Automatic reagent handling and assay processing of human biospecimens inside a transportation container for a medical disaster response against radiation

Adam R. Akkad; Jian Gu; Brett Duane; Alan Norquist; David J. Brenner; Adarsh Ramakumar; Frederic Zenhausern

doi:10.1371/journal.pone.0268508

Peer Review History

Original SubmissionMarch 18, 2022
11 Apr 2022 Decision Letter - Talib Al-Ameri, Editor PONE-D-22-08129Automatic Reagent Handling and Assay Processing of Human Biospecimens inside a Transportation Container for a Medical Disaster Response Against RadiationPLOS ONE Dear Dr. Gu, 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. Please submit your revised manuscript by May 26 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 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 ****** 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 ****** 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: This manuscript describes the development of a shipping container that would allow blood cell culturing during transportation from the site of collection to the laboratory where processing would occur. This type of device would shorten the time to dose estimates for biodosimetry assays and would have an impact on large scale events. The concept of the device is very interesting, however, there are a few unanswered questions below: 1. These devices seem large, heavy and potentially costly. There was not indication of the cost of this box. 2. The authors stated that more tubes could be loaded in each box. This would be essential for mass casualty situations. It would be nice to know an estimate of the tube capacity of the system. 3. The shipping scenario tested was ground based and quite short. Has the container been tested on flights or ground transportation of longer duration? It has been tested for drops and tilts but what about extreme vibrations that might be experienced on flight take off/landing? 4. Fig 2, F – this image is hard to make out. Overall the resolution of the figures is poor. 5. Are there any issues with shipping devices by plane that contain batteries? Has the device been discussed with transportation authorities 6. Is there a vision for how these devices would be deployed? For example, would they be stockpiled in one location and sent to the site of the incident? 7. Since the MN/BN at the high end of the dose response curve is lower for the SSI than for the conventional method, would you recommend having a calibration curve generated for this type of cell processing? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Revision 1
26 Apr 2022 Author Response April 22, 2022 RE: Rebuttal letter for manuscript PONE-D-22-08129 “Automatic Reagent Handling and Assay Processing of Human Biospecimens inside a Transportation Container for a Medical Disaster Response Against Radiation” Dear PLOS ONE Editor: We have revised our manuscript according to the Editor and reviewer’s comments. The changes and comments are summarized below: 1. Ensure manuscript meets PLOS ONE’s style requirements a. The title has been revised according PLOS ONE format guidelines; b. Corresponding authors have been revised according guidelines; c. The headings have been revised with three tiers, font sizes, sentence style etc. according to guidelines; d. Figure citations and captions have been revised according to guidelines; e. In text reference citations have been revised to brackets according to guidelines; they were also reformatted in the “References” section; f. Supporting information materials have been named according to guidelines; 2. Amended statement of Competing Interests to declare patent The new declaration statement can be: I have read the journal’s policy and the authors of this manuscript have the following competing interests: F.Z., B.D., J.G., A.N., D.J.B. have filed a patent application PCT/US2019/64737, titled “Smart Storage container for Health Logistics”. This does not alter our adherence to PLOS ONE policies on sharing data and materials. 3. Funding info in Acknowledgements The funding information has been removed from the “Acknowledgements”. The current Funding Statement is ok. 4. Review reference list The references are all correct. They have been reformatted using a better software. One new reference was added regarding regulation on lithium battery (Ref [22]). Reviewer’s comments to the Author (Reviewer #1): 1. These devices seem large, heavy and potentially costly. There was not indication of the cost of this box. We added the comments of cost in “Discussion” line 321-358. The container could be large like now due to the fact of accommodating large number of samples. The weight and cost are some limitations of the current iQ5 shipping incubator, which should be replaced in the future by a new shipping container we reported recently. Future development aims to reduce the overall cost to ~ $100-200/96 sample rack. 2. The authors stated that more tubes could be loaded in each box. This would be essential for mass casualty situations. It would be nice to know an estimate of the tube capacity of the system. More tube capacity per SSI and cost depend on future miniaturization of the tube and micropipette, which we explained more in “Discussion” line 331-339. We expect >10x 96-tube racks could be accommodated in the future. 