Detection of Heterogeneous Cells in Cell Spheroids by Applying High-Frequency Second-Order Sensitivity Matrix Electrical Impedance Tomography (HSSM-EIT)

The high-frequency second-order sensitivity matrix electrical impedance tomography (HSSM-EIT) method has been proposed to detect heterogeneous cells in cell spheroids by coupling the high-frequency and second-order sensitivity matrix electrical impedance tomography (EIT). The sensitivity matrix with the first and second-order terms of Taylor’s formula (Jacobian and Hessian) is applied to the image reconstruction of cell spheroids with the high-frequency injected current at 1 MHz, at which the impedance reflects intracellular contents to visualize the cytoplasm conductivity distribution of cell spheroids. The cell spheroids with five composition percentages of the wild type (WT) and green fluorescent protein type (GFPT) of MRC-5 human lung fibroblast cell line are 100/0%, 75/25%, 50/50%, 25/75%, and 0/100%, and were cultured to mimic heterogeneous cells. As a result, the cell spheroid images reconstructed by HSSM-EIT clearly visualize the heterogeneity stage rather than the images reconstructed by general first-order sensitivity matrix EIT; moreover, the cytoplasm conductivity of the cell spheroid is decreased with the increase of GFPT percentage. In order to confirm the cytoplasm conductivity reconstructed by HSSM-EIT, an equivalent circuit model containing a cell spheroid and extracellular fluid is employed to calculate the cytoplasm conductivity $\sigma _{\mathrm{ cyto}}$ from the measurement of electrochemical impedance spectroscopy. The result shows that $\sigma _{\mathrm{ cyto}}$ is also decreased with the increase of GFPT percentage, which shows the same trend as the cytoplasm conductivity reconstructed by HSSM-EIT.