Rapid Tooling for Microinjection Moulding of Proof-of-Concept Microfluidic Device: Resin Insert Capability and Preliminary Validation

Round 1

Reviewer 1 Report

This work shows a low-cost method to produce injection molded microfluidics. The work demonstrates channels with 200 um with various shapes with a simple microfluidics use case. The authors should consider large area application and a small use case to boost the motivation that they are pursuing.

·      Could you please comment on the minimum mold thickness that you can produce? And the cost of such structure.

·      The authors compare different methods at the introduction part. 3D direct ink writing and 3D printing should be included to that discussion and the Table 1.

Some examples:  

https://doi.org/10.1002/cplu.201700440, https://doi.org/10.1002/adma.201004625 or similar

·      Would it be possible to produce the inserts using flexible material? Please comment on the fabricating flexible microfluidic channels?

·      Could you please explain the cracks on the samples?

·      Could you please comment on the size of the channels? 200 um is material limited?

·      What would be the maximum thickness of the active layer, to increase the capacity?

·      How did you extract the mappings of flatness variation? Just bare thickness measurements?

·      Please include how the roughness is measured.

·      The authors should demonstrate more complex channels to motivate better applications (serpentine, longer or reservoirs)

·      SEM or better microscopy pictures can give more idea of defects and actual channel width and depth.

·      Last 3 figures can be combined together.

minor issues

Author Response

Reviewer #1:

This work shows a low-cost method to produce injection molded microfluidics. The work demonstrates channels with 200 um with various shapes with a simple microfluidics use case.

The authors thank the reviewer for these interesting comments and modified the article according to the following suggestions:

1. The authors should consider large area application and a small use case to boost the motivation that they are pursuing.

The authors improve introduction with new citation [38-44] to boost motivation as the reviewer suggested.

2. Could you please comment on the minimum mold thickness that you can produce? And the cost of such structure.

The author added this information in the introduction about the technology resolution (25 µm) and in the conclusion highlighting that MJ can reproduce these inserts with production cost lower than $10.

3. The authors compare different methods at the introduction part. 3D direct ink writing and 3D printing should be included to that discussion and the Table 1.

Some examples:

https://doi.org/10.1002/cplu.201700440,

https://doi.org/10.1002/adma.201004625 or similar

The authors updated Table 1 to include information pertaining to 3D printing, even though the application of this technology, as discussed in the cited article, leans more towards laboratory rather than industrial use. Specifically, the 3D printing method described was confined to creating a singular customized solution, whereas the proposal was to employ 3D printing technology for the production of tools.

4. Would it be possible to produce the inserts using flexible material? Please comment on the fabricating flexible microfluidic channels

The authors lacked experience in this area; however, generally speaking, flexibility is a characteristic more aptly suited for parts rather than inserts. This is because excessive flexibility in inserts could compromise the precision stability of the parts.

5. Could you please explain the cracks on the samples?

Yes, totally in agree with this comment the authors added in the results that cracks were due to the compression forces that occurs during the filling step of the injection moulding process,

6. Could you please comment on the size of the channels? 200 µm is material limited?

Certainly, because the layer height resolution is 25 µm, preliminary research indicated that a minimum of 4 layers must be printed to ensure the robustness of a designed feature. Materials and Methods were updated with this.

7. What would be the maximum thickness of the active layer, to increase the capacity?

The maximum layer height is 50 µm. However, increasing thickness to enhance capacity is not the focus here; material jetting technology's production rate is closely linked to the parts' height, regardless of whether the heat drops or not. The process necessitates movement along the print plate, implying that the fill level of the print plate does not significantly influence production time. For instance, the time required to produce one of the inserts was specifically within the range of 2 hours and 30 minutes and producing 10 parts took the same amount of production time. Given the considerations mentioned, the process allows for printing parts thinner than might otherwise be possible, to improve their resolution.

8. How did you extract the mappings of flatness variation? Just bare thickness measurements?

The authors better explain in chapter 3.2 of was the area chosen for flatness analysis. The scanning frequency (0.1 mm) was reported too.

