Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Non-invasive, transdermal, path-selective and specific glucose monitoring via a graphene-based platform


Currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Here, we report a path-selective, non-invasive, transdermal glucose monitoring system based on a miniaturized pixel array platform (realized either by graphene-based thin-film technology, or screen-printing). The system samples glucose from the interstitial fluid via electroosmotic extraction through individual, privileged, follicular pathways in the skin, accessible via the pixels of the array. A proof of principle using mammalian skin ex vivo is demonstrated for specific and ‘quantized’ glucose extraction/detection via follicular pathways, and across the hypo- to hyper-glycaemic range in humans. Furthermore, the quantification of follicular and non-follicular glucose extraction fluxes is clearly shown. In vivo continuous monitoring of interstitial fluid-borne glucose with the pixel array was able to track blood sugar in healthy human subjects. This approach paves the way to clinically relevant glucose detection in diabetics without the need for invasive, finger-stick blood sampling.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Principle of a pixel-based array targeting transdermal individual preferential glucose pathways.
Fig. 2: Individual pixel and array concept, and extraction–detection operation cycle.
Fig. 3: Deconstructed pixel device.
Fig. 4: A functional, fully integrated, CVD graphene-based 2 × 2 pixel array on a flexible substrate.
Fig. 5: Second-generation, screen-printed, 2 × 2 array.


  1. Wild, S., Roglic, G., Green, A., Sicree, R. & King, H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27, 1047–1053 (2004).

    Article  Google Scholar 

  2. McGarraugh, G., Brazg, R. & Weinstein, R. Freestyle Navigator continuous glucose monitoring system with Trustart algorithm, a 1-hour warm-up time. J. Diabetes Sci. Technol. 5, 99–106 (2011).

    Article  Google Scholar 

  3. Mamkin, I., Ten, S., Bhandari, S. & Ramchandani, N. Real-time continuous glucose monitoring in the clinical setting: the good, the bad, and the practical. J. Diabetes Sci. Technol. 2, 882–889 (2008).

    Article  Google Scholar 

  4. Torjman, M. C., Dalal, N. & Goldberg, M. E. Glucose monitoring in acute care: technologies on the horizon. J. Diabetes Sci. Technol. 2, 178–181 (2008).

    Article  Google Scholar 

  5. Burge, M. R., Mitchell, S., Sawyer, A. & Schade, D. S. Continuous glucose monitoring: the future of diabetes management. Diabetes Spectr. 21, 112–119 (2008).

    Article  Google Scholar 

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

    Google Scholar 

  7. Lee, H. et al. A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. Nat. Nanotech. 11, 566–572 (2016).

    Article  Google Scholar 

  8. Heikenfeld, J. Non-invasive analyte access and sensing through eccrine sweat: challenges and outlook circa 2016. Electroanalysis 28, 1242–1249 (2016).

    Article  Google Scholar 

  9. Yan, Q. et al. Measurement of tear glucose levels with amperometric glucose biosensor/capillary tube configuration. Anal. Chem. 83, 8341–8346 (2011).

    Article  Google Scholar 

  10. Yao, H., Shum, A. J., Cowan, M., Lähdesmäki, I. & Parviz, B. A. A contact lens with embedded sensor for monitoring tear glucose level. Biosens. Bioelectron. 26, 3290–3296 (2011).

    Article  Google Scholar 

  11. Zhang, W., Du, Y. & Wang, M. L. Noninvasive glucose monitoring using saliva nano-biosensor. Sens. Biosens. Res. 4, 23–29 (2015).

    Google Scholar 

  12. Yeh, S.-J., Hanna, C. F. & Khalil, O. S. Monitoring blood glucose changes in cutaneous tissue by temperature-modulated localized reflectance measurements. Clin. Chem. 49, 924–934 (2003).

    Article  Google Scholar 

  13. Weinzimer, S. A. Analysis. Pendra: the once and future noninvasive continuous glucose monitoring device? Diabetes Technol. Ther. 6, 442–444 (2004).

