Design, Simulation and Fabrication of Silicon Microneedles for Bio-Medical Applications
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Published:
Jul 27, 2010
Keywords:
Silicon Microneedles Transdermal Drug Delivery Structural Analysis Computational Fluid Dynamic Analysis Inductively Coupled Plasma Etching
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Abstract
In this paper, design, analysis and fabrication of hollow out-of-plane silicon microneedles for transdermal drug delivery (TDD) have been presented. Combination of isotropic and anisotropic etching process has been used to facilitate the fabrication of microneedles in inductively coupled plasma (ICP) etcher. Using ANSYS, structural and micro°uidic analysis has
been performed before the fabrication to insure the microneedle design suitability for TDD. In finite element analysis (FEM), the effect of axial and transverse load on single microneedle has been investigated to envisage the mechanical properties of microneedle. The analysis predicts that the resultant stresses due to applied bending and axial loads are in the safe range. In computational fluid dynamic (CFD) static analysis, the fluid flow rate through 5 x 5 microneedle array has been investigated by applying the pressure 10 kPa to 130 kPa at the inlet to insure that the microneedles are capable for flow of drug up to the desired range for TDD.
Article Details
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Ashraf, M. W., Tayyaba, S., Afzulpurkar, N., Nisar, A., Bohez, E. L. J., Lomas, T., & Tuantranont, A. (2010). Design, Simulation and Fabrication of Silicon Microneedles for Bio-Medical Applications. ECTI Transactions on Electrical Engineering, Electronics, and Communications, 9(1), 83–91. https://doi.org/10.37936/ecti-eec.201191.172302
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References
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[12] S. Khumpuang1, M. Horade, K. Fujioka, and S. Sugiyama, "Geometrical Strengthening and tipsharping of a microneedle array fabricated by X-ray lithography," Microsist Technol. Vol. 13, pp. 209-214.
[13] L. M. Yu, F. E. H. Tay, D. G. Guo, L. Xu, K. L. Yap, "A microfabricated electrode with hollow microneedles for ECG measurements," Sens Actuator A 151, pp. 17-22, 2009.
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[23] J. Jiang, J. S. Moore, H. F. Edelhauser, and M. R. Prausnitz, "Intrascleral Drug Delivery to the Eye Using Hollow Microneedles," Pharm. Res. Vol. 26, pp. 395-403.
[24] P. Griss and G. Stemme, "Novel side opened out-of-plane microneedles for microfluidic transdermal interfacing," In: The ¯fteenth IEEE international conference on micro electro mechanical systems, pp. 467-470, 2002.
[25] S. Khumpuang, R. Maeda, and S. Sugiyama, "Design and fabrication of coupled microneedle array and insertion guide array for safe penetration through skin," In: International symposium of micromechatronics and human scienc, 2003.
[26] E. V. Mukherjee, S. D. Collins, R. R. Isseroff, and L. Smith, "Microneedle array for transdermal biological fluid extraction and in situ analysis," Sens Actuators A 114, pp. 267-275, 2004.
[27] N. Wilke, A. Mulcahy, S. R. Ye, and, A. Morrissey, "Process optimization and characterization of silicon microneedles fabricated by wet etch technology," Microelectron J, Vol. 36, pp. 650-656, 2005.
[28] T. Shibata, A. Nakanishi, T. Sakai, N. Kato, T. Kawashima, T. Mineta, and E. makino, "Fabrication and mechanical characterization of microneedle array for cell surgery," In: Actuators and Microsystems Conference, pp 719-722, 2007.
[29] C. S. Kolli and A. K. Banga, "Characterization of Solid Maltose Microneedles and their Use for Transdermal Delivery," Pharm. Res. Vol. 25, pp. 104-113, 2008. 1449-1463, 2001.
[30] M. W. Ashraf, S. Tayyaba, A. Nisar, N. Afzulpurkar, and A. Tuantranont, "Coupled Multifield Analysis of Integrated Microfluidic Device for Transdermal Drug Delivery Applications", In: INMIC, 13th Multitopic Int. Conf. 2009.
