Skip to main content
Log in

An Injectable PEG-BSA-Coumarin-GOx Hydrogel for Fluorescence Turn-on Glucose Detection

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Diabetes mellitus is a chronic metabolic disorder, requiring vigilant monitoring of blood glucose levels. In this study, an injectable fluorescent enzymatic hydrogel was designed for rapid glucose detection. The leakage-free glucose-responsive hydrogel was constructed by the covalent linkage of a multi-arm poly-(ethylene glycol) (PEG), bovine serum albumin (BSA), glucose oxidase (GOx), and 4-(aminomethyl)-6,7-dimethoxycoumarin (Coumarin-NH2). The GOx serves as glucose-recognition element and the pH-sensitive Coumarin-NH2 as a fluorescence turn-on reporter. The material properties of the fluorescent hydrogel were systematically characterized which show high elasticity with good mechanical strength. Upon the addition of glucose, the as-developed fluorescent hydrogel shows a fast response time, good sensitivity, and good reproducibility at physiological pH and ambient temperature. The glucose-sensing mechanism is based on the oxidation of the glucose by GOx that generates protons to change the local pH. Consequently, protonation of the covalently immobilized and pH-sensitive Coumarin-NH2 turns on the fluorescence of the coumarin. The fluorescence hydrogel developed holds great promise as an injectable, implantable glucose-sensing biomaterials for in vivo continuous glucose monitoring.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Reference

  1. Control, D., & Trial, C. (2005). Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. The New England Journal of Medicine, 353, 2643.

    Article  Google Scholar 

  2. Shamoon, H., Duffy, H., Fleischer, N., Engel, S., Saenger, P., Strelzyn, M., Litwak, M., Wylierosett, J., Farkash, A., & Geiger, D. (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine, 329, 977–986.

    Article  Google Scholar 

  3. Reach, G., & Wilson, G. S. (1992). Can continuous glucose monitoring be used for the treatment of diabetes? Analytical Chemistry, 64, 381A–386A.

    CAS  Google Scholar 

  4. Sun, X., Stagon, S., Huang, H., Chen, J., & Lei, Y. (2014). Functionalized aligned silver nanorod arrays for glucose sensing through surface enhanced Raman scattering. RSC Advances, 4, 23382–23388.

    Article  CAS  Google Scholar 

  5. Newman, J. D., & Turner, A. P. (2005). Home blood glucose biosensors: a commercial perspective. Biosensors and Bioelectronics, 20, 2435–2453.

    Article  CAS  Google Scholar 

  6. Klonoff, D. C. (2005). Continuous glucose monitoring roadmap for 21st century diabetes therapy. Diabetes Care, 28, 1231–1239.

    Article  Google Scholar 

  7. Pickup, J. C., Hussain, F., Evans, N. D., Rolinski, O. J., & Birch, D. J. (2005). Fluorescence-based glucose sensors. Biosensors and Bioelectronics, 20, 2555–2565.

    Article  CAS  Google Scholar 

  8. Chan, W. C., Maxwell, D. J., Gao, X., Bailey, R. E., Han, M., & Nie, S. (2002). Luminescent quantum dots for multiplexed biological detection and imaging. Current Opinion in Biotechnology, 13, 40–46.

    Article  CAS  Google Scholar 

  9. Clapp, A. R., Medintz, I. L., Mauro, J. M., Fisher, B. R., Bawendi, M. G., & Mattoussi, H. (2004). Fluorescence resonance energy transfer between quantum dot donors and dye-labeled protein acceptors. Journal of the American Chemical Society, 126, 301–310.

    Article  CAS  Google Scholar 

  10. Mopidevi, S., Chen, J., Ma, X., Galil, K. H. A. E. and Lei, Y. (2015) PEG-fluorescein-GOx hydrogel for glucose biosensing. ScienceJet, 4. Article # 159.

  11. Odaci, D., Gacal, B. N., Gacal, B., Timur, S., & Yagci, Y. (2009). Fluorescence sensing of glucose using glucose oxidase modified by PVA-pyrene prepared via “click” chemistry. Biomacromolecules, 10, 2928–2934.

    Article  CAS  Google Scholar 

  12. Vaddiraju, S., Burgess, D. J., Tomazos, I., Jain, F. C., & Papadimitrakopoulos, F. (2010). Technologies for continuous glucose monitoring: current problems and future promises. Journal of Diabetes Science and Technology, 4, 1540–1562.

    Article  Google Scholar 

  13. Gerlach, G., & Arndt, K.-F. (2009). Hydrogel sensors and actuators: engineering and technology. Springer Science & Business Media.

  14. Lim, N. C., Pavlova, S. V., & Brückner, C. (2008). Squaramide hydroxamate-based chemidosimeter responding to iron (III) with a fluorescence intensity increase. Inorganic Chemistry, 48, 1173–1182.

    Article  Google Scholar 

  15. Peng, H. T., Blostein, M. D., & Shek, P. N. (2009). Experimental optimization of an in situ forming hydrogel for hemorrhage control. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 89, 199–209.

