Study of Circulating Tumor Cells Using Microfluidic Technology: From Isolation to Analysis

An intimidating aspect of cancer is its ability to spread out to distant organs causing 90% of cancer-associated deaths. This metastatic progression is driven by circulating tumor cells (CTCs) shed from the primary tumor into bloodstream of carcinoma patients. Consequently, the analysis of CTCs holds great promise as a potential biomarker in areas of cancer diagnosis, monitoring, and evaluation of therapeutic efficacy for personalized medicine, which can serve as surrogate for invasive tissue biopsy. However, CTCs are extremely rare with a frequency of only 1-10 cells surrounded by billions of normal blood cells in 1mL of blood.

In this talk, the shortcomings of existing CTC isolation methods are investigated followed by implementation of new microfluidic-based platforms improving the sensitivity, specificity, and throughput for CTC enrichment. First, an affinity-based CTC isolation chip is introduced incorporating functional graphene oxide to increase the surface area on which tumor specific capture antibody is presented. The two-dimensional surface-capture approach shows improved sensitivity of CTC collection while maintaining high viability of CTCs, which allow further downstream analysis and culturing. Next, a size based CTC isolation chip is proposed utilizing the inertial force effects to isolate CTCs by differentially focusing. This high-throughput, label-free selection approach enables to enrich CTCs of broader spectrum, especially from tumors with unknown markers. Finally, a catheter based in-vivo CTC isolation system is implemented to harvest CTCs from direct connection to the patient blood veins using a dual lumen catheter. The continuous screening of large blood volumes instead of single blood draw can enable enrichment of higher number of CTCs that can help deconstruct the heterogenetic properties of CTCs and overcome the limited detection rate observed mostly in early stage cancer patients.