Investigating Laser Ablation Process Parameters for the Fabrication of Customized Microneedle Arrays for Therapeutic Applications
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Research Design
2.2.1. Pilot Study
2.2.2. Design of Experiment
2.2.3. Predictive Model
- y denotes the predicted response for the experiments (diameter and height).
- b0 denotes the intercept coefficient.
- b1–b5 denote the coefficients of the respective input factors waveform, power, pulse width, repetition, and interval, respectively.
- x1–x5 denote the predictor values for the respective experiment input factors: waveform, power, pulse width, repetition, and interval, respectively.
2.2.4. Mechanical Characterization
3. Results and Discussions
3.1. Pilot Study
3.1.1. Waveform
3.1.2. Laser Power
3.1.3. Pulse Width
3.1.4. Number of Repetitions
3.1.5. Interval Time
3.2. Design of Experiments
3.2.1. Normality Check
3.2.2. Response Surface Analysis
3.2.3. Predictive Model
3.3. Mechanical Characterization of Microneedles
3.4. Discussion and Future Directions
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | Level 1 | Level 2 |
---|---|---|
Waveform | Square | Trapezoid |
Laser power | 30 w | 40 w |
Laser pulse width | 3 ms | 5 ms |
Number of repetitions | 50 times | 100 times |
Interval time | 0 ms | 50 ms |
Parameter | Values Available | Optimal Choice | Reason | Values to Exclude |
---|---|---|---|---|
Waveform | Square, triangle, or trapezoid shape | Trapezoid or Square | A trapezoid will result in having a pyramid or cone shape. A square will result in a fair needle shape. | Triangle form required high laser power values, which resulted in a large diameter of the needle. |
Power (watts) | 0 watts to 200 watts | 30 watts to 40 watts | Seek desired outcomes | Power below 30 watts will not result in any holes and is too low to create a needle. Higher power will cause a larger diameter. |
Pulse Width (ms) | 0 to 10 ms | 3 to 5 ms | Seek desired outcomes | Values higher than 5 ms will cause a larger diameter. |
Number of repetitions | 0 to 500 times | 50 to 100 times | Seek desired outcomes | Values higher than 100 times will cause a larger diameter. |
Interval time (ms) | 0 to 200 ms | 0 to 50 ms | Seek desired outcomes | Values higher than 50 ms will cause a larger diameter. |
Parameters | Run 1 | Run 2 | Run 3 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
No. | Waveform | Power (watts) | Pulse Width (ms) | Repetitions | Interval (ms) | Diameter (μm) | Height (μm) | Diameter (μm) | Height (μm) | Diameter (μm) | Height (μm) |
1 | Square | 30 | 3 | 50 | 0 | 917 | 800 | 931 | 796 | 958 | 762 |
2 | 30 | 3 | 50 | 50 | 687 | 456 | 782 | 492 | 593 | 505 | |
3 | 30 | 3 | 100 | 0 | 1083 | 995 | 1193 | 1033 | 1068 | 917 | |
4 | 30 | 3 | 100 | 50 | 897 | 691 | 858 | 788 | 887 | 673 | |
5 | 30 | 5 | 50 | 0 | 1144 | 1105 | 1013 | 1089 | 1175 | 1153 | |
6 | 30 | 5 | 50 | 50 | 922 | 871 | 997 | 893 | 940 | 821 | |
7 | 30 | 5 | 100 | 0 | 1278 | 1171 | 1235 | 1002 | 1193 | 1155 | |
8 | 30 | 5 | 100 | 50 | 1004 | 856 | 952 | 876 | 964 | 924 | |
9 | 40 | 3 | 50 | 0 | 1100 | 1011 | 1287 | 945 | 1161 | 1057 | |
10 | 40 | 3 | 50 | 50 | 933 | 808 | 939 | 829 | 948 | 766 | |
11 | 40 | 3 | 100 | 0 | 1250 | 1094 | 1267 | 1154 | 1319 | 1213 | |
