Biomedical Microdevices

, 20:89 | Cite as

Paper-based graphene oxide biosensor coupled with smartphone for the quantification of glucose in oral fluid

  • Yuan Jia
  • Hao SunEmail author
  • Xiao Li
  • Dongke Sun
  • Tao HuEmail author
  • Nan Xiang
  • Zhonghua NiEmail author


Rapid, disposable, point-of-care (POC) oral fluid testing has gained considerable attention in recent years as saliva contains biomarker and components of the serum proteome that offer important information on both oral and systemic disease. Microfluidic paper-based analytical devices (μPADs) coupled with smartphone reflectance sensing systems have long been considered to be an effective POC tool for the diagnostics of biomarkers in oral fluid. However, the existing portable systems are limited by the poor color distribution in the detection area as well as not being universally applicable. Therefore, using the properties of nanomaterials to our advantage, we present a simple, universally applicable approach that features graphene oxide (GO) coated μPADs coupled with smartphone-based colorimetric detection for the direct quantification of glucose. An integrated portable system is used to implement the approach. Owing to the enhanced reagents absorptivity, reactive efficiency and homogeneity of color distribution from the deposition of GO, the glucose assay performance was improved. Also, by using a self-developed app, the glucose concentrations in physiological range can be automatically quantified. Finally, the approach is universally applicable as the modification of μPADs with GO can be achieved without the use of any linker, binder or retention aid, which avoids possible enzyme cross contamination. The system was first calibrated by standard glucose buffer solutions, and the limit of detection as well as the linear dynamic range were found to be 0.02 mM and 0~1 mM, respectively, which are appropriate for analyzing glucose concentrations in a clinically relevant range. Finally, the system was used for quantifying glucose concentrations in artificial saliva and the results obtained using our portable system showed reasonable agreement with the actual use concentrations. Thus, the utility of the system in sensitively quantifying glucose concentrations in a portable, and repeatable manner is demonstrated.


Graphene oxide Paper microfluidics Smartphone-based analytics Oral fluid sensing 



The authors gratefully acknowledge financial support from the Natural Science Foundation of Jiangsu Province (Award No. SBK2018041725); Fundamental Research Funds for Southeast University (Award No. 3202008801), Southeast University ESI Key Subjects Fund (Award NO. 3302001801C1), the National Natural Science Foundation of China (Award No. 61604042), Fujian Province Outstanding Youth Talent Program (Award No. 601931), Fujian Provincial Natural Science Foundation (Award No. 2017 J01501), and the instrument access from National Science Park of Fuzhou University.

Supplementary material

10544_2018_332_MOESM1_ESM.docx (729 kb)
ESM 1 (DOCX 728 kb)


