Hydrogel Glucose Sensor with In Vivo Stable Fluorescence Intensity Relying on Antioxidant Enzymes for Continuous Glucose Monitoring

Jun Sawayama; Teru Okitsu; Akihiro Nakamata; Yoshihiro Kawahara; Shoji Takeuchi

doi:10.1016/j.isci.2020.101243

Hydrogel Glucose Sensor with In Vivo Stable Fluorescence Intensity Relying on Antioxidant Enzymes for Continuous Glucose Monitoring

iScience. 2020 Jun 26;23(6):101243. doi: 10.1016/j.isci.2020.101243. Epub 2020 Jun 6.

Authors

Jun Sawayama¹, Teru Okitsu¹, Akihiro Nakamata², Yoshihiro Kawahara², Shoji Takeuchi³

Affiliations

¹ Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, Japan.
² Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
³ Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, Japan; Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. Electronic address: takeuchi@hybrid.t.u-tokyo.ac.jp.

Abstract

Hydrogel glucose sensors with boronic acid-based fluorescence intensity theoretically hold promise to improve in vivo continuous glucose monitoring (CGM) by facilitating long-lasting accuracy. However, these sensors generally degrade after implantation and the fluorescence intensity decreases immediately over time. Herein, we describe a hydrogel glucose sensor with in vivo stability based on boronic acid-based fluorescence intensity, integrating two antioxidant enzymes, superoxide dismutase (SOD), and catalase. These protected the arylboronic acid from being degraded by hydrogen peroxide in vitro and preserved the boronic acid-based fluorescence intensity of the hydrogel glucose sensors in rats for 28 days. These antioxidant enzymes also allowed the hydrogel glucose sensor attached to a homemade semi-implantable CGM device to trace blood glucose concentrations in rats for 5 h with the accuracy required for clinical settings. Hydrogel glucose sensors with boronic acid-based fluorescence intensity containing SOD and catalase could comprise a new strategy for in vivo CGM.

Keywords: Biochemical Mechanism; Glycobiology; Medical Device; Sensor.