Transdermal Uygulamalar için Silisyum Karbür Esaslı Sekiz Lümenli Mikroiğnenin Geliştirilmesi ve Karakterizasyonu

Year 2025, EARLY VIEW, 1 - 1

Sema Nur Sahın , Hamid Asadi Dereshgi , Yasin Özçelep

https://doi.org/10.2339/politeknik.1601979

Abstract

Mikroiğneler ilaçların ve biyomoleküllerin etkili ve ağrısız şekilde transdermal iletimini sağlayan biyomedikal uygulamalarda büyük potansiyele sahip gelişmiş cihazlardır. Bu çalışmayla, akışkan akışını optimize etmek ve tıkanıklıkları en aza indirmek amacıyla ucu sekiz lümenle entegre edilmiş ve transdermal tedavinin verimliliği ile güvenilirliğini artıran silisyum karbür tabanlı yeni bir mikroiğne tasarımı önerilmiştir. Çalışmada mikroiğnenin mekanik ve akışkan özellikleri 0.001 hassasiyetle sonlu elemanlar analizi (FEA) kullanılarak incelenmiştir. Analizde su, etanol, kan ve gliserol akışkanları dikkate alınmıştır. Lümenlerdeki maksimum basınçların ortalaması ve toplam debiler, 10 Pa ile 100 Pa arasında 10 Pa artışlarla değişen giriş basınçlarında elde edilmiştir. Lümenlerden elde edilen toplam debiler giriş basıncıyla %99'un üzerinde lineer bir ilişki göstermiştir. Ayrıca mikroiğnenin mekanik davranışı eksenel ve eğilme yükleri altında incelenmiştir. Silisyum karbür ve çoklu lümen yapısı kullanılan bu tasarımın önceki modellere göre mikroiğnenin performansını, mekanik stabilitesini ve akışkan iletim verimliliğini artırdığı gözlenmiştir. Akışkan iletimi için dayanıklı ve verimli bir mikroiğne tasarımıyla önemli bir gelişme kaydedilmiş ve bu tasarım, gelecekteki biyomedikal yenilikler için bir ölçüt oluşturmuştur.

Keywords

Silisyum Karbür , Çoklu Lümenli Mikroiğneler , Akışkan Akışının Optimizasyonu , Mekanik Davranış Analizi , Sonlu Elemanlar Analizi

Project Number

2022-ST-002

Development and Characterization of a Silicon Carbide-Based Eight-Lumen Microneedle for Transdermal Applications

Abstract

Microneedles are advanced devices that ensure efficient, painless transdermal delivery of drugs and biomolecules, with significant potential in biomedical applications. In this study, a novel silicon carbide-based microneedle design was proposed, featuring a tip integrated with eight lumens that optimized fluid flow and minimized blockages, thereby improving the efficiency and reliability of transdermal therapy. The study performed finite element analysis (FEA) of the microneedle with a sensitivity of 0.001, investigating its mechanical and fluidic properties. The analysis considered the fluids water, ethanol, blood, and glycerol. The mean maximum pressures in the lumens and the total flow rates were obtained at inlet pressures ranging from 10 Pa to 100 Pa in 10 Pa increments. The flow rates through the lumens exhibited a near-linear relationship with inlet pressure, maintaining a linearity that exceeded 99%. Additionally, the mechanical behavior of the microneedle was investigated under axial and bending loading. This design, utilizing silicon carbide and a multi-lumen structure, was observed to improve the performance, mechanical stability, and fluid delivery efficiency of the microneedle compared to previous models. A significant advancement was achieved with a durable, efficient microneedle design for fluid delivery, setting a benchmark for future biomedical innovations.

Keywords

Silicon Carbide , Multi-lumen Microneedles , Fluid Flow Optimization , Mechanical Behavior Analysis , Finite Element Analysis

Ethical Statement

The authors of this article declare that the materials and methods used in this study do not require ethical committee permission and/or legal-special permission.

Supporting Institution

Istanbul Arel University

Project Number

2022-ST-002

Thanks

The authors also acknowledge the Artificial Intelligence Studies, Application, and Research Center (ArelMED-I) at Istanbul Arel University for providing essential technical support in numerical analysis.

