Advertisement

BioNanoScience

, Volume 4, Issue 2, pp 119–127 | Cite as

Surface Enhanced Raman Spectroscopy-Based Method for Leukemia Biomarker Detection Using Magnetic Core @ Gold Shell Nanoparticles

  • Dora MehnEmail author
  • Carlo Morasso
  • Renzo Vanna
  • Domitilla Schiumarini
  • Marzia Bedoni
  • Fabio Ciceri
  • Furio Gramatica
Article

Abstract

We present here the surface-enhanced Raman spectroscopic (SERS)-based detection of the Wilm’s tumor gene (WT1) sequence using dye-labeled reporter oligonucleotide and magnetic core @ gold shell nanoparticles. Thiolated single-stranded DNA (ssDNA) complementers of the WT1 sequence were used to functionalize the gold shell with capture oligonucleotides in a facile and fast two-step method. The signal amplification performance of the core @ shell colloidal SERS substrate was tested using malachite green as label dye. The Raman signal enhancing efficacy of the magnetic core @ gold shell nanomaterial was compared with the efficacy of spherical gold particles produced using the conventional citrate reduction method. The core @ shell particles were found to be superior both regarding robustness in SERS and facile separation in a heterogeneous reaction system. The core @ shell particles functionalized with target specific oligonucleotide were able to capture the WT1 target and worked as Raman signal amplifiers in our assay system. The good physicochemical characteristics of these particles and the sensitivity observed in SERS experiments allow us to expect good performance in the further development steps of a novel, fast and reliable spectroscopic method for WT1 detection in minimal residual disease patients.

Keywords

SERS Biomarker Leukemia WT1 Magnetic nanoparticle Gold shell 

Notes

Acknowledgments

Funding for this research was provided by Fondazione Cariplo (International Recruitment Call 2011 Project: an innovative, nanostructured biosensor for early diagnosis and minimal residual disease assessment of cancer, using surface-enhanced Raman spectroscopy), and was also supported by the Italian Ministry of Health (Conto Capitale 2010: Realizzazione e validazione di una core facility di biofotonica clinica per diagnosi precocee monitoraggio di minimal residual disease in patologie tumorali). The authors thank Prof. Elena Bianca Donetti (University of Milan) for the TEM images of nanoparticles.