    Article  Google Scholar 

  14. Yu, S. et al. In vitro glucose measurement using tunable mid-infrared laser spectroscopy combined with fiber-optic sensor. Biomed. Opt. Express 5, 275–286 (2014).

    Article  Google Scholar 

  15. Potts, R. O., Tamada, J. A. & Tierney, M. J. Glucose monitoring by reverse iontophoresis. Diabetes Metab. Res. Rev. 18, S49–S53 (2002).

    Article  Google Scholar 

  16. Tierney, M. J. Electrochemical sensor with dual purpose electrode. US patent 5,954,685 (1999).

  17. Sage, B. H. Jr. FDA panel approves Cygnus’s noninvasive GlucoWatch. Diabetes Technol. Ther. 2, 115–116 (2000).

    Article  Google Scholar 

  18. Marro, D., Kalia, Y. N., Delgado-Charro, M. B. & Guy, R. H. Contributions of electromigration and electroosmosis to iontophoretic drug delivery. Pharm. Res. 18, 1701–1708 (2001).

    Article  Google Scholar 

  19. Boyne, M. S., Silver, D. M., Kaplan, J. & Saudek, C. D. Timing of changes in interstitial and venous blood glucose measured with a continuous subcutaneous glucose sensor. Diabetes 52, 2790–2794 (2003).

    Article  Google Scholar 

  20. Garg, S. K. et al. Correlation of fingerstick blood glucose measurements with GlucoWatch Biographer glucose results in young subjects with type 1 diabetes. Diabetes Care 22, 1708–1714 (1999).

    Article  Google Scholar 

  21. Basu, A. et al. Time lag of glucose from intravascular to interstitial compartment in humans. Diabetes 62, 4083–4087 (2013).

    Article  Google Scholar 

  22. Rebrin, K. & Steil, G. M. Can interstitial glucose assessment replace blood glucose measurements? Diabetes Technol. Ther. 2, 461–472 (2000).

    Article  Google Scholar 

  23. Wang, P. M., Cornwell, M. & Prausnitz, M. R. Minimally invasive extraction of dermal interstitial fluid for glucose monitoring using microneedles. Diabetes Technol. Ther. 7, 131–141 (2005).

    Article  Google Scholar 

  24. Sieg, A., Guy, R. H. & Delgado-Charro, M. B. Electroosmosis in transdermal iontophoresis: implications for noninvasive and calibration-free glucose monitoring. Biophys. J. 87, 3344–3350 (2004).

    Article  Google Scholar 

  25. Turner, N. G. & Guy, R. H. Visualization and quantitation of iontophoretic pathways using confocal microscopy. J. Invest. Dermatol. Sympos. Proc. 3, 136–142 (1998).

    Article  Google Scholar 

  26. Bath, B. D., White, H. S. & Scott, E. R. Visualization and analysis of electroosmotic flow in hairless mouse skin. Pharm. Res. 17, 471–475 (2000).

    Article  Google Scholar 

  27. Otberg, N. et al. Variations of hair follicle size and distribution in different body sites. J. Invest. Dermatol. 122, 14–19 (2004).

    Article  Google Scholar 

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

    Article  Google Scholar 

  29. Alshammari, A. et al. A modular bioplatform based on a versatile supramolecular multienzyme complex directly attached to graphene. Appl. Mater. Interfaces 8, 21077–21088 (2016).

    Article  Google Scholar 

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

    Article  Google Scholar 

  31. Spasenovic, M. The price of graphene, (Graphenea, 2013).

  32. Schmook, F. P., Meingassner, J. G. & Billich, A. Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int. J. Pharm. 215, 51–56 (2001).

    Article  Google Scholar 

  33. Sekkat, N. & Guy, R. H. in Pharmacokinetic Optimization in Drug Research (eds Testa, B. et al.) 155–172 (Wiley-VCH, Lausanne, 2007).

