Design and analyses of a transdermal drug delivery device (TD3 )

In this paper, we introduce a novel type of transdermal drug delivery device (TD3 ) with a micro-electro-mechanical system (MEMS) design using computer-aided design (CAD) techniques as well as computational fluid dynamics (CFD) simulations regarding the fluid interaction inside the device during the...

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Autores:
Fonthal Rico, Faruk
García Cruz, Jennifer
Ríos Afanador, Ismael Alberto
Tipo de recurso:
Article of journal
Fecha de publicación:
2019
Institución:
Universidad Autónoma de Occidente
Repositorio:
RED: Repositorio Educativo Digital UAO
Idioma:
eng
OAI Identifier:
oai:red.uao.edu.co:10614/13434
Acceso en línea:
https://hdl.handle.net/10614/13434
Palabra clave:
Sistemas microelectromecánicos
Dispositivos electromecánicos
Sistemas microelectromecánicos
Microelectromechanical systems
Electromechanical devices
Transdermal drug delivery
Micro-electro-mechanical systems (MEMS)
Finite element analysi
Microstructures
Computational fluid dynamic
Rights
openAccess
License
Derechos reservados - MDPI, 2019
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oai_identifier_str oai:red.uao.edu.co:10614/13434
network_acronym_str REPOUAO2
network_name_str RED: Repositorio Educativo Digital UAO
repository_id_str
dc.title.eng.fl_str_mv Design and analyses of a transdermal drug delivery device (TD3 )
title Design and analyses of a transdermal drug delivery device (TD3 )
spellingShingle Design and analyses of a transdermal drug delivery device (TD3 )
Sistemas microelectromecánicos
Dispositivos electromecánicos
Sistemas microelectromecánicos
Microelectromechanical systems
Electromechanical devices
Transdermal drug delivery
Micro-electro-mechanical systems (MEMS)
Finite element analysi
Microstructures
Computational fluid dynamic
title_short Design and analyses of a transdermal drug delivery device (TD3 )
title_full Design and analyses of a transdermal drug delivery device (TD3 )
title_fullStr Design and analyses of a transdermal drug delivery device (TD3 )
title_full_unstemmed Design and analyses of a transdermal drug delivery device (TD3 )
title_sort Design and analyses of a transdermal drug delivery device (TD3 )
dc.creator.fl_str_mv Fonthal Rico, Faruk
García Cruz, Jennifer
Ríos Afanador, Ismael Alberto
dc.contributor.author.none.fl_str_mv Fonthal Rico, Faruk
dc.contributor.author.spa.fl_str_mv García Cruz, Jennifer
Ríos Afanador, Ismael Alberto
dc.subject.armarc.spa.fl_str_mv Sistemas microelectromecánicos
Dispositivos electromecánicos
Sistemas microelectromecánicos
topic Sistemas microelectromecánicos
Dispositivos electromecánicos
Sistemas microelectromecánicos
Microelectromechanical systems
Electromechanical devices
Transdermal drug delivery
Micro-electro-mechanical systems (MEMS)
Finite element analysi
Microstructures
Computational fluid dynamic
dc.subject.armarc.eng.fl_str_mv Microelectromechanical systems
Electromechanical devices
dc.subject.proposal.eng.fl_str_mv Transdermal drug delivery
Micro-electro-mechanical systems (MEMS)
Finite element analysi
Microstructures
Computational fluid dynamic
