Integration of Hierarchical Micro-/Nanostructures in a Microfluidic Chip for Efficient and Selective Isolation of Rare Tumor Cells.

Circulating tumor cells (CTCs) are important clinical markers for both cancer early diagnosis and prognosis. Various techniques have been developed in the past decade to isolate and quantify these cells from the blood while microfluidic technology attracts significant attention due to better controlled microenvironment. When combined with advanced nanotechnologies, CTC isolation performance in microfluidic devices can be further improved. In this article, by extending the wavy-herringbone concept developed earlier in our team, we prepared a hierarchical microfluidic chip by introducing a uniform coating of nanoparticles with anti-epithelial cell adhesion molecule (EpCAM) on wavy microgrooves. This hierarchical structured platform not only maintains the capture purity of the wavy-herringbone structure but improves the capture efficiency thanks to the larger surface area to volume ratio brought by nanoparticles. Our results demonstrated a capture efficiency of almost 100% at a low shear rate of 60/s. Even at a higher shear rate of 400/s, the hierarchical micro/nanostructures demonstrated an enhancement of up to ~3-fold for capture efficiency (i.e., 70%) and ~1.5-fold for capture purity (i.e., 68%), compared to wavy-herringbone structures without nanoparticle coating. With these promising results, this hierarchical structured platform represents a technological advancement for CTC isolation and cancer care.