles Taxonomy, https://credit.niso.org/) for standardised contribution descriptions. All authors should have agreed to their individual contributions ahead of submission and these should accurately reflect contributions to the work. Please refer to our general author guidelines https://www.rsc.org/journals-books-databases/author-and-reviewer-hub/authors-information/responsibilities/ for more information.

Please submit your revised manuscript as soon as possible using this link :

*** PLEASE NOTE: This is a two-step process. After clicking on the link, you will be directed to a webpage to confirm. ***

https://mc.manuscriptcentral.com/dd?link_removed

(This link goes straight to your account, without the need to log in to the system. For your account security you should not share this link with others.)

Alternatively, you can login to your account (https://mc.manuscriptcentral.com/dd) where you will need your case-sensitive USER ID and password.

You should submit your revised manuscript as soon as possible; please note you will receive a series of automatic reminders. If your revisions will take a significant length of time, please contact me. If I do not hear from you, I may withdraw your manuscript from consideration and you will have to resubmit. Any resubmission will receive a new submission date.

The Royal Society of Chemistry requires all submitting authors to provide their ORCID iD when they submit a revised manuscript. This is quick and easy to do as part of the revised manuscript submission process.   We will publish this information with the article, and you may choose to have your ORCID record updated automatically with details of the publication.

Please also encourage your co-authors to sign up for their own ORCID account and associate it with their account on our manuscript submission system. For further information see: https://www.rsc.org/journals-books-databases/journal-authors-reviewers/processes-policies/#attribution-id

I look forward to receiving your revised manuscript.

Yours sincerely,
Professor Jason Hein
Associate Editor, Digital Discovery

************

Reviewer 1

A very well written and thoroughly conducted study on automated sampling in high throughput. Not enough recognition goes into these systematic studies, which are essential for successful automation experiments. No revisions needed.

Reviewer 2

The authors introduce a novel automated method for sample collection using additive manufacturing of a vial holder, specifically designed for synthesis robots and liquid handling robots. Notably, this research does not perform code development or data generation. Nevertheless, it falls within the scope of the Digital Discovery journal, specifically in the category of "Novel experimental automation for chemistry, biochemical, biomedical, and materials science," with the subcategory of "New Robotic Setup." As the data reviewer, I have examined the data collection mechanism employed in this study and have several queries that I would appreciate the authors addressing in response to the following comments.

1. The authors discussed evaporation experiments on page 3, but they did not account for the crucial external factors of temperature and humidity at the experimental location. Since evaporation is dependent on these conditions, it is important to consider how to incorporate external factors in the research. How can external conditions effect on the method proposed in this experiment?

2. The evaporation rates of different chemicals can vary significantly, with some evaporating rapidly and others exhibiting slower evaporation. However, the authors of the study did not demonstrate the effectiveness of their proposed method on a diverse range of liquids by testing it with different chemicals.

3. The proposed technique aims to facilitate sample collection for high-throughput experimentation. However, the authors only considered a limited number of vials in their experiment. In the context of high-throughput experimentation, where numerous vials are typically involved, it would be beneficial for the authors to address this aspect in their paper and provide a discussion or considerations regarding the scalability of their technique to handle potentially hundreds, thousands or more vials.

4. Did the authors take into account the size of needles and the surface area of the vials in their research? These parameters could potentially have an impact on the effectiveness of their proposed method.

Reviewer 3

This manuscript deals with the very practical issues around sample taking in HTE robotic setups. There is a lot of merit around the work, yet I partially wondered where the line between very important practical issue and scientific triviality actually lies. Having given this quite depressing statement, I do appreciate the detailed work of the authors.
Some points the authors want to consider:
- obviously the rate of evaporation will depend significantly on the vapour pressure of substances. It would be interesting to compare different solvents and to correlate their loss with their vapour partial pressure. This would add significantly to the usefulness of data.
- Obviously, the answer to the whoe issue is online monitoring, hence to measure properties of samples without any delay. The authors should comment on this in detail, and give an overview of the entire field. Right now, their results are very specific to their own setup

Dear Professor Hein,

thank you for the consideration of our manuscript and the helpful comments of the referees. We carefully prepared a revised version and included the suggestions of the referees accordingly.
In the following, we answered the comments of the referees and explained the changes in the revised version of our manuscript. The according paragraphs and modifications are highlighted in the manuscript. We believe that we have answered all questions and comments of the reviewers satisfactorily and hope that our manuscript is now suitbale for publication in Digital Discovery.
We are looking forward to your reply. Please contact me for any further questions.