description In this paper, we introduce a novel type of transdermal drug delivery device (TD3 ) with a micro-electro-mechanical system (MEMS) design using computer-aided design (CAD) techniques as well as computational fluid dynamics (CFD) simulations regarding the fluid interaction inside the device during the actuation process. For the actuation principles of the chamber and microvalve, both thermopneumatic and piezoelectric principles are employed respectively, originating that the design perfectly integrates those principles through two different components, such as a micropump with integrated microvalves and a microneedle array. The TD3 has shown to be capable of delivering a volumetric flow of 2.92 × 10−5 cm3 /s with a 6.6 Hz membrane stroke frequency. The device only needs 116 Pa to complete the suction process and 2560 Pa to complete the discharge process. A 38-microneedle array with 450 µm in length fulfills the function of permeating skin, allowing that the fluid reaches the desired destination and avoiding any possible pain during the insertion
publishDate 2019
dc.date.issued.none.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2021-11-11T17:31:25Z
dc.date.available.none.fl_str_mv 2021-11-11T17:31:25Z
dc.type.spa.fl_str_mv Artículo de revista
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dc.identifier.issn.none.fl_str_mv 14243210
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identifier_str_mv 14243210
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dc.language.iso.eng.fl_str_mv eng
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dc.relation.citationedition.spa.fl_str_mv Volumen 19, número 23 (2019)
dc.relation.citationendpage.spa.fl_str_mv 11
dc.relation.citationissue.spa.fl_str_mv 23
dc.relation.citationstartpage.spa.fl_str_mv 1
dc.relation.citationvolume.spa.fl_str_mv 19
dc.relation.cites.eng.fl_str_mv García, J., Ríos, I., Fonthal Rico F. (2019). Design and analyses of a transdermal drug delivery device (TD3). Sensors. (Vol. 19 (23), pp. 1-11. https://doi.org/10.3390/s19235090
dc.relation.ispartofjournal.eng.fl_str_mv Sensors
dc.relation.references.none.fl_str_mv 1. Hood, R.R.; Kendall, E.L.; DeVoe, D.L.; Quezado, Z.; Junqueira, M.J.; Finkel, C.; Vreeland, W.N. Microfluidic formation of nanoscale liposomes for passive transdermal drug delivery. In Proceedings of the Microsystems for Measurement and Instrumentation (MAMNA), Gaithersburg, MD, USA, 14 May 2013; pp. 12–15.
2. Dolz˙an, T.; Vrtacˇnik, D.; Resnik, D.; Aljancˇicˇ, U.; Moz˙ ek, M.; Pecˇar, B.; Amon, S. Design of transdermal drug delivery system with PZT actuated micropump. In Proceedings of the 37th International Convention on Information and Communication Technology, Electronics and Microelectronics (MIPRO), Opatija, Croatia, 26–30 May 2014; pp. 96–99.
3. Lee, H.; Song, C.; Baik, S.; Kim, D.; Hyeon, T.; Kim, D.H. Device-assisted transdermal drug delivery. Adv. Drug Deliv. Rev. 2018, 127, 35–45. [CrossRef] [PubMed]
4. Mousoulis, C.; Ochoa, M.; Papageorgiou, D.; Ziaie, B. A Skin-Contact-Actuated Micropump for Transdermal Drug Delivery. IEEE Trans. Biomed. Eng. 2011, 58, 1492–1498. [CrossRef] [PubMed]
5. Camovic´, M.; Bišcˇevic´, A.; Brcˇic´, I.; Borcˇak, K.; Bušatlic´, S.; C´ enanovic´, N.; Mulalic´, A.; Osmanlic´, M.; Sirbubalo, M.; Tucak, A.; et al. Coated 3d printed PLA microneedles as transdermal drug delivery systems. IFMBE Proc. 2020, 73, 735–742. [CrossRef]
6. Wang, W.; Soper, S.A. Bio-MEMS Technologies and Applications, 1st ed.; CRC Press: Boca Raton, NY, USA, 2006; pp. 7–237. ISBN 9780849335327.
7. Ashraf, M.W.; Tayyaba, S.; Afzulpurkr, N. Tapered tip hollow silicon microneedles for transdermal drug delivery. In Proceedings of the 2nd International Conference on Mechanical and Electronics Engineering (ICMEE), Kyoto, Japan, 1–3 August 2010.
8. Jurcicek, P.; Zou, H.; Zhang, S.; Liu, C. Design and fabrication of hollow out-of-plane silicon microneedles. IET Micro Nano Lett. 2013, 8, 78–81. [CrossRef]
9. Varadan, V.K.; Vinoy, K.J.; Gopalakrishnan, S. Smart Material Systems and MEMS: Design and Development Methodologies, 1st ed.; JohnWiley & Sons: Chichester, UK, 2006; ISBN 9780470093610.
