Abstract
Microneedle (MN) is a key technology of the biomedical engineering field due to its capability of accessing the biological information in a minimally invasive manner. One of the huge demands for next-generation healthcare monitoring is continuous monitoring, especially of blood glucose concentration. For this, MN should be kept inserted into the human skin for a certain period of time, enduring stresses induced by daily human motion and at the same time measuring biomarkers in ISF. However, conventional MNs for biosensing are not suitable for a long term insertion due to the rigid structure and biological risks of MN breakage. In this study, a novel MN structure is proposed and investigated by combining flexible “sponge-like” porous PDMS matrix and coating by biodissolving hyaluronic acid (HA). The fabricated porous MNs coated with HA show ideal mechanical characteristics, by which the MNs are rigid enough to penetrate the skin and become flexible after insertion into the skin. It is also shown that the MN array successfully extracts ISF in vitro and in vivo not by capillary action but by repeated compressions. The results show the applicability of the flexible MNs to continuous blood glucose monitoring.
Similar content being viewed by others
References
Y. Bo-Ming, L. Jian-Hua, A geometry model for tortuosity of flow path in porous media. Chin. Phys. Lett. 21(8), 1569–1571 (2004). https://doi.org/10.1088/0256-307x/21/8/044
M.S. Boyne, D.M. Silver, J. Kaplan, C.D. Saudek, Timing of changes in interstitial and venous blood glucose measured with a continuous subcutaneous glucose sensor. Diabetes. 52(11), 2790–2794 (2003). https://doi.org/10.2337/diabetes.52.11.2790
M. Brown, S. Jones, Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin. J. Eur. Acad. Dermatol. Venereol. 19 (3), 308–318 (2005). https://doi.org/10.1111/j.1468-3083.2004.01180.x
E.M. Cahill, S. Keaveney, V. Stuettgen, P. Eberts, P. Ramos-Luna, N. Zhang, M. Dangol, E.D. O’Cearbhaill, Metallic microneedles with interconnected porosity: A scalable platform for biosensing and drug delivery. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2018.09.007 (2018)
K.J. Cha, D.S. Kim, A portable pressure pump for microfluidic lab-on-a-chip systems using a porous polydimethylsiloxane (pdms) sponge. Biomed. Microdevices. 13(5), 877 (2011). https://doi.org/10.1007/s10544-011-9557-z
A.A. Chavan, H. Li, A. Scarpellini, S. Marras, L. Manna, A. Athanassiou, D. Fragouli, Elastomeric nanocomposite foams for the removal of heavy metal ions from water. ACS Applied Materials & Interfaces. 7(27), 14778–14784 (2015)
S.J. Choi, T.H. Kwon, H. Im, D.I. Moon, D.J. Baek, M.L. Seol, J.P. Duarte, Y.K. Choi, A polydimethylsiloxane (pdms) sponge for the selective absorption of oil from water. ACS Applied Materials & Interfaces. 3(12), 4552–4556 (2011). https://doi.org/10.1021/am201352w
M.J. Fokkert, P.R. van Dijk, M.A. Edens, S. Abbes, D. de Jong, R.J. Slingerland, H.J.G. Bilo, Performance of the freestyle libre flash glucose monitoring system in patients with type 1 and 2 diabetes mellitus. BMJ Open Diabetes Research and Care, 5(1). https://doi.org/10.1136/bmjdrc-2016-000320 (2017)
S.K. Garg, R.O. Potts, N.R. Ackerman, S.J. Fermi, J.A. Tamada, H.P. Chase, Correlation of fingerstick blood glucose measurements with glucowatch biographer glucose results in young subjects with type 1 diabetes. Diabetes Care. 22(10), 1708–1714 (1999). https://doi.org/10.2337/diacare.22.10.1708
S. Gholami, M.M. Mohebi, E. Hajizadeh-Saffar, M.H. Ghanian, I. Zarkesh, H Baharvand, Fabrication of microporous inorganic microneedles by centrifugal casting method for transdermal extraction and delivery. Int. J. Pharm. 558, 299–310 (2019). https://doi.org/10.1016/j.ijpharm.2018.12.089
H.S. Gill, D.D. Denson, B.A. Burris, M.R. Prausnitz, Effect of microneedle design on pain in human volunteers. The Clinical Journal of Pain. 24(7), 585–594 (2008)
P. Griss, G. Stemme, in Novel, side opened out-of-plane microneedles for microfluidic transdermal interfacing. Technical Digest. MEMS 2002 IEEE International Conference. Fifteenth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No.02CH37266). https://doi.org/10.1109/MEMSYS.2002.984303, (2002), pp. 467–470