  1. O. Amor-Gutierrez, E.C. Rama, A. Costa-Garcia, M.T. Fernandez-Abedul, Paper-based maskless enzymatic sensor for glucose determination combining ink and wire electrodes. Biosens. Bioelectron. 93, 40–45 (2017)CrossRefGoogle Scholar
  2. D.W. Boukhvalov, M.I. Katsnelson, Modeling of graphite oxide. J. Am. Chem. Soc. 130, 10697–10701 (2008) 2008/08/13CrossRefGoogle Scholar
  3. D. Calabria, C. Caliceti, M. Zangheri, M. Mirasoli, P. Simoni, A. Roda, Smartphone-based enzymatic biosensor for oral fluid L-lactate detection in one minute using confined multilayer paper reflectometry. Biosens. Bioelectron. 94, 124–130 (2017)CrossRefGoogle Scholar
  4. D.M. Cate, J.A. Adkins, J. Mettakoonpitak, C.S. Henry, Recent developments in paper-based microfluidic devices. Anal. Chem. 87, 19–41 (2015)CrossRefGoogle Scholar
  5. S. Chaiyo, E. Mehmeti, W. Siangproh, T.L. Hoang, H.P. Nguyen, O. Chailapakul, et al., Non-enzymatic electrochemical detection of glucose with a disposable paper-based sensor using a cobalt phthalocyanine ionic liquid graphene composite. Biosens. Bioelectron. 102, 113–120 (Apr 2018)CrossRefGoogle Scholar
  6. J.F. Chang, H.Y. Li, T. Hou, W.N. Duan, F. Li, Paper-based fluorescent sensor via aggregation induced emission fluorogen for facile and sensitive visual detection of hydrogen peroxide and glucose. Biosens. Bioelectron. 104, 152–157 (2018)CrossRefGoogle Scholar
  7. G.M. Duran, T.E. Benavidez, A. Rios, C.D. Garcia, Quantum dot-modified paper-based assay for glucose screening. Microchim. Acta 183, 611–616 (2016)CrossRefGoogle Scholar
  8. E. Evans, E.F.M. Gabriel, W.K.T. Coltro, C.D. Garcia, Rational selection of substrates to improve color intensity and uniformity on microfluidic paper-based analytical devices. Analyst 139, 2127–2132 (2014)CrossRefGoogle Scholar
  9. F. Figueredo, P.T. Garcia, E. Cortón, W.K.T. Coltro, Enhanced analytical performance of paper microfluidic devices by using Fe3O4 nanoparticles, MWCNT, and Graphene oxide. ACS Appl. Mater. Interfaces 8, 11–15 (2016) 2016/01/13CrossRefGoogle Scholar
  10. E.F.M. Gabriel, P.T. Garcia, F.M. Lopes, W.K.T. Coltro, Paper-based colorimetric biosensor for tear glucose measurements. Micromachines, 8 (2017)Google Scholar
  11. R.W. Hart, M.G. Mauk, C. Liu, X. Qiu, J.A. Thompson, D. Chen, et al., Point-of-care oral-based diagnostics. Oral Dis. 17, 745–752 (2011)CrossRefGoogle Scholar
  12. M.A. Hegener, H. Li, D. Han, A.J. Steckl, G.M. Pauletti, Point-of-care coagulation monitoring: First clinical experience using a paper-based lateral flow diagnostic device. Biomed. Microdevices 19 (2017)Google Scholar
  13. A.L. Horst, J.M. Rosenbohm, N. Kolluri, J. Hardick, C.A. Gaydos, M. Cabodi, et al., A paperfluidic platform to detect Neisseria gonorrhoeae in clinical samples. Biomed. Microdevices 20, 1–7 (2018)CrossRefGoogle Scholar
  14. Y. Jia, H. Dong, J.P. Zheng, H. Sun, Portable detection of trace metals in airborne particulates and sediments via mu PADs and smartphone. Biomicrofluidics 11 (2017)Google Scholar
  15. J.V. Jokerst, A. Raamanathan, N. Christodoulides, P.N. Floriano, A.A. Pollard, G.W. Simmons, et al., Nano-bio-chips for high performance multiplexed protein detection: Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels. Biosens. Bioelectron. 24, 3622–3629 (2009)CrossRefGoogle Scholar
  16. S.C. Kim, U.M. Jalal, S.B. Im, S. Ko, J.S. Shim, A smartphone-based optical platform for colorimetric analysis of microfluidic device. Sensors Actuators B Chem. 239, 52–59 (Feb 2017)CrossRefGoogle Scholar
  17. S. Kumar, S. Padmashree, R. Jayalekshmi, Correlation of salivary glucose, blood glucose and oral candidal carriage in the saliva of type 2 diabetics: A case-control study. Contemp Clin Dent 5, 312–317 (2014)Google Scholar
  18. X. Li, C. Zhao, X. Liu, An electrochemical microfluidic paper-based glucose sensor integrating zinc oxide nanowires, in 2015 28th IEEE International Conference on Micro Electro Mechanical Systems (MEMS) (2015) pp. 447–450Google Scholar
