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

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. Multi‐zone node‐pore sensing (mz‐visco‐NPS) is an innovative method to measure single‐cell viscoelasticity. This study demonstrates that mz‐visco‐NPS can measure viscoelastic changes of cells and viscoelastic properties of human mammary epithelial cells across a continuum of epithelial transformation states. With a throughput of 600 cells per hour and demonstrated ease‐of‐use, mz‐visco‐NPS reveals a remarkable single‐cell heterogeneity that will otherwise be masked by ensemble average.