BME MS Defense: Laura Western

Microtube Device Functionalized With Immobilized Selectins for Capture of Circulating Tumor Cells and Study of Cancer Stem Cells Under Flow

Supervised by Prof. Michael King

Abstract

Circulating tumor cells (CTC) have the potential to be used clinically as a diagnostic tool and a treatment tool in the field of oncology. As a diagnostic tool, CTC may be used to indicate the presence of a tumor before the tumor is large enough to cause noticeable symptoms. As a treatment tool, CTC isolated from patients may be used to test the efficacy of chemotherapy options to personalize patient treatment. One way for tumors to spread is through metastasis via the circulatory system. CTC are able to exploit the natural leukocyte recruitment process that is initially mediated by rolling on transient selectin bonds. The microtube will take advantage of this naturally occurring recruitment step to isolate CTC from whole blood by flowing sample through selectin and antibody- coated microtubes.

Whole blood was spiked with a known concentration of labeled cancer cells and then perfused through pre-coated microtubes. The microtube was then rinsed to remove unbound cells and the number of labeled cells captured on the lumen was assessed. CTC were successfully captured from whole blood at a clinically relevant level on the order of 10 cells per mL. Combination tubes with selectin and antibody coated surface exhibited higher capture rate than tubes coated with selectin alone or antibody alone. Additionally, samples of buffy coat from prostate, breast, and colon cancer patients were perfused through the microtube and CTC were successfully isolated. The in vivo process of selectin-mediated CTC recruitment to distant vessel walls can be used in vitro to target CTC to a tube lumen. The microtube device can be used to capture CTC of hematopoietic and epithelial tumor origin and is demonstrated sensitivity down to the order of 10 CTC per mL.