Design of a Cell Phone Lens-Based Miniature Microscope with Configurable Magnification Ratio

Round 1

Reviewer 1 Report

I have problems reviewing this manuscript!

This is a very nice student work at master degree! It shows a lot of competence in dealing with the problems and shows a good quality work. If it was submitted on an advanced teaching journal, I would strongly recommend it for publication.

Concerning publication on a science journal, I have doubts if it is sufficiently innovative to deserve publication.

For me the major point on it is the replacement of an expensive aspherical lens for the objective by an inexpensive mass-produced multi-lens system from a cellphone camera. Keeping aberrations at a low level.

 

The design with the objective and ocular designed to infinite conjugates follows the trend to reduce the tube length from the standard 160 mm of old microscopes to a length as short as desired.

The USB connected, cheap microscopes, are around for many years. The one presented is a better version with interchangeable objective lens. (I have to confess that is difficult to me call this a microscope: For me, a microscope starts at a magnification of 40, bellow this magnification, I call it a loupe.)

As it is said in the manuscript, the versions to adapt to the cellphone sometimes make it difficult to use. This is the reason for the USB connected microscopes sold everywhere on the Net. The quality is low since they aren´t pretend to compete with high end microscopes, but only for easy use in pre-sampling the specimens to bring back to the lab. For a more demanding field work, a portable microscope (40 to 200 magnification) with the ocular lens replaced by a USB camera is used.

As said in the manuscript the short working distance is a problem in this device since the objective is designed for a very short working distance. This is a limitation for the loupe use with leaves or stone chips on the field, that is a must for these small amplification devices.

 

I consider this work a very nice engineering project, with many important details, but I can´t find a sufficiently new idea to be published on a scientific journal.

Author Response

Thank you for your review. We acknowledge your concern about the novelty of the manuscript. However, we still believe that it is worth reporting in a scientific journal for the following reasons.

1. Cell phone based miniature microscopes are continuously attracting attentions [1,2,3]. The built miniature microscope in this manuscript has achieved one of the best performances of such microscopes, i.e. the highest resolution power reaching 600lp/mm, large FOV(7213×5443 um), low distortion, really compact size and very low cost. The resolving ability is approaching a 5X-10X common objective, which is enough for many field imaging or pre-screening applications, and outperforms a general loupe. We demonstrated firstly moving the tube module out of the cell phone, so the ultimate microscope cab as compact as a 15mm cube, which is much easier to handle than the cell phone.

[1] B. Dai, Z. Jiao, L. Zheng, H. Bachman, Y. Fu, X. Wan, Y. Zhang, Y. Huang, X. Han, C. Zhao, T. J. Huang*, S. Zhuang, D. Zhang*, “Colour compound lenses for a portable fluorescence microscope,” Light: Science & Applications, vol. 8, article no. 75, Aug. 2019.

[2] Szydlowski, N. A. , et al. "Cell phone digital microscopy using an oildroplet." Biomedical Optics Express 11.5(2020).

[3] Febo, R. D. ,  L. Casas , and  A. Antonini . "A smartphone‐based petrographic microscope." Microscopy Research and Technique (2021).

2. Furthermore, the proposed scheme has firstly pointed out the magnification ratio can be switched by interchanging the off-the-shelf cell phone camera lens. The concept is simple, yet it offers a feasible low cost solution for the fixed FOV problem faced by former cell phone microscopes.   
3. We agree with you that the performance of proposed microscope scheme is not enough for many micro-imaging application scenarios, however we think it can be a good platform for conducting many novel researches. We have added in the manuscript a special section to introduce some novel applications which are underway based on the built miniature microscope, and hope that it may inspire more ideas for the proposed scheme.

The following paragraph is added in the revised manuscipt：

More importantly, the proposed concept can be used as a miniature platform for various interesting micro-imaging research applications. In the cell culture applications, the real-time microscopic wireless observation can be realized (Figure 10A). The compact size of the microscope module makes it possible to be placed inside the temperature controlled cell culturing tank, and the captured images can be transferred via the cell phone in a real-time manner. In addition, the low cost of the miniature microscope makes it possible to deploy such a module array to monitor an array of cell culturing plates simultaneously. This research is already in progress and has aroused great interest. In this paper, we have demonstrated the maximum magnification of 11.5× and a ~600lp/mm resolution power, which is already one of the best results for such kind of cell phone microscopes. However, the higher resolution is still expected to gain more application possibilities. We have already been investigating the schemes of combining the proposed miniature microscope with other principles, such as total internal reflection imaging(Figure 10B) and structured light imaging(Figure 10C), etc. The proposed scheme enjoys a relatively large FOV in the flat field, making it suitable for carrying out such super resolution methods. In the near future, the advanced fluorescence microscopy with low cost and high resolution will be completely possible. Other interesting applications may include the plant leaf or water particle real time monitoring, etc. In many applications, the ~1mm long working distance of the proposed microscope is acceptable, and as long as this is satisfied, many application schemes can be imagined and designed, on merit of its compact size, reasonable resolution power, large FOV, tale-communication ability and low cost.

