Title:  High Throughput, Label-free Enrichment of Circulating Tumor Cells Via Micromachined Polymer Devices

Committee:

Dr. Fatih Sarioglu, ECE, Chair, Advisor

Dr. Bruno Frazier, ECE

Dr. John McDonald, Biosciences

Dr. Levent Degertekin, ECE

Dr. Tobey McDonald, Emory

Abstract: Circulating tumor cells (CTCs) are the cells that detach from the primary tumor and intravasate into bloodstream of patients. CTCs are responsible for distant organ metastasis and inherit valuable information for the clinical management of the disease. While accessing these valuable tumor cells from bloodstream, called liquid biopsy, is easier and less invasive for patients compared to standard tissue biopsy, efficient enrichment of them from blood is a technical challenge. CTCs are mixed with approximately billion times more populated blood cells in circulation. Moreover, heterogeneity of tumor cells, a major cause of failure in prognosis and prediction, necessitates extremely sensitive technologies for isolation and downstream analyses. Besides single CTCs, even more rare aggregates of CTCs, called CTC clusters, also contribute to cancer metastasis with a much greater metastatic propensity. In addition to the aforementioned challenges, enrichment of CTC clusters requires gentle operating conditions due to fragility of these aggregates. In this thesis, we present two distinct technologies for efficient enrichment and molecular analysis of CTCs and CTC clusters, and their use with clinical samples. First, we introduce the “Cluster-Wells” which combines the throughput and practicality of membrane filtration with the sensitive and deterministic screening afforded by microfluidic chips for gentle isolation of CTC clusters at 25 mL/h blood processing rate. Then, we introduce the "Sacrificial Biochip" technology for isolation and lossless retrieval of single CTCs from unprocessed whole blood, which allows direct integration of the developed assay with downstream analyses owing to the vanishing feature of the device. Efficient and gentle isolation of CTCs and CTC clusters has a great potential for the acceleration of research on their role in diagnosing, monitoring, and treating cancer.