References

  1. 1.
    Sant, M., Allemani, C., Tereanu, C., De Angelis, R., Capocaccia, R., Visser, O., et al. (2010). Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood, 116, 3724–3734. doi: 10.1182/blood-2010-05-282632.CrossRefGoogle Scholar
  2. 2.
    Paietta, E. (2012). Minimal residual disease in acute myeloid leukemia: coming of age. Hematalogy, ASH Education Book, 2012(1), 35–42. doi: 10.1182/asheducation-2012.1.35.CrossRefGoogle Scholar
  3. 3.
    Estey, E., & Döhner, H. (2006). Acute myeloid leukaemia. Lancet, 368, 1894–1907. doi: 10.1016/S0140-6736(06)69780-8.CrossRefGoogle Scholar
  4. 4.
    Jorgensen, J. L., & Chen, S. S. (2011). Monitoring of minimal residual disease in acute myeloid leukemia: methods and best applications. Clinical Lymphoma, Myeloma & Leukemia, 11(Suppl 1), S49–S53. doi: 10.1016/j.clml.2011.03.023.CrossRefGoogle Scholar
  5. 5.
    Buccisano, F., Maurillo, L., Del Principe, M. I., et al. (2012). Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. Blood, 119, 332–341. doi: 10.1182/blood-2011-08-363291.CrossRefGoogle Scholar
  6. 6.
    Steinbach, D., & Debatin, K.-M. (2008). What do we mean by sensitivity when we talk about detecting minimal residual disease? Leukemia, 22, 1638–1639. doi: 10.1038/leu.2008.33.CrossRefGoogle Scholar
  7. 7.
    Ross, D. M., Branford, S., Melo, J. V., Hughes, T. P. (2009). Reply to ‘What do we mean by sensitivity when we talk about detecting minimal residual disease?’. Leukemia, 23(4), 819–820. doi: 10.1038/leu.2008.330.CrossRefGoogle Scholar
  8. 8.
    Rossi, G., Minervini, M. M., Carella, A. M., et al. (2012). Comparison between multiparameter flow cytometry and WT1-RNA quantification in monitoring minimal residual disease in acute myeloid leukemia without specific molecular targets. Leukemia Research, 36(4), 401–406. doi: 10.1016/j.leukres.2011.11.020.CrossRefGoogle Scholar
  9. 9.
    Bergmann, L., Miething, C., Maurer, U., Brieger, J., Karakas, T., Weidmann, E., et al. (1997). High levels of Wilms’ tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood, 90, 1217–1225.Google Scholar
  10. 10.
    Willasch, A. M., Gruhn, B., Coliva, T., Kalinova, M., Schneider, G., Kreyenberg, H., et al. (2009). High levels of Wilms’ tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Leukemia, 23, 1472–1479. doi: 10.1038/leu.2009.51.CrossRefGoogle Scholar
  11. 11.
    Huh, Y. S. (2009). Surface enhanced Raman spectroscopy and its application to molecular and cellular analysis. Microfluidics and Nanofluidics, 6, 285–297. doi: 10.1007/s10404-008-0392-3.CrossRefGoogle Scholar
  12. 12.
    Lutz, B. R., Dentinger, C. E., Nguyen, N. L., Sun, L., Zhang, J., Allen, A. N., et al. (2008). Spectral analysis of multiplex Raman probe signatures. ACS Nano, 2, 2306–2314. doi: 10.1021/nn800243g.CrossRefGoogle Scholar
  13. 13.
    Cao, Y. C., Jin, R., Mirkin, C. A. (2002). Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science, 297, 1536–1540. doi: 10.1126/science.297.5586.1536.CrossRefGoogle Scholar
  14. 14.
    Zhang, Y., Huang, Y., Zhai, F., Du, R., Liu, Y., Lai, K. (2012). Analyses of enrofloxacin, furazolidone and malachite green in fish products with surface-enhanced Raman spectroscopy. Food Chemistry, 135, 845–850.CrossRefGoogle Scholar
  15. 15.
    del Campo, A., Sen, T., Lellouche, J.-P., Bruce, I. J. (2005). Multifunctional magnetite and silica-magnetite nanoparticles: synthesis, surface activation and applications in life sciences. Journal of Magnetism and Magnetic Materials, 293, 33–40. doi: 10.1016/j.jmmm.2005.01.040.CrossRefGoogle Scholar
  16. 16.
    Chowdhurya, M. H., Campbell, C. J., Theofanidou, E., Lee, S. J., Baldwin, A., Sing, G., et al. (2006). Plasmonics in Biology and Medicine III, edited by Vo-Dinh T, Lakowicz JR, Gryczynski Z, Proceedings of SPIE Vol. 6099, 609905, 1605-7422/06/$15 doi: 10.1117/12.646464.
  17. 17.
    Oldenburg, S. J., Averitt, R. D., Westcott, S. L., Halas, N. J. (1998). Nanoengineering of optical resonances. Chemical Physics Letters, 288, 243–247. doi: 10.1016/S0009-2614(98)00277-2.CrossRefGoogle Scholar
  18. 18.
    Frens, G. (1973). Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nature Physical Sciences, 241, 20–21. doi: 10.1038/physci241020a0.CrossRefGoogle Scholar
  19. 19.
    Long, N. N., Vu, L. V., Kiem, C. D., Doanh, S. C., Nguyet, T. C., Hang, P. T., et al. (2009). Synthesis and optical properties of colloidal gold nanoparticles. Journal of Physics: Conference Series, 187, 012026. doi: 10.1088/1742-6596/187/1/012026.Google Scholar
  20. 20.
    Massart, R. (1981). Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Transactions on Magnetics, 17, 1247–1248. doi: 10.1109/TMAG.1981.1061188.CrossRefGoogle Scholar
  21. 21.
    Sapsford, K. E., Tyner, K. M., Dair, B. J., Deschamps, J. R., Mendintz, I. L. (2011). Analyzing nanomaterial bioconjugates: a review of current and emerging purification and characterization techniques. Analytical Chemistry, 83, 4453–4488. doi: 10.1021/ac200853a.CrossRefGoogle Scholar
  22. 22.
    Gabert, J., Beillard, E., van der Velden, V. H. J., Bi, W., Grimwade, D., Pallisgaard, N., et al. (2003). Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – a Europe against cancer program. Leukemia, 17, 2318–2357. doi: 10.1038/sj.leu.2403135.CrossRefGoogle Scholar
  23. 23.
    Beillard, E., Pallisgaard, N., van der Velden, V. H. J., Bi, W., Dee, R., van der Schoot, E., et al. (2003). Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program. Leukemia, 17, 2474–2486. doi: 10.1038/sj.leu.2403136.CrossRefGoogle Scholar
  24. 24.
    Zhang, X., Servos, M. R., Liu, J. (2012). Instantaneous and quantitative functionalization of gold nanoparticles with thiolated DNA using a pH-assisted and surfactant-free route. Journal of the American Chemical Society, 134, 7266–7269. doi: 10.1021/ja3014055.CrossRefGoogle Scholar
  25. 25.
    Jubb, A. M., & Allen, H. C. (2010). Vibrational spectroscopic characterization of hematite, maghemite, and magnetite thin films produced by vapor deposition. ACS Applaied Materials and Interfaces, 2, 2804–2812. doi: 10.1021/am1004943.CrossRefGoogle Scholar
  26. 26.
    Kouassi, G. K., & Irudayaraj, J. (2006). Magnetic and gold-coated magnetic nanoparticles as a DNA sensor. Analytical Chemistry, 78, 3234–3241. doi: 10.1021/ac051621j.CrossRefGoogle Scholar
  27. 27.
    Morasso, C., Mehn, D., Vanna, R., Bedoni, M., Forvi, E., Colombo, M., et al. (2014). One-step synthesis of star-like gold nanoparticles for surface enhanced Raman spectroscopy. Materials Chemistry and Physics, 143(3), 1215–1221.CrossRefGoogle Scholar
  28. 28.
    Gu, G. H., & Suh, J. S. (2010). Silver nanorods used to promote SERS as a quantitative analytical tool. Journal of Raman Spectroscopy, 41, 624–627. doi: 10.1002/jrs.2487.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Dora Mehn
    • 1
    Email author
  • Carlo Morasso
    • 1
  • Renzo Vanna
    • 1
  • Domitilla Schiumarini
    • 1
  • Marzia Bedoni
    • 1
  • Fabio Ciceri
    • 2
  • Furio Gramatica
    • 1
  1. 1.IRCCS Fondazione Don Carlo Gnocchi ONLUSMilanItaly
  2. 2.IRCCS Ospedale San RaffaeleMilanItaly

Personalised recommendations