Supramolecular host–guest carrier based on maltose-modified hyperbranched polymer and polyelectrolyte multilayers: toward stable and reusable glucose biosensor

  • Samaa R. SalemEmail author
  • John L. Sullivan
  • Paul D. Topham
  • Brian J. Tighe
Original Paper


Regards to the global prevalence of diabetes, clinical management should tackle the awkwardness of continuous glucose monitoring systems (CGMS). Although CGMS are commercially accepted, they are still suffering due to their low sustainability and reusability. One method to circumvent these shortcomings is the immobilization of enzymes onto stable carriers. In this contribution, our aim was to build up a highly stable and reproducible enzyme-based host–guest carrier from maltose-modified hyperbranched poly(ethylene imine) (PEI-Mal-C) and polyelectrolyte multilayers (PEMs) to monitor glucose level. Thus, enzymes, such as glucose oxidase (GOx) and horseradish peroxide (POx), were immobilized in core–shell PEI-Mal-C and highly packaged in carrier-based PEM. Herein, the PEM was created using the layer-by-layer protocol, where a consecutive deposition of polyions was achieved. Therein, the polycation PEI-Mal-C was alternatively deposited with different polyanions, e.g., poly(acrylic acid) and heparin (HE), on a solid substrate. The enzyme immobilization, leaching and enzymatic activity were investigated through different modules, including ultraviolet–visible (UV–Vis) spectrophotometer, rheometer, X-ray spectroscopy, contact angle meter, atomic force microscopy and conductometer. To conclude, our approach enabled the use of immobilized GOx/POx for more than one time with the significantly similarly fitted regression calibration curve. It is implied that this work will be the first step to construct a stable hyperbranched glyconanomaterial-immobilized enzyme based on assembled multilayers, with the potential to be applied in a stable and reusable biosensor.


Carrier-based polyelectrolyte multilayers Core–shell hyperbranched glycopolymer Reproducibility Stability Coatings Glucose oxidase immobilization 



Still, the implementation of this study would not have been possible if we did not have the boost of many individuals and organizations. We are grateful to the School of Chemical Engineering and Applied Chemistry (CEAC), Aston University, Birmingham, UK, and both Prof. Brian J. Tighe and Paul D. Topham for providing facilities and equipment for achieving these goals. Moreover, we have to express our appreciation for Science and Technology Development Funds (STDF), Egypt, Newton Fund, British Council and the National Research Centre (NRC), Egypt, for their kind support of this study and providing a scholarship. All grateful thankfulness for the Department of Polymer Science, the University of Sheffield for their generous present of silicon wafers.


No financial support was provided.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

289_2019_2902_MOESM1_ESM.docx (307 kb)
Supplementary material 1 (DOCX 306 kb)


