Skip to main content
Log in

Flexible and porous microneedles of PDMS for continuous glucose monitoring

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • L. Lin, A.P. Pisano, Silicon-processed microneedles. J. Microelectromech. Syst. 8(1), 78–84 (1999). https://doi.org/10.1109/84.749406

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  MATH  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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)

    Google Scholar 

  • 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

    Article  Google Scholar 

Download references

Acknowledgements

This work was partially supported by the JSPS Core-to-Core Program (A. Advanced Research Networks).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kai Takeuchi.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10544-020-00532-1

Keywords

Navigation