Biomedical Microdevices

, Volume 16, Issue 6, pp 927–935 | Cite as

A point-of-care testing system with Love-wave sensor and immunogold staining enhancement for early detection of lung cancer

  • Yingchang Zou
  • Xi Zhang
  • Chao An
  • Chunxue Ran
  • Kejing Ying
  • Ping Wang


It has been reported that detection of exhaled breath condensate (EBC) is available for studies of pulmonary diseases, especially lung disease. In order to detect lung cancer (LC) at early stage, a point-of-care testing system suitable for measurement of tumor markers in EBC is developed. The assay, based on gold nanoparticle sandwich immunoassay and subsequent gold staining, was performed on a Love-wave sensor packaged inside a chip cartridge. Benefit from high sensitivity of Love-wave sensor, oriented immobilization of coating antibodies and immunogold staining enhancement, the present immunosensor could provide a sensitive, specific and rapid measurement. Carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCC) in EBC collected from 17 patients with LC and 13 healthy volunteers were detected by this system. Results were compared with commercial chemiluminescence immunoassay and showed high correlation between two methods. Additionally, it revealed significantly statistical differences existing between two groups of subjects. These results indicate that the present system is suitable for detection of tumor markers in EBC and could be used as assistant tools for early detection of LC.


Exhaled breath condensate Early detection Immunogold staining enhancement Love-wave sensor 



