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Reduction of measurement noise in a continuous glucose monitor by coating the sensor with a zwitterionic polymer

Nature Biomedical Engineering volume 2, pages 894–906 (2018)Cite this article

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Abstract

Continuous glucose monitors (CGMs), used by patients with diabetes mellitus, can autonomously track fluctuations in blood glucose over time. However, the signal produced by CGMs during the initial recording period following sensor implantation contains substantial noise, requiring frequent recalibration via finger-prick tests. Here, we show that coating the sensor with a zwitterionic polymer, found via a combinatorial chemistry approach, significantly reduces signal noise and improves CGM performance. We evaluated the polymer-coated sensors in mice as well as in healthy and diabetic non-human primates, and show that the sensors accurately record glucose levels without the need for recalibration. We also show that the coated sensors significantly abrogated immune responses, as indicated by histology, fluorescent whole-body imaging of inflammation-associated protease activity and gene expression of inflammation markers. The polymer coating may allow CGMs to become standalone measuring devices.

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Fig. 1: Illustration of CGM sensing in vivo.
Fig. 2: Zwitterionic polymer coating of Medtronic CGMs.
Fig. 3: Sensing performance in SKH1 mouse model.
Fig. 4: CGM biocompatibility in SKH1 mouse model is improved with the coating.
Fig. 5: Sensing performance of CGMs in NHP model.

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Acknowledgements

This work was supported by the Leona M. and Harry B. Helmsley Charitable Trust Foundation (2015PG-T1D063), Juvenile Diabetes Research Foundation (JDRF) (Grant 17-2007-1063) and National Institutes of Health (Grants EB000244, EB000351, DE013023 and CA151884), and through a generous gift from the Tayebati Family Foundation. J.C.D. was supported by JDRF postdoctoral fellowship (Grant 3-PDF-2015-91-A-N). J.O. is supported by the National Institutes of Health (NIH/NIDDK) R01DK091526 and the Chicago Diabetes Project. X.X. was supported by the 100 Talents Program of Sun Yat-Sen University (76120-18821104) and 1000 Talents Youth Program of China and acknowledges financial support from the National Natural Science Foundation of China (Grant No.51705543, 61771498 and 31530023) and Science and Technology Program of Guangzhou, China (Grant No. 20180310097). In addition, of extreme importance, the authors thank the Histology and Whole Animal Imaging cores for use of resources (Swanson Biotechnology Center, David H. Koch Institute for Integrative Cancer Research at MIT).

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  1. These authors contributed equally: Xi Xie, Joshua C. Doloff, Volkan Yesilyurt, Atieh Sadraei.

Authors and Affiliations

  1. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Xi Xie, Joshua C. Doloff, Volkan Yesilyurt, Atieh Sadraei, Omid Veiseh, Shady Farah, Arturo Vegas, Jie Li, Weiheng Wang, Andrew Bader, Hok Hei Tam, Katrina Ann Williamson, Robert Langer & Daniel G. Anderson

  2. State Key Laboratory of Optoelectronic Materials and Technologies, School of Electronics and Information Technology, Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Xi Xie, Jun Tao, Hui-jiuan Chen & Boru Yang

  3. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Joshua C. Doloff, Atieh Sadraei, Omid Veiseh, Shady Farah, Hok Hei Tam, Robert Langer & Daniel G. Anderson

  4. Department of Anesthesiology, Boston Children’s Hospital, Boston, MA, USA

    Joshua C. Doloff, Volkan Yesilyurt, Omid Veiseh, Shady Farah, Arturo Vegas, Jie Li, Andrew Bader, Robert Langer & Daniel G. Anderson

  5. Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA

    James J. McGarrigle, Mustafa Omami, Douglas Isa, Sofia Ghani, Ira Joshi & Jose Oberholzer

  6. School of Engineering and Applied Sciences, Biomedical Engineering, Harvard University, Cambridge, MA, USA

    Katrina Ann Williamson

  7. Harvard-MIT Division of Health Science Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA

    Robert Langer & Daniel G. Anderson

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Contributions

X.X., J.C.D., V.Y., A.S. and D.G.A. designed experiments, analysed data and wrote the manuscript. X.X., J.C.D., V.Y., A.S., J.J.M., M.O., S.F., D.I., S.G., I.J., J.L., W.W., A.B. and K.A.W. performed experiments. X.X., J.C.D., V.Y., A.S., H.H.T., J.T., H.-j.C. and B.Y. performed statistical analyses of datasets and aided in the preparation of displays communicating datasets. R.L. and D.G.A. provided conceptual advice. R.L. and D.GA. supervised the study. All authors discussed the results and assisted in the preparation of the manuscript.

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Correspondence to Daniel G. Anderson.

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Xie, X., Doloff, J.C., Yesilyurt, V. et al. Reduction of measurement noise in a continuous glucose monitor by coating the sensor with a zwitterionic polymer. Nat Biomed Eng 2, 894–906 (2018). https://doi.org/10.1038/s41551-018-0273-3

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