Assay based on electrical impedance spectroscopy to discriminate between normal and cancerous mammalian cells

Abstract

In this work we present an assay to discriminate between normal and cancerous cells. The method is based on the measurement of electrical impedance spectra of in vitro cell cultures. We developed a protocol consisting on four consecutive measurement phases, each of them designed to obtain different information about the cell cultures. Through the analysis of the measured data, 26 characteristic features were obtained for both cell types. From the complete set of features, we selected the most relevant in terms of their discriminant capacity by means of conventional statistical tests. A linear discriminant analysis was then carried out on the selected features, allowing the classification of the samples in normal or cancerous with 4.5% of false positives and no false negatives.

Design and testing of a microelectrode array with spatial resolution for detection of cancerous cells in mixed cultures

“…(i) Growth phase: the cells attach and spread over the entire culture surface, including the microelectrodes, and the system's impedance increases. In this phase, impedance was registered as a function of time at two different frequencies, namely 4775 Hz and 100 kHz, which were selected according to the sensitivity of the measurement [13]. Based on prior results, we designed this measurement to have a duration of 15 h in order to capture the whole dynamics of the process.…”

“…(iii) Wounding phase: during this phase, the confluent cell monolayer is deliberately damaged to carry out a wounding assay. A specific technique aimed to obtain information about the wounding dynamics has been recently developed [20] and used to discriminate between normal and cancerous cells [13]. We used a similar A c c e p t e d M a n u s c r i p t technique in this work, with some variations.…”

“…Following the method presented in a previous work [13], from the data obtained through the measurement protocol described in Section 2.2 we extracted characteristic features related to the specific behavior of both cell types. Each sample was associated with a vector x, whose coordinates represent the values of each feature in a multidimensional space, and training sets were formed with values of x for each population.…”

“…The features marked with the + sign are considered relevant in the proposed discrimination model. They were selected by means of the F, t and Kolmogorov-Smirnov tests as described in a previous work [13]. G: growth phase.…”

Electrical Impedance Spectroscopy for Monitoring Chemoresistance of Cancer Cells

“…EIS relies on cell polarization generated by an electric field and the interaction of ions along the cell surface [ 13 ]. Impedance-based biosensors have been used to distinguish many types of human and mouse cancer cells based on their dielectric properties (impedance and capacitance) [ 14 , 15 , 16 , 17 ]. EIS is advantageous because it enables real time measurements of cell dynamics.…”