S. Hirobe, H. Azukizawa, K. Matsuo, Y. Zhai, Y.S. Quan, F. Kamiyama, H. Suzuki, I. Katayama, N. Okada, S. Nakagawa, Development and clinical study of a self-dissolving microneedle patch for transcutaneous immunization device. Pharm. Res. 30(10), 2664–2674 (2013). https://doi.org/10.1007/s11095-013-1092-6
Q. Hou, D.W. Grijpma, J. Feijen, Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique. Biomaterials. 24(11), 1937–1947 (2003). https://doi.org/10.1016/S0142-9612(02)00562-8
L. Humrez, M. Ramos, A. Al-Jumaily, M. Petchu, J. Ingram, Synthesis and characterisation of porous polymer microneedles. J. Polym. Res. 18(5), 1043–1052 (2011). https://doi.org/10.1007/s10965-010-9505-2
M. Khorasani, H. Mirzadeh, Z. Kermani, Wettability of porous polydimethylsiloxane surface: morphology study. Appl. Surf. Sci. 242(3), 339–345 (2005). https://doi.org/10.1016/j.apsusc.2004.08.035
J.D. Kim, M. Kim, H. Yang, K. Lee, H. Jung, Droplet-born air blowing: Novel dissolving microneedle fabrication. J. Control. Release. 170(3), 430–436 (2013). https://doi.org/10.1016/j.jconrel.2013.05.026
M. Kim, H. Yang, H. Kim, H. Jung, H. Jung, Novel cosmetic patches for wrinkle improvement: retinyl retinoate- and ascorbic acid-loaded dissolving microneedles. Int. J. Cosmet. Sci. 36(3), 207–212 (2014). https://doi.org/10.1111/ics.12115
S. Kurokawa, N. Takama, B. Kim, in Development of blood extracting microneedle for blood multidiagnostic chip. 2017 JSPE Autumn Conference, (2017), p. 943
J.P. Le Floch, B. Bauduceau, M Lévy, H. Mosnier-Pudar, C. Sachon, B. Kakou, Self-monitoring of blood glucose, cutaneous finger injury, and sensory loss in diabetic patients. Diabetes Care. 31(10), e73–e73 (2008). https://doi.org/10.2337/dc08-1174
J.W. Lee, J.H. Park, M.R. Prausnitz, Dissolving microneedles for transdermal drug delivery. Biomaterials. 29(13), 2113–2124 (2008). https://doi.org/10.1016/j.biomaterials.2007.12.048
J. Li, B. Liu, Y. Zhou, Z. Chen, L. Jiang, W. Yuan, L. Liang, Fabrication of a ti porous microneedle array by metal injection molding for transdermal drug delivery. Plos One. 12(2), 1–15 (2017). https://doi.org/10.1371/journal.pone.0172043
L. Lin, A.P. Pisano, Silicon-processed microneedles. J. Microelectromech. Syst. 8(1), 78–84 (1999). https://doi.org/10.1109/84.749406
L. Liu, H. Kai, K. Nagamine, Y. Ogawa, M. Nishizawa, Porous polymer microneedles with interconnecting microchannels for rapid fluid transport. RSC Adv. 6, 48630–48635 (2016). https://doi.org/10.1039/C6RA07882F
D. Loewenstein, C. Stake, M. Cichon, Assessment of using fingerstick blood sample with i-stat point-of-care device for cardiac troponin i assay. Am. J. Emerg. Med. 31(8), 1236–1239 (2013). https://doi.org/10.1016/j.ajem.2013.04.031
E.Z. Loizidou, N.T. Inoue, J. Ashton-Barnett, D.A. Barrow, C.J. Allender, Evaluation of geometrical effects of microneedles on skin penetration by ct scan and finite element analysis. Eur. J. Pharm. Biopharm. 107, 1–6 (2016). https://doi.org/10.1016/j.ejpb.2016.06.023
K. van der Maaden, R. Luttge, P.J. Vos, J. Bouwstra, G. Kersten, I. Ploemen, Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays. Drug Delivery and Translational Research. 5(4), 397–406 (2015). https://doi.org/10.1007/s13346-015-0238-y
A.V. Mohan, J.R. Windmiller, R.K. Mishra, J. Wang, Continuous minimally-invasive alcohol monitoring using microneedle sensor arrays. Biosensors and Bioelectronics. 91, 574–579 (2017). https://doi.org/10.1016/j.bios.2017.01.016
K. Mooney, J.C. McElnay, R.F. Donnelly, Children’s views on microneedle use as an alternative to blood sampling for patient monitoring. Int. J. Pharm. Pract. 22 (5), 335–344 (2013). https://doi.org/10.1111/ijpp.12081
K. Nagamine, J. Kubota, H. Kai, Y. Ono, M. Nishizawa, An array of porous microneedles for transdermal monitoring of intercellular swelling. Biomed. Microdevices. 19(3), 68 (2017). https://doi.org/10.1007/s10544-017-0207-y