12 | 40 | 3 | 100 | 50 | 1013 | 860 | 1027 | 949 | 1019 | 877 | |
13 | 40 | 5 | 50 | 0 | 1441 | 1481 | 1377 | 1057 | 1456 | 1532 | |
14 | 40 | 5 | 50 | 50 | 1009 | 997 | 1049 | 933 | 1038 | 998 | |
15 | 40 | 5 | 100 | 0 | 1638 | 1485 | 1638 | 1461 | 1663 | 1422 | |
16 | 40 | 5 | 100 | 50 | 1372 | 1157 | 1350 | 1095 | 1320 | 1103 | |
17 | Trapezoid | 30 | 3 | 50 | 0 | 843 | 577 | 806 | 545 | 808 | 560 |
18 | 30 | 3 | 50 | 50 | 230 | 0 | 195 | 0 | 254 | 0 | |
19 | 30 | 3 | 100 | 0 | 928 | 785 | 934 | 779 | 937 | 844 | |
20 | 30 | 3 | 100 | 50 | 605 | 323 | 597 | 374 | 607 | 323 | |
21 | 30 | 5 | 50 | 0 | 1018 | 810 | 932 | 800 | 903 | 803 | |
22 | 30 | 5 | 50 | 50 | 827 | 610 | 892 | 605 | 916 | 598 | |
23 | 30 | 5 | 100 | 0 | 1157 | 1035 | 1084 | 1108 | 1151 | 1125 | |
24 | 30 | 5 | 100 | 50 | 1000 | 815 | 964 | 934 | 950 | 902 | |
25 | 40 | 3 | 50 | 0 | 953 | 835 | 927 | 735 | 913 | 824 | |
26 | 40 | 3 | 50 | 50 | 760 | 575 | 820 | 543 | 801 | 496 | |
27 | 40 | 3 | 100 | 0 | 992 | 1206 | 1029 | 1165 | 981 | 1267 | |
28 | 40 | 3 | 100 | 50 | 649 | 728 | 692 | 770 | 624 | 770 | |
29 | 40 | 5 | 50 | 0 | 1039 | 1148 | 1040 | 1051 | 1022 | 1076 | |
30 | 40 | 5 | 50 | 50 | 930 | 924 | 946 | 788 | 909 | 797 | |
31 | 40 | 5 | 100 | 0 | 1286 | 1223 | 1248 | 1734 | 1184 | 1005 | |
32 | 40 | 5 | 100 | 50 | 1101 | 1224 | 1009 | 1126 | 1015 | 1154 |
Observation | Effect | est1 | Effects |
---|---|---|---|
1 | A | −113.30 | −226.60 |
2 | B | 96.61 | 193.22 |
3 | C | 121.76 | 243.52 |
4 | D | 70.11 | 140.22 |
5 | E | −126.11 | −252.22 |
6 | AB | −27.19 | −54.39 |
7 | AC | 16.53 | 33.06 |
8 | AD | −6.78 | −13.56 |
9 | AE | 4.82 | 9.64 |
10 | BC | −3.51 | −7.02 |
11 | BD | −9.94 | −19.89 |
12 | BE | 2.40 | 4.81 |
13 | CD | 9.49 | 18.97 |
14 | CE | 23.21 | 46.43 |
15 | DE | −4.30 | −8.60 |
16 | ABC | −26.94 | −53.89 |
17 | ACD | 1.13 | 2.27 |
18 | ABD | −22.13 | −44.27 |
19 | ABE | 20.63 | 41.27 |
20 | ACE | 31.19 | 62.39 |
21 | ADE | −3.49 | −6.97 |
22 | BCD | 37.34 | 74.68 |
23 | BCE | −23.84 | −47.68 |
24 | BDE | −9.65 | −19.31 |
25 | CDE | −7.55 | −15.10 |
26 | ABCD | 0.53 | 1.06 |
27 | ABCE | −8.07 | −16.14 |
28 | ABDE | −20.13 | −40.27 |
29 | ACDE | −7.03 | −14.06 |
30 | BCDE | 21.67 | 43.35 |
31 | ABCDE | 7.40 | 14.81 |
Observation | Effect | est1 | Effects |
---|---|---|---|
1 | A | −96.62 | −193.25 |
2 | B | 145.37 | 290.75 |
3 | C | 145.31 | 290.62 |
4 | D | 96.10 | 192.20 |
5 | E | −155.41 | −310.83 |
6 | AB | 19.39 | 38.79 |
7 | AC | 29.08 | 58.16 |
8 | AD | 50.12 | 100.25 |
9 | AE | −4.18 | −8.37 |
10 | BC | −22.25 | −44.50 |
11 | BD | −3.41 | −6.83 |
12 | BE | −0.85 | −1.70 |
13 | CD | −9.60 | −19.20 |
14 | CE | 29.79 | 59.58 |
15 | DE | 7.79 | 15.58 |
16 | ABC | −13.14 | −26.29 |
17 | ACD | 4.00 | 8.00 |
18 | ABD | 6.35 | 12.70 |
19 | ABE | 19.87 | 39.75 |
20 | ACE | 28.10 | 56.20 |
21 | ADE | −7.89 | −15.79 |
22 | BCD | 17.20 | 34.41 |
23 | BCE | −14.31 | −28.62 |
24 | BDE | −2.18 | −4.37 |
25 | CDE | 2.83 | 5.66 |
26 | ABCD | −20.60 | −41.20 |
27 | ABCE | −5.00 | −10.00 |
28 | ABDE | −9.45 | −18.91 |
29 | ACDE | 9.39 | 18.79 |
30 | BCDE | 9.77 | 19.54 |
31 | ABCDE | 15.41 | 30.83 |
Coefficients | Standard Error | t Stat | p-Value | Lower 95% | Upper 95% | Lower 95.0% | Upper 95.0% | |
---|---|---|---|---|---|---|---|---|