Best regards

Prof. Dr. Ulrich S. Schubert



Referee #1:
A very well written and thoroughly conducted study on automated sampling in high throughput. Not enough recognition goes into these systematic studies, which are essential for successful automation experiments. No revisions needed.
We would like to thank the reviewer for his/her positive evaluation of our manuscript!

Referee #2:
The authors introduce a novel automated method for sample collection using additive manufacturing of a vial holder, specifically designed for synthesis robots and liquid handling robots. Notably, this research does not perform code development or data generation. Nevertheless, it falls within the scope of the Digital Discovery journal, specifically in the category of "Novel experimental automation for chemistry, biochemical, biomedical, and materials science," with the subcategory of "New Robotic Setup." As the data reviewer, I have examined the data collection mechanism employed in this study and have several queries that I would appreciate the authors addressing in response to the following comments.
We would like to thank the reviewer for his/her positive evaluation of our manuscript!

1. The authors discussed evaporation experiments on page 3, but they did not account for the crucial external factors of temperature and humidity at the experimental location. Since evaporation is dependent on these conditions, it is important to consider how to incorporate external factors in the research. How can external conditions effect on the method proposed in this experiment?
We added the information about the humidity and temperature at the place of sampling to the manuscript. We also explained the expected behavior of the samples if changes in the humidity and temperature are occurring.

2. The evaporation rates of different chemicals can vary significantly, with some evaporating rapidly and others exhibiting slower evaporation. However, the authors of the study did not demonstrate the effectiveness of their proposed method on a diverse range of liquids by testing it with different chemicals.
Additional to the previously conducted experiments we performed an evaporation experiment series with six different liquids, representing a wide range of vapor pressures. The experiments agree with the previously made statement that our method is superior compared to the previously used method, in particular for easily evaporable substances.

3. The proposed technique aims to facilitate sample collection for high-throughput experimentation. However, the authors only considered a limited number of vials in their experiment. In the context of high-throughput experimentation, where numerous vials are typically involved, it would be beneficial for the authors to address this aspect in their paper and provide a discussion or considerations regarding the scalability of their technique to handle potentially hundreds, thousands or more vials.
We thank the reviewer for this comment and added more considerations about the scalability of the new method.

4. Did the authors take into account the size of needles and the surface area of the vials in their research? These parameters could potentially have an impact on the effectiveness of their proposed method.
We agree with the reviewer that a detailed investigation of factors such as the surface area and the needle size could play a vital role for the sampling process. We added information about the utilized needles and surface area of the sampling vials to our manuscript to clarify that point in more detail.

Referee #3:
This manuscript deals with the very practical issues around sample taking in HTE robotic setups. There is a lot of merit around the work, yet I partially wondered where the line between very important practical issue and scientific triviality actually lies. Having given this quite depressing statement, I do appreciate the detailed work of the authors.
We would like to thank the reviewer for his/her feedback around our work!
1. Obviously the rate of evaporation will depend significantly on the vapour pressure of substances. It would be interesting to compare different solvents and to correlate their loss with their vapour partial pressure. This would add significantly to the usefulness of data.

We performed an experiment series with six different liquids in a range of vapour pressures from 5 to 580 mbar. The experiments showed that there are different areas with regards to evaporation tendency and effectiveness of our proposed method which is superior to the currently employed methods. We discussed the new results in detail in the manuscript.