10. Cong, W.; Jin-seong, K.; Jungyul, P. Micro check valve integrated magnetically actuated micropump for implantable drug delivery. In Proceedings of the 19th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS), Kaohsiung, Taiwan, 18–22 June 2017; pp. 1711–1713.
11. Shoji, E. Fabrication of a diaphragm micropump system utilizing the ionomer-based polymer actuator. Sens. Actuators B Chem. 2016, 237, 660–665. [CrossRef]
12. Garcia, J.; Rios, I.; Fonthal, F. Structural and microfluidic analysis of microneedle array for drug delivery. In Proceedings of the 31st Symposium on Microelectronics Technology and Devices IEEE SBMicro 2016, Belo Horizonte, Brazil, 29 August–3 September 2016; pp. 1–4.
13. Kawun, P.; Leahy, S.; Lai, Y. A thin PDMS nozzle/di user micropump for biomedical applications. Sens. Actuators B Chem. 2016, 249, 149–154. [CrossRef]
14. Singh, S.; Kumar, N.; George, D.; Sen, A.K. Analytical modeling, simulations and experimental studies of a PZT actuated planar valveless PDMS micropump. Sens. Actuators B Chem. 2015, 225, 81–94. [CrossRef]
15. Nguyen, N.T.; Mousavi, S.A.; Kashaninejad, N.; Phan, D.T. Design, fabrication and characterization of drug delivery systems based on lab-on-a-chip technology. Adv. Drug Deliv. Rev. 2013, 65, 1403–1419. [CrossRef] [PubMed]
16. Davis, S.P.; Martanto,W.; Allen, M.G.; Prausnitz, M.R. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans. Biomed. Eng. 2005, 52, 909–915. [CrossRef] [PubMed]
17. Roxhed, N.T.; Gasser, C.; Griss, P.; Holzapfel, G.A.; Stemme, G. Penetration-enhanced ultrasharp microneedles and prediction on skin interaction for e cient transdermal drug delivery. J. Microelectromech. Syst. 2007, 16, 1429–1440. [CrossRef]
18. Sanjay, S.T.; Zhou,W.; Dou, M.; Tavakoli, H.; Ma, L.; Xu, F.; Li, X. Recent advances of controlled drug delivery using microfluidic platforms. Adv. Drug Deliv. Rev. 2018, 128, 3–28. [CrossRef] [PubMed]
19. Bao, S.J.; Xie, D.L.; Zhang, J.P.; Chang, W.R.; Liang, D.C. Crystal structure of desheptapeptide (B24–B30) insulin at 1.6 Å resolution: Implications for receptor binding. Proc. Natl. Acad. Sci. USA 1997, 94, 2975–2980. [CrossRef] [PubMed]
dc.rights.spa.fl_str_mv Derechos reservados - MDPI, 2019
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spelling Fonthal Rico, Farukvirtual::1746-1García Cruz, Jennifer678452ac098b2be6b666ccb001c2c900Ríos Afanador, Ismael Alberto16cdba7f27db3c91a2232509f87ea2672021-11-11T17:31:25Z2021-11-11T17:31:25Z201914243210https://hdl.handle.net/10614/13434In this paper, we introduce a novel type of transdermal drug delivery device (TD3 ) with a micro-electro-mechanical system (MEMS) design using computer-aided design (CAD) techniques as well as computational fluid dynamics (CFD) simulations regarding the fluid interaction inside the device during the actuation process. For the actuation principles of the chamber and microvalve, both thermopneumatic and piezoelectric principles are employed respectively, originating that the design perfectly integrates those principles through two different components, such as a micropump with integrated microvalves and a microneedle array. The TD3 has shown to be capable of delivering a volumetric flow of 2.92 × 10−5 cm3 /s with a 6.6 Hz membrane stroke frequency. The device only needs 116 Pa to complete the suction process and 2560 Pa to complete the discharge process. A 38-microneedle array with 450 µm in