Micro-elastography on spheroids using a magnetic pulse as a shear wave source and the impact of cavitation on their mechanical properties

Abstract

In the context of development of a new treatment against pancreatic adenocarcinoma combining chemotherapy and cavitation, it is interesting to be able to mechanically characterize spheroid tumor models. Spheroids, which are clusters of cancerous cells (KPC) and fibroblasts (iMEF), are made using magnetic nanoparticles which are linked to the cells. Then, by using magnetic cell culture plates, cells aggregate, until forming a spheroid. Hence magnetic nanoparticles are incorporated in the spheroid, and can be used to generate elastic waves inside. A 5-ms magnetic pulse is induced in a coil, allowing to induce vibrations inside the spheroid placed in its center. It is observed using an optical microscope and an ultrafast camera. Then, tracking algorithms allow to measure the displacements at each point of the image, and for each time step. Next, noise correlation algorithms are used to retrieve the local velocity of shear waves inside the spheroid. Therefore, we obtained shear wave velocity maps of spheroids, using a non-destructive method. The influence of trypsine (known for disrupting the bounds between the cells) on shear wave velocity maps has been studied. As expected, a decrease in the wave velocity has been observed, attesting that this method is sensitive to elasticity. Furthermore, the impact of cavitation inside the spheroid has been investigated. Cavitation designates the bubble generation using ultrasound. It has been shown that cavitation also leads to a substantial decrease in the velocity of shear waves.