Quantification of the heterogeneity in breast cancer cell lines using whole-cell impedance spectroscopy

Purpose: Quantification of the heterogeneity of tumor cell populations is of interest for many diagnostic and therapeutic applications, including determining the cancerous stage of tumors. We attempted to differentiate human breast cancer cell lines from different pathologic stages and compare that with a normal human breast tissue cell line by characterizing the impedance properties of each cell line. Experimental Design: A microelectrical impedance spectroscopy system has been developed that can trap a single cell into an analysis cavity and measure the electrical impedance of the captured cell over a frequency range from 100 Hz to 3.0 MHz. Normal human breast tissue cell line MCF-10A, early-stage breast cancer cell line MCF-7, invasive human breast cancer cell line MDA-MB-231, and metastasized human breast cancer cell line MDA-MB-435 were used. Results: The whole-cell impedance signatures show a clear difference between each cell line in both magnitude and phase of the electrical impedance. The membrane capacitance calculated from the impedance data was 1.94 +/- 0.14, 1.86 +/- 0.11, 1.63 +/- 0.17, and 1.57 +/- 0.12 mu F/cm(2) at 100 kHz for MCF-10A, MCF-7, MDA-MB-231, and MDA-MB-435, respectively. The calculated resistance for each cancer cell line at 100 kHz was 24.8 +/- 1.05, 24.8 +/- 0.93, 24.9 +/- 1.12, and 26.2 +/- 1.07 MOhm, respectively. The decrease in capacitances of the cancer cell lines compared with that of the normal cell line MCF-10A was 4.1%, 16.0%, and 19.1%, respectively, at 100 kHz. Conclusions: These findings suggest that microelectrical impedance spectroscopy might find application as a method for quantifying progression of cancer cells without the need for tagging or modifying the sampled cells.