length fulfills the function of permeating skin, allowing that the fluid reaches the desired destination and avoiding any possible pain during the insertion11 páginasapplication/pdfengMDPIBasel, SwitzerlandDerechos reservados - MDPI, 2019https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)http://purl.org/coar/access_right/c_abf2Design and analyses of a transdermal drug delivery device (TD3 )Artículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Sistemas microelectromecánicosDispositivos electromecánicosSistemas microelectromecánicosMicroelectromechanical systemsElectromechanical devicesTransdermal drug deliveryMicro-electro-mechanical systems (MEMS)Finite element analysiMicrostructuresComputational fluid dynamicVolumen 19, número 23 (2019)1123119García, J., Ríos, I., Fonthal Rico F. (2019). Design and analyses of a transdermal drug delivery device (TD3). Sensors. (Vol. 19 (23), pp. 1-11. https://doi.org/10.3390/s19235090Sensors1. Hood, R.R.; Kendall, E.L.; DeVoe, D.L.; Quezado, Z.; Junqueira, M.J.; Finkel, C.; Vreeland, W.N. Microfluidic formation of nanoscale liposomes for passive transdermal drug delivery. In Proceedings of the Microsystems for Measurement and Instrumentation (MAMNA), Gaithersburg, MD, USA, 14 May 2013; pp. 12–15.2. Dolz˙an, T.; Vrtacˇnik, D.; Resnik, D.; Aljancˇicˇ, U.; Moz˙ ek, M.; Pecˇar, B.; Amon, S. Design of transdermal drug delivery system with PZT actuated micropump. In Proceedings of the 37th International Convention on Information and Communication Technology, Electronics and Microelectronics (MIPRO), Opatija, Croatia, 26–30 May 2014; pp. 96–99.3. Lee, H.; Song, C.; Baik, S.; Kim, D.; Hyeon, T.; Kim, D.H. Device-assisted transdermal drug delivery. Adv. Drug Deliv. Rev. 2018, 127, 35–45. [CrossRef] [PubMed]4. Mousoulis, C.; Ochoa, M.; Papageorgiou, D.; Ziaie, B. A Skin-Contact-Actuated Micropump for Transdermal Drug Delivery. IEEE Trans. Biomed. Eng. 2011, 58, 1492–1498. [CrossRef] [PubMed]5. Camovic´, M.; Bišcˇevic´, A.; Brcˇic´, I.; Borcˇak, K.; Bušatlic´, S.; C´ enanovic´, N.; Mulalic´, A.; Osmanlic´, M.; Sirbubalo, M.; Tucak, A.; et al. Coated 3d printed PLA microneedles as transdermal drug delivery systems. IFMBE Proc. 2020, 73, 735–742. [CrossRef]6. Wang, W.; Soper, S.A. Bio-MEMS Technologies and Applications, 1st ed.; CRC Press: Boca Raton, NY, USA, 2006; pp. 7–237. ISBN 9780849335327.7. Ashraf, M.W.; Tayyaba, S.; Afzulpurkr, N. Tapered tip hollow silicon microneedles for transdermal drug delivery. In Proceedings of the 2nd International Conference on Mechanical and Electronics Engineering (ICMEE), Kyoto, Japan, 1–3 August 2010.8. Jurcicek, P.; Zou, H.; Zhang, S.; Liu, C. Design and fabrication of hollow out-of-plane silicon microneedles. IET Micro Nano Lett. 2013, 8, 78–81. [CrossRef]9. Varadan, V.K.; Vinoy, K.J.; Gopalakrishnan, S. Smart Material Systems and MEMS: Design and Development Methodologies, 1st ed.; JohnWiley & Sons: Chichester, UK, 2006; ISBN 9780470093610.10. Cong, W.; Jin-seong, K.; Jungyul, P. Micro check valve integrated magnetically actuated micropump for implantable drug delivery. In Proceedings of the 19th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS), Kaohsiung, Taiwan, 18–22 June 2017; pp. 1711–1713.11. Shoji, E. Fabrication of a diaphragm micropump system utilizing the ionomer-based polymer actuator. Sens. Actuators B Chem. 2016, 237, 660–665. [CrossRef]12. Garcia, J.; Rios, I.; Fonthal, F. Structural