Stiffness Dependent Separation of Cells in a Microfluidic Device

Rapidly sorting and separating cells are critical for detecting diseases such as cancers and infections and can enable a great number of applications in bio-related science and technology. While a variety of techniques demonstrate separation by physical parameters such as size[1] and mass[2], inexpensive and easy to use methods are needed to separate cells by mechanical compliance. A number of pathophysiological states of individual cells result in drastic changes in stiffness in comparison with healthy counterparts. Mechanical stiffness has been utilized to identify abnormal cell populations in detecting cancer[3–5] and identifying infectious disease[4, 6]. Recently, microfluidic methods were developed to classify and enrich cell populations utilizing mechanical stiffness[7–9]. We demonstrate a new strategy to continuously and non-destructively separate cells into subpopulations of soft and stiff cells. In our microfluidic separation method, we employ a microchannel with the top wall decorated by a periodic array of rigid diagonal ridges (Fig. 1). The gap between the ridges and the bottom channel wall is smaller than the cell diameter, thus the cells are periodically compressed by the ridges. The difference in mechanical resistance to compression of cells gives rise to a stiffness-dependent force associated with cell passage through narrow constrictions formed by the consecutive channel ridges. This elastic force is directed normal to the compressive diagonal ridges and, therefore, deflects cells propelled by the flow in the lateral direction with a rate proportional to their compliance. In this paper, we employ this principle to separate modified lymphoblastic cells with dissimilar mechanical stiffness in high-throughput.