Microfluidic Impedance-Deformability Cytometry for Label-Free Single Neutrophil Mechanophenotyping

The intrinsic biophysical states of neutrophils are associated with immune dysfunctions in diseases. While advanced image-based biophysical flow cytometers can probe cell deformability at high throughput, it is nontrivial to couple different sensing modalities (e.g., electrical) to measure other critical cell attributes including cell viability and membrane integrity. Herein, an optics-free impedance-deformability cytometer for multiparametric single cell mechanophenotyping is reported. The microfluidic platform integrates hydrodynamic cell pinching, and multifrequency impedance quantification of cell size, deformability, and membrane impedance (indicative of cell viability and activation). A newly-defined electrical deformability index is validated by numerical simulations, and shows strong correlations with the optical cell deformability index of HL-60 experimentally. Human neutrophils treated with various biochemical stimul are further profiled, and distinct differences in multimodal impedance signatures and UMAP analysis are observed. Overall, the integrated cytometer enables label-free cell profiling at throughput of >1000 cells min(-1) without any antibodies labeling to facilitate clinical diagnostics.

Automated summary

This study reports an optics-free impedance-deformability cytometer for multiparametric single cell mechanophenotyping. By profiling human neutrophils, distinct differences in multimodal impedance signatures under various biochemical stimulations were observed.