Analytical and Bioanalytical Chemistry

, Volume 401, Issue 8, pp 2455–2463

Cancer, pre-cancer and normal oral cells distinguished by dielectrophoresis

  • H. J. Mulhall
  • F. H. Labeed
  • B. Kazmi
  • D. E. Costea
  • M. P. Hughes
  • M. P. Lewis
Original Paper

Abstract

Most oral cancers are oral squamous cell carcinomas (OSCC) that arise from the epithelial lining of the oral mucosa. Given that the oral cavity is easily accessible, the disease lends itself to early detection; however, most oral cancers are diagnosed at a late stage, and approximately half of oral cancer sufferers do not survive beyond five years, post-diagnosis. The low survival rate has been attributed to late detection, but there is no accepted, reliable and convenient method for the detection of oral cancer and oral pre-cancer. Dielectrophoresis (DEP) is a label-free technique which can be used to obtain multi-parametric measurements of cell electrical properties. Parameters such as cytoplasmic conductivity and effective membrane capacitance (CEff) can be non-invasively determined by the technique. In this study, a novel lab-on-a-chip device was used to determine the cytoplasmic conductivity and CEff of primary normal oral keratinocytes, and pre-cancerous and cancerous oral keratinocyte cell lines. Our results show that the electrical properties of normal, pre-cancerous and cancerous oral keratinocytes are distinct. Furthermore, increasing CEff and decreasing cytoplasmic conductivity correlate with disease progression which could prove significant for diagnostic and prognostic applications. DEP has the potential to be used as a non-invasive technique to detect oral cancer and oral pre-cancer. Clinical investigation is needed to establish the reliability and temporal relationship of the correlation between oncologic disease progression and the electrical parameters identified in this study. To use this technique as an OSCC detection tool in a clinical setting, further characterisation and refinement is warranted.

Keywords

OSCC Oral cancer Dielectrophoresis DEP Diagnostics Detection 

Supplementary material

216_2011_5337_MOESM1_ESM.zip (10.1 mb)
Supplementary material, approximately 10.0 MB.

