Skip to main content
Log in

Microfluidic chip connected to porous microneedle array for continuous ISF sampling

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Minimally invasive biosensing using microneedles (MNs) is a desirable technology for continuous healthcare monitoring. Among a wide range of MNs, porous MNs are expected to be applied for sampling of interstitial fluids (ISF) by connecting the internal tissue to external measurement devices. In order to realize a continuous measurement of biomarkers in ISF through porous MNs, their integration with a microfluidic chip is a promising approach due to its applicability to micro-total analysis system (μTAS) technology. In this study, we developed a fluidic system to directly interface porous MNs to a microfluidic chip consisting of a capillary pump for the continuous sampling of ISF. The porous and flexible MNs made of PDMS are connected to the microfluidic chip fabricated by standard microelectro-mechanical system (MEMS) processes, showing a continuous flow of phosphate buffered saline (PBS). The developed device will lead to the minimally invasive and continuous biosampling for long-term healthcare monitoring.

Graphical abstract

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
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Availability of data and materials

The data that support the findings of this study are available from the corresponding author, [author initials], upon reasonable request.

References

  1. Mukerjee EV, Collins SD, Isseroff RR, Smith RL. Microneedle array for transdermal bio- logical fluid extraction and in situ analysis. Sens Actuators, A. 2004;114(2):267–75.

    Article  CAS  Google Scholar 

  2. Strambini LM, Longo A, Scarano S, Prescimone T, Palchetti I, Minunni M, Giannessi D, Barillaro G. Self-powered microneedle-based biosensors for pain-free high-accuracy measurement of glycaemia in interstitial fluid. Biosens Bioelectron. 2015;66:162–8.

    Article  CAS  Google Scholar 

  3. Chua B, Desai SP, Tierney MJ, Tamada JA, Jina AN. Effect of microneedles shape on skin penetration and minimally invasive continuous glucose monitoring in vivo. Sens Actuators, A. 2013;203:373–81.

    Article  CAS  Google Scholar 

  4. Chen D, Wang C, Chen W, Chen Y, Zhang JX. Pvdf-nafion nanomembranes coated microneedles for in vivo transcutaneous implantable glucose sensing. Biosensors and Bioelectronics. 2015;74:1047–1052.

  5. Chinnadayyala SR, Park I, Cho S. Nonenzymatic determination of glucose at near neutral ph values based on the use of nafion and platinum black coated microneedle electrode array. Microchim Acta. 2018;185(5):250.

    Article  Google Scholar 

  6. Sharma S, Saeed A, Johnson C, Gadegaard N, Cass AE. Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring. Sensing and Bio-Sensing Res. 2017;13:104–108.

  7. Humrez L, Ramos M, Al-Jumaily A, Petchu M, Ingram J. Synthesis and characterisation of porous polymer microneedles. J Polym Res. 2011;18(5):1043–52.

    Article  CAS  Google Scholar 

  8. Verhoeven M, Bystrova S, Winnubst L, Qureshi H, de Gruijl TD, Scheper RJ, Luttge R. Applying ceramic nanoporous microneedle arrays as a transport interface in egg plants and an ex-vivo human skin model. Microelectron Eng. 2012;98:659–62.

    Article  CAS  Google Scholar 

  9. Liu L, Kai H, Nagamine K, Ogawa Y, Nishizawa M. Porous polymer microneedles with interconnecting microchannels for rapid fluid transport. RSC Adv. 2016;6:48630–5.

    Article  CAS  Google Scholar 

  10. Nagamine K, Kubota J, Kai H, Ono Y, Nishizawa M. An array of porous microneedles for transdermal monitoring of intercellular swelling. Biomed Microdevice. 2017;19(3):68.

    Article  Google Scholar 

  11. Takeuchi K, Takama N, Kinoshita R, Okitsu T, Kim B. Flexible and porous microneedles of pdms for continuous glucose monitoring. Biomed Microdevice. 2020;22(4):79.

    Article  CAS  Google Scholar 

  12. Pu Z, Zou C, Wang R, Lai X, Yu H, Xu K, Li D. A continuous glucose monitoring device by graphene modified electrochemical sensor in microfluidic system. Biomicrofluidics. 2016;10(1):011910.

  13. Zhao Y, Li S, Davidson A, Yang B, Wang Q, Lin Q. A mems viscometric sensor for continuous glucose monitoring. J Micromech Microeng. 2007;17(12):2528.

    Article  CAS  Google Scholar 

  14. Rebrin K,  Sheppard Jr NF, Steil GM. Use of subcutaneous interstitial fluid glucose to estimate blood glucose: Revisiting delay and sensor offset. J Diabetes Sci Technol. 2010;4(5):1087–1098.

  15. Keenan DB, Mastrototaro JJ, Voskanyan G, Steil GM. Delays in minimally invasive continuous glucose monitoring devices: a review of current technology. J Diabetes Sci Technol. 2009;3(5):1207–1214.

  16. Takeuchi K, Takama N, Kim B, Sharma K, Paul O, Ruther P. Mi- crofluidic chip to interface porous microneedles for isf collection. Biomed Microdevice. 2019;21(1):28.

    Article  Google Scholar 

  17. Ishino C, Reyssat M, Reyssat E, Okumura K, Quéré D. Wicking within forests of micropillars EPL (Europhysics Letters). 2007;79(5):56005.

    Article  Google Scholar 

  18. Zimmermann M, Schmid H, Hunziker P, Delamarche E. Capillary pumps for autonomous capillary systems. Lab Chip. 2007;7:119–25.

    Article  CAS  Google Scholar 

  19. Pocock G, Richards CD, Richards DA. Human physiology, Oxford university press. 2013.

  20. Pitts KL, Abu-Mallouh S, Fenech M. Contact angle study of blood dilutions on common microchip materials. J Mech Behav Biomed Mater. 2013;17:333–6.

    Article  CAS  Google Scholar 

  21. Bruus H. Theoretical microfluidics, Oxford university press. 2007.

  22. Yao W, Li Y, Ding G. Interstitial fluid flow: the mechanical environment of cells and foundation of meridians, evidence-based complementary and alternative medicine. 2012:9.

  23. Takeuchi K, Mu F, Matsumoto Y, Suga T. Room temperature wafer bonding of glass using aluminum oxide intermediate layer. Adv Mater Interfaces. 2021;:2001741.

Download references

Acknowledgements

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

Funding

This work was partially supported by the JSPS Core-to-Core Program (A. Advanced Research Networks) and the Precise Measurement Technology Promotion Foundation (PMTP-F).

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by K. Takeuchi, N. Takama, and BJ. Kim. The first draft of the manuscript was written by K. Takeuchi, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kai Takeuchi.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

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., Sharma, K. et al. Microfluidic chip connected to porous microneedle array for continuous ISF sampling. Drug Deliv. and Transl. Res. 12, 435–443 (2022). https://doi.org/10.1007/s13346-021-01050-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-021-01050-0

Keywords

Navigation