Specific coating antibody


Specific detecting antibody


Gold nanoparticles


Bovine serum albumin


Carcinoembryonic antigen


Chemiluminescence immunoassay


Computerized tomography


Exhaled breath condensate


Interdigital transducers


Lung cancer


Neuron specific enolase


Phosphate buffered saline




Plasma enhanced chemical vapour deposition




Quartz crystal microbalance


Surface acoustic wave


Squamous cell carcinoma antigen


Staphylococcal protein A


Surface plasmon resonance



This work was supported by the following grants: National Natural Science Foundation of China No. 61320106002 to PW, No. 81201166 to XC, Research Fund for the Doctoral Program of Education Ministry of China No. 20120101130011 to PW, No. 20120101120165 to XC, Zhejiang Key Science and Technology Innovation Team 2011R50018 to XC.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. G.E. Carpagnano, M.P. Foschino-Barbaro, O. Resta, E. Gramiccioni, F. Carpagnano, Oncology 66, 180 (2004)CrossRefGoogle Scholar
  2. H.P. Chan, C. Lewis, P.S. Thomas, Lung Cancer 63, 164 (2009)CrossRefGoogle Scholar
  3. E. Dalaveris, T. Kerenidi, A. Katsabeki-Katsafli, T. Kiropoulos, K. Tanou, K.I. Gourgoulianis, K. Kostikas, Lung Cancer 64, 219 (2009)CrossRefGoogle Scholar
  4. D.H. Dinh, É. Pascal, L. Vellutini, B. Bennetau, D. Rebière, C. Dejous, D. Moynet, C. Belin, J.-P. Pillot, Sensors Actuators B 146, 289 (2010)CrossRefGoogle Scholar
  5. Q. Fu, J. Zhu, J.E. Van Eyk, Clin. Chem. 56, 314 (2010)CrossRefGoogle Scholar
  6. M. Ganguli, J.V. Babu, S. Maiti, Langmuir 20, 5165 (2004)CrossRefGoogle Scholar
  7. K.C. Grabar, K.R. Brown, C.D. Keating, S.J. Stranick, S.-L. Tang, M.J. Natan, Anal. Chem. 69, 471 (1997)CrossRefGoogle Scholar
  8. F. Gruhl, B. Rapp, M. Rapp, K. Länge, 73–76 (2010)Google Scholar
  9. Z. Ha, K. Zhou, X. Chen, Z. Yang, L. He, 49–52 (2007)Google Scholar
  10. H.-C. Hao, D.-J. Yao, 2117–2121 (2010)Google Scholar
  11. C. Hao, Y. Lu, L. Duan, B. Wu, M. Musideke, J. Yao, 88092H-88092H-4 (2013)Google Scholar
  12. C.S. Holgate, P. Jackson, P.N. Cowen, C.C. Bird, J. Histochem. Cytochem. 31, 938 (1983)CrossRefGoogle Scholar
  13. J. Hunt, J. Allergy Clin. Immunol. 110, 28 (2002)CrossRefGoogle Scholar
  14. E. Jantus-Lewintre, M. UsцЁ, E. Sanmartц╜n, C. Camps, Lung Cancer 3, 21 (2012)Google Scholar
  15. S. Kojima, M. Hirata, H. Shinohara, E. Ueno, Radiol. Phys. Technol. 1, (2013)Google Scholar
  16. S.L. La’ulu, W.L. Roberts, Am. J. Clin. Pathol. 127, 436 (2007)CrossRefGoogle Scholar
  17. P. Lackie, R. Hennessy, G. Hacker, J. Polak, Histochemistry 83, 545 (1985)CrossRefGoogle Scholar
  18. H.J. Lee, K. Namkoong, E.C. Cho, C. Ko, J.C. Park, S.S. Lee, Biosens. Bioelectron. 24, 3120 (2009)CrossRefGoogle Scholar
  19. H.C. Lu, H.M. Chen, Y.S. Lin, J.W. Lin, Biotechnol. Prog. 16, 116 (2000)CrossRefGoogle Scholar
  20. I.-H. Min, L. Choi, K.-S. Ahn, B.K. Kim, B.Y. Lee, K.S. Kim, H.N. Choi, W.-Y. Lee, Biosens. Bioelectron. 26, 1326 (2010)CrossRefGoogle Scholar
  21. M. Moeremans, G. Daneels, A. Van Dijck, G. Langanger, J. De Mey, J. Immunol. Methods 74, 353 (1984)CrossRefGoogle Scholar
  22. Y. Nagasaki, H. Kobayashi, Y. Katsuyama, T. Jomura, T. Sakura, J. Colloid Interface Sci. 309, 524 (2007)CrossRefGoogle Scholar
  23. H. Oh, K. Lee, K. Eun, S.-H. Choa, S.S. Yang, J. Micromech. Microeng. 22, 025002 (2012)CrossRefGoogle Scholar
  24. D.M. Parkin, F. Bray, J. Ferlay, P. Pisani, CA Cancer J. Clin. 55, 74 (2005)CrossRefGoogle Scholar
  25. J.M. Pingarrón, P. Yáñez-Sedeño, A. González-Cortés, Electrochim. Acta 53, 5848 (2008)CrossRefGoogle Scholar
  26. M.D. Schlensog, T. Gronewold, M. Tewes, M. Famulok, E. Quandt, Sensors Actuators B 101, 308 (2004)CrossRefGoogle Scholar
  27. G. Sener, E. Ozgur, E. Yılmaz, L. Uzun, R. Say, A. Denizli, Biosens. Bioelectron. 26, 815 (2010)CrossRefGoogle Scholar
  28. R. Siegel, D. Naishadham, A. Jemal, CA Cancer J. Clin. 63, 11 (2013)CrossRefGoogle Scholar
  29. R.J. Skipworth, G.D. Stewart, M. Bhana, J. Christie, C.M. Sturgeon, D.C. Guttridge, A.D. Cronshaw, K.C. Fearon, J.A. Ross, Int. J. Oncol. 36, 973 (2010)Google Scholar
  30. K. Sokolov, M. Follen, J. Aaron, I. Pavlova, A. Malpica, R. Lotan, R. Richards-Kortum, Cancer Res. 63, 1999 (2003)Google Scholar
  31. H.-J. Sung, J.-Y. Cho, BMB Rep. 41, 615 (2008)CrossRefGoogle Scholar
  32. Z. Wang, J. Lee, A.R. Cossins, M. Brust, Anal. Chem. 77, 5770 (2005)CrossRefGoogle Scholar
  33. S. Zhang, K. Bao, N.J. Halas, H. Xu, P. Nordlander, Nano Lett. 11, 1657 (2011)CrossRefGoogle Scholar
  34. B. Zheng, S. Cheng, W. Liu, M.H.-W. Lam, H. Liang, Anal. Biochem. (2013)Google Scholar
  35. Y. Zou, L. Wang, C. Zhao, Y. Hu, S. Xu, K. Ying, P. Wang, X. Chen, J. Breath Res. 7, 047101 (2013)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yingchang Zou
    • 1
  • Xi Zhang
    • 1
  • Chao An
    • 1
  • Chunxue Ran
    • 2
  • Kejing Ying
    • 2
  • Ping Wang
    • 1
    • 3
  1. 1.Biosensor National Special Lab, Key Lab for Biomedical Engineering of Ministry of Education, Department of Biomedical EngineeringZhejiang UniversityHangzhouChina
  2. 2.Zhejiang Sir Run Run Shaw Hospital, Department of MedicineZhejiang UniversityHangzhouChina
  3. 3.Department of Biomedical Engineering, Zhouyiqing Building, Yuquan CampusZhejiang UniversityHangzhouChina

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