References

  1. 1.
    Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45(4–5):309–316CrossRefGoogle Scholar
  2. 2.
    Silverman S (2003) Oral cancer, 5th edn. B.C. Becker Inc., LondonGoogle Scholar
  3. 3.
    Horner MJ, Ries LAG, Krapcho M, Neyman N, Aminou R, Howlader N, Altekruse SF, Feuer EJ, Huang L, Mariotto A, Miller BA, Lewis DR, Eisner MP, Stinchcomb DG (eds) (2008) E.B., SEER Cancer Statistics Review, 1975–2006 National Cancer Institute, Bethesda, MDGoogle Scholar
  4. 4.
    Silverman SJ (2001) Demographics and occurrence of oral and pharyngeal cancers: the outcomes, the trends, the challenge. J Am Dent Assoc 132(suppl_1):7S–11SGoogle Scholar
  5. 5.
    Al-Dakkak I (2010) Diagnostic delay broadly associated with more advanced stage oral cancer. Evid Based Dent 11(1):24CrossRefGoogle Scholar
  6. 6.
    Bagan J, Sarrion G, Jimenez Y (2010) Oral cancer: clinical features. Oral Oncol 46(6):414–417CrossRefGoogle Scholar
  7. 7.
    Silverman S Jr (2007) Mucosal lesions in older adults. J Am Dent Assoc 138(suppl_1):41S–46SGoogle Scholar
  8. 8.
    Silverman S (1988) Early diagnosis of oral cancer. Cancer 62(S1):1796–1799CrossRefGoogle Scholar
  9. 9.
    Shafer WG, Waldron CA (1975) Erythroplakia of the oral cavity. Cancer 36:1021–1028CrossRefGoogle Scholar
  10. 10.
    Sandler HC (1962) Cytological screening for early mouth cancer. Interim report of the Veterans Administration Co-operative Study of Oral Exfoliative Cytology. Cancer 15(6):1119–1124CrossRefGoogle Scholar
  11. 11.
    Burzynski N, Firriolo F, Butters J, Sorrell C (1997) Evaluation of oral cancer screening. J Cancer Educ 12(2):95–99Google Scholar
  12. 12.
    Malaowalla AM, Silverman S, Mani NJ, Bilimoria KF, Smith LW (1976) Oral cancer in 57,518 industrial workers of Gujarat India. A prevalence and follow-up study. Cancer 37(4):1882–1886CrossRefGoogle Scholar
  13. 13.
    Bouquot JE (1986) Common oral lesions found during a mass screening examination. J Am Dent Assoc 112(1):50–57Google Scholar
  14. 14.
    Sciubba JJ, Collaborative Oral, C.S.G (1999) Improving detection of precancerous and cancerous oral lesions—computer-assisted analysis of the oral brush biopsy. J Am Dent Assoc 130(10):1445–1457Google Scholar
  15. 15.
    Christian DC (2002) Computer-assisted analysis of oral brush biopsies at an oral cancer screening program. J Am Dent Assoc 133(3):357–362Google Scholar
  16. 16.
    Burt JPH, Pethig R, Gascoyne PRC, Becker FF (1990) Dielectrophoretic characterisation of Friend murine erythroleukaemic cells as a measure of induced differentiation. Biochim Biophys Acta 1034(1):93–101CrossRefGoogle Scholar
  17. 17.
    Huang Y, Wang X-B, Becker FF, Gascoyne PRC (1996) Membrane changes associated with the temperature-sensitive P85gag-mos-dependent transformation of rat kidney cells as determined by dielectrophoresis and electrorotation. Biochim Biophys Acta (BBA)-Biomembranes 1282(1):76–84CrossRefGoogle Scholar
  18. 18.
    Gascoyne P, Pethig R, Satayavivad J, Becker FF, Ruchirawat M (1997) Dielectrophoretic detection of changes in erythrocyte membranes following malarial infection. Biochim Biophys Acta (BBA)-Biomembranes 1323(2):240–252CrossRefGoogle Scholar
  19. 19.
    Gascoyne PRC, Noshari J, Becker FF, Pethig R (1994) Use of dielectrophoretic collection spectra for characterizing differences between normal and cancerous cells. Industry Applications, IEEE Transactions on 30(4):829–834CrossRefGoogle Scholar
  20. 20.
    An J, Lee J, Lee S, Park J, Kim B (2009) Separation of malignant human breast cancer epithelial cells from healthy epithelial cells using an advanced dielectrophoresis-activated cell sorter (DACS). Anal Bioanal Chem 394(3):801–809CrossRefGoogle Scholar
  21. 21.
    Broche LM, Bhadal N, Lewis MP, Porter S, Hughes MP, Labeed FH (2007) Early detection of oral cancer—is dielectrophoresis the answer? Oral Oncol 43(2):199–203CrossRefGoogle Scholar
  22. 22.
    Yang L, Arias L, Lane T, Yancey M, Mamouni J (2011) Real-time electrical impedance-based measurement to distinguish oral cancer cells and non-cancer oral epithelial cells. Anal Bioanal Chem 399(5):1823–1833CrossRefGoogle Scholar
  23. 23.
    Broche LM, Hoettges KF, Ogin SL, Kass GEN, Hughes MP (2011) Rapid, automated measurement of dielectrophoresis forces using DEP-activated microwells. Electrophoresis (in press)Google Scholar
  24. 24.
    Pohl HA (1978) Dielectrophoresis the behavior of neutral matter in nonuniform electric fields. Cambridge University Press, Cambridge, NYGoogle Scholar
  25. 25.
    Huang Y, Holzel R, Pethig R, Wang X-B (1992) Differences in the AC electrodynamics of viable and non-viable yeast cells determined through combined dielectrophoresis and electrorotation studies. Phys Med Biol 37(7):1499–1517CrossRefGoogle Scholar
