Isolation of Circulating Tumor Cells Using Stiffness-Based Filtration Platform

Abstract

Analysis of isolated cancer cells in circulation is proven to help determine the success of the cancer treatment and understand the genetic signature of cancer disease. Scarcity of these cells in blood circulation (1–10 CTC in 1ml blood) however, makes the isolation process extremely challenging. Ever improving CTC isolation methods fall into two main categories: 1.Immunomagnetic separation based on antibody binding to tumor specific biomarkers expressed on the cell 2. Physical separation based on the size of the CTCs. Efficiency in cell isolation is still low in these techniques due to the variation in expression level of tumor specific antigens and tumor cell size. Therefore, tumor cell isolation strategies using new CTC biomarkers must be explored. In this study, we investigated the feasibility of using mechanical stiffness difference in order to detect and isolate the circulating tumor cells from the blood cells. AFM nanindentation experiments revealed that cancer cells are significantly softer than the surrounding white blood cells and therefore, stiffness can be used as a biomarker for CTC isolation. In addition, finite element analysis simulations have shown that CTC isolation can be performed at high efficiency using stiffness-based isolation. Therefore, stiffness based isolation has a potential to achieve fast, label-free isolation of CTCs at high efficiency for clinical applications.