As label-free biomarkers, electrical properties of single cells have been widely used for cell-type classification and cell-status evaluation. However, as intrinsic bioelectrical markers, previously reported membrane capacitance and cytoplasmic resistance (e.g., specific membrane capacitance C_{specific membrane} and cytoplasmic conductivity σ_cytoplasm) of tumor subtypes were derived from tens of single cells, lacking statistical significance due to low cell numbers. In this study, tumor subtypes were constructed based on phenotype (treatment with 4-methylumbelliferone) or genotype (knockdown of ROCK1) modifications and then aspirated through a constriction-channel based impedance flow cytometry to characterize single-cell C_{specific membrane} and σ_cytoplasm. Thousands of single tumor cells with phenotype modifications were measured, resulting in significant differences in 1.64 ± 0.43 μF/cm² vs. 1.55 ± 0.47 μF/cm² of C_{specific membrane} and 0.96 ± 0.37 S/m vs. 1.24 ± 0.47 S/m of σ_cytoplasm for 95C cells (792 cells of 95C-control vs. 1529 cells of 95C-pheno-mod); 2.56 ± 0.88 μF/cm² vs. 2.33 ± 0.56 μF/cm² of C_{specific membrane} and 0.83 ± 0.18 S/m vs. 0.93 ± 0.25 S/m of σ_cytoplasm for H1299 cells (962 cells of H1299-control vs. 637 cells of H1299-pheno-mod). Furthermore, thousands of single tumor cells with genotype modifications were measured, resulting in significant differences in 3.82 ± 0.92 vs. 3.18 ± 0.47 μF/cm² of C_{specific membrane} and 0.47 ± 0.05 vs. 0.52 ± 0.05 S/m of σ_cytoplasm (1100 cells of A549-control vs. 1100 cells of A549-geno-mod). These results indicate that as intrinsic bioelectrical markers, specific membrane capacitance and cytoplasmic conductivity can be used to classify tumor subtypes.

中文翻译：

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利用基于收缩通道的阻抗流式细胞术和光学成像对肿瘤亚型进行分类

作为无标记生物标志物，单细胞的电特性已被广泛用于细胞类型分类和细胞状态评估。然而，作为内在生物电标志物，先前报道的肿瘤亚型的膜电容和细胞质电阻（例如，特定膜电容C_特定膜和细胞质电导率σ_细胞质）来自数十个单细胞，由于细胞数量少而缺乏统计学意义。在这项研究中，肿瘤亚型是基于表型（用 4-甲基伞形酮治疗）或基因型（敲除 ROCK1）修饰构建的，然后通过基于收缩通道的阻抗流式细胞术抽吸来表征单细胞C_特异性膜和σ_细胞质。测量数千单个肿瘤细胞的表型与修改的，从而导致显著差异在1.64±0.43μF/厘米²与1.55±0.47μF/厘米²的Ç_特异性膜和0.96±0.37 S /米对比1.24±0.47 S / 95C 细胞的σ_细胞质的m （95C-对照的 792 个细胞与 95C-pheno-mod 的 1529 个细胞）；2.56±0.88μF/厘米²与2.33±0.56μF/厘米²的Ç_特异性膜和0.83±0.18 S /米对比0.93±0.25 S /米σ_细胞质对于 H1299 细胞（H1299-对照的 962 个细胞与 H1299-pheno-mod 的 637 个细胞）。此外，测量数千单个肿瘤细胞基因型的修饰，导致显著差异在3.82±0.92对比3.18±0.47μF/厘米²的Ç_特异性膜和0.47±0.05对0.52±0.05 S / m的σ_细胞质（ 1100 个 A549-对照细胞与 1100 个 A549-基因-mod 细胞）。这些结果表明，作为内在生物电标志物，特定的膜电容和细胞质电导率可用于对肿瘤亚型进行分类。