Skip to main content

Advertisement

SpringerLink
Log in

Differentiation Between Normal and Cancerous Human Urothelial Cell Lines Using Micro-Electrical Impedance Spectroscopy at Multiple Frequencies

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

Abstract

The present study aims to investigate differences in impedance between normal (SV-HUC-1) and cancerous (TCCSUP) human urothelial cell lines at multiple frequencies by using a micro-electrical impedance spectroscopy (µEIS) device. A µEIS device was designed to measure the impedance of SV-HUC-1 and TCCSUP cells as the cells passed the sensing electrodes in the microfluidic channel. The cellular impedance was measured at frequencies of 10, 50, 100, 500 kHz, and 1 MHz, and the impedance values were compared at each frequency to investigate differences between the two cell lines. Additionally, the linear correlation between impedance and frequency was analyzed. The number of SV-HUC-1 and TCCSUP cells measured was 13 and 9, 21 and 10, 16 and 24, 8 and 8, and 11 and 22 cells at the frequencies of 10, 50, 100, 500 kHz, and 1 MHz, respectively. TCCSUP had significantly smaller amplitudes than SV-HUC-1 at 10, 50, and 100 kHz (p = 0.030, p = 0.031, and p < 0.001, respectively). Moreover, significant differences in phase angle were observed between cell lines at 100, 500 kHz, and 1 MHz (p < 0.001 in all). A significant difference between cell lines in terms of amplitude and phase angle was observed concurrently at 100 kHz. The amplitude of both the cell lines was negatively correlated to frequency, while the phase angle presented no correlation. In conclusion, the µEIS device could effectively differentiate between SV-HUC-1 and TCCSUP on the basis of their impedance.

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. Ferlay, J., Shin, H. R., Bray, F., Forman, D., Mathers, C., & Parkin, D. M. (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International Journal of Cancer, 127(12), 2893–2917.

    Article  Google Scholar 

  2. Babjuk, M., Oosterlinck, W., Sylvester, R., Kaasinen, E., Böhle, A., Palou-Redorta, J., et al. (2011). EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. European Urology, 59(6), 997–1008.

    Article  Google Scholar 

  3. Stenzl, A., Cowan, N. C., De Santis, M., Kuczyk, M. A., Merseburger, A. S., Ribal, M. J., et al. (2011). Treatment of muscle invasive and metastatic bladder cancer: Update of the EAU guidelines. European Urology, 59(6), 1009–1018.

    Article  Google Scholar 

  4. Kaufman, D. S., Shipley, W. U., & Feldman, A. S. (2009). Bladder cancer. Lancet, 374(9685), 2349–2392.

    Article  Google Scholar 

  5. van Rhijn, B. W., Burger, M., Lotan, Y., Solsona, E., Stief, C. G., Sylvester, R. J., et al. (2009). Recurrence and progression of disease in non-muscle-invasive bladder cancer: From epidemiology to treatment strategy. European Urology, 56(3), 430–442.

    Article  Google Scholar 

  6. van der Aa, M. N., Steyerberg, E. W., Sen, E. F., Zwarthoff, E. C., Kirkels, W. J., van der Kwast, T. H., et al. (2008). Patients’ perceived burden of cystoscopic and urinary surveillance of bladder cancer: A randomized comparison. BJU International, 101(9), 1106–1110.

    Article  Google Scholar 

  7. Carmack, A. J., & Soloway, M. S. (2006). The diagnosis and staging of bladder cancer: From RBCs to TURs. Urology, 67(3 Suppl 1), 3–8.

    Article  Google Scholar 

  8. Gutierrez Banos, J. L., Rebollo Rodrigo, M. H., Antolin Juarez, F. M., & Martín García, B. (2001). NMP 22, BTA stat test and cytology in the diagnosis of bladder cancer: A comparative study. Urologia Internationalis, 66(4), 185–190.

    Article  Google Scholar 

  9. Pfister, C., Chautard, D., Devonec, M., Perrin, P., Chopin, D., Rischmann, P., et al. (2003). Immunocyt test improves the diagnostic accuracy of urinary cytology: Results of a French multicenter study. The Journal of Urology, 169(3), 921–924.

    Article  Google Scholar 

  10. Grossman, H. B., Messing, E., Soloway, M., Tomera, K., Katz, G., Berger, Y., et al. (2005). Detection of bladder cancer using a point-of-care proteomic assay. The Journal of American Medical Association, 293(7), 810–816.