  34. Diabetes UK. Blood sugar level ranges (Diabetes UK, 2017);

  35. Pauli, G. F., Gödecke, T., Jaki, B. U. & Lankin, D. C. Quantitative 1h NMR. Development and potential of an analytical method: an update. J. Nat. Prod. 75, 834–851 (2012).

    Article  Google Scholar 

  36. Fabry, P. & Fouletier, J. (eds) Chemical and Biological Microsensors: Applications in Fluid Media (Wiley-ISTE, London, 2009).

  37. ICH Harmonised Tripartite Guideline (ICH, Geneva, 2005).

  38. Alegret, S. & Merkoci, A. (eds) Electrochemical Sensor Analysis (Elsevier Science, Amsterdam, 2007).

  39. Tamada, J. A. et al. Noninvasive glucose monitoring: comprehensive clinical results. JAMA 282, 1839–1844 (1999).

    Article  Google Scholar 

  40. Li, X. et al. Transfer of large-area graphene films for high-performance transparent conductive electrodes. Nano Lett. 9, 4359–4363 (2009).

    Article  Google Scholar 

  41. Polk, B. J., Stelzenmuller, A., Mijares, G., MacCrehan, W. & Gaitan, M. Ag/AgCl microelectrodes with improved stability for microfluidics. Sens. Actuat. B 114, 239–247 (2006).

    Article  Google Scholar 

  42. Gao, W. et al. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 529, 509–514 (2016).

    Article  Google Scholar 

  43. Shrivastava, A. G. & Vipin, B. Methods for the determination of limit of detection and limit of quantitation of the analytical methods. Chron. Young. Sci. 2, 21–25 (2011).

    Article  Google Scholar 

  44. Alkire, R. C. et al. (eds) Bioelectrochemistry: Fundamentals, Applications and Recent Developmentus (Wiley, Hoboken, NJ, 2011).

  45. Petrucci, R. H. General Chemistry: Principles & Modern Applications 9th edn (Prentice Hall, Upper Saddle River, NJ, 2007).

    Google Scholar 

  46. He, D., Garg, S. & Waite, T. D. H2O2-mediated oxidation of zero-valent silver and resultant interactions among silver nanoparticles, silver ions, and reactive oxygen species. Langmuir 28, 10266–10275 (2012).

    Article  Google Scholar 

Download references


This work was supported by a Science and Innovation Award (EP/G036101/1) from the UK Engineering and Physical Sciences Research Council, and a MRC Confidence-in-Concepts grant (MC-PC-14106) from the UK Medical Research Council. L.L. acknowledges a studentship funded by the Sir Halley Stewart Trust, UK. The authors thank T. Woodman (University of Bath) for his assistance with the 1H-qNMR measurements and analysis.

Author information

Authors and Affiliations



A.I., R.H.G. and R.M.T. designed the overall work programme. B.G.R.D. performed the work related to the deconstructed pixel device. L.L. and F.D. performed the work related to the planar thin-film/CVD graphene pixel array integrated on a flexible substrate. L.L. performed the work related to the screen-printed arrays, with input from F.D. F.M. provided advice on the implementation of the electrochemistry experiments. A.I. rationalized the array characteristics via simulations, and A.I. and F.D. proposed the detailed pixel array architecture (for both generations, thin-film and screen-printed, of prototypes). A.I., R.H.G. and R.M.T. supervised the deconstructed pixel device research, while A.I. and R.H.G. supervised the pixel array research. A.I. and R.H.G. wrote the paper, and all authors provided comments and agreed with the final form of the manuscript.

Corresponding author

Correspondence to Adelina Ilie.

Ethics declarations

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.

Supplementary information

Supplementary Information

Supplementary Text, Supplementary Figures 1–18, Supplementary Tables 1–2 and Supplementary References

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lipani, L., Dupont, B.G.R., Doungmene, F. et al. Non-invasive, transdermal, path-selective and specific glucose monitoring via a graphene-based platform. Nature Nanotech 13, 504–511 (2018).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Find nanotechnology articles, nanomaterial data and patents all in one place. Visit Nano by Nature Research