References

• [1] Sackmann E. K., Fulton A. L. and Beebe D. J., “The present and future role of microfluidics in biomedical research”, Nature, 507(7491): 181–189, (2014).
• [2] Torkay G. and Öztürk A. B., “Mikroakışkan çiplere kök hücre ve doku mühendisliği perspektifinden bakış”, Journal of Polytechnic-Politeknik Dergisi, 27(2): 429–433, (2023).
• [3] Asadi Dereshgi H., Dal H. and Yildiz M. Z., “Piezoelectric micropumps: State of the art review”, Microsystem Technologies, 27(12): 4127–4155, (2021).
• [4] Asadi Dereshgi H., Yıldız M. and Parlak N., “Performance comparison of novel single and bi-diaphragm PZT based valveless micropumps”, Journal of Applied Fluid Mechanics, 13(2): 401–412, (2020).
• [5] Zhang X., Zhou C., Chen T., Jiang Z., Lu C., Wu C., Pan X., Huang Z. and Peng T., “State-of-the-art strategies to enhance the mechanical properties of microneedles”, International Journal of Pharmaceutics, 663: 124547, (2024).
• [6] Ai X., Yang J., Liu Z., Guo T. and Feng N., “Recent progress of microneedles in transdermal immunotherapy: a review”, International Journal of Pharmaceutics, 662: 124481, (2024).
• [7] Prausnitz M. R., “Microneedles for transdermal drug delivery”, Advanced drug delivery reviews, 56(5): 581–587, (2004).
• [8] Hao Y., Li W., Zhou X., Yang F. and Qian Z., “Microneedles-based transdermal drug delivery systems: a review”, Journal of biomedical nanotechnology, 13(12): 1581–1597, (2017).
• [9] Yang J., Liu X., Fu Y. and Song Y., “Recent advances of microneedles for biomedical applications: drug delivery and beyond”, Acta Pharmaceutica Sinica B, 9(3): 469–483, (2019).
• [10] Gerstel M. S. and Place V. A., “Drug delivery device”, US Patent No. 3964482, (1976).
• [11] Henry S., McAllister D. V., Allen M. G. and Prausnitz M. R., “Microfabricated microneedles: a novel approach to transdermal drug delivery”, Journal of pharmaceutical sciences, 87(8): 922–925, (1998).
• [12] Cammarano A., Iacono S. D., Battisti M., De Stefano L., Meglio C. and Nicolais L., “A Systematic Review of Microneedles Technology in Drug Delivery through a Bibliometric and Patent Overview”, Heliyon, 10: e40658, (2024).
• [13] Ayittey P. N., Walker J. S., Rice J. J. and De Tombe P. P., “Glass microneedles for force measurements: a finite-element analysis model”, Pflügers Archiv-European Journal of Physiology, 457: 1415–1422, (2009).
• [14] Ashaf M. W., Tayyaba S. and Afzulpurkr N., “Tapered tip hollow silicon microneedles for transdermal drug delivery”, 2nd International Conference on Mechanical and Electronics Engineering, 1: 469–473, (2010).
• [15] Kong X. Q., Zhou P. and Wu C. W., “Numerical simulation of microneedles' insertion into skin”, Computer methods in biomechanics and biomedical engineering, 14(9): 827–835, (2011).
• [16] Chen S., Li N. and Chen J., “Finite element analysis of microneedle insertion into skin”, Micro & Nano Letters, 7(12): 1206–1209, (2012).
• [17] Chiu C. Y., Kuo H. C., Lin Y., Lee J. L., Shen Y. K. and Kang S. J., “Optimal design of microneedles inserts into skin by numerical simulation”, Key Engineering Materials, 516: 624–628, (2012).
• [18] Olatunji O., Das D. B. and Nassehi V., “Modelling transdermal drug delivery using microneedles: Effect of geometry on drug transport behaviour”, Journal of pharmaceutical sciences, 101(1): 164–175, (2012).
• [19] Boonma A., Narayan R. J. and Lee Y. S., “Analytical modeling and evaluation of microneedles apparatus with deformable soft tissues for biomedical applications”, Computer-Aided Design and Applications, 10(1): 139–157, (2013).
• [20] Kanakaraj U. and Lhaden T., “Analysis of structural mechanics of solid microneedle using COMSOL software”, International Conference on Innovations in Information, Embedded and Communication Systems (Iciiecs), 1–5, (2015).