  1. 1.
    Chen C, Zhao X-L, Li Z-H, Zhu Z-G, Qian S-H, Flewitt AJ (2017) Continuous glucose monitoring (CGM) in very low birth weight newborns needing parenteral nutrition: validation and glycemic percentiles. Sensor 17:182CrossRefGoogle Scholar
  2. 2.
    Schuster KM, Barre K, Inzucchi SE, Udelsman R, Davis KA (2014) Continuous glucose monitoring in the surgical intensive care unit: concordance with capillary glucose. J Trauma Acute Care Surg 76:798CrossRefGoogle Scholar
  3. 3.
    Gough DA, Kumosa LS, Routh TL, Lin JT, Lucisano JY (2010) Function of an implanted tissue glucose sensor for more than 1 year in animals. Sci Transl Med 2:42ra53CrossRefGoogle Scholar
  4. 4.
    Bruen D, Delaney C, Florea L, Diamond D (2017) Glucose sensing for diabetes monitoring: recent developments. Sensors 17:1866CrossRefGoogle Scholar
  5. 5.
    Bailey T, Bode BW, Christiansen MP, Klaff LJ, Alva S (2015) The performance and usability of a factory-calibrated flash glucose monitoring system. Diabetes Technol Ther 17:787CrossRefGoogle Scholar
  6. 6.
    Harris JM, Reyes C, Lopez GPJ (2013) Common causes of glucose oxidase instability in vivo biosensing: a brief review. Diabetes Sci Technol 7:1030CrossRefGoogle Scholar
  7. 7.
    Decher G (1997) Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science 277:1232CrossRefGoogle Scholar
  8. 8.
    Decher G, Hong JD, Schmitt J (1992) Buildup of ultrathin multilayer films by a self-assembly process: III. Consecutively alternating adsorption of anionic and cationic polyelectrolytes on charged surfaces. Thin Solid Films 210–211(Part 2):831CrossRefGoogle Scholar
  9. 9.
    Zhang J, Senger B, Vautier D, Picart C, Schaaf P, Voegel JC, Lavalle P (2005) Natural polyelectrolyte films based on layer-by layer deposition of collagen and hyaluronic acid. Biomaterials 26:3353CrossRefGoogle Scholar
  10. 10.
    Sukhishvili SA, Kharlampieva E, Izumrudov V (2006) Where polyelectrolyte multilayers and polyelectrolyte complexes meet. Macromolecules 39:8873CrossRefGoogle Scholar
  11. 11.
    Salem S, Müller M, Torger B, Janke A, Eichhorn KJ, Voit B, Appelhans D (2015) Glycopolymer polyelectrolyte multilayers composed of heparin and maltose-modified poly (ethylene imine) as a strong/weak polyelectrolyte system for future drug delivery coatings: influence of pH and sugar architecture on growth of multilayers and multilayer swelling and stability. Macromol Chem Phys 216:182CrossRefGoogle Scholar
  12. 12.
    Salem S (2015) Glycopolymer polyelectrolyte multilayers based on maltose-modified hyperbranched poly(ethyleneimine) for future drug delivery coatings and biomedical applications. Doctoral dissertation, Saechsische Landesbibliothek-Staats-und Universitaetsbibliothek DresdenGoogle Scholar
  13. 13.
    Jimenez A, Armada MP, Losada J, Villena C, Alonso B, Casado CM (2014) Amperometric biosensors for NADH based on hyperbranched dendritic ferrocene polymers and Pt nanoparticles. Sensors Actuators B Chem 190:111CrossRefGoogle Scholar
  14. 14.
    Li H, Zhao F, Yue L, Li S, Xiao F (2016) Nonenzymatic electrochemical biosensor based on novel hydrophilic ferrocene-terminated hyperbranched polymer and its application in glucose detection. Electroanalysis 28:1003CrossRefGoogle Scholar
  15. 15.
    Zheng Y, Li S, Weng Z, Gao C (2015) Hyperbranched polymers: advances from synthesis to applications. Chem Soc Rev 44:4091CrossRefGoogle Scholar
  16. 16.
    Caminade A-M, Yan D, Smith DK (2015) Dendrimers and hyperbranched polymers. Chem Soc Rev 44:3870CrossRefGoogle Scholar
  17. 17.
    Appelhans D, Komber H, Quadir MA, Richter S, Schwarz S, van der Vlist J, Aigner A, Müller M, Loos K, Seidel J, Arndt KF (2009) Hyperbranched PEI with various oligosaccharide architectures: synthesis, characterization, ATP complexation, and cellular uptake properties. Biomacromolecules 10:1114CrossRefGoogle Scholar
  18. 18.
    Gorzkiewicz M, Sztandera K, Jatczak-Pawlik I, Zinke R, Appelhans D, Klajnert-Maculewicz B, Pulaski Ł (2018) Terminal sugar moiety determines immunomodulatory properties of poly(propyleneimine) glycodendrimers. Biomacromolecules. 19:1562CrossRefGoogle Scholar
