Abstract

Linking Physical Phenotype to Drug Resistance: Single-Cell Mechanical Measurements of Acute Promyelocytic Leukemia

Lydia Sohn, Professor, Department of Mechanical Engineering, University of California, Berkeley

We have developed an efficient, label-free method of screening cells for their phenotypic profile, which we call Node-Pore Sensing (NPS).  NPS involves measuring the modulated current pulse caused by a cell transiting a microfluidic channel that has been segmented by a series of inserted nodes.  By simply inserting between two nodes a “contraction” channel through which cells can squeeze, we can use NPS to measure simultaneously physical properties of cells, including size, resistance to deformation, transverse deformation, and ability to recover from deformation.  “Mechano-NPS”, as we now call our method, can distinguish malignant from non-malignant epithelial cells and discriminate between sub-lineages and, chronological age groups of primary human mammary epithelial cells.  As I will discuss, we have recently been using mechano-NPS to study acute promyelocytic leukemia (APL) cells, showing that mechanical phenotyping is predictive of the leukemia’s response to retinoic acid (RA), a first-line chemotherapeutic for APL. By measuring cell recovery, mechano-NPS provides information on a cell’s viscoelastic behavior.  While this confers the advantage of making more in-depth biophysical analyses of single cells, it also potentially provides new information to be included in a diagnostic classification.