Title:
Negative Enrichment of Circulating Tumor Cells Via 3D Printed Microfluidic Device
Negative Enrichment of Circulating Tumor Cells Via 3D Printed Microfluidic Device
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Chu, Chia-Heng
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Sarioglu, A. Fatih
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Abstract
Circulating tumor cells (CTCs) are cells that detach from the primary tumor inside the cancer patient’s body to circulate in the bloodstream and cause the metastasis of the cancer. Routine and reliable isolation of CTCs from peripheral blood would both allow effective monitoring of the disease burden and guide the development of personalized treatments for cancer patients. Negative enrichment of CTCs by depleting normal blood cells from patient samples not only ensures against a biased selection of a subpopulation but also allows the assay to be used on patients with different tumor types. In my doctoral thesis, I developed an additively manufactured microfluidic device that can negatively enrich viable CTCs from clinically-relevant volumes of unmanipulated whole blood samples. The microfluidic device depletes nucleated blood cells based on their surface antigens and the smaller anucleated cells based on their size contrast with the tumor cells. Also, enriched CTCs are made available off the device in a suspension making our technique compatible with standard immunocytochemical, molecular and functional assays. The densely micropatterned 3D device could deplete >99.5% of white blood cells from 10 mL of unmanipulated whole blood while recovering >90% of spiked tumor cells. I also demonstrated the clinical utility of the device by isolating CTCs from blood samples collected from patients with prostate and pancreatic cancers. This creates a universal CTC assay that can differentiate tumor cells from normal blood cells with the specificity of clinically established membrane antigens yet with no labels on the sample offers the potential to enable routine screening of blood samples for tumor load at the point-of-care.
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Date Issued
2021-07-27
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Dissertation