Multi-Zone Visco-Node-Pore Sensing: A Microfluidic Platform for Multi-Frequency Viscoelastic Phenotyping of Single Cells.

ABSTRACT

This study introduces multi-zone visco-Node-Pore Sensing (mz-visco-NPS), an electronic-based microfluidic platform for single-cell viscoelastic phenotyping. mz-visco-NPS implements a series of sinusoidal-shaped contraction zones that periodically deform a cell at specific strain frequencies, leading to changes in resistance across the zones that correspond to the cell's frequency-dependent elastic G' and viscous G″ moduli. mz-visco-NPS is validated by measuring the viscoelastic changes of MCF-7 cells when their cytoskeleton is disrupted. mz-visco-NPS is also employed to measure the viscoelastic properties of human mammary epithelial cells across the entire continuum of epithelial transformation states, from average- and high-risk primary epithelial cells, to immortal non-malignant (MCF-10A), malignant (MCF-7), and metastatic (MDA-MB-231) cell lines. With a throughput of 600 cells per hour and demonstrated ease-of-use, mz-visco-NPS reveals a remarkable level of single-cell heterogeneity that would otherwise be masked by ensemble averaging.