Intercept | 89.13 | 91.36 | 0.97 | 0.33 | −92.36 | 270.63 | −92.36 | 270.63 |
Waveform | −226.60 | 19.81 | −11.43 | 0.00 | −265.97 | −187.23 | −265.97 | −187.23 |
Power | 19.32 | 1.98 | 9.74 | 0.00 | 15.38 | 23.26 | 15.38 | 23.26 |
Pulse width | 121.76 | 9.90 | 12.28 | 0.00 | 102.07 | 141.44 | 102.07 | 141.44 |
Repetition | 2.80 | 0.39 | 7.07 | 0.00 | 2.01 | 3.59 | 2.01 | 3.59 |
Interval | −5.04 | 0.39 | −12.72 | 0.00 | −5.83 | −4.25 | −5.83 | −4.25 |
Coefficients | Standard Error | t Stat | p-Value | Lower 95% | Upper 95% | Lower 95.0% | Upper 95.0% | |
---|---|---|---|---|---|---|---|---|
Intercept | −544.87 | 121.12 | −4.49 | 0.00 | −785.50 | −304.24 | −785.50 | −304.24 |
Waveform | −193.25 | 26.27 | −7.35 | 0.00 | −245.45 | −141.04 | −245.45 | −141.04 |
Power | 29.07 | 2.62 | 11.06 | 0.00 | 23.85 | 34.29 | 23.85 | 34.29 |
Pulse width | 145.31 | 13.13 | 11.06 | 0.00 | 119.21 | 171.41 | 119.21 | 171.41 |
Repetition | 3.84 | 0.52 | 7.31 | 0.00 | 2.80 | 4.88 | 2.80 | 4.88 |
Interval | −6.21 | 0.52 | −11.83 | 0.00 | −7.26 | −5.17 | −7.26 | −5.17 |
Multiple R | 0.931 |
R Square | 0.867 |
Adjusted R Square | 0.860 |
Standard Error | 97.091 |
Observations | 96 |
df | SS | MS | F | p Value | |
Regression | 31 | 6,283,437.91 | 202,691.55 | 112.28 | <0.0001 |
Residual | 64 | 115,533.33 | 1805.21 | ||
Total | 95 | 6,398,971.24 |
Multiple R | 0.919 |
R Square | 0.845 |
Adjusted R Square | 0.836 |
Standard Error | 128.721 |
Observations | 96 |
df | SS | MS | F | p Value | |
---|---|---|---|---|---|
Regression | 31 | 8,949,791.96 | 288,702.96 | 26.43 | <0.0001 |
Residual | 64 | 699,162.00 | 10,924.41 | ||
Total | 95 | 9,648,953.96 |
Tukey’s Studentized Range (HSD) Test for Output | ||||
---|---|---|---|---|
Alpha | 0.05 | |||
Error Degrees of Freedom | 64 | |||
Error Mean Square | 10,924.41 | |||
Critical Value of Studentized Range | 2.82522 | |||
Minimum Significant Difference | 42.622 | |||
Means with the same letter are not significantly different. | ||||
Tukey Grouping | Mean | N | Waveform | |
A | 993.65 | 48 | 1 | |
B | 800.40 | 48 | 2 | |
Tukey Grouping | Mean | N | Power | |
A | 1042.40 | 48 | 40 | |
B | 751.65 | 48 | 30 | |
Tukey Grouping | Mean | N | Pulse | |
A | 1042.33 | 48 | 5 | |
B | 751.71 | 48 | 3 | |
Tukey Grouping | Mean | N | Repetition | |
A | 993.13 | 48 | 100 | |
B | 800.92 | 48 | 50 | |
Tukey Grouping | Mean | N | Interval | |
A | 800.40 | 48 | 0 | |
B | 800.40 | 48 | 50 |
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Aldawood, F.K.; Andar, A.; Desai, S. Investigating Laser Ablation Process Parameters for the Fabrication of Customized Microneedle Arrays for Therapeutic Applications. Pharmaceutics 2024, 16, 885. https://doi.org/10.3390/pharmaceutics16070885
Aldawood FK, Andar A, Desai S. Investigating Laser Ablation Process Parameters for the Fabrication of Customized Microneedle Arrays for Therapeutic Applications. Pharmaceutics. 2024; 16(7):885. https://doi.org/10.3390/pharmaceutics16070885
Chicago/Turabian StyleAldawood, Faisal Khaled, Abhay Andar, and Salil Desai. 2024. "Investigating Laser Ablation Process Parameters for the Fabrication of Customized Microneedle Arrays for Therapeutic Applications" Pharmaceutics 16, no. 7: 885. https://doi.org/10.3390/pharmaceutics16070885