Biomechanical Phenotyping of Circulating Tumor Cells: A Window to Study Cancer Metastasis

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Blood-borne cancerous tumor cells are shed by both primary and metastatic tumors and they are thought to contribute to the spread of cancer to distant sites in the body. There is, therefore, a great interest in using a blood sample to capture and measure the properties of circulating tumor cells in order to predict the response of the tumor to therapy. Despite their importance, the current understanding of circulating tumor cells is extremely poor. This project will build a novel device that will separate these cells from the blood and rapidly measure their biological and biomechanical properties. The developed device will be useful beyond the isolation and measurement of tumor cell properties, as the other cellular components of blood could also be separated and mechanically measured using the device. The research will have broad impacts on students from different educational levels and genders and ethnicities, by exposing them to exciting challenges in science and engineering that have relevance to our society.It still remains a major challenge in understanding the biology of circulating tumor cells, and ultimately, improving the systems level understanding of blood-borne metastasis in cancer. This research will address the challenge in understanding the biological nature of circulating tumor cells by establishing a cell sorting device that can efficiently capture and isolate the circulating tumor cells without using any capture antibody. A microfluidic deformability microcytometer array will also be developed for high-throughput multiparametric single-cell biochemical and biomechanical phenotyping of live single circulating tumor cells. Experimental results from the deformability microcytometer will be further used to guide developments of a contact element / cohesive zone model and finite element simulation for quantifications of cell stiffness and expression levels of surface antigens of circulating tumor cells. The research team will further integrate the technological platforms with preclinical murine xenograft models to investigate the timing of circulating tumor cell release from primary tumors and their heterogeneity and biomechanical and biochemical properties.