Node-Pore Sensing: How a (Humble) Four-Terminal Measurement Can Measure the Mechanical Properties of Single Cells

Monday, October 4, 2021

We have developed an electronic method to screen cells for their phenotypic profile, which we call Node-Pore Sensing (NPS).  NPS involves using a four-terminal measurement to measure the modulated current pulse caused by a cell transiting a microfluidic channel that has been segmented by a series of inserted nodes.  Previously, we showed that when segments between the nodes are functionalized with different antibodies corresponding to distinct cell-surface antigens, immunophenotyping can be achieved.  In this talk, I will show how we have significantly advanced NPS by simply inserting between two nodes a straight “contraction” channel through which cells can squeeze.  “Mechano-NPS”, as we now call our method, can simultaneously measure a cell’s size, resistance to deformation, transverse deformation, and ability to recover from deformation.  When the contraction channel is sinusoidal in shape, resulting in cells being periodically squeezed, mechano-NPS can also measure the viscoelastic properties of cells.  I will describe how we have used mechano-NPS to distinguish chronological age groups and breast-cancer risk groups of primary human mammary epithelial cells and identify drug-resistant acute promyelocytic leukemia cells—all based on mechanical properties.  I will also describe the development of the next-generation NPS platform which utilizes advanced signal processing algorithms—Barker and Gold codes—directly encoded in the NPS channels to thus achieve multiplexing. 

Department of Mechanical Engineering, University of California, Berkeley, CA