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

L. Sohn
University of California, Berkeley,
United States

Keywords: mechanophenotyping, microfluidics, cancer, signal processing

Summary:

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.