and microfluidic analysis of microneedle array for drug delivery. In Proceedings of the 31st Symposium on Microelectronics Technology and Devices IEEE SBMicro 2016, Belo Horizonte, Brazil, 29 August–3 September 2016; pp. 1–4.13. Kawun, P.; Leahy, S.; Lai, Y. A thin PDMS nozzle/di user micropump for biomedical applications. Sens. Actuators B Chem. 2016, 249, 149–154. [CrossRef]14. Singh, S.; Kumar, N.; George, D.; Sen, A.K. Analytical modeling, simulations and experimental studies of a PZT actuated planar valveless PDMS micropump. Sens. Actuators B Chem. 2015, 225, 81–94. [CrossRef]15. Nguyen, N.T.; Mousavi, S.A.; Kashaninejad, N.; Phan, D.T. Design, fabrication and characterization of drug delivery systems based on lab-on-a-chip technology. Adv. Drug Deliv. Rev. 2013, 65, 1403–1419. [CrossRef] [PubMed]16. Davis, S.P.; Martanto,W.; Allen, M.G.; Prausnitz, M.R. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans. Biomed. Eng. 2005, 52, 909–915. [CrossRef] [PubMed]17. Roxhed, N.T.; Gasser, C.; Griss, P.; Holzapfel, G.A.; Stemme, G. Penetration-enhanced ultrasharp microneedles and prediction on skin interaction for e cient transdermal drug delivery. J. Microelectromech. Syst. 2007, 16, 1429–1440. [CrossRef]18. Sanjay, S.T.; Zhou,W.; Dou, M.; Tavakoli, H.; Ma, L.; Xu, F.; Li, X. Recent advances of controlled drug delivery using microfluidic platforms. Adv. Drug Deliv. Rev. 2018, 128, 3–28. [CrossRef] [PubMed]19. Bao, S.J.; Xie, D.L.; Zhang, J.P.; Chang, W.R.; Liang, D.C. Crystal structure of desheptapeptide (B24–B30) insulin at 1.6 Å resolution: Implications for receptor binding. Proc. Natl. Acad. Sci. USA 1997, 94, 2975–2980. [CrossRef] [PubMed]GeneralPublication2bf30a66-1e41-42a5-8415-189ea7ccdfa8virtual::1746-12bf30a66-1e41-42a5-8415-189ea7ccdfa8virtual::1746-1https://scholar.google.com/citations?user=zxVYtU0AAAAJ&hl=envirtual::1746-10000-0002-9331-0491virtual::1746-1https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000895857virtual::1746-1LICENSElicense.txtlicense.txttext/plain; charset=utf-81665https://red.uao.edu.co/bitstreams/89960119-dae9-4b75-b76b-f6dc37e52eac/download20b5ba22b1117f71589c7318baa2c560MD52ORIGINALDesign and analyses of a transdermal drug delivery device (TD3).pdfDesign and analyses of a transdermal drug delivery device (TD3).pdfTexto archivo completo del artículo de revista, PDFapplication/pdf796032https://red.uao.edu.co/bitstreams/ad18288f-2bc4-41c2-91c9-2855a2b81312/downloadb832f9be6a633448d1f017a21183a8ffMD53TEXTDesign and analyses of a transdermal drug delivery device (TD3).pdf.txtDesign and analyses of a transdermal drug delivery device (TD3).pdf.txtExtracted texttext/plain35575https://red.uao.edu.co/bitstreams/69213a26-8c16-4893-a2bc-c4bf2161fcc5/download8ab25f258e050e88281cb2137e0df32cMD54THUMBNAILDesign and analyses of a transdermal drug delivery device (TD3).pdf.jpgDesign and analyses of a transdermal drug delivery device (TD3).pdf.jpgGenerated Thumbnailimage/jpeg14724https://red.uao.edu.co/bitstreams/5183a783-82b2-4483-a07c-96ae26d18b2d/downloade1cdbe45547470ea26a85e7808d99fb3MD5510614/13434oai:red.uao.edu.co:10614/134342024-03-12 14:43:22.334https://creativecommons.org/licenses/by-nc-nd/4.0/Derechos reservados - MDPI, 2019open.accesshttps://red.uao.edu.coRepositorio Digital Universidad Autonoma de Occidenterepositorio@uao.edu.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