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Article
Peer-Review Record

Design and Development of a Traveling Wave Ferro-Microfluidic Device and System Rig for Potential Magnetophoretic Cell Separation and Sorting in a Water-Based Ferrofluid

Micromachines 2023, 14(4), 889; https://doi.org/10.3390/mi14040889
by Rodward L. Hewlin, Jr. 1,*, Maegan Edwards 1,2 and Christopher Schultz 1
Reviewer 1:
Reviewer 2:
Reviewer 3: Anonymous
Micromachines 2023, 14(4), 889; https://doi.org/10.3390/mi14040889
Submission received: 4 April 2023 / Revised: 18 April 2023 / Accepted: 19 April 2023 / Published: 21 April 2023
(This article belongs to the Special Issue Microfluidic Device Fabrication and Cell Manipulation)

Round 1

Reviewer 1 Report

The author presented the design and development of a simple traveling wave ferro-microfluidic device and system rig purposed for the potential manipulation and magnetophoretic separation of cells in water-based ferrofluids. They proposed the method for tailoring cobalt ferrite nanoparticles for specific diameter size ranges (10-20nm), the development of a ferro-microfluidic device for potentially separating cells and magnetic nanoparticles, and the development of a water-based ferrofluid with magnetic nanoparticles and non-magnetic microparticles, etc. The author conducted many experiments and provided detailed descriptions in the article. However, the Figures in the manuscript are not standardized, such as inconsistent font and size, and many of the figures can be integrated together. It is not clear what figures a and b in Figure 17 represent respectively. The same problem also appears in Figure 28.

Please check the grammar and spelling of the full text.

Author Response

Thank you for your review and comments.  The subcaptions have been revised in these images.  The formatting issues have also been addressed.  We have scanned the manuscript and corrected grammatical and spelling errors as well.

Reviewer 2 Report

This work presents the design and development of a simple traveling wave ferro-microfluidic device and system rig purposed for the potential manipulation and magnetophoretic separation of cells in a water-based ferrofluid.    The work includes designing a heat sink for the device, preparing cobalt ferrite nanoparticles, tailoring a water-based ferrofluid for the particles, and performing particle dynamics studies to characterize the behavior of the particles under applied current, frequency, and fundamental electrode spacing. This is a very interesting work, but the following issues need further clarification by the authors.

1.         The research background and the amount of references on this work are somewhat limit, and the author could add a description of the current state of research on magnetic particle manipulation and traveling wave magneto-hydrodynamic manipulation, as well as the advanced and breakthrough of the device in this study.

2.         The author put the preparation of magnetic nanoparticles and the development of water-based magnetic fluids into the main work contribution, is this preparation method used for the first time? What are the advantages of them?

3.         Please check if the "170°" in line 101 should be "270°".

4.         How is the operating frequency determined when the device is used, and what are the effects of different frequencies?

5.         The viscosity of water-based magnetic fluid at 20°C is inconsistent with the statement on line 249 and line 413, please confirm.

6.         The result in Figure 7 is somewhat difficult to understand, only in the area of the output pads and electrode sharp turn there is a clear color, what is the temperature range in the rest of the area?

7.         Should the legend ".5A" in Figure 9 be changed to "0.5A", please confirm.

8.         Whether the temperature of the device changes during a long working time? What is the longest time for the device to work stably?

9.         The expression in Figure 14 is the third batch, the above text says it is the second batch, please confirm.

10.     What are the advantages of image cross-correlation technique over another method? How is the accuracy of the results processed using this method guaranteed?

11.     Figure 14 mentioned in line 516 is a particle size distribution map, which does not match the description in the text, and similarly Figure 16 mentioned in line 533 is an SEM image, which does not match the description in the text, please confirm.

12.     How should the negative velocity in Figure 22 be interpreted, and does it represent a certain direction?

13.     Why the velocity is low at the first electrode for small pitches and increases thereafter. And there is no such phenomenon with large pitch?

 Moderate editing of English language

Author Response

Reviewer2

 

This work presents the design and development of a simple traveling wave ferro-microfluidic device and system rig purposed for the potential manipulation and magnetophoretic separation of cells in a water-based ferrofluid.    The work includes designing a heat sink for the device, preparing cobalt ferrite nanoparticles, tailoring a water-based ferrofluid for the particles, and performing particle dynamics studies to characterize the behavior of the particles under applied current, frequency, and fundamental electrode spacing. This is a very interesting work, but the following issues need further clarification by the authors.

  1. The research background and the amount of references on this work are somewhat limit, and the author could add a description of the current state of research on magnetic particle manipulation and traveling wave magneto-hydrodynamic manipulation, as well as the advanced and breakthrough of the device in this study.

Response: Thank you we have added recent references 2019-2023 to the literature review and revised the review.  We have added over 14 references.