Once again, thank you for your comments. The revised manuscript is attached.

Author Response File: Author Response.docx

Reviewer 2 Report

Authors proposed the cell phone applications using several camera lens to make a small size miniature microscope with variable magnification ratio. I saw several similar approaches from several papers, however, authors' approach using currently used camera lens could provide simple microscopy is also interesting. However, there are too small numbers (14) of the references cannot verify the proposed approaches from previous literature. Authors also need to add some missing references and previous paper reviews. In addition, there are some grammar mistakes so it is better to ask your colleague faculty to check the English grammar or use professional English services in entire manuscript because some units and values need to have some spaces and countless words cannot use "the". Therefore, the manuscript needs to be revised. 1. In the reference section, authors should use abbreviated journal names. 2. In the reference section, please do not use double-spacing. 3. In Figure 9, there are too small size graphs. 4. In Tables 1 and 2, letter sizes need to be increased. 5. In Figure 6, letters are not clear to be seen. 6. In Figure 4, please use larger fonts such as Cell phone, sample, light source. 7. In Figure 3, it is hard to see the values of several hundreds um. 8. Please increase Figure 2a font sizes. 9. In Figure 1, please draw the light paths from CMOS image sensor before sample. 10. Authors need to provide the authors' information. 11. Please provide the author contribution, data availability, and acknowledgement sections. 12. Please use proper minus sign for all digits. Please check others. 13. Please have the space between the digit and unit such as 5443um in Line 333. 14. Please add the reference (The microscope has supported human beings to observe and recognize things on a~) with the reference (Schiffer, Michael B., and Andrea R. Miller. The material life of human beings: Artifacts, behavior, and communication. Psychology Press, 1999.) or anothr reference. 15. Please add the reference (Such reversed camera lens based miniature microscopes can conduct micro-) with the reference (Kim, K.M.; Choe, S.-H.; Ryu, J.-M.; Choi, H. Computation of Analytical Zoom Locus Using Padé Approximation. Mathematics 2020, 8, 581. ) 16. Please add the reference (Miniature microscopes still suffer from following limitations~) with the reference (Helmchen, Fritjof, et al. "A miniature head-mounted two-photon microscope: high-resolution brain imaging in freely moving animals." Neuron 31.6 (2001): 903-912.) or another reference. 17. Please add the reference (Reversed camera lens based miniature microscopes can provide high-resolution low-distortion microscope ) with the reference (Rolland, Jannick P., and Henry Fuchs. "Optical versus video see-through head-mounted displays in medical visualization." Presence: Teleoperators & Virtual Environments 9.3 (2000): 287-309. ) or another reference. 18. Please add the reference (Microscopic imaging requires precise control of the working distance between the microscope and the sample ) with the reference (Dufrêne, Yves F., et al. "Imaging modes of atomic force microscopy for application in molecular and cell biology." Nature nanotechnology 12.4 (2017): 295-307. ) or another reference.

Author Response

Thank you for your comments concerning our manuscript. These suggestions are all helpful and valueble for improving our paper. We have studied comments carefully and revised the article according to your suggestions as following.  

Point 1: In the reference section, authors should use abbreviated journal names. 


Response 1: Thank you for your comment. We have modified the journal name in the references.

Point 2: In the reference section, please do not use double-spacing.

Response 2: Thank you for your comment. We have changed it to 0.95 line spacing according to the template.

Point 3: In Figure 9, there are too small size graphs. 


Response 3: Thank you for your comment. We have changed the layout of the graphs to make it clearer

Point 4: In Tables 1 and 2, letter sizes need to be increased.

Response 4: Thank you for your comment. We have increased the sizes of letters in  Table 1and 2.

Point 5: In Figure 6, letters are not clear to be seen.

Response 5: Thank you for your comment. We have increased the sizes of letters in  Figure 6.

Point 6: In Figure 4, please use larger fonts such as Cell phone, sample, light source.

Response 6: Thank you for your comment. We have increased the sizes of fonts in  Figure 4.

Point 7: In Figure 3, it is hard to see the values of several hundreds um.


Response 7: Thank you for your comment. We have changed the text color of the scale to make it easier to distinguish in picture

Point 8: Please increase Figure 2a font sizes. 


