Label-free isolation of circulating tumor cells (CTCs) from breast cancer patients using parallel multi-orifice flow fractionation (p-MOFF)

Circulating tumor cells (CTCs), which are detached from primary cancer and circulate in peripheral blood, are known to cause the metastatic cancer. Therefore isolation of CTCs can serve as a powerful tool for cancer prognosis, diagnosis of minimal residual disease, assessment of tumor sensitivity to anticancer drugs, and personalization of anticancer therapy. In this paper, we introduce the parallel multi-orifice flow fractionation (p-MOFF) device which is connected by four single MOFF channel for the isolation of CTCs from whole blood of the metastatic breast cancer patients. For the experimentation of feasibility, we separated over 90% of human breast cancer cell line (MCF-7, MDA-MB-231 cells), and eliminate 90.80 % of WBCs from individual experiment at 600 μL/min inlet flow rate and 240 μL/min outlet flow rate. Based on this result, we have attempted to isolate CTCs from whole blood under the same conditions. Then we identify CTCs using immune staining method. Because our devices do not require any labeling processes (e.g. EpCAM antibody), heterogeneous CTCs can be isolated regardless of EpCAM expression.