Article | Published:

A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy

Nature Nanotechnology volume 11, pages 566572 (2016) | Download Citation

Abstract

Owing to its high carrier mobility, conductivity, flexibility and optical transparency, graphene is a versatile material in micro- and macroelectronics. However, the low density of electrochemically active defects in graphene synthesized by chemical vapour deposition limits its application in biosensing. Here, we show that graphene doped with gold and combined with a gold mesh has improved electrochemical activity over bare graphene, sufficient to form a wearable patch for sweat-based diabetes monitoring and feedback therapy. The stretchable device features a serpentine bilayer of gold mesh and gold-doped graphene that forms an efficient electrochemical interface for the stable transfer of electrical signals. The patch consists of a heater, temperature, humidity, glucose and pH sensors and polymeric microneedles that can be thermally activated to deliver drugs transcutaneously. We show that the patch can be thermally actuated to deliver Metformin and reduce blood glucose levels in diabetic mice.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    et al. Large-scale pattern growth of graphene films for stretchable transparent electrodes. Nature 457, 706–710 (2009).

  2. 2.

    et al. Roll-to-roll production of 30-inch graphene films for transparent electrodes. Nature Nanotech. 5, 574–578 (2010).

  3. 3.

    , , & Measurement of the elastic properties and intrinsic strength of monolayer graphene. Science 321, 385–388 (2008).

  4. 4.

    Graphene transistors. Nature Nanotech. 5, 487–496 (2010).

  5. 5.

    , & Graphene photonics and optoelectronics. Nature Photon. 4, 611–622 (2010).

  6. 6.

    et al. Transparent, low-power pressure sensor matrix based on coplanar-gate graphene transistors. Adv. Mater. 26, 4735–4740 (2014).

  7. 7.

    et al. Transparent flexible organic transistors based on monolayer graphene electrodes on plastic. Adv. Mater. 23, 1752–1756 (2011).

  8. 8.

    et al. Biomedical applications of graphene and graphene oxide. Acc. Chem. Res. 46, 2211–2224 (2011).

  9. 9.

    et al. High performance three-dimensional chemical sensor platform using reduced graphene oxide formed on high aspect-ratio micro-pillars. Adv. Funct. Mater. 25, 883–890 (2015).

  10. 10.

    et al. Electrical graphene aptasensor for ultra-sensitive detection of anthrax toxin with amplified signal transduction. Small 9, 3352–3360 (2013).

  11. 11.

    et al. Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications. Nature Commun. 5, 5258 (2014).

  12. 12.

    et al. Extremely efficient flexible organic light-emitting diodes with modified graphene anode. Nature Photon. 6, 105–110 (2012).

  13. 13.

    et al. 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium. Nature Commun. 5, 3329 (2014).

  14. 14.

    et al. A potentiometric tattoo sensor for monitoring ammonium in sweat. Analyst 138, 7031–7038 (2013).

  15. 15.

    et al. Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration. Anal. Chem. 85, 6553–6560 (2013).

  16. 16.

    et al. Tattoo-based noninvasive glucose monitoring: a proof-of-concept study. Anal. Chem. 87, 394–398 (2015).

  17. 17.

    et al. An electrically and mechanically self-healing composite with pressure- and flexion-sensitive properties for electronic skin applications. Nature Nanotech. 7, 825–832 (2012).

  18. 18.

    et al. Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring. Nature Commun. 4, 1859 (2013).

  19. 19.

    et al. Electronic dura mater for long-term multimodal neural interfaces. Science 347, 159–163 (2015).

  20. 20.

    et al. Elastomeric electronic skin for prosthetic tactile sensation. Adv. Funct. Mater. 25, 2287–2295 (2015).

  21. 21.

    et al. Multifunctional wearable devices for diagnosis and therapy of movement disorders. Nature Nanotech. 9, 397–404 (2014).

  22. 22.

    et al. Stretchable silicon nanoribbon electronics for skin prosthesis. Nature Commun. 5, 5747 (2014).

  23. 23.

    , , , & Correlation between sweat glucose and blood glucose in subjects with diabetes. Diabetes Technol. Ther. 14, 398–402 (2012).

  24. 24.

    et al. Evaluation of a minimally invasive system for measuring glucose area under the curve during oral glucose tolerance tests: usefulness of sweat monitoring for precise measurement. J. Diabetes Sci. Tehcnol. 7, 678–688 (2013).

  25. 25.

    , , , & Glucose detection in human sweat using an electronic nose. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2013, 1462–1465 (2013).

  26. 26.

    et al. Dissolving polymer micro-needle patches for influenza vaccination. Nature Med. 16, 915–920 (2010).

  27. 27.

    et al. Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Adv. Mater. 20, 933–938 (2008).

  28. 28.

    et al. Emerging applications of phase-change materials (PCMs): teaching an old dog new tricks. Angew. Chem. Int. Ed. 53, 3780–3795 (2014).

  29. 29.

    et al. Soft microfluidic assemblies of sensors, circuits, and radios for the skin. Science 344, 70–74 (2014).

