A dielectric affinity glucose microsensor using hydrogel-functionalized coplanar electrodes

  • Zhixing Zhang
  • Panita Maturavongsadit
  • Junyi Shang
  • Jing Yan
  • Dachao Li
  • Qian Wang
  • Qiao Lin
Research Paper
  • 278 Downloads
Part of the following topical collections:
  1. 2016 International Conference of Microfluidics, Nanofluidics and Lab-on-a-Chip, Dalian, China

Abstract

This paper presents a dielectric affinity microsensor that consists of an in situ prepared hydrogel attached to a pair of coplanar electrodes for dielectrically based affinity detection of glucose in subcutaneous tissue in continuous glucose monitoring applications. The hydrogel, incorporating N-3-acrylamidophenylboronic acid that recognizes glucose via affinity binding, is synthetically prepared on the electrodes via in situ gelation. When implanted in subcutaneous tissue, glucose molecules in interstitial fluid diffuse rapidly through the hydrogel and bind to the phenylboronic acid moieties. This induces a change in the hydrogel’s permittivity and hence in the impedance between the electrodes, which can be measured to determine the glucose concentration. The in situ hydrogel preparation allows for a reduced hydrogel thickness (~10 µm) to enable the device to respond rapidly to glucose concentration changes in tissue, as well as covalent electrode attachment of the hydrogel to eliminate the need for semipermeable membranes that would otherwise be required to restrain the sensing material within the device. Meanwhile, the use of coplanar electrodes is amenable to the in situ preparation and facilitates glucose accessibility of the hydrogel, and combined with dielectrically based transduction, also eliminates mechanical moving parts often found in existing affinity glucose microsensors that can be fragile and complicated to fabricate. Testing of the device in phosphate-buffered saline at pH 7.4 and 37 °C has shown that at glucose concentrations ranging from 0 to 500 mg/dL, the hydrogel-based microsensor exhibits a rapid, repeatable, and reversible response. In particular, in the glucose concentration range of 40–100 mg/dL, which is of great clinical interest to monitoring normal and low blood sugar levels, the device response is approximately linear with a resolution of 0.32 mg/dL based on effective capacitance and 0.27 mg/dL based on effective resistance, respectively. Thus, the device holds the potential to enable reliable and accurate continuous monitoring of glucose in subcutaneous tissue.

Keywords

Affinity sensing Coplanar electrodes Synthetic hydrogel Continuous glucose monitoring 

Notes

Acknowledgements

We gratefully acknowledge financial support from the National Institutes of Health (Grant Nos. 1DP3DK101085-01 and 2P41EB002033-19A1), the National Science Foundation (Grant No. ECCS-1509760), and the National Natural Science Foundation of China (Grant No. 61428402).

