Characterization of single-cell biophysical properties and cell type classification using dielectrophoresis model reduction method

Abstract

Characterization of single-cell biophysical properties and cell type classification are significant to study cytopathology, cell sorting, drug screening, etc. Existing methods usually suffer from unsatisfied measurement accuracy and low efficiency. We propose a new dielectrophoresis (DEP) model reduction method to characterize biophysical properties and classify cell types of single cells in situ by directly solving a reduced DEP model from DEP-based cell moving velocities. Cell radius, specific membrane capacitance and cytoplasm conductivity of single cells are directly calculated by using a solution method rather than traditional nonlinear DEP spectrum fitting. The frequencies of DEP signals used for determining the cellular parameters are optimized to achieve minimum errors. By this way, the measurement accuracy and efficiency are greatly improved. Using a homemade electrode-array chip allows simultaneous measurements on multiple single-cells and facilitates high-throughput analyses. We perform experimental measurements on four typical cell lines, including adherent cells (HeLa and MCF-7) and suspension cells (Jurkat and GM12878), cancer cells (HeLa, MCF-7 and Jurkat) and normal cells (GM12878), and demonstrate statistically significant differences in their biophysical properties, which can be used to classify cell types. The proposed model reduction method provides an accurate and efficient approach for characterizing single-cell biophysical properties and classifying cell types, while with real-time, in-situ, label-free, and less invasive advantages.