  30. 30.

    et al. Soft network composite materials with deterministic and bio-inspired designs. Nature Commun. 6, 6566 (2015).

  31. 31.

    et al. Stretchable gold conductors on elastomeric substrates. Appl. Phys. Lett. 82, 2404–2406 (2003).

  32. 32.

    et al. Highly bendable, transparent thin-film transistors that use carbon-nanotube-based conductors and semiconductors with elastomeric dielectrics. Adv. Mater. 18, 304–309 (2006).

  33. 33.

    et al. Highly stretchable and transparent nanomesh electrodes made by grain boundary lithography. Nature Commun. 5, 3121 (2014).

  34. 34.

    et al. Localization of folds and cracks in thin metal films coated on flexible elastomer foams. Adv. Mater. 25, 3117–3121 (2013).

  35. 35.

    et al. An ultra-lightweight design for imperceptible plastic electronics. Nature 499, 458–463 (2013).

  36. 36.

    , , & Flexible organic transistors and circuits with extreme bending stability. Nature Mater. 9, 1015–1022 (2010).

  37. 37.

    et al. Organic nonvolatile memory transistors for flexible sensor arrays. Science 326, 1516–1519 (2009).

  38. 38.

    Glycemic management of type 2 diabetes mellitus. N. Engl. J. Med. 366, 1319–1327 (2012).

  39. 39.

    Classification and treatment of tremor. J. Am. Med. Assoc. 266, 1115–1117 (1991).

  40. 40.

    , & Metformin. N. Engl. J. Med. 334, 574–579 (1996).

  41. 41.

    , & Dissolving microneedles for transdermal drug delivery. Biomaterials 29, 2113–2124 (2008).

  42. 42.

    et al. Microneedle integrated transdermal patch for fast onset and sustained delivery of lidocaine. Mol. Pharm. 10, 4272–4280 (2013).

  43. 43.

    , , & Self-setting bioceramic microscopic protrusions for transdermal drug delivery. J. Mater. Chem. B 2, 5992–5998 (2014).

  44. 44.

    , & Transdermal delivery of metformin. US patent 13/504,799 (2012).

  45. 45.

    & Transdermal drug delivery. Nature Biotechnol. 26, 1261–1268 (2008).

  46. 46.

    et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346, 393–403 (2002).

Download references

Acknowledgements

This work was supported by IBS-R006-D1.

Author information

Author notes

    • Hyunjae Lee
    • , Tae Kyu Choi
    •  & Young Bum Lee

    These authors contributed equally to this work

Affiliations

  1. Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-742, Republic of Korea

    • Hyunjae Lee
    • , Tae Kyu Choi
    • , Young Bum Lee
    • , Hye Rim Cho
    • , Taeghwan Hyeon
    • , Seung Hong Choi
    •  & Dae-Hyeong Kim
  2. School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 151-742, Republic of Korea

    • Hyunjae Lee
    • , Tae Kyu Choi
    • , Young Bum Lee
    • , Taeghwan Hyeon
    •  & Dae-Hyeong Kim
  3. Department of Radiology, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea

    • Hye Rim Cho
    •  & Seung Hong Choi
  4. MC10, 10 Maguire Rd., Lexington, Massachusetts 02140, USA

    • Roozbeh Ghaffari
  5. Center for Mechanics of Solids, Structures and Materials, Department of Aerospace Engineering and Engineering Mechanics, Texas Materials Institute, University of Texas at Austin, 210 E 24th Street, Austin, Texas 78712, USA

    • Liu Wang
    •  & Nanshu Lu
  6. Department of Anatomy, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea

    • Hyung Jin Choi
  7. Department of Chemistry, Seoul National University, Seoul 151-747, Republic of Korea

    • Taek Dong Chung
  8. Advanced Institutes of Convergence Technology, Gyeonggi-do 443-270, Republic of Korea

    • Taek Dong Chung

Authors

  1. Search for Hyunjae Lee in:

  2. Search for Tae Kyu Choi in:

  3. Search for Young Bum Lee in:

  4. Search for Hye Rim Cho in:

  5. Search for Roozbeh Ghaffari in:

  6. Search for Liu Wang in:

  7. Search for Hyung Jin Choi in:

  8. Search for Taek Dong Chung in:

  9. Search for Nanshu Lu in:

  10. Search for Taeghwan Hyeon in:

  11. Search for Seung Hong Choi in:

  12. Search for Dae-Hyeong Kim in:

Contributions

H.L., T.K.C., Y.B.L. and D.-H.K. designed the experiments. H.L., T.K.C., Y.B.L., H.R.C., L.W., H.J.C., T.D.J., N. L., T.H., S.H.C. and D.-H.K. performed experiments and analysis. H.L., T.K.C., Y.B.L., H.J.C., R. G., T.D.J., N. L., T.H., S.H.C. and D.-H.K. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Dae-Hyeong Kim.

Supplementary information

PDF files

  1. 1.

    Supplementary information

    Supplementary information

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nnano.2016.38

Further reading