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BioNanoScience

, Volume 5, Issue 4, pp 189–195 | Cite as

Memristive Biosensors for PSA-IgM Detection

  • I. Tzouvadaki
  • C. Parrozzani
  • A. Gallotta
  • G. De Micheli
  • S. Carrara
Article

Abstract

Prostate cancer is the most common cancer among men except for skin cancer, and the detection at early stages is crucial. In the present work, nanofabricated memristive biosensors are subjected to surface bio-modification targeting at prostate-specific antigen (PSA) IgM detection. The electrical response of the nanofabricated devices examined before and after the bio-modification achieves a label-free detection for three biomarker concentrations. The presence of biomolecules linked to the surface of the nanostructures is detected by a voltage gap appearing in the memristive electrical characteristics. Enzyme-linked immunosorbent assay methodology is further applied to verify the efficiency of the application of diverse biomarker concentrations on the surface. Scanning electron microscopy shows details on the morphology of the nanofabricated structures before and after the bio-modification, and confocal microscopy is implemented to obtain a 3D fluorescent signal distribution of the biomolecules. The system shows the potential for applications in molecular diagnostics and for implementation targeting at the early detection of the prostate cancer disease.

Keywords

Silicon nanowire arrays Memristive behavior Biosensor ELISA PSA-IgM 

Notes

Acknowledgments

The authors gratefully acknowledge the staff of the Cmi Clean Room of EPFL for assisting with technical advice and M. Zervas for the fruitful discussions regarding the fabrication process and G. Knott for the SEM imaging with ZEISS Gemini500.