References

  1. Ballerstädt R, Ehwald R (1994) Suitability of aqueous dispersions of dextran and Concanavalin A for glucose sensing in different variants of the affinity sensor. Biosens Bioelectron 9(8):557–567CrossRefGoogle Scholar
  2. Guenther M, Wallmersperger T, Gerlach G (2014) Piezoresistive chemical sensors based on functionalized hydrogels. Chemosensors 2(2):145–170CrossRefGoogle Scholar
  3. Heller A (1999) Implanted electrochemical glucose sensors for the management of diabetes. Annu Rev Biomed Eng 1(1):153–175CrossRefGoogle Scholar
  4. Heo YJ, Shibata H, Okitsu T, Kawanishi T, Takeuchi S (2011) Long-term in vivo glucose monitoring using fluorescent hydrogel fibers. Proc Natl Acad Sci 108(33):13399–13403CrossRefGoogle Scholar
  5. Huang X, Leduc C, Ravussin Y, Li S, Davis E, Song B et al (2014) A differential dielectric affinity glucose sensor. Lab Chip 14(2):294–301CrossRefGoogle Scholar
  6. Keenan DB, Mastrototaro JJ, Voskanyan G, Steil GM (2009) Delays in minimally invasive continuous glucose monitoring devices: a review of current technology. J Diabetes Sci Technol 3(5):1207–1214CrossRefGoogle Scholar
  7. Kremer F, Schönhals A (2012) 2 Broadband dielectric measurement techniques (10–6 Hz to 1012 Hz). Springer, BerlinGoogle Scholar
  8. Krogstad AL, Jansson PA, Gisslen P, Lonnroth P (1996) Microdialysis methodology for the measurement of dermal interstitial fluid in humans. Br J Dermatol 134(6):1005–1012. doi:10.1111/j.1365-2133.1996.tb07934.x CrossRefGoogle Scholar
  9. Kuenzi S, Meurville E, Ryser P (2010) Automated characterization of dextran/concanavalin a mixtures—a study of sensitivity and temperature dependence at low viscosity as basis for an implantable glucose sensor. Sens Actuators B Chem 146(1):1–7CrossRefGoogle Scholar
  10. Lei M, Baldi A, Nuxoll E, Siegel RA, Ziaie B (2006) A hydrogel-based implantable micromachined transponder for wireless glucose measurement. Diabetes Technol Ther 8(1):112–122CrossRefGoogle Scholar
  11. Li S, Huang X, Davis EN, Lin Q, Wang Q (2008) Development of novel glucose sensing fluids with potential application to microelectromechanical systems-based continuous glucose monitoring. J Diabetes Sci Technol 2(6):1066–1074CrossRefGoogle Scholar
  12. Li SQ, Davis EN, Anderson J, Lin Q, Wang Q (2009) Development of boronic acid grafted random copolymer sensing fluid for continuous glucose monitoring. Biomacromol 10(1):113–118. doi:10.1021/bm8009768 CrossRefGoogle Scholar
  13. Liu C, Hofstadler SA, Bresson JA, Udseth HR, Tsukuda T, Smith RD et al (1998) On-line dual microdialysis with ESI-MS for direct analysis of complex biological samples and microorganism lysates. Anal Chem 70(9):1797–1801CrossRefGoogle Scholar
  14. Luo J, Luo P, Xie M, Du K, Zhao B, Pan F et al (2013) A new type of glucose biosensor based on surface acoustic wave resonator using Mn-doped ZnO multilayer structure. Biosens Bioelectron 49:512–518CrossRefGoogle Scholar
  15. Ni NT, Laughlin S, Wang YJ, Feng Y, Zheng YJ, Wang BH (2012) Probing the general time scale question of boronic acid binding with sugars in aqueous solution at physiological pH. Bioorganic Med Chem 20(9):2957–2961. doi:10.1016/j.bmc.2012.03.014 CrossRefGoogle Scholar
  16. Oh S, Lee JS, Jeong KH, Lee LP (2003) Minimization of electrode polarization effect by nanogap electrodes for biosensor applications. Mems-03: IEEE the sixteenth annual international conference on micro electro mechanical systems. pp 52–55Google Scholar
  17. Ricci F, Moscone D, Tuta C, Palleschi G, Amine A, Poscia A et al (2005) Novel planar glucose biosensors for continuous monitoring use. Biosens Bioelectron 20(10):1993–2000CrossRefGoogle Scholar
  18. Schultz JS, Mansouri S, Goldstein IJ (1982) Affinity Sensor - a New Technique for Developing Implantable Sensors for Glucose and Other Metabolites. Diabetes Care 5(3):245–253. doi:10.2337/diacare.5.3.245 CrossRefGoogle Scholar
  19. Shang J, Yan J, Zhang Z, Huang X, Maturavongsadit P, Song B et al (2016) A hydrogel-based glucose affinity microsensor. Sens Actuators B Chem 237:992–998. doi:10.1016/j.snb.2016.03.146 CrossRefGoogle Scholar
  20. Shibata H, Heo YJ, Okitsu T, Matsunaga Y, Kawanishi T, Takeuchi S (2010) Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring. Proc Natl Acad Sci 107(42):17894–17898CrossRefGoogle Scholar
  21. Woo HJ, Majid SR, Arof AK (2012) Dielectric properties and morphology of polymer electrolyte based on poly(epsilon-caprolactone) and ammonium thiocyanate. Mater Chem Phys 134(2–3):755–761. doi:10.1016/j.matchemphys.2012.03.064 CrossRefGoogle Scholar
  22. Wu X, Li Z, Chen XX, Fossey JS, James TD, Jiang YB (2013) Selective sensing of saccharides using simple boronic acids and their aggregates. Chem Soc Rev 42(20):8032–8048. doi:10.1039/c3cs60148j CrossRefGoogle Scholar
  23. Zhao YJ, Li SQ, Davidson A, Yang BZ, Wang Q, Lin Q (2007) A MEMS viscometric sensor for continuous glucose monitoring. J Micromech Microeng 17(12):2528–2537. doi:10.1088/0960-1317/17/12/020 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Zhixing Zhang
    • 1
  • Panita Maturavongsadit
    • 2
  • Junyi Shang
    • 1
  • Jing Yan
    • 2
  • Dachao Li
    • 3
  • Qian Wang
    • 2
  • Qiao Lin
    • 1
  1. 1.Department of Mechanical EngineeringColumbia UniversityNew YorkUSA
  2. 2.Department of Chemistry and BiochemistryUniversity of South CarolinaColumbiaUSA
  3. 3.College of Precision Instrument and Opto-electronics EngineeringTianjin UniversityTianjinChina

Personalised recommendations