[31] S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, "Micro machined needles for the transdermal drug delivery of drugs," In proc. IEEE workshop MEMS, 494-498, 1998.
[32] J. H. Park, S. Davis, Y. K. Yoon, M. G. Allen, M. R. Prausnitz, "Micromachined biodegradable microstructures," In: 16th IEEE Int. Conf. on MicroElectro Mechanical Systems, Kyoto, Japan 371-374, 2003.
[33] J. H. Park, M. G. Allen, M. R. Prausnitz, "Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery," J. Contr. Rel., Vol. (104), No. 1, pp. 51-66, 2005.
[34] K. Kim, D. Park, H. Lu, K-H. Kim, JB Lee, "A tapered hollow metallic microneedle array using backside exposure of SU-8," J. Micromech Microeng., Vol. 14, pp. 597-603, 2004.
[35] S. J. Moon, and S. S. Lee, "A novel fabrication method of a microneedle array using inclined deep x-ray exposure," J. Micromech. Microeng., Vol. 15, pp. 903-911, 2005.
[36] J. D. Zahn, N. H. Talbot, D. Liepmann, A. P. Pisano, A.P, "Micro fabricated polysilicon microneedles for minimally invasive biomedical devices," Biomed. Microdevices 2: 295-303, 2000.
[37] J. Gere , and S. Timoshenko, Mechanics of materials. Fourth ed. 1997.
[38] W. S. Janna , Design of fluid thermal system, Boston, MA : PWS Pub., 2nd ed. (1998).
[39] N. Wilke , C. Hibert, J. O'Brien, and A. Morrissey, "Silicon microneedle electrode array with temperature monitoring for electropo-ration," Sensors and Actuators A. 123-124: 319-325, 2005.
[40] P. Zhang, C. Dalton, G. A. Jullien, "Design and fabrication of MEMS-based microneedles arrays for medical Applications," Microsyst Technol 15, pp. 1073-1082, 2009.
[41] Z. Ding, FJ. Verbaan, M. Bivas-Benita, L. Bungener, A. Huckriede, DJ. Berg, G. Kersten and JA. Bouwstra, "Microneedles arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice," J Control Release, 136(1), pp. 71-8, 2009.
[42] M. I. Haq, E. Smith, D. N. John, M. Kalavala, C. Edwards, A. Anstey, A. Morrissey, and J. C. Birchall, "Clinical administration of microneedles: skin puncture, pain and sensation," Biomed Microdevices11, pp. 35-47, 2009.
[2] YB Scuetz, A. Naik, RH. Guy, and YN Kalia, "Emerging strategies for the transdermal delivery of peptide and protein drugs," Expert Opin. Drug Deliv. Vol. 2, pp. 533-548, 2005.
[3] P. Karande, A. Jain, and S. Mitragotri, "Discovery of transdermal penetration enhancers by high throughput screening," Nat. Biotechnol. Vol. 22, pp. 192-197, 2004.
[4] A. Arora, MR. Prausnitzc, and S. Mitragotri, "Micro-scale devices for transdermal drug delivery," Int. J. Pharm. Vol. 364. pp. 227-236, 2008.
[5] B. A. Qallaf and D. B. Das, "Optimization of square microneedle arrays for increasing drug permeability in skin," Chemical Engieering Sci Vol. 63, pp 2523-2535, 2008.
[6] D. W. Bodhale, A. Nisar, N. Afzulpurkar, "Structural and microfluidic analysis of hollow side-open polymeric microneedles for transdermal drug delivery applications," Microfluid Nanofluid, Vol. 8, pp. 373-392, 2010.
[7] B. Chen. J. Wei, F. E. H. Tay, W, Y. T. Wong, and C. Iliescu, "Silicon microneedle array with biodegradable tips for transdemal drug delivery," Microsyst Techno 14, pp. 1015-1019, 2008.
[8] J. Ji, F. Tay, and J. Miao, "Microfabricated Hollow Microneedle Array Using ICP Etcher," Journal of Physics, Con¯rence series 34, pp. 1132-136, 2006.
