Skip to main content

Advertisement

SpringerLink
Log in

Fabrication and Characterization of an Aptamer-Based N-type Silicon Nanowire FET Biosensor for VEGF Detection

  • Original Article
  • Published:
Journal of Medical and Biological Engineering Aims and scope Submit manuscript

Abstract

Purpose

Cancer detection is an important part of modern medical diagnosis and many strategies based on nanotechnology had been developed in recent years. Of which, silicon nanowire (SiNW) field-effect transistor (FET) biosensor via DNA aptamer capture is considered as an interesting and viable option. Hence, in this report, we had assembled a n-type triple SiNW FET biosensor for the detection of vascular endothelial growth factor (VEGF) via surface functionalized DNA aptamer for a proof-of-concept.

Method

The SiNW FET biosensor was fabricated via "top-down" approach and the physical nature of the nanowire assembly was examined via atomic force microscopy (AFM) as well as scanning electron microscopy (SEM). We had subsequently grafted VEGF specific DNA aptamer via conventional EDC/NHS chemistry and later measured the conductance of the nanowires in a four-point probe detector for VEGF detection.

Result

We had demonstrated that the detection of VEGF was possible even at a concentration of 2.59 nM which was highly comparable to the other common biosensors for detection of VEGF protein.

Conclusion

In addition to being scalable with complementary metal–oxide–semiconductor (CMOS) technology, the findings as demonstrated from our simple SiNW FET biosensor setup had helped to provide better insights towards optimizing the approach for the development of the next generation of miniature biosensors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Anand, S., Singh, A., Amin, S. I., & Thool, A. S. (2019). Design and performance analysis of dielectrically modulated doping-less tunnel FET-based label free biosensor. IEEE Sensors Journal, 19(12), 4369–4374.

    Google Scholar 

  2. Lin, C. H., Hung, C. H., Hsiao, C. Y., Lin, H. C., Ko, F. H., & Yang, Y. S. (2009). Poly-silicon nanowire field-effect transistor for ultrasensitive and label-free detection of pathogenic avian influenza DNA. Biosensors and Bioelectronics, 24(10), 3019–3024.

    Google Scholar 

  3. Tian, M., Xu, S.C., Zhang, J.Y., Wang, X.X., Li, Z. H., Liu, H. L., et al. (2018). RNA Detection based on graphene field-effect transistor biosensor. Advances in Condensed Matter Physics, 2018, 8146765.

    Google Scholar 

  4. Majd, S. M., Salimi, A., & Ghasemi, F. (2018). An ultrasensitive detection of miRNA-155 in breast cancer via direct hybridization assay using two-dimensional molybdenum disulfide field-effect transistor biosensor. Biosensors and Bioelectronics, 105, 6–13.

    Google Scholar 

  5. Rahong, S., Yasui, T., Kaji, N., & Baba, Y. (2016). Recent developments in nanowires for bio-applications from molecular to cellular levels. Lab on a Chip, 16(7), 1126–1138.

    Google Scholar 

  6. Puppo, F., Doucey, M. A., Delaloye, J. F., Moh, T., Pandraud, G., Sarro, P. M., et al. (2016). SiNW-FET in-air biosensors for high sensitive and specific detection in breast tumor extract. IEEE Sensors Journal, 16(10), 3374–3381.

    Google Scholar 

  7. Lin, Y. R., Tsai, W. T., Wu, Y. C., & Lin, Y. H. (2017). Ultra thin poly-Si nanosheet junctionless field-effect transistor with nickel silicide contact. Materials, 10(11), 1276.

    Google Scholar 

  8. Vieira, N. C. S., Figueiredo, A., Faceto, A. D., de Queiroz, A. A. A., Zucolotto, V., & Guimaraes, F. E. G. (2012). Dendrimers/TiO2 nanoparticles layer-by-layer films as extended gate FET for pH detection. Sensors and Actuators B-Chemical, 169, 397–400.