  26. 26.
    Irimajiri A, Hanai T, Inouye A (1979) Dielectric theory of multi-stratified shell-model with its application to a lymphoma cell. J Theor Biol 78(2):251–269CrossRefGoogle Scholar
  27. 27.
    Hoettges KF, Hubner Y, Broche LM, Ogin SL, Kass GEN, Hughes MP (2008) Dielectrophoresis-activated multiwell plate for label-free high-throughput drug assessment. Am Chem Soc 80(6):2063–2068Google Scholar
  28. 28.
    Hubner Y, Hoettges KF, Kass GEN, Ogin SL, Hughes MP (2005) Parallel measurements of drug actions on erythrocytes by dielectrophoresis, using a three-dimensional electrode design. Nanobiotechnol IEE Proc 152(4):150–154CrossRefGoogle Scholar
  29. 29.
    Pethig R, Jakubek LM, Sanger RH, Heart E, Corson ED, Smith PJS (2005) Electrokinetic measurements of membrane capacitance and conductance for pancreatic beta-cells. IEE Proc Nanobiotechnol 152(6):189–193CrossRefGoogle Scholar
  30. 30.
    Gascoyne PRC, Pethig R, Burt JPH, Becker FF (1993) Membrane changes accompanying the induced differentiation of friend murine erythroleukemia cells studied by dielectrophoresis. Biochim Biophys Acta (BBA)-Biomembranes 1149(1):119–126CrossRefGoogle Scholar
  31. 31.
    Broche LM, Labeed FH, Hughes MP (2005) Extraction of dielectric properties of multiple populations from dielectrophoretic collection spectrum data. Phys Med Biol 50(10):2267–2274CrossRefGoogle Scholar
  32. 32.
    Morgan H, Green NG (2003) AC electrokinetics: colloids and nanoparticles, 1st edn. Research Studies, WillistonGoogle Scholar
  33. 33.
    Pethig R, Kell DB (1987) The passive electrical properties of biological systems—their significance in physiology, biophysics and biotechnology. Phys Med Biol 32(8):933–970CrossRefGoogle Scholar
  34. 34.
    Wang X-B, Huang Y, Gascoyne PRC, Becker FF, Hölzel R, Pethig R (1994) Changes in fiend murine erythroleukaemia cell membranes during induced differentiation determined by electrorotation. Biochim Biophys Acta (BBA)-Biomembranes 1193(2):330–344CrossRefGoogle Scholar
  35. 35.
    Ratanachoo K, Gascoyne PRC, Ruchirawat M (2002) Detection of cellular responses to toxicants by dielectrophoresis. Biochim Biophys Acta (BBA)-Biomembranes 1564(2):449–458CrossRefGoogle Scholar
  36. 36.
    Labeed FH, Coley HM, Hughes MP (2006) Differences in the biophysical properties of membrane and cytoplasm of apoptotic cells revealed using dielectrophoresis. Biochim Biophys Acta 1760(6):922–929CrossRefGoogle Scholar
  37. 37.
    Partin AW, Isaacs JT, Treiger B, Coffey DS (1988) Early cell motility changes associated with an increase in metastatic ability in rat prostatic cancer cells transfected with the v-Harvey-ras oncogene. Cancer Res 48(21):6050–6053Google Scholar
  38. 38.
    Nicolas AFVL, Marc EB, Marc MM (1992) Invasive epithelial cells show more fast plasma membrane movements than related or parental non-invasive cells. Cytometry 13(1):9–14CrossRefGoogle Scholar
  39. 39.
    Jiang WG (1995) Focus on science—membrane ruffling of cancer cells: a parameter of tumour cell motility and invasion. Eur J Surg Oncol 21(3):307–309CrossRefGoogle Scholar
  40. 40.
    Becker FF, Wang XB, Huang Y, Pethig R, Vykoukal J, Gascoyne PRC (1994) The removal of human leukaemia cells from blood using interdigitated microelectrodes. Journal of Physics D: Applied Physics 27(12):2659–2662CrossRefGoogle Scholar
  41. 41.
    Becker FF, Wang X, Huang Y, Pethig R, Vykoukal J, Gascoyne PRC (1995) Separation of human breast cancer cells from blood by differential dielectric affinity. Proc Natl Acad Sci U S A 92:860–864CrossRefGoogle Scholar
  42. 42.
    Bhoopathi V, Kabani S, Mascarenhas AK (2009) Low positive predictive value of the oral brush biopsy in detecting dysplastic oral lesions. Cancer 115(5):1036–1040CrossRefGoogle Scholar
  43. 43.
    Epstein JB, Silverman S Jr, Epstein JD, Lonky SA, Bride MA (2008) Analysis of oral lesion biopsies identified and evaluated by visual examination, chemiluminescence and toluidine blue. Oral Oncol 44(6):538–544CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • H. J. Mulhall
    • 1
  • F. H. Labeed
    • 1
  • B. Kazmi
    • 2
  • D. E. Costea
    • 4
  • M. P. Hughes
    • 1
  • M. P. Lewis
    • 2
    • 3
  1. 1.Faculty of Engineering and Physical SciencesUniversity of SurreySurreyUK
  2. 2.UCL Eastman Dental InstituteLondonUK
  3. 3.Muscle Cellular and Molecular Physiology Research Group, ISPARUniversity of BedfordshireBedfordUK
  4. 4.Department of Pathology, The Gade InstituteUniversity of Bergen, Haukeland HospitalBergenNorway

Personalised recommendations