Applied Magnetic Resonance

, Volume 50, Issue 1–3, pp 357–370 | Cite as

Development of a Microfluidic NMR Device for Rapid and Quantitative Detection of Tumor Markers

  • Rongsheng LuEmail author
  • Pengkun Lei
  • Qing Yang
  • Zhonghua Ni
  • Hong YiEmail author
Original Paper


In this work, a low-field microfluidic nuclear magnetic resonance (NMR) detection device was developed by fabricating a multi-layer microfluidic NMR probe. In combination with biological sensor technology based on immunomagnetic nanoparticles (IMNPs), the microfluidic NMR detection device was used to rapidly distinguish the concentration of target tumor markers. The experimental results show that the concentration of the target tumor markers can be differentiated with high sensitivity and specificity by the rate of the transverse relaxation time change ΔT2 even with interference from other biomarkers. A good linear relationship between ΔT2 and the concentration of the target tumor markers was also found, indicating that the microfluidic NMR device could be used for quantitative detection of tumor markers. Finally, the validity of the microfluidic NMR device for detecting target tumor markers was proved by comparison with a commercial cell counter, and the results detected by the two devices have a good consistency with a correlation coefficient of 0.996. In conclusion, the presented low-field microfluidic NMR device is a potential tool for the rapid and accurate quantitative detection of tumor markers.



We gratefully thank the financial supports from National Key Scientific Instrument and Equipment Development Project of China under Grant no. 51627808, National Natural Science Foundation of China under Grant no. 51605089, and Jiangsu Province National Natural Science Foundation of China under Grant no. BK20150609.