    Google Scholar 

  9. Lin, Y. H., Lin, W. S., Wong, J. C., Hsu, W. C., Peng, Y. S., & Chen, C. L. (2017). Bottom-up assembly of silicon nanowire conductometric sensors for the detection of apolipoprotein A1, a biomarker for bladder cancer. Microchimica Acta, 184(7), 2419–2428.

    Google Scholar 

  10. Gao, A. R., Lu, N., Dai, P. F., Li, T., Pei, H., Gao, X. L., et al. (2011). Silicon-nanowire-based CMOS-compatible field-effect transistor nanosensors for ultrasensitive electrical detection of nucleic acids. Nano Letters, 11(9), 3974–3978.

    Google Scholar 

  11. Cui, Y., Wei, Q., Park, H., & Lieber, C. M. (2001). Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science, 293(5533), 1289–1292.

    Google Scholar 

  12. Syedmoradi, L., Ahmadi, A., Norton, M. L., & Omidfar, K. (2019). A review on nanomaterial-based field effect transistor technology for biomarker detection. Microchimica Acta, 186(11), 739.

    Google Scholar 

  13. Cui, Y., & Lieber, C. M. (2001). Functional nanoscale electronic devices assembled using silicon nanowire building blocks. Science, 291(5505), 851–853.

    Google Scholar 

  14. Gao, A. R., Chen, S. X., Wang, Y. L., & Li, T. (2018). Silicon nanowire field-effect-transistor-based biosensor for biomedical applications. Sensors and Materials, 30(8), 1619–1628.

    Google Scholar 

  15. 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(4), 1711–1724.

    Google Scholar 

  16. Lin, C. H., Chu, C. J., Teng, K. N., Su, Y., Jr., Chen, C. D., Tsai, L. C., et al. (2012). Recovery based nanowire field-effect transistor detection of pathogenic avian influenza DNA. Japanese Journal of Applied Physics, 51(2), 02BL02.

    Google Scholar 

  17. Yang, F., & Zhang, G.-J. (2014). Silicon nanowire-transistor biosensor for study of molecule-molecule interactions. Reviews in Analytical Chemistry, 33(2), 95–110.

    Google Scholar 

  18. Zhou, F., Li, Z. Y., Bao, Z. T., Feng, K., Zhang, Y., & Wang, T. (2015). Highly sensitive, label-free and real-time detection of alpha-fetoprotein using a silicon nanowire biosensor. Scandinavian Journal of Clinical and Laboratory Investigation, 75(7), 578–584.

    Google Scholar 

  19. Yang, C. Y., Chiang, H. C., Kuo, C. J., Hsu, C. W., Chan, S. F., Lin, Z. Y., et al. (2018). Hepatocellular carcinoma diagnosis by detecting alpha-fucosidase with a silicon nanowire field-effect transistor biosensor. ECS Journal of Solid State Science and Technology, 7(7), Q3153–Q3158.

    Google Scholar 

  20. Hobbs, R. G., Petkov, N., & Holmes, J. D. (2012). Semiconductor nanowire fabrication by bottom-up and top-down paradigms. Chemistry of Materials, 24(11), 1975–1991.

    Google Scholar 

  21. Zhang, A., & Lieber, C. M. (2016). Nano-bioelectronics. Chemical Reviews, 116(1), 215–257.

    Google Scholar 

  22. Kakeji, Y., Koga, T., Sumiyoshi, Y., Shibahara, K., Oda, S., Maehara, Y., et al. (2002). Clinical significance of vascular endothelial growth factor expression in gastric cancer. Journal of Experimental and Clinical Cancer Research, 21(1), 125–129.

    Google Scholar 

  23. Gasparini, G. (2000). Prognostic value of vascular endothelial growth factor in breast cancer. The Oncologist, 5(S1), 37–44.

    Google Scholar 

  24. Holmes, D. I. R., & Zachary, I. (2005). The vascular endothelial growth factor (VEGF) family: Angiogenic factors in health and disease. Genome Biology, 6(2), 209.