  1. The author put the preparation of magnetic nanoparticles and the development of water-based magnetic fluids into the main work contribution, is this preparation method used for the first time? What are the advantages of them?

Response:  This is not the first time.  There are very few works using this method however.  As mentioned in our conclusion, we aim to create biocompatible ferrofluids for cellular studies.  This work is preliminary work to prove the concept viable for separating magnetic and non magnetic entities.

  1. Comment: Please check if the "170°" in line 101 should be "270°".

Response: Yes, and this has been changed.  Thank you very much.

  1. How is the operating frequency determined when the device is used, and what are the effects of different frequencies?

Response: The operating frequency is set with the waveform generator and is also measured from the oscilloscope.  The phase angles are as well.  This is described in detail in section 2.

  1. The viscosity of water-based magnetic fluid at 20°C is inconsistent with the statement on line 249 and line 413, please confirm.

Response:  This has been corrected.  This was an oversight on our part.  Thank you.

  1. The result in Figure 7 is somewhat difficult to understand, only in the area of the output pads and electrode sharp turn there is a clear color, what is the temperature range in the rest of the area?

Response: Thank you as mentioned in the manuscript, the larger areas will produce more heat as well as sharp turns.  This is similar to the flow of fluid in conduits with sharp turns that promote energy losses.  We rectified this in the final design by rounding the turns.

  1. Comment: Should the legend ".5A" in Figure 9 be changed to "0.5A", please confirm.

Response:  Thank you, yes this has been modified.

  1. Whether the temperature of the device changes during a long working time? What is the longest time for the device to work stably?

Response:  The temperature remains steady state after 30s.  The Neslab rig is able to effectively remove heat from the heating block as mentioned in the manuscript.  We were able to run experiments longer than ten minutes using the set point temperatures.

  1. Comment: The expression in Figure 14 is the third batch, the above text says it is the second batch, please confirm.

Response:  Yes,  thank you, this had been changed.  This is the second batch.

  1. What are the advantages of image cross-correlation technique over another method? How is the accuracy of the results processed using this method guaranteed?

Response:  Cross correlation is very accurate.  Cross correlation is a qualitative method used to map the trajectory of illuminated particles in several frames.  The method resolves the images to vectors.

  1. Figure 14 mentioned in line 516 is a particle size distribution map, which does not match the description in the text, and similarly Figure 16 mentioned in line 533 is an SEM image, which does not match the description in the text, please confirm.

Response:  This was an oversight, this was due to the section being switched.  This manuscript was originally intended for the IJMS in which the results section comes before the methodology. Our apologies, this has been corrected.

  1. How should the negative velocity in Figure 22 be interpreted, and does it represent a certain direction?

Response: Yes, this is directional and has been included in the manuscript.

  1. Why the velocity is low at the first electrode for small pitches and increases thereafter. And there is no such phenomenon with large pitch?

Response:  This is observed in all cases if you zoom in on all contours.  This is believe to be attributed to the polarity changes at the electrodes that creates a push/pull effect. 

 

Reviewer 3 Report

This paper describes the design and development of a simple traveling-wave iron microfluidic device and system device for the potential manipulation of cells and magnetohydrodynamic separation in water-based ferrofluids. The model effectively removes heat from the circuit board, thus allowing a range of input currents and frequencies to manipulate non-magnetic particles. The results show that non-magnetic and magnetic particles can be separated and, in some cases, moved continuously through the channel according to amperage, size, frequency, and electrode spacing. The content of this paper is clear and fluent, with high research value, but there are the following problems:

 

1. The references cited in the last five years are less, please add if necessary.

2. In the first half of this paper, it is mentioned that this is the design and development of a traveling wave iron microfluidic device and system device for the potential manipulation of cells and magnetohydrodynamic separation in water-based ferrofluids, which is then replaced by non-ferromagnetic nanoparticles. Is this method feasible and does it have an effect on the activity of cells?

Author Response

Reviewer 3

  1. The references cited in the last five years are less, please add if necessary.

Response: Thank you we have added recent references 2019-2023 to the literature review and revised the review.  We have added over 14 references.

  1. In the first half of this paper, it is mentioned that this is the design and development of a traveling wave iron microfluidic device and system device for the potential manipulation of cells and magnetohydrodynamic separation in water-based ferrofluids, which is then replaced by non-ferromagnetic nanoparticles. Is this method feasible and does it have an effect on the activity of cells?

Comment:  Thank you for your review.  The non-magnetic particles are surrogates for cells as mentioned in the abstract.  Also the feasibility of this method will be tested with live cells as mentioned in our planned future work as listed in the conclusion of the manuscript.

Round 2

Reviewer 2 Report

 I have no more questions.

 I have no more questions.

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