[9] M.S. Gerstel, and V.A. Place, "Drug Delivery Device," US 3 964 482 patent, 1976.
[10] P. K. Campbell, K. E. Jones, R. J. Huber, K. W. Horch and R. A. Normann, "A silicon-based three-dimensional neural interface: manufacturing processes for an intracortical electrode array," IEEE Trans Biomed Eng 38(8), 1991, pp.758-768.
[11] T. Shibata, A. Nakanishi, T. Sakai, N. Kato, T. Kawashima, T. Mineta, and E. Makino, "Fabrication and mechanical characterization of microneedle array for for cell surgery," In: Actuators and Microsystems Conference, pp 719-722.
[12] S. Khumpuang1, M. Horade, K. Fujioka, and S. Sugiyama, "Geometrical Strengthening and tipsharping of a microneedle array fabricated by X-ray lithography," Microsist Technol. Vol. 13, pp. 209-214.
[13] L. M. Yu, F. E. H. Tay, D. G. Guo, L. Xu, K. L. Yap, "A microfabricated electrode with hollow microneedles for ECG measurements," Sens Actuator A 151, pp. 17-22, 2009.
[14] JW. Lee, JH. Park, MR. Prausnitz, "Dissolving microneedles for transdermal drug delivery," Biomaterials. Vol. 29, pp. 2113-2124, 2009.
[15] P. Zhang , C. Dalton, and G. A. Jullien, "Design and fabrication of MEMS-based microneedles arrays for medical applications," Microsyst Technol 15, pp. 1073-1082, 2009.
[16] Z. Ding, F. J. Verbaan, M. Bivas-Benita, L. Bungener, A. Huckriede, D. J. van den Berg, G. Kersten, J. A. Bouwstra, "Microneedles arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice," J Control Release. Vol. 136, pp. 71-78, 2009.
[17] S. P. Davis, W. Martanto, M. G. Allen, and M. R. Prausnitz, "Hollow metal microneedles for insulin delivery to diabetic rats," IEEE Trans Biomed Eng 52(5), pp. 909-915.
[18] J. Oh , H. Park, K. Doa, M. Han, D. Hyun, C. Kim, C. Kim, S. S. Lee, S. Hwang, S. Shin, C. Cho, "Influence of the delivery systems using a microneedle array on the permeation of a hydrophilic molecule, calcein,"Eur. J. Pharm. Biopharm. Vol. 69, pp. 1040-1045, 2009.
[19] M. W. Ashraf, S. Tayyaba, N. Afzulpurkar, "MEMS based Polymeric Drug Delivery System," CASE 2010, 6th IEEE Conference on Automation Science and Engineering, August 21-24, 2010, Toronto, Canada.
[20] R. Bhandari, S. Negi, L. Rieth, R. A. Norman, and F. Solzbacher, "A Novel Mask-Less Method of Fabricating High Aspect Ratio Microneedles for Blood Sampling," In: IEEE, 2008 Electronic Components and Technology Conference. 1306-1309.
[21] S. Rajaraman, and H. T. Henderson, "A unique fabrication approach for microneedles using coherent porous silicon technology," Sens. Actuator B 105, pp. 443-448.
[22] F. Sammoura, J. Kang, Y. Heo, T. Jung and L. Lin, "Polymeric microneedle fabrication using a microinjection molding technique," Microsyst Techno. 13, pp. 517-522.
[23] J. Jiang, J. S. Moore, H. F. Edelhauser, and M. R. Prausnitz, "Intrascleral Drug Delivery to the Eye Using Hollow Microneedles," Pharm. Res. Vol. 26, pp. 395-403.
[24] P. Griss and G. Stemme, "Novel side opened out-of-plane microneedles for microfluidic transdermal interfacing," In: The ¯fteenth IEEE international conference on micro electro mechanical systems, pp. 467-470, 2002.