    Google Scholar 

  25. Kluger, H. M., Siddiqui, S. F., Angeletti, C., Sznol, M., Kelly, W. K., Molinaro, A. M., et al. (2008). Classification of renal cell carcinoma based on expression of VEGF and VEGF receptors in both tumor cells and endothelial cells. Laboratory Investigation, 88(9), 962–972.

    Google Scholar 

  26. Yukata, K., Matsui, Y., Goto, T., Kubo, T., & Yasui, N. (2005). Differential expression of VEGF isoforms and VEGF receptors in cartilaginous tumors. Anticancer Research, 25(2A), 955–957.

    Google Scholar 

  27. Teke, M., Sayikli, C., Canbaz, C., & Sezginturk, M. K. (2014). A novel biosensing system using biological receptor for analysis of vascular endothelial growth factor. International Journal of Peptide Research and Therapeutics, 20(2), 221–230.

    Google Scholar 

  28. Li, J., Sun, K., Chen, Z., Shi, J., Zhou, D., & Xie, G. (2016). A fluorescence biosensor for VEGF detection based on DNA assembly structure switching and isothermal amplification. Biosensors and Bioelectronics, 89, 964–969.

    Google Scholar 

  29. Pan, L. H., Kuo, S. H., Lin, T. Y., Lin, C. W., Fang, P. Y., & Yang, H. W. (2017). An electrochemical biosensor to simultaneously detect VEGF and PSA for early prostate cancer diagnosis based on graphene oxide/ssDNA/PLLA nanoparticles. Biosensors and Bioelectronics, 89, 598–605.

    Google Scholar 

  30. Lin, C. W., Wei, K. C., Liao, S. S., Huang, C. Y., Sun, C. L., Wu, P. J., et al. (2015). A reusable magnetic graphene oxide-modified biosensor for vascular endothelial growth factor detection in cancer diagnosis. Biosensensors and Bioelectronics, 67, 431–437.

    Google Scholar 

  31. Ni, S., Shen, Z., Zhang, P., & Liu, G. (2020). Enhanced performance of an electrochemical aptasensor for real-time detection of vascular endothelial growth factor (VEGF) by nanofabrication and ratiometric measurement. Analytica Chimica Acta, 1121, 74.

    Google Scholar 

  32. Ambhorkar, P., Wang, D. Z., Ko, H., Lee, S., Koo, K. I., Kim, K., et al. (2018). Nanowire-based biosensors: From growth to applications. Micromachines, 9, 679.

    Google Scholar 

  33. Lengauer, W., Binder, S., Aigner, K., Ettmayer, P., Guillou, A., Debuigne, J., et al. (1995). Solid-state properties of group IVB carbonitrides. Journal of Alloys and Compounds, 217, 137–147.

    Google Scholar 

  34. Khung, Y. L., Graney, S. D., & Voelcker, N. H. (2006). Micropatterning of porous silicon films by direct laser writing. Biotechnology Progress, 22(5), 1388–1393.

    Google Scholar 

  35. Kaur, H., & Yung, L. Y. L. (2012). Probing high affinity sequences of DNA aptamer against VEGF165. PLoS ONE, 7(2), e31196.

    Google Scholar 

  36. Khung, Y. L., & Narducci, D. (2013). Synergizing nucleic acid aptamers with 1-dimensional nanostructures as label-free field-effect transistor biosensors. Biosensors and Bioelectronics, 50, 278–293.

    Google Scholar 

  37. Elfstrom, N., Juhasz, R., Sychugov, I., Engfeldt, T., Karlstrom, A. E., & Linnros, J. (2007). Surface charge sensitivity of silicon nanowires: Size dependence. Nano Letters, 7(9), 2608–2612.

    Google Scholar 

  38. Lee, H. S., Kim, K. S., Kim, C. J., Hahn, S. K., & Jo, M. H. (2009). Electrical detection of VEGFs for cancer diagnoses using anti-vascular endotherial growth factor aptamer-modified Si nanowire FETs. Biosensors and Bioelectronics, 24(6), 1801–1805.

