Hideaki Shibataa,b,c,1, Yun Jung Heoa,b,1, Teru Okitsua,d, Yukiko Matsunagaa,b, Tetsuro Kawanishia,c, and Shoji Takeuchia,b,2
aLife Bio Electromechanical Autonomous Nano Systems (BEANS) Center, BEANS Project, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan;
bInstitute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan;
cTERUMO Co. R and D Headquarters, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan; and
dTransplant Unit, Kyoto University Hospital, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Edited by Mark E. Davis, California Institute of Technology, Pasadena, CA, and approved August 17, 2010 (received for review May 20, 2010)
1H.S. and Y.J.H. contributed equally to this work.
Fluorescent microbeads hold great promise for in vivo continuous glucose monitoring with wireless transdermal transmission and long-lasting activity. The full potential of fluorescent microbeads has yet to be realized due to insufficient intensity for transdermal transmission and material toxicity. This paper illustrates the highly-sensitive, biostable, long-lasting, and injectable fluorescent microbeads for in vivo continuous glucose monitoring. We synthesized a fluorescent monomer composed of glucose-recognition sites, a fluorogenic site, spacers, and polymerization sites. The spacers are designed to be long and hydrophilic for increasing opportunities to bind glucose molecules; consequently, the fluorescent monomers enable high-intensive responsiveness to glucose. We then fabricated injectable-sized fluorescent polyacrylamide hydrogel beads with high uniformity and high throughput. We found that our fluorescent beads provide sufficient intensity to transdermally monitor glucose concentrations in vivo. The fluorescence intensity successfully traced the blood glucose concentration fluctuation, indicating our method has potential uses in highly-sensitive and minimally invasive continuous blood glucose monitoring.
fluorescent hydrogel, microfluidics, diboronic acid, continuous glucose monitoring, diabetes mellitus
2To whom correspondence should be addressed.
Author contributions: H.S., Y.J.H., T.O., Y.M., T.K., and S.T. designed research; H.S., Y.J.H., T.O., and Y.M. performed research; T.K. contributed new reagents/analytic tools; H.S., Y.J.H., Y.M., and S.T. analyzed data; and H.S., Y.J.H., T.O., Y.M., T.K., and S.T. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
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