  19. Z.X. Li, Y.H. Zhu, W.J. Zhang, C.H. Xu, Y.J. Pan, Y. Zhao, A low-cost and high sensitive paper-based microfluidic device for rapid detection of glucose in fruit. Food Anal. Methods 10, 666–674 (2017)CrossRefGoogle Scholar
  20. L. Magro, B. Jacquelin, C. Escadafal, P. Garneret, A. Kwasiborski, J.C. Manuguerra, et al., Paper-based RNA detection and multiplexed analysis for Ebola virus diagnostics. Sci. Rep. 7 (2017)Google Scholar
  21. R.C. Murdock, L. Shen, D.K. Griffin, N. Kelley-Loughnane, I. Papautsky, J.A. Hagen, Optimization of a paper-based ELISA for a human performance biomarker. Anal. Chem. 85, 11634–11642 (2013)CrossRefGoogle Scholar
  22. E.A. Oblath, W.H. Henley, J.P. Alarie, J.M. Ramsey, A microfluidic chip integrating DNA extraction and real-time PCR for the detection of bacteria in saliva. Lab Chip 13, 1325–1332 (2013)CrossRefGoogle Scholar
  23. T. Ogirala, A. Eapen, K.G. Salvante, T. Rapaport, P.A. Nepomnaschy, A.M. Parameswaran, Smartphone-based colorimetric ELISA implementation for determination of women's reproductive steroid hormone profiles. Med. Biol. Eng. Comput. 55, 1735–1741 (2017)CrossRefGoogle Scholar
  24. T.S. Park, W.Y. Li, K.E. McCracken, J.Y. Yoon, Smartphone quantifies Salmonella from paper microfluidics. Lab Chip 13, 4832–4840 (2013)CrossRefGoogle Scholar
  25. C. Parolo, A. Merkoci, Paper-based nanobiosensors for diagnostics. Chem. Soc. Rev. 42, 450–457 (2013)CrossRefGoogle Scholar
  26. M. Parrilla, R. Canovas, F.J. Andrade, Paper-based enzymatic electrode with enhanced potentiometric response for monitoring glucose in biological fluids. Biosens. Bioelectron. 90, 110–116 (2017)CrossRefGoogle Scholar
  27. A. Priye, S.S. Wong, Y.P. Bi, M. Carpio, J. Chang, M. Coen, et al., Lab-on-a-drone: Toward pinpoint deployment of smartphone-enabled nucleic acid-based diagnostics for Mobile health care. Anal. Chem. 88, 4651–4660 (2016)CrossRefGoogle Scholar
  28. A. Roda, E. Michelini, M. Zangheri, M. Di Fusco, D. Calabria, P. Simoni, Smartphone-based biosensors: A critical review and perspectives. Trac-Trends Anal Chem 79, 317–325 (2016)Google Scholar
  29. N.C. Sekar, S.A.M. Shaegh, S.H. Ng, L. Ge, S.N. Tan, A paper-based amperometric glucose biosensor developed with Prussian blue-modified screen-printed electrodes. Sensors Actuators B Chem. 204, 414–420 (2014)CrossRefGoogle Scholar
  30. Y.J. Song, K.G. Qu, C. Zhao, J.S. Ren, X.G. Qu, Graphene oxide: Intrinsic peroxidase catalytic activity and its application to glucose detection. Adv. Mater. 22, 2206–2210 (May 2010)CrossRefGoogle Scholar
  31. Y. Xu, M. Liu, N. Kong, J. Liu, Lab-on-paper micro- and nano-analytical devices: Fabrication, modification, detection and emerging applications. Microchim. Acta 183, 1521–1542 (May 01 2016)CrossRefGoogle Scholar
  32. Y. Yao, C.S. Zhang, A novel screen-printed microfluidic paper-based electrochemical device for detection of glucose and uric acid in urine. Biomed. Microdevices 18 (2016)Google Scholar
  33. Y. Yao, L. Zeng, Y. Huang, The enhancement of chondrogenesis of ATDC5 cells in RGD-immobilized microcavitary alginate hydrogels. J. Biomater. Appl. 31, 92–101 (2016)CrossRefGoogle Scholar
  34. A.K. Yetisen, J.L. Martinez-Hurtado, A. Garcia-Melendrez, F.D. Vasconcellos, C.R. Lowe, A smartphone algorithm with inter-phone repeatability for the analysis of colorimetric tests. Sensors Actuators B Chem. 196, 156–160 (2014)CrossRefGoogle Scholar
  35. M. Zarei, Infectious pathogens meet point-of-care diagnostics. Biosens. Bioelectron. 106, 193–203 (2018)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Mechanical EngineeringSoutheast UniversityNanjingChina
  2. 2.Jiangsu Key Laboratory for Design & Manufacture of Micro-Nano Biomedical InstrumentsSoutheast UniversityNanjingChina
  3. 3.School of Mechanical Engineering and AutomationFuzhou UniversityFuzhouChina
  4. 4.Fujian Provincial Collaborative Innovation Center of High-End Equipment ManufacturingFuzhouChina

Personalised recommendations