title: Bioimpedance rise in response to histone deacetylase inhibitor is a marker of mammary cancer cells within a mixed culture of normal breast cells.
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.
authors.affiliation: VT MEMS Lab, The Bradley Department of Electrical and Computer Engineering, Virginia Tech. Blacksburg, Virginia 24061, United States. vaishnas@vt.edu
authors.forename: Vaishnavi
authors.initials: V
authors.lastname: Srinivasaraghavan
authors.forename: Jeannine
authors.initials: J
authors.lastname: Strobl
authors.forename: Masoud
authors.initials: M
authors.lastname: Agah
mesh_terms: D014408:Biomarkers, Tumor; D015374:Biosensing Techniques / Q000295:instrumentation*; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation*; D018920:Coculture Techniques; D017097:Electric Impedance; D004867:Equipment Design; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids; D015739:Nocodazole; D000077337:Vorinostat
chemical_list: D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D006655:Histone Deacetylases; D015739:Nocodazole