Quantifying Cellular Elasticity using Quantitative Phase Microscopy Measurements of Electromagnetically Actuated Magnetic Microsphere Indentation

Abstract

Metastasis is responsible for 90% of cancer cell deaths, and mechanical properties of cancer cells are an important and emerging indicator of cancer cell metastatic potential. Therefore, screening the mechanical properties of cancer cells, alone and in response to chemotherapy, provides an important indicator of disease progression and drug effectiveness. There are many existing approaches to measuring cell mechanical properties, however the mechanical constraints of these systems cannot be readily combined with measurements of cell growth or death to quantify the full response of cancer cells to potential therapies. Quantitative phase microscopy (QPM) is an established approach for determining the growth response of cancer cells to a variety of chemotherapies, from small-molecule inhibitors to adoptive immunotherapies, by quantifying the rate of increase or decrease in cell mass over time. In this work we describe a system based on QPM that quantifies cell mechanical properties using an Arudino microcontroller to control electromagnet-driven oscillation and indentation of magnetic nickel microspheres distributed on top of adherent cells in vitro. QPM measures cell mass as well as magnetic microsphere indentation and relaxation over time, and can therefore simultaneously quantify cell growth, stiffness, and viscosity. Electromagnet actuation allows for rapid modulation of the indentation force applied to cells for simultaneous, high-throughput measurements of mechanical responses at up to several hundred locations within each field of view. In combination with the ability of QPM to rapidly determine the effects of chemotherapeutics on cancer cell growth, this system will enable selection of treatments to better target both the growth and mechanical properties of cancer cells, in an effort to select and design optimal chemotherapeutic strategies to combat metastasis.