A serial micropipette microfluidic device with applications to cancer cell repeated deformation studies

Cells are complex viscoelastic materials that are frequently in deformed morphological states, particularly during the cancer invasion process. The ability to study cell mechanical deformability in an accessible way can be enabling in many areas of research where biomechanics is important, from cancer metastasis to immune response to stem cell differentiation. Furthermore, phenomena in biology are frequently exhibited in high multiplicity. For instance, during metastasis, cells undergoing non-proteolytic invasion squeeze through a multitude of physiological barriers, including many small pores in the dense extracellular matrix (ECM) of the tumor stroma. Therefore, it is important to perform multiple measurements of the same property even for the same cell in order to fully appreciate its dynamics and variability, especially in the high recurrence regime. We have created a simple and minimalistic micropipette system with automated operational procedures that can sample the deformation and relaxation dynamics of single-cells serially and in a parallel manner. We demonstrated its ability to elucidate the impact of an initial cell deformation event on subsequent deformations for untreated and paclitaxel treated MDA-MB-231 metastatic breast cancer cells, and we examined contributions from the cell nucleus during whole-cell micropipette experiments. Finally we developed an empirical model that characterizes the serial factor, which describes the reduction in cost for cell deformations across sequential constrictions. We performed experiments using spatial, temporal, and force scales that match physiological and biomechanical processes, thus potentially enabling a qualitatively more pertinent representation of the functional attributes of cell deformability.