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

Abstract

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 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 compositions percentages of 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%, 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 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 σcyto from the measurement of electrochemical impedance spectroscopy. The result shows that σcyto is also decreased with the increase of GFPT percentage, which shows the same trend as the cytoplasm conductivity reconstructed by HSSM-EIT.