9. Please include how the roughness is measured.

The authors better explain in chapter 3.2 of was the area chosen for roughness analysis and how was measured (laser probe scanning)

10. The authors should demonstrate more complex channels to motivate better applications (serpentine, longer or reservoirs)

The authors are totally in agree with the reviewer. In this work it was already tested inserts with a more complex geometry in the second experimental phase, as reported in paragraph 2.3. Microstructured inserts with a typical lab-on-chip geometry, containing straight and crossed microchannels and reservoirs were tested, and the results are reported in paragraph 3.2. A more complex channels will be a challenge for future works

11. SEM or better microscopy pictures can give more idea of defects and actual channel width and depth.

The authors fully agree with the reviewer; SEM (Scanning Electron Microscopy) analysis would indeed provide a more detailed view of defects. However, in this article, the focus was primarily on evaluating the workability of the proposed solution. The objective was to investigate whether this technology could accurately replicate the typical features of a microfluidic device and whether these micro features could withstand the typical parameters of the molding process, thus being capable of producing samples with this level of complexity. To verify the complete replication of channels, the authors designed a microfluidic test. Certainly, as the reviewer suggested, once the feasibility has been demonstrated, future efforts will concentrate on optimizing the part geometry, at which point SEM analysis will become crucial.

12. Last 3 figures can be combined together.

Following reviewer suggestion figure 12 and 13 were combined together

Reviewer 2 Report

The paper presents a method for creating a concept microfluidic device using microinjection moulding.  This paper provides guidance for the mass production of microfluidic chips. It first examines the effect of insert orientation on the printing plate and its impact on the finished product's quality. It then investigates the quality of the product after multiple injection moulding and discusses the factors that affect the finished product's quality. The work is significant, and the results are reliable.It can be published in Applied Sciecnes.The followings are minor comments.

L100：The commas should be dots.

L208: "All the inserts exhibited cracks along their cross-sections". Please provide an objective analysis of the reason.

Figure 4(e): It should be "V90",not "V00"

Figure 10: The Letter number of the third picture should be "c”.

Author Response

Reviewer #2:

The paper presents a method for creating a concept microfluidic device using microinjection moulding. This paper provides guidance for the mass production of microfluidic chips. It first examines the effect of insert orientation on the printing plate and its impact on the finished product's quality. It then investigates the quality of the product after multiple injection moulding and discusses the factors that affect the finished product's quality. The work is significant, and the results are reliable. It can be published in Applied Sciences followings are minor comments.

The authors thank the reviewer for these comments and modified the article according to them.

1. L100：The commas should be dots.

The authors are sorry for the mistake and correct it

2. L208: "All the inserts exhibited cracks along their cross-sections". Please provide an objective analysis of the reason.

The authors in the 3.1 results chapter explained the reasons

3. Figure 4(e): It should be "V90”, not "V00"

The authors thank the reviewer for this mistake and correct it

4. Figure 10: The Letter number of the third picture should be "c”.

The authors thank the reviewer for this mistake and correct it

Reviewer 3 Report

This manuscript can be accepted after minor but mandatory revision. The authors stated that it is a microfluidic device. Therefore, the authors are expected to conduct some preliminary experiments showing that it is a microfluidic device. For example, the authors can conduct the typical demonstration showing that  it can generate some micro-bubbles or it can be used to test some biological molecules in tiny concentrations such as nmol or picomol.

 SEM characterization is suggested to be done in order to see the surface morphology or roughness of the micro-channel.

Minor editing of English language required

Author Response

This manuscript can be accepted after minor but mandatory revision.

1. The authors stated that it is a microfluidic device. Therefore, the authors are expected to conduct some preliminary experiments showing that it is a microfluidic device. For example, the authors can conduct the typical demonstration showing that it can generate some micro-bubbles or it can be used to test some biological molecules in tiny concentrations such as nmol or picomol.

The authors apologize for this misunderstanding. We stated that we tested resin inserts with a typical LOC geometry containing straight and crossed microchannels and reservoirs, to produce PMMA parts. Subsequently, as reported in Section 4, these samples were bonded to other PMMA parts for the preliminary microfluidic test using the tracer fluid. The verification confirmed the presence of channels and the correct flow of fluid from the two inlets to the outlet. With this positive result, the next studies will focus on the prototyping of a microfluidic device with biological validation. To improve clarity, we have replaced the term "device" with "tester" in paragraph 4.

2. SEM characterization is suggested to be done in order to see the surface morphology or roughness of the micro-channel.

The authors fully agree with the reviewer; SEM (Scanning Electron Microscopy) analysis would indeed provide a more detailed view of defects. However, in this article, the focus was primarily on evaluating the workability of the proposed solution. The objective was to investigate whether this technology could accurately replicate the typical features of a microfluidic device and whether these micro features could withstand the typical parameters of the molding process, thus being capable of producing samples with this level of complexity. To verify the complete replication of channels, the authors designed a microfluidic test. Certainly, as the reviewer suggested, once the feasibility has been demonstrated, future efforts will concentrate on optimizing the part geometry, at which point SEM analysis will become crucial.

Round 2

Reviewer 1 Report

Thanks for responding point by point. The answers provided are sufficient.

Reviewer 3 Report

This manuscript can be accepted  since all the concerns from the reviewers have been addressed.