2. Obviously, the answer to the whoe issue is online monitoring, hence to measure properties of samples without any delay. The authors should comment on this in detail, and give an overview of the entire field. Right now, their results are very specific to their own setup

Providing an overview of the entire field of online monitoring would be a good topic for a review article and goes far beyond the scope of the presented research as we focused our work on the offline sampling process. Nevertheless, we adapted the introduction to give more information on currently available techniques for online monitoring which is mainly used for flow-chemistry applications.

11-Sep-2023

Dear Professor Schubert:

Manuscript ID: DD-ART-04-2023-000074.R1
TITLE: Best practice for sampling in automated parallel synthesizers

Thank you for your submission to Digital Discovery, published by the Royal Society of Chemistry. I sent your manuscript to reviewers and I have now received their reports which are copied below.

I have carefully evaluated your manuscript and the reviewers’ reports, and the reports indicate that major revisions are necessary.

Please submit a revised manuscript which addresses all of the reviewers’ comments. Further peer review of your revised manuscript may be needed. When you submit your revised manuscript please include a point by point response to the reviewers’ comments and highlight the changes you have made. Full details of the files you need to submit are listed at the end of this email.

Digital Discovery strongly encourages authors of research articles to include an ‘Author contributions’ section in their manuscript, for publication in the final article. This should appear immediately above the ‘Conflict of interest’ and ‘Acknowledgement’ sections. I strongly recommend you use CRediT (the Contributor Roles Taxonomy, https://credit.niso.org/) for standardised contribution descriptions. All authors should have agreed to their individual contributions ahead of submission and these should accurately reflect contributions to the work. Please refer to our general author guidelines https://www.rsc.org/journals-books-databases/author-and-reviewer-hub/authors-information/responsibilities/ for more information.

Please submit your revised manuscript as soon as possible using this link:

*** PLEASE NOTE: This is a two-step process. After clicking on the link, you will be directed to a webpage to confirm. ***

https://mc.manuscriptcentral.com/dd?link_removed

(This link goes straight to your account, without the need to log on to the system. For your account security you should not share this link with others.)

Alternatively, you can login to your account (https://mc.manuscriptcentral.com/dd) where you will need your case-sensitive USER ID and password.

You should submit your revised manuscript as soon as possible; please note you will receive a series of automatic reminders. If your revisions will take a significant length of time, please contact me. If I do not hear from you, I may withdraw your manuscript from consideration and you will have to resubmit. Any resubmission will receive a new submission date.

The Royal Society of Chemistry requires all submitting authors to provide their ORCID iD when they submit a revised manuscript. This is quick and easy to do as part of the revised manuscript submission process.   We will publish this information with the article, and you may choose to have your ORCID record updated automatically with details of the publication.

Please also encourage your co-authors to sign up for their own ORCID account and associate it with their account on our manuscript submission system. For further information see: https://www.rsc.org/journals-books-databases/journal-authors-reviewers/processes-policies/#attribution-id

I look forward to receiving your revised manuscript.

Yours sincerely,
Professor Jason Hein
Associate Editor, Digital Discovery

************

Reviewer 4

This is a straightforward paper from a lab that excels in the use of automation for parallel polymer chemistry. It discusses different thoughts and considerations when sampling from vials. Overall, the results are fine and in many cases states the obvious. The comparison between slitted vs regular septa provides the most interesting results. However, I believe it is missing an important study that would be of interest to this community. Single instance sampling is of course important, but sampling multiple times from the same vial is perhaps even more relevant. In automated polymer chemistry, it would be nice to sample molecular weight and track conversion. Therefore, this study should include a new experiment comparing the integrity of the different septa designs during multiple sampling attempts. How many times can you sample from slitted vs regular septa before large holes form and evaporation occurs? This study should be included to raise the impact of its results.

Dear Professor Hein,

thank you for the consideration of our manuscript and the helpful comments of the referee. We carefully prepared a revised version of the manuscript and included the suggestions of the referees accordingly.
In the following, we answered the comment of the referee and explained the changes in the revised version of our manuscript. The according paragraphs and modifications are highlighted in the manuscript. We believe that we have answered all questions and comments of the reviewers satisfactorily and hope that our manuscript is now suitbale for publication in Digital Discovery.
We are looking forward to your reply. Please contact me for any further questions.