• [21] García J., Rios I. and Fonthal F., “Structural and microfluidic analysis of microneedle array for drug delivery”, 31st Symposium on Microelectronics Technology and Devices (SBMicro), 1–4, (2016).
• [22] Loizidou E. Z., Inoue N. T., Ashton-Barnett J., Barrow D. A. and Allender C. J., “Evaluation of geometrical effects of microneedles on skin penetration by CT scan and finite element analysis”, European Journal of Pharmaceutics and Biopharmaceutics, 107: 1–6, (2016).
• [23] Zhang Y. H., A Campbell S. and Karthikeyan S., “Finite element analysis of hollow out-of-plane HfO 2 microneedles for transdermal drug delivery applications”, Biomedical Microdevices, 20: 1–7, (2018).
• [24] Chen Z., Lin Y., Lee W., Ren L., Liu B., Liang L., Wang Z. and Jiang L., “Additive manufacturing of honeybee-inspired microneedle for easy skin insertion and difficult removal”, ACS applied materials & interfaces, 10(35): 29338–29346, (2018).
• [25] Amiri Y. and Vahidi B., “Three dimensional simulation of the microneedle penetration process in the skin by finite element method”, 26th National and 4th International Iranian Conference on Biomedical Engineering (ICBME), 70–74, (2019).
• [26] Sarmadi M., McHugh K., Langer R. and Jaklenec A., “Multi-objective optimization of microneedle design for transdermal drug delivery”, Stress, 10: 15, (2019).
• [27] Sawon M. A. and Samad M. F., “Design and Analysis of Silicon Carbide Microneedle for Transdermal Drug Delivery”, IEEE Region 10 Symposium (TENSYMP), 1343–1346, (2020).
• [28] Abidin H. E. Z., Ooi P. C., Tiong T. Y., Marsi N., Ismardi A., Noor M. M., Fathi N. A. F. N. Z., Abd Aziz N., Sahari S. K., Sugandi G., Yunas J., Dee C. F., Majlis B. Y. and Hamzah A. A., “Stress and deformation of optimally shaped silicon microneedles for transdermal drug delivery”, Journal of Pharmaceutical Sciences, 109(8): 2485–2492, (2020).
• [29] Shu W., Heimark H., Bertollo N., Tobin D. J., O'Cearbhaill E. D. and Annaidh A. N., “Insights into the mechanics of solid conical microneedle array insertion into skin using the finite element method”, Acta Biomaterialia, 135: 403–413, (2021).
• [30] Radhika C. and Gnanavel B. K., “Finite element analysis of polymer microneedle for transdermal drug delivery”, Materials Today: Proceedings, 39: 1538–1542, (2021).
• [31] Castilla-Casadiego D. A., Carlton H., Gonzalez-Nino D., Miranda-Muñoz K. A., Daneshpour R., Huitink D., Prinz G., Powell J., Greenlee L. and Almodovar J., “Design, characterization, and modeling of a chitosan microneedle patch for transdermal delivery of meloxicam as a pain management strategy for use in cattle”, Materials Science and Engineering: C, 118: 111544, (2021).
• [32] Yan Q., Weng J., Shen S., Wang Y., Fang M., Zheng G., Yang Q. and Yang G., “Finite element analysis for biodegradable dissolving microneedle materials on skin puncture and mechanical performance evaluation”, Polymers, 13(18): 3043, (2021).
• [33] Chandbadshah S. B. V. J. and Mannayee G., “Structural analysis and simulation of solid microneedle array for vaccine delivery applications”, Materials Today: Proceedings, 65: 3774–3779, (2022).
• [34] Lechuga Y., Kandel G., Miguel J. A. and Martinez M., “Development of an Automated Design Tool for FEM-Based Characterization of Solid and Hollow Microneedles”, Micromachines, 14(1): 133, (2023).
• [35] Sawon M. A. and Samad M. F., “Design and optimization of a microneedle with skin insertion analysis for transdermal drug delivery applications”, Journal of Drug Delivery Science and Technology, 63: 102477, (2021).
• [36] Haldkar R. K., Gupta V. K., Sheorey T. and Parinov I. A., “Design, modeling, and analysis of piezoelectric-actuated device for blood sampling”, Applied Sciences, 11(18): 8449, (2021).