References

  1. 1.
    Lacroix-Desmazes, S., Kaveri, S. V., Mouthon, L., Ayouba, A., Malanchere, E., Coutinho, A., et al. (1998). Self-reactive antibodies (natural autoantibodies) in healthy individuals. Journal of Immunological Methods, 216, 117–137.CrossRefGoogle Scholar
  2. 2.
    Varambally, S., Bar-Dayan, Y., Bayry, J., Lacroix-Desmazes, S., Horn, M., Sorel, M., et al. (2004). Natural human polyreactive IgM induce apoptosis of lymphoid cell lines and human peripheral blood mononuclear cells. International Immunology, 16, 517–524.CrossRefGoogle Scholar
  3. 3.
    Pontisso, P., Calabrese, F., Benvegnu, L., Lise, M., Belluco, C., Ruvoletto, M. G., et al. (2004). Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma. British Journal of Cancer, 90, 833–837.CrossRefGoogle Scholar
  4. 4.
    Beneduce, L., Castaldi, F., Marino, M., Tono, N., Gatta, A., Pontisso, P., et al. (2004). Improvement of liver cancer detection with simultaneous assessment of circulating levels of free alpha-fetoprotein (AFP) and AFP-IgM complexes. The International Journal of Biological Markers, 19, 155–159.Google Scholar
  5. 5.
    Beneduce, L., Castaldi, F., Marino, M., Quarta, S., Ruvoletto, M., Benvegnu, L., et al. (2005). Squamous cell carcinoma antigen IgM complexes as novel biomarkers for hepatocellular carcinoma. Cancer, 103, 2558–2565.CrossRefGoogle Scholar
  6. 6.
    Pontisso, P., Quarta, S., Caberlotto, C., Beneduce, L., Marino, M., Bernardinello, E., et al. (2006). Progressive increase of SCCAIgM immune complexes in cirrhotic patients is associated with development of hepatocellular carcinoma. International Journal of Cancer, 119, 735–740.CrossRefGoogle Scholar
  7. 7.
    Castaldi, F., Marino, M., Beneduce, L., Belluco, C., De Marchi, F., Mammano, E., et al. (2005). Detection of circulating CEAIgM complexes in early stage (stage 1) colorectal cancer. The International Journal of Biological Markers, 20, 204–208.Google Scholar
  8. 8.
    Goc, S., & Jankovic, M. (2013). Evaluation of molecular species of prostate-specific antigen complexed with immunoglobulin M in prostate cancer and benign prostatic hyperplasia. Disease Markers, 35(6), 847–855.CrossRefGoogle Scholar
  9. 9.
    Beneduce, L., Prayer-Galetti, T., Giustinian, A. M., Gallotta, A., Betto, G., Pagano, F., et al. (2007). Detection of prostate-specific antigen coupled to immunoglobulin M in prostate cancer patients. Cancer Detection and Prevention, 31(5), 402–7.CrossRefGoogle Scholar
  10. 10.
    Strukov, D., Snider, G., Stewart, D., Williams, S. (2008). The missing memristor found. Nature, 453, 80–83.CrossRefGoogle Scholar
  11. 11.
    Chua, L. (1971). Memristor—the missing circuit element. IEEE Transactions on Circuit Theory, 18(5), 507–519.CrossRefGoogle Scholar
  12. 12.
    Wua, J., & Mc Creery, R. (2009). Solid-state electrochemistry in molecule/TiO2 molecular heterojunctions as the basis of the TiO2 memristor. Journal of the Electrochemical Society, 156(1), 29–37.CrossRefGoogle Scholar
  13. 13.
    Rose, G., Rajendran, J., Manem, H., Karri, R., Pino, R. (2012). Leveraging memristive systems in the construction of digital logic circuits. Proceedings of the IEEE, 100(6), 2033–2049.CrossRefGoogle Scholar
  14. 14.
    Pershin, Y., & Di Ventra, M. (2010). Experimental demonstration of associative memory with memristive neural networks. Neural Networks, 23(7), 881–886.CrossRefGoogle Scholar
  15. 15.
    Indiveri, G., Linares-Barranco, B., Legenstein, R., Deligeorgis, G., Prodromakis, T. (2013). Integration of nanoscale memristor synapses in neuromorphic computing architectures. Nanotechnology, 24, 384010.CrossRefGoogle Scholar
  16. 16.
    Gelencser, A., Prodromakis, T., Toumazou, C., Roska, T. (2012). Biomimetic model of the outer plexiform layer by incorporating memristive devices. Physical Review E, 85, 041918.CrossRefGoogle Scholar
  17. 17.
    Sacchetto, D., Gaillardon, P. E., Zervas, M., Carrara, S., De Micheli, G., Leblebici, Y. (2013). Applications of multi-terminal memristive devices: a review. IEEE Circuits and Systems, 13(2), 23–41.CrossRefGoogle Scholar
  18. 18.
    Gaillardon, P. E., Sacchetto, D., Bobba, S., Leblebici, Y. (2012). GMS: generic memristive structure for non-volatile FPGAs. Santa Cruz: IFIP/IEEE International Conference on Very Large Scale Integration (VLSI-SoC).Google Scholar
  19. 19.
    Sacchetto, D., Doucey, M. A., De Micheli, G., Leblebici, Y., Carrara, S. (2011). New insight on biosensing by nano-fabricated memristors. BioNanoScience, 1, 1–3.CrossRefGoogle Scholar
  20. 20.
    Carrara, S., Sacchetto, D., Doucey, M. A., Baj-Rossi, C., De Micheli, G., Leblebici, Y. (2012). Applications of multi-terminal memristive devices: a review. Sensors Actuators B: Chemical, 171–172, 449–457.CrossRefGoogle Scholar
  21. 21.
    Patolsky, F., Zheng, G., Lieber, C. M. (2006). Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species. Nature Protocols, 1, 1711–1724.CrossRefGoogle Scholar
  22. 22.
    Zhou, X. T., Hu, J. Q., Li, C. P., Ma, D. D. D., Lee, S. T. (2003). Silicon nanowires as chemical sensors. Chemical Physics Letters, 369, 220–224.CrossRefGoogle Scholar
  23. 23.
    Janata, J., & Josowicz, M. (2003). Conducting polymers in electronic chemical sensors. Nature Materials, 2, 19–24.CrossRefGoogle Scholar
  24. 24.
    Zheng, G., Patolsky, F., Cuil, Y., Wang, W., Lieber, C. (2005). Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nature Biotechnology, 23(3), 12941301.Google Scholar
  25. 25.
    Stern, E., Vacic, A., Mark, A. R. (2008). Semiconducting nanowire field effect transistor biomolecular sensors IEEE trans. Electronic Devices, 55(11), 31193130.CrossRefGoogle Scholar
  26. 26.
    Puppo, F., Dave, A., Doucey, M. A., Sacchetto, D., Baj-Rossi, C., Leblebici, Y., et al. (2014). Memristive biosensors under varying humidity conditions. IEEE Transactions on NanoBioscience, 13(1), 19–30.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • I. Tzouvadaki
    • 1
  • C. Parrozzani
    • 2
  • A. Gallotta
    • 2
  • G. De Micheli
    • 1
  • S. Carrara
    • 1
  1. 1.Integrated System LaboratoryEPFLLausanneSwitzerland
  2. 2.Xeptagen SpaVeniceItaly

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