Electrical Impedance Spectroscopy
The core technology behind Zilico’s products is electrical impedance spectroscopy (EIS). This is a measure of the impedance (resistivity) of cells across a range of frequencies producing a spectrum showing the change of impedance with frequency. These changes can be related to changes in the underlying nature of the biological tissue.
Biological tissues have electrical impedance, which is a function of frequency. The reason for this dependence is that tissues contain components with both resistive and charge storage (capacitive) properties, so giving rise to a complex electrical impedance. The magnitude of the impedance and the dependence of impedance on frequency are both a function of tissue composition.
CIN (cervical intraepithelial neoplasia) is associated with losses in the layer of flattened epithelial cells close to the surface of the cervix. Furthermore, the nuclear: cytoplasmic ratio and the extra-cellular space both increase, while the usual layered structure of cervical epithelium breaks down (see figure).
Because of these cytological changes, the tissue’s impedance spectra alter markedly as cervical epithelium cells transform into CIN. Cervical impedance spectrometry uses these changes to differentiate CIN from healthy epithelium. (Impedance measures the resistance to the flow of an alternating electrical current).
The Lancet published the pilot ‘proof of principle’ study in 2000. [i] Since then, an extensive and growing body of evidence suggests that electrical impedance spectrometry is easy to use, sensitive and specific, and offers real time results.
Other subsequent studies have been published in peer reviewed journals. See list below.
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Progression of epithelium from normal through CIN to invasive cervical cancer
The figure above shows how the regular arrangement of cells in normal cervical epithelium becomes increasingly disorganised as the tissue changes to finally become an invasive cancer. These changes start in the lower, basal cell layers in the early stages of disease (CIN 1) becoming more extensive until they encompass the entire thickness of the epithelium by the late stages (CIN 3). EIS is able to detect the early stages of disease even though they take place beneath the surface of the cervix.
Publications
[i] Brown BH, Tidy JA, Boston K et al Relation between tissue structure and imposed electrical current flow in cervical neoplasia Lancet 2000;355:892-
[ii] Abdul S, Brown BH, Milnes P, Tidy JA. The use of electrical impedance spectroscopy in the detection of cervical intraepithelial neoplasia Int J Gynecol Cancer 2006;16:1823–1832
[iii] Abdul S, Brown BH, Milnes P, Tidy JA A clinical study of the use of impedance spectroscopy in the detection of cervical intraepithelial neoplasia (CIN)Gynecologic Oncology Gynecologic Oncology 2005;99:S64-S66
[iv] Brown BH, Milnes P, Abdul S, Tidy JA Detection of cervical intraepithelial neoplasia using impedance spectroscopy: a prospective study BJOG 2005;112:802-6
[v] Balasubramani L, Brown BH, Healey J, Tidy JA. The detection of cervical intraepithelial neoplasia by electrical impedance spectroscopy: The effects of acetic acid and tissue homogeneity Gynecologic Oncologic 2009