Detection of Heterogeneous Cells in Cell Spheroids by Applying High-Frequency Second-Order Sensitivity Matrix Electrical Impedance Tomography (HSSM-EIT)
Detection of Heterogeneous Cells in Cell Spheroids by Applying High-Frequency Second-Order Sensitivity Matrix Electrical Impedance Tomography (HSSM-EIT)
复制标题
DOI：
10.1109/ojim.2022.3212753
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Songshi Li;D. Kawashima;Zengfeng Gao;M. Takei
中科院分区：
文献类型：
--
作者：
Songshi Li;D. Kawashima;Zengfeng Gao;M. Takei
通过将高频和二阶灵敏度矩阵电阻抗成像（EIT）耦合，提出了一种用于检测细胞球体中异质细胞的高频二阶灵敏度矩阵电阻抗成像（HSSM-EIT）方法。将具有Taylor公式（Jacobian和Hessian）的一阶和二阶项的灵敏度矩阵应用于在1 MHz的高频注入电流下的细胞球体的图像重建，其中阻抗反映细胞内内容物以可视化细胞球体的胞质电导率分布。MRC-5人肺成纤维细胞系的野生型（WT）和绿色荧光蛋白型（GFPT）的五种组成百分比的细胞球状体为100/0%、75/25%、50/50%、25/75%和0/100%，并培养以模拟异质细胞。结果表明，HSSM-EIT重建的细胞球体图像比一般一阶灵敏度矩阵EIT重建的图像更清晰地显示了异质性阶段;细胞球体的胞浆电导率随着GFPT百分比的增加而降低。为了证实HSSM-EIT重建的细胞质电导率，采用包含细胞球体和细胞外液的等效电路模型，通过电化学阻抗谱测量计算细胞质电导率σ_{\mathrm{ cyto}}$。结果表明，$sigma { cyto}$随着GFPT百分比的增加而降低，这与HSSM-EIT重建的细胞质电导率的变化趋势一致。
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.