O. Olatunji, D.B. Das, M.J. Garland, L. Belaid, R.F. Donnelly, Influence of array interspacing on the force required for successful microneedle skin penetration: Theoretical and practical approaches. J. Pharm. Sci. 102(4), 1209–1221 (2013). https://doi.org/10.1002/jps.23439
P. Parikh, H. Mochari, L. Mosca, Clinical utility of a fingerstick technology to identify individuals with abnormal blood lipids and high-sensitivity c-reactive protein levels. Am. J. Health. Promot. 23(4), 279–282 (2009). https://doi.org/10.4278/ajhp.071221140
J.H. Park, M.G. Allen, M.R. Prausnitz, Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery. J. Control. Release. 104(1), 51–66 (2005). https://doi.org/10.1016/j.jconrel.2005.02.002
J.H. Park, S.O. Choi, R. Kamath, Y.K. Yoon, M.G. Allen, M.R. Prausnitz, Polymer particle-based micromolding to fabricate novel microstructures. Biomed. Microdevices. 9(2), 223–234 (2007). https://doi.org/10.1007/s10544-006-9024-4
Y. Park, J. Park, G.S. Chu, K.S. Kim, J.H. Sung, B. Kim, Transdermal delivery of cosmetic ingredients using dissolving polymer microneedle arrays. Biotechnol. Bioprocess. Eng. 20(3), 543–549 (2015). https://doi.org/10.1007/s12257-014-0775-0
J.R. Petrie, A.L. Peters, R.M. Bergenstal, R.W. Holl, G.A. Fleming, L. Heinemann, Improving the clinical value and utility of cgm systems: issues and recommendations. Diabetologia. 60(12), 2319–2328 (2017). https://doi.org/10.1007/s00125-017-4463-4
P.P. Samant, M.R. Prausnitz, Mechanisms of sampling interstitial fluid from skin using a microneedle patch. Proc.. Natl.. Acad.. Sci.. 115(18), 4583–4588 (2018). https://doi.org/10.1073/pnas.1716772115
W. Smith, Analytic solutions for tapered column buckling. Computers & Structures. 28(5), 677–681 (1988). https://doi.org/10.1016/0045-7949(88)90011-9
P. Thurgood, S. Baratchi, C. Szydzik, A. Mitchell, K. Khoshmanesh, Porous pdms structures for the storage and release of aqueous solutions into fluidic environments. Lab. Chip. 17, 2517–2527 (2017). https://doi.org/10.1039/C7LC00350A
M. Venugopal, K.E. Feuvrel, D. Mongin, S. Bambot, M. Faupel, A. Panangadan, A. Talukder, R. Pidva, Clinical evaluation of a novel interstitial fluid sensor system for remote continuous alcohol monitoring. IEEE Sensors J. 8(1), 71–80 (2008). https://doi.org/10.1109/JSEN.2007.912544
M. Venugopal, S.K. Arya, G. Chornokur, S. Bhansali, A realtime and continuous assessment of cortisol in isf using electrochemical impedance spectroscopy. Sensors and Actuators A: Physical. 172(1), 154–160 (2011). https://doi.org/10.1016/j.sna.2011.04.028
M. Verhoeven, S. Bystrova, L. Winnubst, H. Qureshi, T.D. de Gruijl, R.J. Scheper, R. Luttge, Applying ceramic nanoporous microneedle arrays as a transport interface in egg plants and an ex-vivo human skin model. Microelectronic Engineering. 98, 659–662 (2012). https://doi.org/10.1016/j.mee.2012.07.022
J. Wu, B. Yu, M. Yun, A resistance model for flow through porous media. Transp.. Porous. Media. 71(3), 331–343 (2008). https://doi.org/10.1007/s11242-007-9129-0
Y. Xie, H. Wang, J. Mao, Y. Li, M. Hussain, J. Zhu, Y. Li, L. Zhang, J. Tao, J. Zhu, Enhanced in vitro efficacy for inhibiting hypertrophic scar by bleomycin-loaded dissolving hyaluronic acid microneedles. J. Mater. Chem. B. 7, 6604–6611 (2019). https://doi.org/10.1039/C9TB01449G
W. Yang, Y.G. Nam, B.K. Lee, K. Han, T.H. Kwon, D.S. Kim, Fabrication of a hydrophilic poly(dimethylsiloxane) microporous structure and its application to portable microfluidic pump. Japanese J. Appl. Phys. 49(6S), 06GM01 (2010)
X. Zhao, L. Li, B. Li, J. Zhang, A. Wang, Durable superhydrophobic/superoleophilic pdms sponges and their applications in selective oil absorption and in plugging oil leakages. J. Mater. Chem. A. 2, 18281–18287 (2014). https://doi.org/10.1039/C4TA04406A
Acknowledgements
This work was partially supported by the JSPS Core-to-Core Program (A. Advanced Research Networks).
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Takeuchi, K., Takama, N., Kinoshita, R. et al. Flexible and porous microneedles of PDMS for continuous glucose monitoring. Biomed Microdevices 22, 79 (2020). https://doi.org/10.1007/s10544-020-00532-1
Accepted:
Published:
DOI: https://doi.org/10.1007/s10544-020-00532-1