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Fabrication of a novel filtration device for circulating tumor cells
Thesis   Open access

Fabrication of a novel filtration device for circulating tumor cells

Marina Korinne Lilieholm
Master of Science (M.S.), Drexel University
Jun 2021
DOI:
https://doi.org/10.17918/00000438
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Abstract

Filters and filtration--Mathematical models
More than 90% of cancer-related deaths are caused by metastasis, which is caused by circulating tumor cells (CTCs). CTCs are shed by the primary tumor, enter the systemic blood circulation before lodging in distant organs, where they seed secondary colonies. Of all tumor cells that disseminate, only a few possess the genetic profile to initiate colonization. Enumeration and molecular analysis of these rare cell populations collected through liquid biopsy possesses inherent clinical relevance and yields insight into the biology of metastasis. However, enrichment of CTCs from whole blood is encumbered by their rarity (approximately 1 CTC for every 10^5 to 10^6 peripheral blood mononuclear cells (PBMCs)) and limited to antibody-dependent and independent capture techniques. Antibody-independent methods are preferred because they capture CTCs in an unbiased fashion; however, these methods deliver excessively diluted cell suspensions, with a few hundred cells in five to ten mL of fluid. Recovery of these cells by centrifugation is lengthy, induces cell damage, is overall incompatible with systematic investigation and has so far prevented full integration of CTC analysis into clinical practice. For these reasons, over the last two decades CTCs evaluation has been dominated by antibody-dependent staining on chip, significantly limiting our breadth of knowledge. Herein we describe the design and production of a device capable of collecting CTCs from diluted suspensions and re-eluting them into a 10-fold smaller volume, thus allowing to bridge the technological gap between CTC capture from blood and downstream molecular analyses.

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