    Article  Google Scholar 

  16. Mossavarali, S., Hosseinkhani, S., Ranjbar, B., & Miroliaei, M. (2006). Stepwise modification of lysine residues of glucose oxidase with citraconic anhydride. International Journal of Biological Macromolecules, 39, 192–196.

    Article  CAS  Google Scholar 

  17. Li, L., Ge, J., Guo, B., & Ma, P. X. (2014). In situ forming biodegradable electroactive hydrogels. Polymer Chemistry, 5, 2880–2890.

    Article  CAS  Google Scholar 

  18. Dinu, M. V., Ozmen, M. M., Dragan, E. S., & Okay, O. (2007). Freezing as a path to build macroporous structures: superfast responsive polyacrylamide hydrogels. Polymer, 48, 195–204.

    Article  CAS  Google Scholar 

  19. Chao, G., Deng, H., Huang, Q., Jia, W., Huang, W., Gu, Y., Tan, H., Fan, L., Liu, C., & Huang, A. (2006). Preparation and characterization of pH sensitive semi-interpenetrating network hydrogel based on methacrylic acid, bovine serum albumin (BSA), and PEG. Journal of Polymer Research, 13, 349–355.

    Article  CAS  Google Scholar 

  20. Kiskan, B., & Yagci, Y. (2007). Thermally curable benzoxazine monomer with a photodimerizable coumarin group. Journal of Polymer Science Part A: Polymer Chemistry, 45, 1670–1676.

    Article  CAS  Google Scholar 

  21. Brøndsted, H. and Kopec̆ek, J. i. (1991) Hydrogels for site-specific oral drug delivery: synthesis and characterization. Biomaterials, 12, 584–592.

  22. Bryant, S. J., Arthur, J. A., & Anseth, K. S. (2005). Incorporation of tissue-specific molecules alters chondrocyte metabolism and gene expression in photocrosslinked hydrogels. Acta Biomaterialia, 1, 243–252.

    Article  Google Scholar 

  23. Chivukula, P., Dušek, K., Wang, D., Dušková-Smrčková, M., Kopečková, P., & Kopeček, J. (2006). Synthesis and characterization of novel aromatic azo bond-containing pH-sensitive and hydrolytically cleavable IPN hydrogels. Biomaterials, 27, 1140–1151.

    Article  CAS  Google Scholar 

  24. Coviello, T., Alhaique, F., Parisi, C., Matricardi, P., Bocchinfuso, G., & Grassi, M. (2005). A new polysaccharidic gel matrix for drug delivery: preparation and mechanical properties. Journal of Controlled Release, 102, 643–656.

    Article  CAS  Google Scholar 

  25. Drury, J. L., Dennis, R. G., & Mooney, D. J. (2004). The tensile properties of alginate hydrogels. Biomaterials, 25, 3187–3199.

    Article  CAS  Google Scholar 

  26. Zhang, X.-Z., Lewis, P. J., & Chu, C.-C. (2005). Fabrication and characterization of a smart drug delivery system: microsphere in hydrogel. Biomaterials, 26, 3299–3309.

    Article  CAS  Google Scholar 

  27. Gayet, J.-C., He, P., & Fortier, G. (1998). Bioartificial polymeric material: poly (ethylene glycol) crosslinked with albumin. II: mechanical and thermal properties. Journal of Bioactive and Compatible Polymers, 13, 179–197.

    CAS  Google Scholar 

  28. Gulrez, S. K., Phillips, G. O., & Al-Assaf, S. (2011). Hydrogels: methods of preparation, characterisation and (applications. ed., ). INTECH Open Access Publisher.

  29. Peppas, N. A., & Barr-Howell, B. D. (1986). Characterization of the crosslinked structure of hydrogels. Hydrogels in Medicine and Pharmacy, 1, 27–56.

    CAS  Google Scholar 

  30. Heo, Y. J., Shibata, H., Okitsu, T., Kawanishi, T. and Takeuchi, S. (2011) Long-term in vivo glucose monitoring using fluorescent hydrogel fibers. Proceedings of the National Academy of Sciences, 108, 13399–13403.

  31. Shibata, H., Heo, Y. J., Okitsu, T., Matsunaga, Y., Kawanishi, T. and Takeuchi, S. (2010) Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring. Proceedings of the National Academy of Sciences, 107, 17894–17898.

Download references

Acknowledgments

The authors greatly appreciate the financial support from NSF, UConn Teaching Assistantship, and NSF GK-12 Fellowship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yu Lei.

Additional information

Gayathri Srinivasan and Jun Chen contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 317 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Srinivasan, G., Chen, J., Parisi, J. et al. An Injectable PEG-BSA-Coumarin-GOx Hydrogel for Fluorescence Turn-on Glucose Detection. Appl Biochem Biotechnol 177, 1115–1126 (2015). https://doi.org/10.1007/s12010-015-1800-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-015-1800-2

Keywords

Navigation