Analytical and Bioanalytical Chemistry

, Volume 410, Issue 18, pp 4387–4395 | Cite as

Preparation of a molecularly imprinted sensor based on quartz crystal microbalance for specific recognition of sialic acid in human urine

  • Xiuzhen QiuEmail author
  • Xian-Yan Xu
  • Xuncai Chen
  • Yiyong Wu
  • Huishi GuoEmail author
Research Paper


A novel molecularly imprinted quartz crystal microbalance (QCM) sensor was successfully prepared for selective determination of sialic acid (SA) in human urine samples. To obtain the QCM sensor, we first modified the gold surface of the QCM chip by self-assembling of allylmercaptane to introduce polymerizable double bonds on the chip surface. Then, SA molecularly imprinted polymer (MIP) nanofilm was attached to the modified QCM chip surface. For comparison, we have also characterized the nonmodified and improved surfaces of the QCM sensor by using atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy. We then tested the selectivity and detection limit of the imprinted QCM sensor via a series of adsorption experiments. The results show a linear response in the range of 0.025–0.50 μmol L−1 for sialic acid. Moreover, the limit of detection (LOD) of the prepared imprinted QCM sensor was found to be 1.0 nmol L−1 for sialic acid, and high recovery values range from 87.6 to 108.5% with RSD < 8.7 (n = 5) for the spiked urine sample obtained. Overall, this work presents how a novel QCM sensor was developed and used to detect sialic acid in human urine samples.

Graphical abstract

Specific recognition of sialic acid by the MIP-QCM sensor system


Sialic acid (SA) Quartz crystal microbalance (QCM) Molecularly imprinted polymer (MIP) Sensor 


Funding information

This work was financially supported by grants from the Natural Science Foundation of Guangdong Province (Nos. 2014A030307024, 2015A030313750) and the Innovation Projects of the Department of Education of Guangdong Province (2014KTSCX169).

Compliance with ethical standards

The authors declare that all individual participants from whom the serum samples were obtained gave informed consent, and the studies have been approved by the Shaoguan University Ethics Committee and have been performed in accordance with ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_1094_MOESM1_ESM.pdf (598 kb)
ESM 1 (PDF 367 kb)