[25] S. Khumpuang, R. Maeda, and S. Sugiyama, "Design and fabrication of coupled microneedle array and insertion guide array for safe penetration through skin," In: International symposium of micromechatronics and human scienc, 2003.
[26] E. V. Mukherjee, S. D. Collins, R. R. Isseroff, and L. Smith, "Microneedle array for transdermal biological fluid extraction and in situ analysis," Sens Actuators A 114, pp. 267-275, 2004.
[27] N. Wilke, A. Mulcahy, S. R. Ye, and, A. Morrissey, "Process optimization and characterization of silicon microneedles fabricated by wet etch technology," Microelectron J, Vol. 36, pp. 650-656, 2005.
[28] T. Shibata, A. Nakanishi, T. Sakai, N. Kato, T. Kawashima, T. Mineta, and E. makino, "Fabrication and mechanical characterization of microneedle array for cell surgery," In: Actuators and Microsystems Conference, pp 719-722, 2007.
[29] C. S. Kolli and A. K. Banga, "Characterization of Solid Maltose Microneedles and their Use for Transdermal Delivery," Pharm. Res. Vol. 25, pp. 104-113, 2008. 1449-1463, 2001.
[30] M. W. Ashraf, S. Tayyaba, A. Nisar, N. Afzulpurkar, and A. Tuantranont, "Coupled Multifield Analysis of Integrated Microfluidic Device for Transdermal Drug Delivery Applications", In: INMIC, 13th Multitopic Int. Conf. 2009.
[31] S. Henry, D. V. McAllister, M. G. Allen, and M. R. Prausnitz, "Micro machined needles for the transdermal drug delivery of drugs," In proc. IEEE workshop MEMS, 494-498, 1998.
[32] J. H. Park, S. Davis, Y. K. Yoon, M. G. Allen, M. R. Prausnitz, "Micromachined biodegradable microstructures," In: 16th IEEE Int. Conf. on MicroElectro Mechanical Systems, Kyoto, Japan 371-374, 2003.
[33] J. H. Park, M. G. Allen, M. R. Prausnitz, "Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery," J. Contr. Rel., Vol. (104), No. 1, pp. 51-66, 2005.
[34] K. Kim, D. Park, H. Lu, K-H. Kim, JB Lee, "A tapered hollow metallic microneedle array using backside exposure of SU-8," J. Micromech Microeng., Vol. 14, pp. 597-603, 2004.
[35] S. J. Moon, and S. S. Lee, "A novel fabrication method of a microneedle array using inclined deep x-ray exposure," J. Micromech. Microeng., Vol. 15, pp. 903-911, 2005.
[36] J. D. Zahn, N. H. Talbot, D. Liepmann, A. P. Pisano, A.P, "Micro fabricated polysilicon microneedles for minimally invasive biomedical devices," Biomed. Microdevices 2: 295-303, 2000.
[37] J. Gere , and S. Timoshenko, Mechanics of materials. Fourth ed. 1997.
[38] W. S. Janna , Design of fluid thermal system, Boston, MA : PWS Pub., 2nd ed. (1998).
[39] N. Wilke , C. Hibert, J. O'Brien, and A. Morrissey, "Silicon microneedle electrode array with temperature monitoring for electropo-ration," Sensors and Actuators A. 123-124: 319-325, 2005.
[40] P. Zhang, C. Dalton, G. A. Jullien, "Design and fabrication of MEMS-based microneedles arrays for medical Applications," Microsyst Technol 15, pp. 1073-1082, 2009.
[41] Z. Ding, FJ. Verbaan, M. Bivas-Benita, L. Bungener, A. Huckriede, DJ. Berg, G. Kersten and JA. Bouwstra, "Microneedles arrays for the transcutaneous immunization of diphtheria and influenza in BALB/c mice," J Control Release, 136(1), pp. 71-8, 2009.
[42] M. I. Haq, E. Smith, D. N. John, M. Kalavala, C. Edwards, A. Anstey, A. Morrissey, and J. C. Birchall, "Clinical administration of microneedles: skin puncture, pain and sensation," Biomed Microdevices11, pp. 35-47, 2009.