Discovery of the correlation between the suspended membrane capacitance and adherent morphology of single cells enriching from clinical pleural effusion revealed by a microfluidic impedance flow cytometry

Cellular adherent morphology and suspended electrical property are two important intrinsic biophysical features of single cells in two states. However, few studies reported their relationship due to lacking systematic methods. Here, we proposed a toolchain for enriching, proliferating single cells from pleural effusions (PEs), and characterizing their adherent morphologies and suspended inherent electrical properties. Our 3D cell sieving device was employed to enrich rare tumor cells from every 50 mL clinical PEs. After proliferated, ten samples were enrolled, whose cells' adherent morphologies were quantified with the elongation ratio (Er). Our microfluidic impedance flow cytometry was developed to characterize ~65,400 suspended single cells' electrical properties (e.g., Csm). Subsequently, we experimentally found that the Csm of 5 spindle-like (mainly Er> 2) samples were all quantified as focused above 1.5 μF/cm2, whereas others' were all focused around 1–1.5 μF/cm2 for 5 round-like (mainly Er≤ 2) samples. Spearman rhos were introduced to further quantify this potential correlation from aspects of proportions (Csm> 1.5 μF/cm2, Er> 2), average, and median, noting as 0.758 (p = 0.011), 0.760 (p = 0.011), and 0.744 (p = 0.014), respectively. Those results revealed a significant correlation between single cells' Er and Csm─which means that the underlying correlation between cells' two label-free biophysical properties presented in two states was discovered.