Design and Numerical Simulation of a Standing Surface Acoustic Wave-Based Microdevice for Whole Blood Cell Separation

Round 1

Reviewer 1 Report (Previous Reviewer 3)

Comments and Suggestions for Authors

The authors have addressed all my concerns. The manuscript has been significantly improved and is suitable for consideration for publication.

Author Response

see attachment.

Author Response File: Author Response.docx

Reviewer 2 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

This paper describes a simulation study about the design and modeling of a standing surface acoustic wave-based microdevice for whole blood cell separation. The modeling work seems to be well executed but we need to validate the results. It is a standard practice that all the theoretical modelings are validated by some experimental results. In this case we obtained a set of numbers that correspond to the optimum configuration that will achieve the successful separation and it would be easier to build the microdevice and assess its performance. 

Author Response

The authors thank the reviewers for their insightful comments and suggestions. Every concern or advice expressed by the reviewers has been addressed in the revised manuscript as well as addressed in this rebuttal. The changes made in the original manuscript are stated in the following. We believe that the revised manuscript is significantly improved by making these changes.

The reviewers’ comments are followed by explanations made by the authors in response to the comments.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report (Previous Reviewer 1)

Comments and Suggestions for Authors

A revised version has been submitted. Although the authors did not validated the results using experimental data they use an alternative with a published work. The authors should explain in the manuscript the rational for the validation including the lack of experimental results and the numerical alternative.

Author Response

Comment:  A revised version has been submitted. Although the authors did not validated the results using experimental data they use an alternative with a published work. The authors should explain in the manuscript the rational for the validation including the lack of experimental results and the numerical alternative.

Answer: Thanks for your comment. We have made the following changes to the manuscript to clarify that the final design was not verified with experimental data. However, published experimental data was used to validate our numerical model in the initial stage.

Furthermore, we have updated the article title to clearly reflect this.

Changes:

Title: Design and numerical simulation of a standing surface acoustic wave-based microdevice for whole blood cell separation

The changes in the introduction:

In SSAW-numerical models, the constitutive equation for piezoelectric, i.e. Helmholtz equations, and the Navier-Stokes equations for fluid mechanics, must be solved simultaneously to accurately capture the underlying physics. The developed model in this work is verified against previously published data ensuring an effective replication of the blood cell behavior in an acoustic field. The numerical results are in good agreement with the published experimental studies, confirming the model's accuracy and providing a powerful tool to further investigate the application of acoustofluidic chips in whole blood cell separation. Finally, utilizing this verified numerical model, a five-outlet channel design is proposed, maintaining the same physical behavior while being optimized for improved separation efficiency.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This paper describes a modeling/simulation of the standing surface acoustic wave based microdevice for whole blood cell separation. This is a useful preliminary work, but it is mandatory to validate the obtained results by applying the obtained theoretical results into a real experiment. Without this validation it is not possible to assess this work.

Reviewer 2 Report

Comments and Suggestions for Authors

In the manuscript ID computation-3263233, the authors studied the simultaneous separation of white blood cells, red blood cells, and platelets in one step, with the aid of numerical calculations. For this purpose, they used the linear constitutive equation for the piezoelectric substrate, the Helmholtz equation for the acoustic field, and the Navier-Stokes equations for fluid mechanics and they predicted accurately the capture blood cell behavior in the standing surface acoustic wave-based device. The linear constitutive equation was solved using the solid mechanics and electrostatics for the piezoelectric part.

In the first part of the paper, they highlight the importance of separating damaged cells from healthy blood cells. Blood cell separation is one of the most critical steps for diagnosing blood cell-related diseases. Any observation that detects an abnormal amount of white blood cells (WBCs), red blood cells (RBCs), and platelets (PLTs) in the blood could be an indication of a particular disease. They also presented the advantages of microfluidic devices and acoustofluidics in manipulating particles.

The microfluidic devices allow portability, integration, and miniaturization at a very small scale (to integrate them into a simple micro-sized system) a whole laboratory having the advantage of significantly reducing the consumption of reagents, energy, time, and implicit money. Microfluidics also bring a better and more efficient performance in particle separation. On the other hand, acoustofluidics, (surface acoustic waves and bulk acoustic waves ) uses acoustic pressure waves on a micro-scale to manipulate particles. Several numerical studies facilitate optimization for boosting separation efficiency. The authors designed a standing surface acoustic wave-based device and simulated the capture of blood cell behaviour in the microchip, with the help of physics, including piezoelectricity, acoustic and fluid mechanics.

The experimental setup consisted of a microfluidic chip with three inlets and five outlets. Standing acoustic waves are generated using two Inter Digital Transducers located on both sides of the channels. They used a LiNbO3 piezoelectric substrate and a microchannel from PDMS . For simulation they used COMPSOL Multiphysics 6.0.  The results were verified using a 2D finite element method simulation.

They concluded that whole blood cell separation can be achieved using a velocity ratio of 6.25, a resonance frequency of 8.28 MHz, and a voltage of 8.5V  through the proposed five-outlet channel microchip.

In my opinion, the paper is well written, and the computational results help the scientific community, to predict and simulate the manipulation (extraction, separation, etc) of blood cells. The paper is also very important research for helping the specialists from the biomedical field.

As a result, I agree with the publication of this paper after minor revisions:

Please respect the mdpi template for Computation journal .

-          The references should be numbers.

Line 156, the font of the “2.1. Governing Equations” should be  Palatino Linotype 10

Tables must be wrote with Palatino Lino type 9, etc.

Please also formatting of Mathematical Components

The text following an equation need not be a new paragraph. Please punctuate equations as regular text.

Reviewer 3 Report

Comments and Suggestions for Authors

The authors studied design and modelling of a standing surface acoustic wave-based microdevice for whole blood cell separation. However, my concerns are 

 

1. Please proofread the spell (COMPSOL Multiphysics and etc.), text font, size etc. 

2. What is c_k in the equation 6? is this typo? 

3. The authors have listed equations; however, the calculated results seem from the FEM simulation. Could you please explain how authors use these equations in the proposed study or explain the results. 

4. The authors concluded "Results show that whole blood cell separation can be achieved using a velocity ratio of 6.25, a resonance frequency of 8.28 MHz, and a voltage of 8.5V through the proposed five-outlet channel microchip.", but could you please suggestion on how to design the system. The number is simply based on some presumption, parameters, and authors are highly suggested to provide the design guidelines how to use their propose model to design general SSAW blood cell separation.

 

Overall, the authors proposed the design, however, authors need to emphasize what are the innovation and significance. It is not well explained what authors' contribution is to develop the model (the model seems from the FEM). The derived number is based on certain situation and did not explain/provide general design concept. 

Comments on the Quality of English Language

NA