Biomechanical Identification and Sorting of Single Cells

Abstract

The mechanical stiffness of individual human cells can be a key parameter that reveals dysfunction of the cell. For example, invasive cancer cells can be several times more deformable than healthy phenotypes. However, for biophysical properties to be utilized in biomedical and diagnostic settings, we will require methods for continuous sorting of cells by differences in stiffness in high throughput. Although separation by such parameters as density is commonly employed, few methods are available for rapid separation by stiffness. Recently, we have created a microfluidic sorting technology which utilizes a combination of hydrodynamic and compressive forces to sort individual cells by stiffness. We utilize this approach to sort a variety of cell mixtures, including different subtypes of leukemia cell models as well as cancer cell models. We further combine computational modeling and experimental studies to predict the movement of compliant cells flowing in microchannels with periodical constrictions to understand how the dynamical interplay between elastic deformation due to viscous flow and the channel geometry can be harnessed to provoke cell segregation. The technology can be altered to highlight other biophysical differences between cells, such as size and viscous relaxation.