• [37] Quispe C. A., Coronado C. J. and Carvalho Jr J. A., “Glycerol: Production, consumption, prices, characterization and new trends in combustion”, Renewable and sustainable energy reviews, 27: 475-493, (2013).
• [38] Bodhale D. W., Nisar A. and Afzulpurkar N., “Structural and microfluidic analysis of hollow side-open polymeric microneedles for transdermal drug delivery applications”, Microfluidics and Nanofluidics, 8: 373–392, (2010).
• [39] Mishra R., Bhattacharyya T. K. and Maiti T. K., “Theoretical analysis and simulation of SU-8 microneedles for effective skin penetration and drug delivery”, IEEE SENSORS, 1–4, (2015).
• [40] Jaman R. U. and Samad M. F., “Design and Performance Analysis of a Silicon Carbide Microneedle for Ibuprofen Drug Delivery”, International Conference on Electrical, Computer and Communication Engineering (ECCE), 1–5, (2023).
• [41] Jaman R. U. and Samad M. F., “Design and analysis of a reservoir-based controllable microneedle for transdermal drug delivery applications”, Drug Delivery and Translational Research, 14(3): 812–825, (2024).
• [42] Ashraf M. W., Tayyaba S., Nisar A., Afzulpurkar N., Bodhale D. W., Lomas T., Poyai A. and Tuantranont A., “Design, fabrication and analysis of silicon hollow microneedles for transdermal drug delivery system for treatment of hemodynamic dysfunctions”, Cardiovascular engineering, 10: 91–108, (2010).
• [43] Ashraf M. W., Tayyaba S., Afzulpurkar N., Nisar A., Bohez E. L. J., Lomas T. and Tuantranont A., “Design, simulation and fabrication of silicon microneedles for bio-medical applications”, ECTI Transactions on Electrical Engineering, Electronics, and Communications, 9(1): 83–91, (2011).
• [44] Perera K. N. M., Awantha W. V. I., Wanasinghe A. T., Herath H. M. D. P., Paththinige S. S., Ekanayaka L. and Amarasinghe Y. W. R., “Design and analysis of a MEMS based transdermal drug delivery system”, Moratuwa Engineering Research Conference (MERCon), 596–601, (2020).
• [45] Loizidou E. Z., Williams N. A., Barrow D. A., Eaton M. J., McCrory J., Evans S. L. and Allender C. J., “Structural characterisation and transdermal delivery studies on sugar microneedles: Experimental and finite element modelling analyses”, European Journal of Pharmaceutics and Biopharmaceutics, 89: 224–231, (2015).
• [46] Ranamukhaarachchi S. A., Padeste C., Dübner M., Häfeli U. O., Stoeber B. and Cadarso V. J., “Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes”, Scientific reports, 6: 29075, (2016).
• [47] Li Y., Zhang H., Yang R., Laffitte Y., Schmill U., Hu W., Kaddoura M., Blondeel E. J. M. and Cui, B., “Fabrication of sharp silicon hollow microneedles by deep-reactive ion etching towards minimally invasive diagnostics”, Microsystems & nanoengineering, 5: 41, (2019).
• [48] Saddow S. E., “Silicon Carbide Biotechnology: A biocompatible semiconductor for advanced biomedical devices and applications”, Elsevier, Amsterdam, Netherlands, (2016).
• [49] Bonaventura G., Iemmolo R., La Cognata V., Zimbone M., La Via F., Fragalà M. E., et al., “Biocompatibility between silicon or silicon carbide surface and neural stem cells”, Scientific Reports, 9: 1-11, (2019).
• [50] Kamiński M., Król K., Kwietniewski N., Myśliwiec M., Sochacki M., Stonio B., Kisiel R., Martychowiec A., Racka-Szmidt K., Werbowy A., Żelazko J., Niedzielski P., Szmidt J., Strójwąs A., “The overview of silicon carbide technology: Status, challenges, Key Drivers, and product roadmap”, Materials, 18: 12, (2024).
• [51] Güder S., “Efficacy of Fractional Microneedle Radiofrequency Application in Abdominal Wrinkles and Sagging: Case Report”, Abant Medical Journal, 9: 47-49, (2020).