3. The shipping scenario tested was ground based and quite short. Has the container been tested on flights or ground transportation of longer duration? It has been tested for drops and tilts but what about extreme vibrations that might be experienced on flight take off/landing? We elaborated more about this limitation in “Discussion” line 340-352. We haven’t tested current container for longer flight transportations, which should be done in further study. However, the mechanical shocks collected from a previous flight test of another container from a round-trip New York, NY to Phoenix, AZ and back should include the “extreme vibrations that might be experienced on flight take off/landing” the reviewer mentioned, which had a value that should be tolerated by this container. We also expect special handling to be provided to these containers (containing large amount of biospecimen) during a nuclear event that could provide decreased mechanical shocks if needed. 4. Fig 2, F – this image is hard to make out. Overall, the resolution of the figures is poor. We have saved the image with a higher resolution. A larger area of the micropipette with cyt-B was also included so that the reader/reviewer can make sense of the image better. We also increased the resolution/size of Fig 3-7 for better viewing purpose. 5. Are there any issues with shipping devices by plane that contain batteries? Has the device been discussed with transportation authorities? We added in “Discussion” line 325-327 that NiMH battery used in this project is not actively regulated (guideline from IATA, International Air Transport Association). We haven’t had discussion with transportation the authorities yet. In the context of our previous container development, we had discussions with experts at FedEx and from these internal discussions, it was assessed that our system was enclosed in multiple layers of containments with minimal risk to transportation, and to the best of our knowledge, was not in conflict with any regulation. We will further confirm this with the transportation authorities in future effort toward potential scale-up fabrication and commercialization. 6. Is there a vision for how these devices would be deployed? For example, would they be stockpiled in one location and sent to the site of the incident? We added the vision of how to use the SSI in “Discussion” line 353-355. We expect SSIs be stockpiled at all major metropolitan areas around the U.S., deployed to the incident site from the closest locations and shipped to cytogenetic labs for analysis. We also had informal discussions with lab personnel at Sonoran Quest Laboratories (Phoenix AZ) who express interest using such of our containers for ground-based logistical applications in more conventional operations. If so, it is foreseeable to have also some of these devices available at distributed sites in clinical laboratories which could be leveraged in the case of an emergency response. 7. Since the MN/BN at the high end of the dose response curve is lower for the SSI than for the conventional method, would you recommend having a calibration curve generated for this type of cell processing? Yes, the current practice is that each cytogenetic laboratory generates its own calibration curve due to the differences of the assay protocol from each lab, such as reported in the “RENEB (Realizing the European Network of Biodosimetry) intercomparison exercises analyzing micronuclei” by Depuydt et al. (2017). I hope we have addressed all the concerns raised during the review process. Should you have any other questions, please feel free to let me know by email: jgu10@arizona.edu or phone 602-827-5950. Best regards, Jian Gu, Ph.D. Associate Professor Center for Applied NanoBioscience and Medicine Department of Basic Medical Sciences The University of Arizona College of Medicine-Phoenix 475 N 5th St, BSPB/Rm E612, Phoenix, AZ 85004 Tel: (602) 827-5950; Fax: (602) 827-2122 Attachments Attachment Submitted filename: Rebuttal letter_final.docx https://doi.org/10.1371/journal.pone.0268508.r002
3 May 2022 Decision Letter - Talib Al-Ameri, Editor Automatic reagent handling and assay processing of human biospecimens inside a transportation container for a medical disaster response against radiation PONE-D-22-08129R1 Dear Dr. Gu, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Talib Al-Ameri, Ph.D Academic Editor PLOS ONE 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 #1: All comments have been addressed ******** 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 #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A ****** 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 #1: Yes ****** 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 #1: 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 #1: The authors have addressed all of my comments. This paper can now be accepted for publication. Thank you. ****** 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 #1: No https://doi.org/10.1371/journal.pone.0268508.r003
Formally Accepted
13 May 2022 Acceptance Letter - Talib Al-Ameri, Editor PONE-D-22-08129R1 Automatic reagent handling and assay processing of human biospecimens inside a transportation container for a medical disaster response against radiation Dear Dr. Gu: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Talib Al-Ameri Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0268508.r004

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