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 μl) 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 μl (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 μl) 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.