  1. 1.
    T.R. Frieden, I. Damon, B.P. Bell, T. Kenyon, S. Nichol, N. Engl. J. Med. 371, 1177 (2014)CrossRefGoogle Scholar
  2. 2.
    R. Etzioni, N. Urban, S. Ramsey, M. McIntosh, S. Schwartz, B. Reid, J. Radich, G. Anderson, L. Hartwell, Nat. Rev. Cancer 3, 243 (2003)CrossRefGoogle Scholar
  3. 3.
    C.A. Batt, Science 316, 1579 (2007)CrossRefGoogle Scholar
  4. 4.
    E.W.M. Kemna, L.I. Segerink, F. Wolbers, I. Vermes, A. van den Berg, Analyst 138, 4585 (2013)ADSCrossRefGoogle Scholar
  5. 5.
    P. Liu, K. Skucha, M. Megens, B. Boser, IEEE. Trans. Magn. 47, 3449 (2011)ADSCrossRefGoogle Scholar
  6. 6.
    S.J. Osterfeld, H. Yu, R.S. Gaster, S. Caramuta, L. Xu, S.J. Han, D.A. Hall, R.J. Wilson, S.H. Sun, R.L. White, R.W. Davis, N. Pourmand, S.X. Wang, Proc. Natl. Acad. Sci. USA 105, 20637 (2008)ADSCrossRefGoogle Scholar
  7. 7.
    M.M. Wang, E. Tu, D.E. Raymond, J.M. Yang, H.C. Zhang, N. Hagen, B. Dees, E.M. Mercer, A.H. Forster, I. Kariv, P.J. Marchand, W.F. Butler, Nat. Biotechnol. 23, 83 (2005)CrossRefGoogle Scholar
  8. 8.
    M. Safavieh, M.U. Ahmed, E. Sokullu, A. Ng, L. Braescu, M. Zourob, Analyst 139, 482 (2014)ADSCrossRefGoogle Scholar
  9. 9.
    J.O. Esteves-Villanueva, H. Trzeciakiewicz, S. Martic, Analyst 139, 2823 (2014)ADSCrossRefGoogle Scholar
  10. 10.
    J.M. Perez, L. Josephson, T. O’Loughlin, D. Hogemann, R. Weissleder, Nat. Biotechnol. 20, 816 (2002)CrossRefGoogle Scholar
  11. 11.
    D. Hogemann, V. Ntziachristos, L. Josephson, R. Weissleder, Bioconjug. Chem. 13, 116 (2002)CrossRefGoogle Scholar
  12. 12.
    M.D. Robinson, I. Mishra, S. Deodhar, V. Patel, K.V. Gordon, R. Vintimilla, K. Brown, L. Johnson, S. O’Bryant, D.P. Cistola, J. Transl. Med. 15, 19 (2017)CrossRefGoogle Scholar
  13. 13.
    Z.X. Luo, L. Fox, M. Cummings, T.J. Lowery, E. Daviso, Trends Anal. Chem. 83, 94 (2016)CrossRefGoogle Scholar
  14. 14.
    D.P. Cistola, M.D. Robinson, Trends Anal. Chem. 83, 53 (2016)CrossRefGoogle Scholar
  15. 15.
    H.Y. Chen, Y. Kim, P. Nath, C. Hilty, J. Magn. Reson. 255, 100 (2015)ADSCrossRefGoogle Scholar
  16. 16.
    V. Demas, J.L. Herberg, V. Malba, A. Bernhardt, L. Evans, C. Harvey, S.C. Chinn, R.S. Maxwell, J. Reimer, J. Magn. Reson. 189, 121 (2007)ADSCrossRefGoogle Scholar
  17. 17.
    Z. Xu, S.J. Zhao, P. Guo, Appl. Magn. Reson. 44, 1405 (2013)CrossRefGoogle Scholar
  18. 18.
    S.S. Zalesskiy, E. Danieli, B. Bluemich, V.P. Ananikov, Chem. Rev. 114, 5641 (2014)CrossRefGoogle Scholar
  19. 19.
    X. Zheng, Y. Qiang, Appl. Magn. Reson. 47, 175 (2016)CrossRefGoogle Scholar
  20. 20.
    R.S. Lu, X.L. Zhou, W.P. Wu, Y.Y. Zhang, Z.H. Ni, Appl. Magn. Reson. 45, 461 (2014)CrossRefGoogle Scholar
  21. 21.
    T.L. Peck, R.L. Magin, J. Kruse, M. Feng, IEEE. Trans. Bio-med. Eng. 41, 706 (1994)CrossRefGoogle Scholar
  22. 22.
    J.E. Stocker, T.L. Peck, A.G. Webb, M. Feng, R.L. Magin, IEEE. Trans. Bio-med. Eng. 44, 1122 (1997)CrossRefGoogle Scholar
  23. 23.
    J.D. Trumbull, I.K. Glasgow, D.J. Beebe, R.L. Magin, IEEE. Trans. Bio-med. Eng. 47, 3 (2000)CrossRefGoogle Scholar
  24. 24.
    J. Dechow, A. Forchel, T. Lanz, A. Haase, Microelectron. Eng. 53, 517 (2000)CrossRefGoogle Scholar
  25. 25.
    C. Massin, F. Vincent, A. Homsy, K. Ehrmann, G. Boero, P.A. Besse, A. Daridon, E. Verpoorte, N.F. de Rooij, R.S. Popovic, J. Magn. Reson. 164, 242 (2003)ADSCrossRefGoogle Scholar
  26. 26.
    C. Massin, C. Boero, F. Vincent, J. Abenhaim, P.A. Besse, R.S. Popovic, Sens. Actuat. A Phys. 97–98, 280 (2002)CrossRefGoogle Scholar
  27. 27.
    H. Wensink, F. Benito-Lopez, D.C. Hermes, W. Verboom, H.J. Gardeniers, D.N. Reinhoudt, D.B.A. Van, Lab. Chip 5, 280 (2005)CrossRefGoogle Scholar
  28. 28.
    T.F. Kong, W.K. Peng, T.D. Luong, N.T. Nguyen, J. Han, Lab. Chip 12, 287 (2012)CrossRefGoogle Scholar
  29. 29.
    D.L. Olson, M.E. Lacey, J.V. Sweedler, Anal. Chem. 70, 645 (1998)CrossRefGoogle Scholar
  30. 30.
    T.L. Peck, R.L. Magin, P.C. Lauterbur, J. Magn. Reson. Ser. B. 108, 114 (1995)CrossRefGoogle Scholar
  31. 31.
    H. Lee, T.J. Yoon, J.L. Figueiredo, F.K. Swirski, R. Weissleder, Proc. Natl. Acad. Sci. USA 106, 12459 (2009)ADSCrossRefGoogle Scholar
  32. 32.
    J.A. Rogers, R.J. Jackman, G.M. Whitesides, D.L. Olson, J.V. Sweedler, Appl. Phys. Lett. 70, 2464 (1997)ADSCrossRefGoogle Scholar
  33. 33.
    V. Malba, R. Maxwell, L.B. Evans, A.E. Bernhardt, M. Cosman, K. Yan, Biomed. Microdevices 5, 21 (2003)CrossRefGoogle Scholar
  34. 34.
    C.H. Ahn, M.G. Allen, IEEE. Trans. Ind. Electron. 45, 866 (1998)CrossRefGoogle Scholar
  35. 35.
    L.O. Sillerud, A.F. McDowell, N.L. Adolphi, R.E. Serda, D.P. Adams, M.J. Vasile, T.M. Alam, J. Magn. Reson. 181, 181 (2006)ADSCrossRefGoogle Scholar
  36. 36.
    R.C. Meier, J. Höfflin, V. Badilita, U. Wallrabe, J.G. Korvink, J. Micromech. Microeng. 24, 045021 (2014)ADSCrossRefGoogle Scholar
  37. 37.
    K. Kratt, V. Badilita, T. Burger, J.G. Korvink, U. Wallrabe, J. Micromech. Microeng. 20, 837 (2010)CrossRefGoogle Scholar
  38. 38.
    S. He, F. Chen, Q. Yang, K. Liu, C. Shan, H. Bian, H. Liu, X. Meng, J. Si, Y. Zhao, X. Hou, J. Micromech. Microeng. 22, 105017 (2012)ADSCrossRefGoogle Scholar
  39. 39.
    Y. Chen, Y. Xianyu, Y. Wang, X. Zhang, R. Cha, J. Sun, X. Jiang, ACS Nano 9, 3184 (2015)CrossRefGoogle Scholar
  40. 40.
    L.-S. Jang, H.-K. Keng, Biomed. Microdevices 10, 203 (2008)CrossRefGoogle Scholar
  41. 41.
    Y. Zhao, Y. Yao, M. Xiao, Y. Chen, C.C.C. Lee, L. Zhang, K.X. Zhang, S. Yang, M. Gu, Food Control 34, 436 (2013)CrossRefGoogle Scholar
  42. 42.
    C. Min, H. Shao, M. Liong, T.J. Yoon, R. Weissleder, H. Lee, ACS Nano 6, 6821 (2012)CrossRefGoogle Scholar
  43. 43.
    J. Taylor-Papadimitriou, J. Burchell, D.W. Miles, M. Dalziel, Biochim. Biophys. Acta 1455, 301 (1999)CrossRefGoogle Scholar
  44. 44.
    S. Nath, P. Mukherjee, Trends Mol. Med. 20, 332 (2014)CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical InstrumentsSoutheast UniversityNanjingPeople’s Republic of China
  2. 2.School of Mechanical EngineeringSoutheast UniversityNanjingPeople’s Republic of China

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