Integración Espacial.

7.5.1 FEM Analysis

In order to validate the modelling used in this study, further analysis was carried out on the maximum stress experienced by a full 9 × 9 array of 400 µm microneedles before mechanical testing was carried out. The geometries used were those selected by the initial modelling: the stepped cone and inverted trumpet. Results from these tests could then be compared with mechanical testing data produced from arrays produced using the same CAD data used in the FEM analysis.

A model was produced in COSMOS similar to that used previously, with each needle in the array subjected to a force on its tip perpendicular to the array plane. This force would increase until the maximum stress in the structure reached that of the tensile strength of the fabrication material. For the mechanical tests, the selected material was EnvisionTEC Perfactory R11, chosen

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as it was a proven reliable material that could be depended on when producing multiple identical arrays for testing. The mechanical properties of R11 (see Table 7.3) were used to create a custom material in COSMOS for the FEM analysis.

Figure 7.10 – Microneedle arrays after simulation. The colour spectrum indicates the stress distribution throughout the needle structures. (a) is an array of stepped cone geometry microneedles, (b) shows an array of inverted trumpet structures.

The results of this analysis are shown in Figure 7.10 and Table 7.4. They show the stress distribution for both geometries are similar, although the stepped cone shows a slight higher failure force per needle. It is likely that the identical tip diameter causes the similar result, and the stepped cone has more material further towards the tip, resulting in the larger break force result.

Inverted

Trumpet Stepped Cone

39 MPa 39 MPa

Material Strength (R11)

Force Level at Max. Stress 16.61 N 17.17 N

Failure Force Per Needle 0.205 N 0.212 N

Table 7.4 – Tabulated failure values for each microneedle design, as calculated in FEM analysis.

By increasing the applied force beyond that of maximum of the material, the normal failure mode can be visualised, as shown in Figure 7.11. As could be expected, with the load being applied axially, the failure mode in both geometries is one of the crushing of the material.

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Figure 7.11 – Representation of simulated failure mode of microneedles under axial load. (a) is an array of stepped cone geometry microneedles, (b) shows an array of inverted trumpet structures.

7.5.2 Mechanical Testing

A test rig was constructed to measure the axial failure force of arrays of our MSL- fabricated microneedle arrays. An overview of the apparatus can be seen in Figure 7.12. Each microneedle array was placed into the sample site, held in position by the pressure generated by a loaded spring. The spring was calibrated as giving a force of 2.27 N/mm, and was mounted on a Schneeberger frictionless table. The position of the table was controlled by the displacement control screw thread, and the displacement was measured using a TESA Displacement probe connected to a readout display. As pressure was applied to the microneedle array, the structures were visualised under an optical microscope mounted above the sample site. A failure force was deemed to have occurred once the needles had deformed significantly. Although this is a subjective measure, the testing of 7 separate but identically fabricated arrays of each geometry keeps error to a minimum. Both arrays consisted of 400 µm tall needle structures, with a 45 µm radius tip, spaced at 700 µm, fabricated from EnvisionTEC Perfactory R11.

The results of the mechanical testing can be seen in Table 7.5 and Figure 7.13. As with the FEM analysis, both geometries produced similar results. However, unlike the FEM data, the mechanical data suggests the inverted trumpet is the strongest shape under axial load. Also

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notable is the expected underestimation in the simulation results compared to those produced via mechanical testing.

Figure 7.12 – Apparatus for mechanical testing of MSL fabricated microneedle arrays. (a) Microneedle sample site, (b) displacement control, (c) Schneeberger Frictionless Table, (d) spring load, (e) TESA Displacement Sensor, (f) TESA Numerical Display, (g) top mounted optical microscope.

Failure Force Per Needle (N)

Sample No. Inverted Trumpet Stepped Cone

1 0.278 0.237 2 0.29 0.282 3 0.292 0.248 4 0.287 0.22 5 0.237 0.255 6 0.251 0.206 7 0.205 0.256

Average Failure Force 0.263 0.243

Table 7.5 – Data collected from MSL microneedle arrays via mechanical testing, via the test rig shown in Figure 11.

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Figure 7.13 – Graphical representation of results gathered from mechanical test rig. The figure compares simulated failure forces (red) to measured failure forces (blue, line indicates average) for (a) inverted trumpet and (b) stepped cone geometries.

A reasonable range of data is present, probably due to deficiencies in the testing procedure. The microscope was only able to focus upon the top row of needles in the array, meaning it was their failure force that was truly being measured, not that of the array as a whole. Post test observation of the arrays showed uneven wear on some samples, suggesting that the force was not evenly spread across the whole array. However, it was observed that the majority of needles underwent a crushing failure mode, indicating that for the most part the force was relatively even. A low number of the structures did however undergo a bowing failure mode, indicating imperfect axial load in some cases. This could go some way to explain the stepped cone geometry being stronger than the inverted trumpet in testing, although simulation results suggested otherwise. The stepped cone design has more material toward the needle tip, which in theory would make it less susceptible to non-axial loads. This weakness would not be found in simulations, which assume perfect axial load.

However, although the testing was not as accurate as could have been achieved, it was perhaps overkill in any case. Assuming an axial load, the 90 µm-diameter needle tips would have been experiencing pressures of around 30 to 32 MPa at the measured point of failure – nearly ten times required pressure in order for a needle structure to pierce the skin [10]. It is therefore

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reasonable to assume that these structures are capable of creating the micropores required for the diffusion of large macromolecules such as insulin across the skin.