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

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.

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Figure 1: Schematic drawings and corresponding images of the GP-hybrid electrochemical devices and thermoresponsive drug delivery microneedles.
Figure 2: Electrochemical, mechanical and electrical characterization of the Au mesh, Au film and GP-hybrid.
Figure 3: Electrochemical and electrical characterization of individual devices and their combined operation in vitro.
Figure 4: Demonstration of the wearable diabetes monitoring and therapy system in vivo.

References

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Lee, C., Wei, X., Kysar, J. W. & Hone, J. Measurement of the elastic properties and intrinsic strength of monolayer graphene. Science 321, 385–388 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Bonaccorso, F., Sun, Z. & Ferrari, A. C. Graphene photonics and optoelectronics. Nature Photon. 4, 611–622 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  9. Duy, L. T. 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).

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  17. Tee, B. C.-K. 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).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  23. Moyer, J., Wilson, D., Finkelshtein, I., Wong, B. & Potts, R. Correlation between sweat glucose and blood glucose in subjects with diabetes. Diabetes Technol. Ther. 14, 398–402 (2012).

    Article  CAS  Google Scholar 

  24. Sakaguchi, K. 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).

    Article  Google Scholar 

  25. Olarte, O., Chilo, J., Pelegri-Sebastia, J., Barbé, K. & Moer, W. V. Glucose detection in human sweat using an electronic nose. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2013, 1462–1465 (2013).

    Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  32. Cao, Q. 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).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  36. Sekitani, T., Zschieschang, U., Klauk, H. & Someya, T. Flexible organic transistors and circuits with extreme bending stability. Nature Mater. 9, 1015–1022 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  40. Bailey, C. J., Path, M. R. C. & Turner, R. C. Metformin. N. Engl. J. Med. 334, 574–579 (1996).

    Article  CAS  Google Scholar 

  41. Lee, J. W., Park, J.-H. & Prausnitz, M. R. Dissolving microneedles for transdermal drug delivery. Biomaterials 29, 2113–2124 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  43. Cai, B., Xia, W., Bredenberg, S. & Engqvist, H. Self-setting bioceramic microscopic protrusions for transdermal drug delivery. J. Mater. Chem. B 2, 5992–5998 (2014).

    Article  CAS  Google Scholar 

  44. Scarbrough, C. A., Scarbrough, S. S. & Shubrook, J. Transdermal delivery of metformin. US patent 13/504,799 (2012).

  45. Prausnitz, M. R. & Langer, R. Transdermal drug delivery. Nature Biotechnol. 26, 1261–1268 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by IBS-R006-D1.

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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.

Corresponding author

Correspondence to Dae-Hyeong Kim.

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The authors declare no competing financial interests.

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Lee, H., Choi, T., Lee, Y. et al. A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. Nature Nanotech 11, 566–572 (2016). https://doi.org/10.1038/nnano.2016.38

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