Sensitivity analysis of electrical bioimpedance patterns of breast cancer cells labeled with magnetic nanoparticles: forming the foundation for a biosensor of circulating tumor cells

Objective: To determine the sensitivity of electrical impedance spectroscopy (EIS) measurements for the detection of a small concentration of breast cancer cells in suspension, previously labeled with magnetic nanoparticles (MNPs) and separated. Additionally, the relation of electrical impedance to the expression of molecular markers was established.Approach: MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines at different concentrations (50, 500 and 5000 cells/500 mu l) were labeled with a magnetic nanoparticle-antibody (MNP-ab) bioconjugate that recognizes the corresponding molecular markers (EpCAM, MUC-1 and HER-2, respectively). Electrical bioimpedance spectra (100 Hz to 1 MHz) were recorded in each case.Main results: At the frequency centered at 100 KHz, EIS displayed a greater sensitivity for magnitude when using 50 cells/500 mu l (4.11 +/- 0.23, 8.81 +/- 1.73 and 17.5 +/- 3.61 ohms for MCF-7, MDA-MB-231 and SK-BR-3, respectively). There were no significant differences between the phases of impedance tested at the greatest sensitivity of 1 KHz (-78.05 +/- 0.53, -79.23 +/- 0.93 and -75.26 +/- 0.72 degrees for MCF-7, MDA-MB-231 and SK-BR-3, respectively).Significance: Under the present conditions, EIS was sensitive enough to detect a low concentration of breast cancer cells (50 cells/500 mu l) and classify the distinct cells lines with a signature impedance pattern, as long as the MNP concentration was very low (0.125 mg MNPs/50 000 cells). The relative expression of the molecular markers on each cancer cell line was related to the magnitude of the electrical impedance.