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

Abstract

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.

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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.

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Acknowledgements

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.

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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.

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Correspondence to Adelina Ilie.

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

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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). https://doi.org/10.1038/s41565-018-0112-4

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