Negative Enrichment of Circulating Tumor Cells Using a Geometrically Activated Surface Interaction Chip

Abstract

Circulating tumor cells (CTCs) have attracted a great deal of attention, as they can be exploited to investigate metastasis. The molecular and cellular characteristics of these cells are little understood because they are rare and difficult to isolate. Many methods of isolation have centered on affinity-based positive enrichment (i.e., capturing target cells and eluting nontarget cells) using epithelial cell adhesion molecule (EpCAM) antibodies. It is known, however, that not all CTCs express the EpCAM antigen because they are heterogeneous by nature. In addition, negative enrichment (i.e., capturing nontarget cells and eluting target cells) has advantages over positive enrichment in isolating CTCs since the former can collect the target cells in an intact form. In this paper, we introduce a geometrically activated surface interaction (GASI) chip with an asymmetric herringbone structure designed to generate enhanced mixing flows, increasing the surface interaction between the nontarget cells and the channel surface. CD45 antibodies were immobilized inside the channel to capture leukocytes and release CTCs to the outlet. Blood samples from breast, lung, and gastric cancer patients were analyzed. The number of isolated CTCs varied from 1 to 51 in 1 mL of blood. Because our device does not require any labeling processes (e.g., EpCAM antibodies), intact and heterogeneous CTCs can be isolated regardless of EpCAM expression.