  1. 1.
    Wulfkuhle JD, Liotta LA, Petricoin EF. Proteomic applications for the early detection of cancer. Nat Rev Cancer. 2003;3:267–75.CrossRefPubMedGoogle Scholar
  2. 2.
    Sankoh S, Thammakhet C, Numnuam A, Limbut W, Kanatharana P, Thavarungkul P. 4-Mercaptophenylboronic acid functionalized gold nanoparticles for colorimetric sialic acid detection. Biosens Bioelectron. 2016;85:743–50.CrossRefPubMedGoogle Scholar
  3. 3.
    Lamari FN, Karamanos NK. Separation methods for sialic acids and critical evaluation of their biologic relevance. J Chromatogr B. 2002;781:3–19.CrossRefGoogle Scholar
  4. 4.
    Karina PG, Martin AC. Sialic acid: a novel marker of cardiovascular disease. Clin Biochem. 2006;39:667–81.CrossRefGoogle Scholar
  5. 5.
    Tebani A, Schlemmer D, Imbard A, Rigal O, Porquet D, Benoist JF. Measurement of free and total sialic acid by isotopic dilution liquid chromatography tandem mass spectrometry method. J Chromatogr B. 2011;879:3694–9.CrossRefGoogle Scholar
  6. 6.
    Van der Ham M, De Koning TJ, Lefeber D, Fleer A, Berthil HC, Prinsen MT, et al. Liquid chromatography–tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid. J Chromatogr B. 2010;878:1098–102.CrossRefGoogle Scholar
  7. 7.
    Orozco-Solano MI, Priego-Capotea F, Luque de Castro MD. Ultrasound-assisted hydrolysis and chemical derivatization combined to lab-on-valve solid-phase extraction for the determination of sialic acids in human biofluids by liquid chromatography-laser induced fluorescence. Anal Chim Acta. 2013;766:69–76.CrossRefPubMedGoogle Scholar
  8. 8.
    Hurum DC, Rohrer JS. Determination of sialic acids in infant formula by chromatographic methods: a comparison of high-performance anion-exchange chromatography with pulsed amperometric detection and ultra-high-performance liquid chromatography methods. J Dairy Sci. 2012;95:1152–61.CrossRefPubMedGoogle Scholar
  9. 9.
    Meininger M, Stepath M, Hennig R, Cajic S, Rapp E, Rotering H, et al. Sialic acid-specific affinity chromatography for the separation of erythropoietin glycoforms using serotonin as a ligand. J Chromatogr B. 2016;1012:193–203.CrossRefGoogle Scholar
  10. 10.
    Spichtig V, Michaud J, Austin S. Determination of sialic acids in milks and milk-based products. Anal Biochem. 2010;405:28–40.CrossRefPubMedGoogle Scholar
  11. 11.
    Song H, Wang Y, Zhang L, Tian L, Luo J, Zhao N, et al. An ultrasensitive and selective electrochemical sensor for determination of estrone 3-sulfate sodium salt based on molecularly imprinted polymer modified carbon paste electrode. Anal Bioanal Chem. 2017;409(27):6509–19.CrossRefPubMedGoogle Scholar
  12. 12.
    Feng F, Zheng JW, Qin P, Han T, Zhao DY. A novel quartz crystal microbalance sensor array based on molecular imprinted polymers for simultaneous detection of clenbuterol and its metabolites. Talanta. 2017;167:94–102.CrossRefPubMedGoogle Scholar
  13. 13.
    Ratautaite V, Plausinaitis D, Baleviciute I, Mikoliunaite L, Ramanaviciene A, Ramanavicius A. Characterization of caffeine-imprinted polypyrrole by a quartz crystal microbalance and electrochemical impedance spectroscopy. Sensors Actuators B Chem. 2015;212:63–71.CrossRefGoogle Scholar
  14. 14.
    Gültekin A, Karanfil G, Kuş M, Sönmezoğlu S, Say R. Preparation of MIP-based QCM sensor for detection of caffeic acid. Talanta. 2014;119:533–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Eren TJ, Atar N, Yola ML, Karimi-Maleh H. A sensitive molecularly imprinted polymer based quartz crystal microbalance sensor for selective determination of lovastatin in red yeast rice. Food Chem. 2015;185:430–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Guo HS, Kim J, Chang SM, Kim W. Chiral recognition of mandelic acid by L-phenylalanine-modified sensor using quartz crystal microbalance. Biosens Bioelectron. 2009;24:2931–4.CrossRefPubMedGoogle Scholar
  17. 17.
    Yola ML, Uzun L, Özaltın N, Denizli A. Development of molecular imprinted nanosensor for determination of tobramycin in pharmaceuticals and foods. Talanta. 2014;120:318–24.CrossRefPubMedGoogle Scholar
  18. 18.
    Ma XT, He XW, Li WY, Zhang YK. Epitope molecularly imprinted polymer coated quartz crystal microbalance sensor for the determination of human serum albumin. Sensors Actuators B Chem. 2017;246:879–86.CrossRefGoogle Scholar
  19. 19.
    Kim JM, Yang JC, Park JY. Quartz crystal microbalance (QCM) gravimetric sensing of theophylline via molecularly imprinted microporous polypyrrole copolymers. Sensors Actuators B Chem. 2015;206:50–5.CrossRefGoogle Scholar
  20. 20.
    EL-Sharif HF, Aizawa H, Reddy SM. Spectroscopic and quartz crystal microbalance (QCM) characterisation of protein-based MIPs. Sensors Actuators B Chem. 2015;206:239–45.CrossRefGoogle Scholar
  21. 21.
    Yang JC, Shin HK, Hong SW, Park JY. Lithographically patterned molecularly imprinted polymer for gravimetric detection of trace atrazine. Sensors Actuators B Chem. 2015;216:476–81.CrossRefGoogle Scholar
  22. 22.
    Gupta VK, Yola ML, Atar N. A novel molecular imprinted sensor based quartz crystal microbalance for determination of kaempferol. Sensors Actuators B Chem. 2014;194:79–85.CrossRefGoogle Scholar
  23. 23.
    Otsuka H, Uchimura E, Koshino H, Okano T, Kataoka K. Anomalous binding profile of phenylboronic acid with N-acetylneuraminic acid (Neu5Ac) in aqueous solution with varying pH. J Am Chem Soc. 2003;125:3493–502.CrossRefPubMedGoogle Scholar
  24. 24.
    Duan SJ, He XW, Chen LX, Zhang YK. 4-Mercaptophenylboronic acid functionalized quartz crystal microbalances sensor for the determination of sialic acid. Chem J Chin Univ. 2012;33:462–9.Google Scholar
  25. 25.
    Gültekin A, Karanfίl G, Sönmezoģlu S, Say R. Development of a highly sensitive MIP based-QCM sensor for selective determination of cholic acid level in body fluids. Mater Sci Eng C. 2014;42:436–42.CrossRefGoogle Scholar
  26. 26.
    Yola ML, Eren TJ, Atar N. Molecular imprinted sensor based on surface plasmon-resonance: application to the sensitive determination of amoxicillin. Sensors Actuators B Chem. 2014;195:28–35.CrossRefGoogle Scholar
  27. 27.
    Homayoonnia S, Zeinali S. Design and fabrication of capacitive sensor based on MOF nanoparticles as sensing layer for VOCs detection. Sensors Actuators B Chem. 2016;237:776–86.CrossRefGoogle Scholar
  28. 28.
    Qiu XZ, Xu XY, Liang Y, Hua YB, Guo HS. Fabrication of a molecularly imprinted polymer immobilized membrane with nanopores and its application in determination of β2-agonists in pork samples. J Chromatogr A. 2016;1249:79–85.CrossRefGoogle Scholar
  29. 29.
    Bakhshpour M, Özgür E, Bereli N, Denizli A. Microcontact imprinted quartz crystal microbalance nanosensor for protein C recognition. Colloids Surf, B. 2017;151:264–70.CrossRefGoogle Scholar
  30. 30.
    Guo HS, Kim J, Pham XH, Chang SM, Kim W. Versatile method for chiral recognition by the quartz crystal microbalance: chiral mandelic acid as the detection model. Langmuir. 2009;25:648–52.CrossRefPubMedGoogle Scholar
  31. 31.
    Wang JH, Hansen EH, Gammelgaard B. Flow injection on-line dilution for multi-element determination in human urine with detection by inductively coupled plasma mass spectrometry. Talanta. 2001;55:117–26.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of Chemistry and Environmental EngineeringShaoguan UniversityShaoguanChina
  2. 2.School of Chemical and Biomolecular EngineeringThe University of SydneySydneyAustralia

Personalised recommendations