    Article  Google Scholar 

  11. Vrooman, O. P., & Witjes, J. A. (2008). Urinary markers in bladder cancer. European Urology, 53(5), 909–916.

    Article  Google Scholar 

  12. Hajdinjak, T. (2008). UroVysion FISH test for detecting urothelial cancers: Meta-analysis of diagnostic accuracy and comparison with urinary cytology testing. Urologic Oncology: Seminars and Original Investigations, 26(6), 646–651.

    Article  Google Scholar 

  13. Rigaud, B., Morucci, J. P., & Chauveau, N. (1996). Bioelectrical impedance techniques in medicine. Part I: Bioimpedance measurement. Second section: Impedance spectrometry. Critical Reviews in Biomedical Engineering, 24(4–6), 257–351.

    Article  Google Scholar 

  14. Morgan, H., Sun, T., Holmes, D., Gawad, S., & Green, N. G. (2007). Single cell dielectric spectroscopy. Journal of Physics D, 40(1), 61–70.

    Article  Google Scholar 

  15. Irwin, J. D., & Nelms, R. M. (2006). Basic engineering circuit analysis (8th ed.). Hoboken: Wiley.

    Google Scholar 

  16. Faes, T. J., van der Meij, H. A., de Munck, J. C., & Heethaar, R. M. (1999). The electric resistivity of human tissues (100 Hz–10 MHz): A meta-analysis of review studies. Physiological Measurement, 20(4), R1–R10.

    Article  Google Scholar 

  17. Gonzalez-Correa, C. A., Brown, B. H., Smallwood, R. H., Kalia, N., Stoddard, C. J., Stephenson, T. J., et al. (1999). Virtual biopsies in Barrett’s esophagus using an impedance probe. Annals of the New York Academy of Sciences, 873, 313–321.

    Article  Google Scholar 

  18. Han, A., Yang, L., & Frazier, A. B. (2007). Quantification of the heterogeneity in breast cancer cell lines using whole-cell impedance spectroscopy. Clinical Cancer Research, 13(1), 139–143.

    Article  Google Scholar 

  19. Kang, G., Yoo, S. K., Kim, H. I., & Lee, J. H. (2012). Differentiation between normal and cancerous cells at the single cell level using 3-D electrode electrical impedance spectroscopy. IEEE Sensors Journal, 12(5), 1084–1089.

    Article  Google Scholar 

  20. Kang, G., Kim, Y. J., Moon, H. S., Lee, J. W., Yoo, T. K., Park, K., et al. (2013). Discrimination between the human prostate normal cell and cancer cell by using a novel electrical impedance spectroscopy controlling the cross-sectional area of a microfluidic channel. Biomicrofluidics, 7(4), 044126.

    Article  Google Scholar 

  21. Chuang, C. H., Huang, Y. W., & Wu, Y. T. (2011). System-level biochip for impedance sensing and programmable manipulation of bladder cancer cells. Sensors, 11(11), 11021–11035.

    Article  Google Scholar 

  22. Huang, Y., Chen, N., Borninski, J., Rubinsky, B. (2003). A novel microfluidic cell-chip for single cell analysis and manipulation. Proceedings of the 16th IEEE International Conference on Microelectromechanical Systems; Kyoto, Japan. Retrieved December 20–23, 2003 from https://doi.org/10.1109/memsys.2003.1189771.

  23. Gawad, S., Cheung, K., Seger, U., Bertsch, A., & Renaud, P. (2004). Dielectric spectroscopy in a micromachined flow cytometer: Theoretical and practical considerations. Lab on a Chip, 4(3), 241–251.

    Article  Google Scholar 

  24. Poenar, D. P., Iliescu, C., Carp, M., Pang, A. J., & Leck, K. J. (2007). Glass-based microfluidic device fabricated by parylene wafer-to-wafer bonding for impedance spectroscopy. Sensors and Actuators A, 139(1–2), 162–171.

    Article  Google Scholar 

  25. Pethig, R. (1984). Dielectric properties of biological materials: Biophysical and medical applications. IEEE Transactions on Electrical Insulation, EI-19(5), 453–474.

    Article  Google Scholar 

  26. Gabriel, S., Lau, R. W., & Gabriel, C. (1996). The dielectric properties of biological tissues: II. Measurements in the frequency range 10 Hz to 20 GHz. Physics in Medicine & Biology, 41(11), 2251–2269.

