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A range of 5 microneedle geometries were designed using the SolidWorks computer aided design (CAD) package. The designs are shown in Figure 7.1. The designs shown were chosen to reflect a selection of the structures found in the literature, allowing the optimum design to be chosen using finite element analysis (FEA) modelling techniques.

Each design has a number of key variables, which can be altered during FEA modelling to produce the optimum combination for each of the geometries shown in Figure 7.1. These key variables are shown in Figure 7.2. The range of variables used in this study are shown in Table 7.1, along with a number of variables taken from the literature for comparison.

Table 7.1 – Range of variables considered in this study, compared to previous work in the literature.

Reference Tip Radius

(µm) Needle Height (µm) Bore Radius (µm) Base Width (deg) Array Spacing (µm) This Study 15 - 60 200 - 1200 15 - 45 150 – 600 200 – 800 McAllister et al [1] 75 500 22.5 300 ~ 400 Stoeber and Liepmann [2] 50 200 20 425 ~ 500 Griss and Stemme [3] 10 200 30

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~ 300

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Figure 7.1 – Microneedle array structures, designed using SoildWorks CAD package. (a) Conical, (b) asymmetric pyramid, (c) stepped cone, (d) symmetric pyramid and (e) inverted trumpet.

Figure 7.2 – Key variables for microneedle geometries tested. Another available variable is the spacing of the array, between microneedle structures.

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Although modelling ranges of all of the variables listed in Table 7.1 would be ideal, it would require too many iterations to be practical. However, the number of design iterations required can be greatly reduced by limiting the parameters varied during the analysis. Davis et al [4] in 2004 found the major factors governing the force required to fracture their hollow nickel microneedles, fabricated using LIGA techniques, were the wall thickness, the wall angle and the needle tip radius. As a result, the parameters varied in this study were the bore diameter (analogous to the wall thickness) and tip radius. Bore variation includes no bore, in effect testing a solid microneedle design. The needle height was set at an arbitrary 400 µm, as it was felt this was long enough for skin penetration, and was a height easily fabricated using the EnvisionTEC Perfactory Mini Multi-Lens system, which has a Z-axis resolution of 25 µm. Finally, the microneedle base width was set at and again arbitrary 300 µm.

Individual CAD files were produced for each geometric variation, and tested using SolidWorks’ built-in FEA modelling suite, COSMOSWorks. The array models were subjected to incremental force on the needle tip, perpendicular to the array plane. The needle is assumed to have failed once the sum of the stress within the structures reaches the tensile strength of a model photopolymer material, in this case the EnvisionTEC Perfactory resin e-Shell 100 (tensile strength 47.8 MPa). Although this method of analysis, known as the Von Mises method, can underestimate the actual strength of the structures in vivo, i.e. when inserted into the skin, this underestimation can be incorporated into the require safety margin required for such devices. The raw data collected is shown in Table 7.2, and shown graphically in Figure 7.3.

There are a number of observations that can be made from the data shown in Table 7.2 and Figure 7.3. The weakest geometry by far is the asymmetric pyramid, with a failure force of less than one tenth of the other symmetric designs. The addition of a central bore to the design, which was offset from the needle tip, exacerbates this weakness far more than in the other symmetric designs, a result which is in line with previous studies [4]. Several examples of

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asymmetric microneedle arrays can be found in the literature, including Gardiniers et al [5] and Moon et al [6], in silicon via micromachining techniques and PMMA via LIGA processes. In both cases, the asymmetric design was used more because of the limitations of the fabrication process, rather than due to any optimisation steps. It is likely that the design is inefficient when handling load due to the force being offset through the structure, and the success of these designs can perhaps be attributed to the higher tensile strengths of the materials used: 6.9 GPa and 76 MPa for silicon [7] and PMMA [8] respectively, compared to the 47.8 MPa of EnvisionTEC e-Shell 100. It is clear that a more efficient design is required for use with weaker photocurable polymers, and therefore the design of the asymmetric pyramid was discarded.

Bore Radius (µm) Tip Radius (µm) 15 30 45 60 Conical 0 0.021 0.110 0.267 0.464 15 0.024 0.104 0.229 0.415 30 0.020 0.102 0.241 0.428 45 0.021 0.104 0.254 0.390 Inverted Trumpet 0 0.024 0.102 0.244 0.419 15 0.025 0.111 0.227 0.419 30 0.024 0.116 0.224 0.464 45 0.024 0.115 0.249 0.416 Symmetric Pyramid 0 0.021 0.091 0.212 0.352 15 0.021 0.089 0.213 0.365 30 0.019 0.091 0.213 0.375 45 0.017 0.091 0.217 0.375 Asymmetric Pyramid 0 0.003 0.014 0.026 0.038 15 0.003 0.013 0.023 0.029 30 0.003 0.013 0.023 0.030 45 0.003 0.011 0.021 0.028 Stepped-Cone 0 0.030 0.118 0.256 0.423 15 0.028 0.101 0.252 0.416 30 0.028 0.104 0.250 0.423 45 0.028 0.104 0.256 0.416

Table 7.2 – Simulated failure forces for six microneedle geometries in arrays of 3 × 3 needles. Forces are expressed in Newtons and are per needle.

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Figure 7.3 – Graphical representations of needle failure force, with respect to microneedle tip and bored radius. All forces in Newtons and are per needle. All radii in micron. Simulated microneedle material is EnvisionTEC e-Shell 100, with a tensile strength of 47.8 MPa.

The data collected shows that, in all the geometries tested, the major variable was the size of the tip, with the bore radius making relatively little difference. This is perhaps not surprising, as a large needle tip will distribute the force more efficiently when in contact with a flat, hard surface, which is applicable in these models. However, although the overall strength of the microneedle structure is important, it is not the only factor governing their efficiency. A sharper needle point will concentrate the force exerted through the needle over a smaller area,

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causing less stress to be placed upon the overall structure. The non-isotropic nature of skin enhances this effect. The relatively low strengths suggested at small tip radius cannot therefore be seen as directly indicative of their performance in vivo. However, as noted earlier, this underestimation can be factored in as part of any safety margins required for microneedle devices, and therefore the data is still meaningful.

In practice however, the needle tip radius is limited by the resolution of the EnvisionTEC Perfactory Mini Multi-Lens system to be used in their fabrication. At the time of this study, the smallest feature size achievable was 30 µm, with the Enhanced Resolution Module (ERM) allowing a pixel accuracy of 15 µm. Therefore, a tip radius of 45 µm was seen as achievable for fabrication and mechanical testing. Of the remaining geometries, the inverted trumpet and stepped cone were chosen over the symmetrical pyramid and conical designs. The symmetrical pyramid was discounted due to its inferior calculated breakage strength. The conical design in theory offers better performance with a 45 µm tip radius. However, the inverted trumpet and stepped cone structures offered better performance at lower tip radii, and therefore were chosen due to the assumption that lower tip radii would be attempted later in the study.