Classification of tumor subtypes leveraging constriction-channel based impedance flow cytometry and optical imaging.

Abstract

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 Cspecific membrane and cytoplasmic conductivity σcytoplasm ) 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 Cspecific membrane and σcytoplasm . 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 Cspecific membrane and 0.96 ± 0.37 S/m vs. 1.24 ± 0.47 S/m of σcytoplasm 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 Cspecific membrane and 0.83 ± 0.18 S/m vs. 0.93 ± 0.25 S/m of σcytoplasm 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 Cspecific membrane and 0.47 ± 0.05 vs. 0.52 ± 0.05 S/m of σcytoplasm (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.

• Authors: Mei Jiang, Xiaojie Wang, Xiaoting Zhao, Yu Teng, Jian Chen, Junbo Wang, Wentao Yue
• Journal: Cytometry. Part A : the journal of the International Society for Analytical Cytology (Cytometry A) Vol. 99 Issue 11 Pg. 1114-1122 (11 2021) ISSN: 1552-4930 [Electronic] United States
• PMID: 33909347 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 International Society for Advancement of Cytometry.

Topics

• Cell Membrane
• Constriction
• Electric Impedance
• Flow Cytometry
• Optical Imaging