    Article  Google Scholar 

  27. Qiao, G., Duan, W., Chatwin, C., Sinclair, A., & Wang, W. (2010). Electrical properties of breast cancer cells from impedance measurement of cell suspensions measurement of cell suspensions. Journal of Physics: Conference Series, 224(1), 1–4.

    Google Scholar 

  28. O’Connell, M. P., Tidy, J., Wisher, S. J., Avis, N. J., Brown, B. H., & Lindow, S. W. (2000). An in vivo comparative study of the pregnant and nonpregnant cervix using electrical impedance measurements. BJOG: An International Journal of Obstetrics & Gynaecology, 107(8), 1040–1041.

    Article  Google Scholar 

  29. Chen, J., Zheng, Y., Tan, Q., Zhang, Y. L., Li, J., Geddie, W. R., et al. (2011). A microfluidic device for simultaneous electrical and mechanical measurements on single cells. Biomicrofluidics, 5(1), 14113.

    Article  Google Scholar 

  30. Park, Y., Kim, H. W., Yun, J., Seo, S., Park, C. J., Lee, J. Z., et al. (2016). Microelectrical impedance spectroscopy for the differentiation between normal and cancerous human urothelial cell lines: Real-time electrical impedance measurement at an optimal frequency. BioMed Research International. https://doi.org/10.1155/2016/8748023.

    Article  Google Scholar 

  31. Sun, T., Bernabini, C., & Morgan, H. (2010). Single-colloidal particle impedance spectroscopy: Complete equivalent circuit analysis of polyelectrolyte microcapsules. Langmuir, 26(6), 3821–3828.

    Article  Google Scholar 

  32. Zhao, Y., Chen, D., Li, H., Luo, Y., Deng, B., Huang, S., et al. (2013). A microfluidic system enabling continuous characterization of specific membrane capacitance and cytoplasm conductivity of single cells in suspension. Biosensors & Bioelectronics, 43, 304–307.

    Article  Google Scholar 

  33. Zheng, Y., Shojaei-Baghini, E., Wang, C., & Sun, Y. (2013). Microfluidic characterization of specific membrane capacitance and cytoplasm conductivity of single cells. Biosensors & Bioelectronics, 42, 496–502.

    Article  Google Scholar 

  34. Hong, J., Lan, K., & Jang, L. (2012). Electrical characteristics analysis of various cancer cells using a microfluidic device based on single-cell impedance measurement. Sensors and Actuators B, 173, 927–934.

    Article  Google Scholar 

  35. Guo, X., Zhu, R., & Zong, X. (2015). A microchip integrating cell array positioning with in situ single-cell impedance measurement. The Analyst, 140(19), 6571–6578.

    Article  Google Scholar 

  36. Jang, L. S., & Wang, M. H. (2007). Microfluidic device for cell capture and impedance measurement. Biomedical Microdevices, 9(5), 737–743.

    Article  Google Scholar 

  37. Das, D., Kamil, F. A., Biswasa, K., & Dasa, S. (2014). Evaluation of single cell electrical parameters from bioimpedance of a cell suspension. RSC Advances, 4(35), 18178–18185.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the “Biomedical Integrated Technology Research” Project through a grant provided by Gwangju Institute of Science and Technology in 2016 and BioNano Health-Guard Research Center funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea as a Global Frontier Project (H-GUARD 2015M3A6B2063547).

Author information

Author notes

  1. Hyeon Woo Kim and Yangkyu Park have contributed equally to this work.

Authors and Affiliations

  1. Department of Urology, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan, 602-739, South Korea

    Hyeon Woo Kim, Jeong Zoo Lee & Dong Gil Shin

  2. School of Mechanical Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro, Buk-gu, Gwangju, 500-712, South Korea

    Yangkyu Park & Jong-Hyun Lee

  3. Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), MEMS and Nano Systems Lab. #317, Dansan Bldg., 123 Cheomdan-gwagiro, Buk-gu, Gwangju, 500-712, South Korea

    Joho Yun, Juhun Lim & Jong-Hyun Lee

Authors
  1. Hyeon Woo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yangkyu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joho Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juhun Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jeong Zoo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dong Gil Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jong-Hyun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dong Gil Shin or Jong-Hyun Lee.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, H.W., Park, Y., Yun, J. et al. Differentiation Between Normal and Cancerous Human Urothelial Cell Lines Using Micro-Electrical Impedance Spectroscopy at Multiple Frequencies. J. Med. Biol. Eng. 39, 86–95 (2019). https://doi.org/10.1007/s40846-018-0426-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40846-018-0426-6

Keywords

Search

Navigation