Three-Chambered Array-Based Impedance Assay: A Real-Time Analysis Technique to Assess Invasive Potential of Cancer Cells by Measuring Electrical Impedance

Cancer-associated stromal cells secrete chemical factors that can trigger the metastatic tumor cells residing on the tissue basement membrane. Consequently, the cancer cells invade the basement membrane and migrate toward the tissue's extracellular space.

To measure the invasive capacity of cancer cells in vitro, begin with a multiwell plate with multiple three-chambered arrays. In each array, the bottom chamber has an adherent culture of stromal cells. The top chamber with fused impedance-measuring microelectrodes - miniature electrodes that measure a cell's electrical activity - is overlaid by cancer cells, which adhere to the extracellular matrix-coated microporous membrane present above the electrodes.

During incubation on an impedance-based analyzer, the stromal cells release chemotactic factors into the medium, which move toward the cancer cells. These factors move through the semi-permeable membrane present at the bottom side of the middle chamber.

The stromal cell-secreted factors signal the adherent cancer cells to transform into invasive phenotypes. In response, the invasive cells migrate through the microporous membrane reaching the interdigitated electrodes on the opposite side of the membrane.

Over time, as more cancer cells stick to the electrodes, they cause cellular impedance - hindrance to the flow of current by cells. The measurement of cellular impedance is indicative of the invasive potential of cancer cells.