Best regards
Ulrich Schubert
Prof. Dr. Ulrich S. Schubert




Referee #4:

This is a straightforward paper from a lab that excels in the use of automation for parallel polymer chemistry. It discusses different thoughts and considerations when sampling from vials. Overall, the results are fine and in many cases states the obvious. The comparison between slitted vs regular septa provides the most interesting results. However, I believe it is missing an important study that would be of interest to this community. Single instance sampling is of course important, but sampling multiple times from the same vial is perhaps even more relevant. In automated polymer chemistry, it would be nice to sample molecular weight and track conversion. Therefore, this study should include a new experiment comparing the integrity of the different septa designs during multiple sampling attempts. How many times can you sample from slitted vs regular septa before large holes form and evaporation occurs? This study should be included to raise the impact of its results.
We thank the reviewer the very helpful comment. We performed the required experiments and included the results in a new section in the manuscript (“Dependence of evaporation on number of septum punctures”). We investigated the evaporation from vials with both kinds of septum lids. Therefore, we punctured the septa between 0 and 30 times which seems to be a reasonable number of samples to take from our suggested 2 mL vessel. We observed that the effect of multiple punctures through the septum on evaporation is very small and generally similar between the regular rubber septum and the slitted septum. However, with the regular septum, cracks occasionally occur in the septum, resulting in significantly higher evaporation.

16-Oct-2023

Dear Professor Schubert:

Manuscript ID: DD-ART-04-2023-000074.R2
TITLE: Best practice for sampling in automated parallel synthesizers

Thank you for submitting your revised manuscript to Digital Discovery. I am pleased to accept your manuscript for publication in its current form.

You will shortly receive a separate email from us requesting you to submit a licence to publish for your article, so that we can proceed with the preparation and publication of your manuscript.

You can highlight your article and the work of your group on the back cover of Digital Discovery. If you are interested in this opportunity please contact the editorial office for more information.

Promote your research, accelerate its impact – find out more about our article promotion services here: https://rsc.li/promoteyourresearch.

If you would like us to promote your article on our Twitter account @digital_rsc please fill out this form: https://form.jotform.com/213544038469056.

By publishing your article in Digital Discovery, you are supporting the Royal Society of Chemistry to help the chemical science community make the world a better place.

With best wishes,

Professor Jason Hein
Associate Editor, Digital Discovery


******
******

Please contact the journal at digitaldiscovery@rsc.org

************************************

DISCLAIMER:

This communication is from The Royal Society of Chemistry, a company incorporated in England by Royal Charter (registered number RC000524) and a charity registered in England and Wales (charity number 207890). Registered office: Burlington House, Piccadilly, London W1J 0BA. Telephone: +44 (0) 20 7437 8656.

The content of this communication (including any attachments) is confidential, and may be privileged or contain copyright material. It may not be relied upon or disclosed to any person other than the intended recipient(s) without the consent of The Royal Society of Chemistry. If you are not the intended recipient(s), please (1) notify us immediately by replying to this email, (2) delete all copies from your system, and (3) note that disclosure, distribution, copying or use of this communication is strictly prohibited.

Any advice given by The Royal Society of Chemistry has been carefully formulated but is based on the information available to it. The Royal Society of Chemistry cannot be held responsible for accuracy or completeness of this communication or any attachment. Any views or opinions presented in this email are solely those of the author and do not represent those of The Royal Society of Chemistry. The views expressed in this communication are personal to the sender and unless specifically stated, this e-mail does not constitute any part of an offer or contract. The Royal Society of Chemistry shall not be liable for any resulting damage or loss as a result of the use of this email and/or attachments, or for the consequences of any actions taken on the basis of the information provided. The Royal Society of Chemistry does not warrant that its emails or attachments are Virus-free; The Royal Society of Chemistry has taken reasonable precautions to ensure that no viruses are contained in this email, but does not accept any responsibility once this email has been transmitted. Please rely on your own screening of electronic communication.

More information on The Royal Society of Chemistry can be found on our website: www.rsc.org