Response 8: Thank you for your comment. We have increased the sizes of letters in  Figure 4.

Point 9: In Figure 1, please draw the light paths from CMOS image sensor before sample. 


Response 9: Thank you for your comment. We have added the light path in Figure 1.

Point 10: Authors need to provide the authors' information. 


Response 10: Thank you for your comment. We have added more authors’ information.

Point 11: Please provide the author contribution, data availability, and acknowledgement sections. 


Response 11: Thank you for your comment. We have added the author contribution, data availability, acknowledgement and conflicts of interest to the end of the article.

Point 12: Please use proper minus sign for all digits. Please check others. 


Response 12: Thank you for your comment. We have changed the “-” to “–” to represent the range of number. Further more, we changed the “x” behind numbers to “×” to correctly  represent magnification.

Point 13: Please have the space between the digit and unit such as 5443um in Line 333. 


Response 13: Thank you for your comment. We have added space between the digit and unit.  

Point 14: Please add the reference (The microscope has supported human beings to observe and recognize things on a~) with the reference (Schiffer, Michael B., and Andrea R. Miller. The material life of human beings: Artifacts, behavior, and communication. Psychology Press, 1999.) or anothr reference. 


Response 14: Thank you for your comment. We have added this reference.

Point 15: Please add the reference (Such reversed camera lens based miniature microscopes can conduct micro-) with the reference (Kim, K.M.; Choe, S.-H.; Ryu, J.-M.; Choi, H. Computation of Analytical Zoom Locus Using Padé Approximation. Mathematics 2020, 8, 581. ) 

Response 15: Thank you for your comment. We have added this reference.

Point 16: Please add the reference (Miniature microscopes still suffer from following limitations~) with the reference (Helmchen, Fritjof, et al. "A miniature head-mounted two-photon microscope: high-resolution brain imaging in freely moving animals." Neuron 31.6 (2001): 903-912.) or another reference. 


Response 16: Thank you for your comment. We have added this reference.

Point 17: Please add the reference (Reversed camera lens based miniature microscopes can provide high-resolution low-distortion microscope ) with the reference (Rolland, Jannick P., and Henry Fuchs. "Optical versus video see-through head-mounted displays in medical visualization." Presence: Teleoperators & Virtual Environments 9.3 (2000): 287-309. ) or another reference. 


Response 17: Thank you for your comment. We have added this reference.

Point 18: Please add the reference (Microscopic imaging requires precise control of the working distance between the microscope and the sample ) with the reference (Dufrêne, Yves F., et al. "Imaging modes of atomic force microscopy for application in molecular and cell biology." Nature nanotechnology 12.4 (2017): 295-307. ) or another reference. 


Response 18: Thank you for your comment. We have added this reference.

We also deleted some unnecessary "the" and revised some grammatical problems. As for the language and style, if it still does not meet the requirements, we can further edit it.

And it is necessary to explain that we have rechecked the data and found that the previous experimental data on G5 lens is incorrect. Therefore, we revised the relevant data in this paper. This modification does not affect the conclusion of this paper. We are very sorry for our negligence.

The revised manuscript is attached

Once again, thank you very much for your comments and suggestions

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The interest in portable small magnification microscopes for field use is rising. In the last decade there is a bubble of publications rising about the use of cellphones for everything, from industrial processes control, to high level computing. I can’t see the difference of using a small computer vs a cellphone dedicated to computing. This is the reason of my previous report conclusions.

This work shows a lot of ingenuity, and included different valences, so I praise it!

Comparing with others works that have been publish in this topic, I think this one brings more science to the discussion, so my proposal is accept with minor revision.

I think the manuscript was improved with the corrections made. But:

Reference 19 is completely out of place! Don’t compare Atomic Force Microscopy with Optical Microscopy! Please chose a reference more appropriate to this field of work.

Author Response

Thank you so much for your careful check. We are glad to have your approval for our works. For your suggestion, we have made the following revise：

Point: Reference 19 is completely out of place! Don’t compare Atomic Force Microscopy with Optical Microscopy! Please chose a reference more appropriate to this field of work.

Response: Thank you for your comments. We have revised the 19 reference(Microscopic imaging requires precise control of working distance between the microscope and sample by means of mechanism or shell) to reference(Fuhong Cai, et al."High-resolution mobile bio-microscope with smartphone telephoto camera lens." Optik 207.(2020):. doi:10.1016/j.ijleo.2020.164449.”)

Reviewer 2 Report

Authors revised the manuscript according to the reviewer's comments so the paper can be accepted.

Author Response

Thank you so much for your careful check. We are very glad to have your approval for our revised manuscript.