An integrated vortex micromixer-microfilter device for highly selective isolation of circulating tumor cells

Abstract

The findings that circulating tumor cells(CTCs) is a significant clinical factor of patients when a carcinoma recurs, and CTCs persist in some patients after removal of the primary tumor have been the main cause for continuous studies of these tumor cells. Current approaches for the size-based isolation of CTCs have encountered technical challenges as some of the CTCs have a size similar to that of leukocytes and therefore CTCs are often lost in the process. Therefore, in this thesis I proposed a novel strategy where most of the CTCs are coated by a large number of microbeads to amplify their size to enable complete discrimination from leukocytes. In addition, all of the microbead labeling processes are carried out in a continuous manner to prevent any loss of CTCs during the isolation process. Thus, a microfluidic mixer was employed to facilitate the efficient and selective labeling of CTCs with anti-epithelial cell adhesion molecule-conjugated beads from peripheral blood samples. After the continuous labeling, the enlarged CTCs were perfectly trapped in a microfilter whereas all of the leukocytes escaped. We also expect the sensitive, simple, and rapid separation platform can be easily modified for collection of other type of rare circulating cells or molecules for early detection, diagnosis, prognosis, and disease monitoring.