Abstract

The Droplet Biopsy Chip for Circulating Tumor Cell Capture

Balaji Panchapakesan, Associate Professor, Department of Mechanical Engineering, Worcester Polytechnic Institute (WPI)

Circulating tumor cells (CTCs) are cells that have shed into the vasculature or lymphatics from a primary tumor and are carried around the body in the circulation. CTCs thus constitute seeds for the subsequent growth of additional tumors (metastasis) in vital distant organs, triggering a mechanism called Epithelial Mesenchymal Transition (EMT). One of the main causes of metastasis is EMT, which results in loss of epithelial characteristics of cancer cells. EMT results in down regulation of Epithelial Cell Adhesion Molecule (EpCAM), which is the primary marker for most commercially available CTC isolation systems today. We have invented the droplet biopsy chip that combines nanotechnology with micro-array manufacturing techniques to conduct droplet biopsy. The chip is a 76 element array consisting of nanotube wells. Antibodies attached to the nanotubes enable the capture of the cells. The hydrophobicity of the nanotube, antibody functionalization and droplet localization enables density gradients that results in separation of blood into different layers resulting in capture of CTCs without leukocyte contamination. Advantages of this technique include both positive and negative selection strategy on the same chip resulting in potential to capture invasive CTC phenotypes. Potentially one can achieve capture of CTCs based on multiple biomarkers, negative selection by depleting leukocytes, and density gradient based selection of nucleated cells, thereby avoiding loss of CTCs due to variation in size, biomarker composition, or lysis resistance, all in a single blood test.