    Google Scholar 

  39. Houck, K. A., Leung, D. W., Rowland, A. M., Winer, J., & Ferrara, N. (1992). Dual regulation of vascular enfothelial growth factor bioavailability by genetic and proteolytic mechanisms. Journal of Biological Chemistry, 267(36), 26031–26037.

    Google Scholar 

  40. Mita, C., Abe, K., Fukaya, T., & Ikebukuro, K. (2014). Vascular endothelial growth factor (VEGF) detection using an aptamer and PNA-based bound/free separation system. Materials, 7(2), 1046–1054.

    Google Scholar 

  41. Lv, Z., Wang, K., & Zhang, X. (2014). A new electrochemical aptasensor for the analysis of the vascular endothelial growth factor. Journal of Immunoassay and Immunochemistry, 35(3), 233–240.

    Google Scholar 

  42. Stern, E., Wagner, R., Sigworth, F. J., Breaker, R., Fahmy, T. M., & Reed, M. A. (2007). Importance of the debye screening length on nanowire field effect transistor sensors. Nano Letters, 7(11), 3405–3409.

    Google Scholar 

  43. Kim, K. M., Kim, H. M., Lee, W. J., Lee, C. W., Kim, T. I., Lee, J. K., et al. (2014). Surface treatment of silica nanoparticles for stable and charge-controlled colloidal silica. International Journal of Nanomedicine, 9, 29–40.

    Google Scholar 

  44. Liu, Y. L., Da, H. M., Chai, Y. Q., Yuan, R., & Liu, H. Y. (2019). Photoelectrochemical aptamer-based sensing of the vascular endothelial growth factor by adjusting the light harvesting efficiency of g-C3N4 via porous carbon spheres. Microchimica Acta, 186(5), 275.

    Google Scholar 

  45. Gao, A. R., Yang, X., Tong, J., Zhou, L., Wang, Y. L., Zhao, J. L., et al. (2017). Multiplexed detection of lung cancer biomarkers in patients serum with CMOS-compatible silicon nanowire arrays. Biosensors and Bioelectronics, 91, 482–488.

    Google Scholar 

Download references

Acknowledgements

The authors would to express their gratitude to the NARLabs for their assistance in the fabrication of the nanodevices.

Funding

The work was carried out with funding under Ministry of Science and Technology in Taiwan (MOST 108-2221-E-035-032, MOST 107-2113-M-039-002-MY2, 106-2221-E-039-005-MY2 and 109-2221-E-039-013-MY2).

Author information

Authors and Affiliations

  1. Ph.D. Program of Electrical and Communications Engineering, Feng Chia University, No. 100 Wenhwa Road, Seatwen, 40724, Taichung, Taiwan

    Serge Ismael Zida & Yue-Der Lin

  2. Master’s Program of Biomedical Informatics and Biomedical Engineering, Feng Chia University, No. 100 Wenhwa Road, Seatwen, 40724, Taichung, Taiwan

    Chu-Chun Yang & Yue-Der Lin

  3. Department of Biological Science and Technology, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan

    Yit Lung Khung

  4. Department of Automatic Control Engineering, Feng Chia University, No. 100 Wenhwa Road. Seatwen, 40724, Taichung, Taiwan

    Yue-Der Lin

Authors
  1. Serge Ismael Zida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chu-Chun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yit Lung Khung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yue-Der Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CCY had performed the surface modifications as well as the detection studies, while SIZ had characterized the surface via AFM and SEM and had written half of the manuscript. YDL had provided all the funding for surface detection studies as well as examining the data while YLK had conceived the project and had written a large fraction of the manuscript.

Corresponding authors

Correspondence to Yit Lung Khung or Yue-Der Lin.

Ethics declarations

Conflicts of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zida, S.I., Yang, CC., Khung, Y.L. et al. Fabrication and Characterization of an Aptamer-Based N-type Silicon Nanowire FET Biosensor for VEGF Detection. J. Med. Biol. Eng. 40, 601–609 (2020). https://doi.org/10.1007/s40846-020-00552-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40846-020-00552-5

Keywords

Search

Navigation