Impedance‐Based Multimodal Electrical‐Mechanical Intrinsic Flow Cytometry

Abstract

AbstractReflecting various physiological states and phenotypes of single cells, intrinsic biophysical characteristics (e.g., mechanical and electrical properties) are reliable and important, label‐free biomarkers for characterizing single cells. However, single‐modal mechanical or electrical properties alone are not specific enough to characterize single cells accurately, and it has been long and challenging to couple the conventionally image‐based mechanical characterization and impedance‐based electrical characterization. In this work, the spatial‐temporal characteristics of impedance sensing signal are leveraged, and an impedance‐based multimodal electrical‐mechanical flow cytometry framework for on‐the‐fly high‐dimensional intrinsic measurement is proposed, that is, Young's modulus E, fluidity β, radius r, cytoplasm conductivity σi, and specific membrane capacitance Csm, of single cells. With multimodal high‐dimensional characterization, the electrical‐mechanical flow cytometry can better reveal the difference in cell types, demonstrated by the experimental results with three types of cancer cells (HepG2, MCF‐7, and MDA‐MB‐468) with 93.4% classification accuracy and pharmacological perturbations of the cytoskeleton (fixed and Cytochalasin B treated cells) with 95.1% classification accuracy. It is envisioned that multimodal electrical‐mechanical flow cytometry provides a new perspective for accurate label‐free single‐cell intrinsic characterization.