  19. 19.
    Studzian M, Szulc A, Janaszewska A, Appelhans D, Pułaski Ł, Klajnert-Maculewicz B (2017) Mechanisms of Internalization of maltose-modified poly(propyleneimine) glycodendrimers into leukemic cell lines. Biomacromolecules 18:1509CrossRefGoogle Scholar
  20. 20.
    Lee KM, Kim KH, Yoon H, Kim H (2018) Chemical design of functional polymer structures for biosensors: from nanoscale to macroscale. Polymers 10:551CrossRefGoogle Scholar
  21. 21.
    Washko W, Rice EW (1961) Determination of glucose by an improved enzymatic procedure. Clin Chem 7:542Google Scholar
  22. 22.
    Wang YH, Gu HY (2009) Hemoglobin co-immobilized with silver–silver oxide nanoparticles on a bare silver electrode for hydrogen peroxide electroanalysis. Microchim Acta 164:41CrossRefGoogle Scholar
  23. 23.
    Zhou M, Diwu Z, Panchuk-Voloshina N, Haugland RP (1997) A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases. Anal Biochem 253:162CrossRefGoogle Scholar
  24. 24.
    Barnes HA, Hutton JF, Walters K (1989) An introduction to rheology, vol 3. Elsevier, AmsterdamCrossRefGoogle Scholar
  25. 25.
    Nunez CM, Chiou B-S, Andrady AL, Khan SA (2000) Solution rheology of hyperbranched polyesters and their blends with linear polymers. Macromolecules 33:1720CrossRefGoogle Scholar
  26. 26.
    Läuger J, Heiko S (2016) Effects of instrument and fluid inertia in oscillatory shear in rotational rheometers. J Rheol 60:393CrossRefGoogle Scholar
  27. 27.
    Dieter GE, Bacon DJ (1986) Mechanical metallurgy. McGraw-hill, New York, p 3Google Scholar
  28. 28.
    Briggs D, Beamson G (1992) Primary and secondary oxygen-induced C1s binding energy shifts in x-ray photoelectron spectroscopy of polymers. Anal Chem 64:1729CrossRefGoogle Scholar
  29. 29.
    Gao C, Yan D (2004) Hyperbranched polymers: from synthesis to applications. Prog Polym Sci 29:183CrossRefGoogle Scholar
  30. 30.
    Torger B, Vehlow D, Urban B, Salem S, Appelhans D, Müller M (2013) Cast adhesive polyelectrolyte complex particle films of unmodified or maltose-modified poly (ethyleneimine) and cellulose sulphate: fabrication, film stability and retarded release of zoledronate. Biointerphases 11:25CrossRefGoogle Scholar
  31. 31.
    Ferry JD (1980) Viscoelastic properties of polymers. Wiley, New YorkGoogle Scholar
  32. 32.
    Sunthar P (2010) Polymer rheology. Springer, New York, pp 171–191Google Scholar
  33. 33.
    Frederick KR, Tung J, Emerick RS, Masiarz FR, Chamberlain SH, Vasavada AM, Rosenberg S, Chakraborty SU, Schopfer LM, Schopter LM (1990) Glucose oxidase from aspergillus niger. J Biol Chem 265:3793Google Scholar
  34. 34.
    Benavidez TE, Torrente D, Marucho M, Garcia CD (2014) Adsorption and catalytic activity of glucose oxidase accumulated on OTCE upon the application of external potential. J Colloid Interface Sci 435:164CrossRefGoogle Scholar
  35. 35.
    Harris JM, Reyes C, Lopez GP (2013) Common causes of glucose oxidase instability in in vivo biosensing: a brief review. J Diabetes Sci Technol 7:1030CrossRefGoogle Scholar
  36. 36.
    Nemati M, Hosseini SM, Bagheripour E, Madaeni SS (2016) Surface modification of cation exchange membranes by graft polymerization of PAA-co-PANI/MWCNTs nanoparticles. Kor J Chem Eng 33:1037CrossRefGoogle Scholar
  37. 37.
    Ji J, Joh H-I, Chung Y, Kwon Y (2017) Glucose oxidase and polyacrylic acid based water swellable enzyme–polymer conjugates for promoting glucose detection. Nanoscale 9:15998CrossRefGoogle Scholar
  38. 38.
    Zaldivar G, Tagliazucchi M (2016) Layer-by-layer self-assembly of polymers with pairing interactions. ACS Macro Lett 5:862CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Polymers and PigmentNational Research CentreGizaEgypt
  2. 2.Surface Science Group, School of Engineering and Applied ScienceAston UniversityBirminghamUK
  3. 3.Aston Institute of Material Research (AIMR)Aston UniversityBirminghamUK
  4. 4.The School of Chemical Engineering and Applied Science (CEAC)Aston UniversityBirminghamUK

Personalised recommendations