Enhanced Monte Carlo Simulations for Electron Energy Loss Mitigation in Real-Space Nanoimaging of Thick Biological Samples and Microchips

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript provides insights into using Monte Carlo simulations to mitigate electron energy loss in thick sample imaging. I recommend a major revision to address the following issues.

1.  How is the energy spread of "3*10^-5" in the section 2.1 obtained? Is it a non-dimensional value?

2. The Reviewer is curious about the qualifier "advanced" used in the title. Why are such simulations considered advanced?

3. Clarifying the differences between spatial resolution and image quality is recommended.

4. At the end of the introduction section, the authors must comment/discuss the implications of this work better, especially regarding drug development. 

5. References [12,13] must be cited separately as "Henderson [12]" and "Peet et al. [13]".

6. Why have the authors defined the angle interval d𝜃 in this manner (page 3, lines 101-103)?

7. The notation "Energy loss (MEL)" (Figure 3, x-axis) is confusing. Could you improve the explanation?

8. Please identify Figure 3-6's panel labels on the top-left corners.

9. Can the lower shift observed in Figure 5d-e be corrected using a Gaussian fit?

10. How does your previous study (reference [6]) contribute to interpreting the current results? Please improve this discussion in the revised manuscript.

11. Which sample compositions would be interesting for a follow-up evaluation? Please, discuss such next steps in the final paragraph of the revised conclusion.

12. The Appendix can be converted into a Supporting Information file.

Author Response

Dear reviewer,

we appreciate you for spending valuable time reviewing our paper and providing highly constructive advice and suggestions. We have implemented all the recommended changes based on your suggestions, which have greatly improved the quality of our manuscript.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Thanks for the invitation to review this work. The article introduces a simulation tool to estimate the Electron Energy Loss Spectrum (EELS) for Transmission Electron Microscopy (TEM) applications, focusing on minimizing energy loss in imaging thick biological samples and microchips. It leverages recent advancements in high-energy MeV-TEM/STEM technology, integrating it with Monte Carlo (MC) simulation techniques. However, potential issues including a lack of clarity and detail in describing assumptions, and parameter estimation may lead to inaccuracies in the Monte Carlo simulations and EELS integration.

 

1.     Lack of detail and clarity in model assumptions and EELS parameters could lead to inaccuracies.

2.     Simulation outcomes, involving energy loss across different thicknesses using GF-EELS and MELM, need explicit validation and discussion of discrepancies. For EELS data, it's crucial to outline assumptions clearly to prevent misleading interpretations.

3.     The effectiveness of GF-EELS and MELM for thin and thick samples requires identification of accuracy divergence points to guide result applicability.

4.     Parameter estimation for cross-section and beam attributes should be detailed for accuracy.

 

5.     Consider including citations of Exploration, J. Mater. Chem. A, 2024, 10.1039/D4TA07127A

Author Response

Dear reviewer,

we appreciate you for spending valuable time reviewing our paper and providing highly constructive advice and suggestions. We have implemented all the recommended changes based on your suggestions, which have greatly improved the quality of our manuscript.

Sincerely, 

Xi Yang

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The paper is devoted for advanced Monte Carlo simulations for electron energy loss mitigation in real space nanoimaging of thick biological samples and microchips. The topic is generally interesting, however the paper contain unexplained places and need major revisions.

In abstract is written ‘’The finding will guide the selection of optimal beam settings. Thereby enhancing resolution for nanoimaging of thick  biological samples and microchips.’’ Please explain in the paper text how.

Fig. 1 should be commented in the paper text.

Fig. 2 please explain why MFP is independent on electron energy for energies biggest as 1 eV.

Fig. 4, please explain why energy loss is nonlinear function of sample thickness.

Please explain the high noise level for results presented in Fig. 6.

Conclusions should be rewritten in more informative way.

Author Response

Dear reviewer,

we appreciate the reviewer for spending valuable time reviewing our paper and providing highly constructive advice and suggestions. We have implemented all the recommended changes based on the referee’s suggestions, which have greatly improved the quality of our manuscript.

Sincerely, 

Xi Yang

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed all my concerns, offering a detailed point-by-point discussion alongside the revised content. The manuscript has also seen improvement. I recommend accepting this version for publication as it stands.

Reviewer 2 Report

Comments and Suggestions for Authors

Thanks for the invitation to review this work. The authors have tried to improve the work and solve the previous concerns. The article is recommended for publication.

Reviewer 3 Report

Comments and Suggestions for Authors

Authors make proper corrections according to reviewer remarks and I suggest to publish the paper as it is.