Bioimpedance rise in response to histone deacetylase inhibitor is a marker of mammary cancer cells within a mixed culture of normal breast cells

Lab Chip. 2012 Dec 21;12(24):5168-79. doi: 10.1039/c2lc40778g.

Abstract

Detection of a few cancer cells within a complex cellular mixture is a key challenge presented by clinical human biopsy samples. We have designed and tested a microfabricated bioimpedance device that can detect a few human MDA-MB-231 breast cancer cells in a mixed cell culture model of a breast tissue sample. The normal tissue components were modelled using non-cancerous MCF10A human breast epithelial cells and normal human HS68 fibroblasts. The sensor is a silicon chip 0.5 cm in diameter that contains one counter electrode and four 40 μm-wide multi-branched sensing electrodes. The cells' bioimpedances were characterized in pure monocultures and in mixed cell cultures following a brief cultivation on the sensor. After cell seeding, a stable bioimpedance signal was achieved indicative of cell attachment. A cancer-selective bioimpedance signal was elicited by addition of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor with selective actions on the cytoskeleton in breast cancer cells. SAHA elicited a 50% rise in peak bioimpedance in MDA-MB-231 breast cancer cells by 15 h. In mixed cultures of MDA-MB-231, MCF10A, and HS68 cells, the contribution of cancer cells present in the mixture dominated impedance response to SAHA. A single adherent cancer cell on any one of four electrodes in a background of ∼100 normal cells resulted in ≥5% increase in bioimpedance. The estimated sensitivity of this device is therefore one cancer cell among a background of 400 normal cells or the equivalent of 25 cancer cells in a biopsy sample of 10 000 cells.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers, Tumor*
  • Biosensing Techniques / instrumentation*
  • Breast / cytology*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Separation / instrumentation*
  • Coculture Techniques
  • Electric Impedance
  • Equipment Design
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism*
  • Humans
  • Hydroxamic Acids
  • Nocodazole
  • Vorinostat

Substances

  • Biomarkers, Tumor
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Vorinostat
  • Histone Deacetylases
  • Nocodazole