Combination of mechanical and molecular filtration for enhanced enrichment of circulating tumor cells

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  1. Available on September 6, 2017
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DOIResolve DOI: http://doi.org/10.1021/acs.analchem.6b01324
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TypeArticle
Journal titleAnalytical Chemistry
ISSN0003-2700
1520-6882
Volume88
Issue17
Pages85108517
AbstractCirculating tumor cells (CTCs) have been linked to cancer progression but are difficult to isolate, as they are very rare and heterogeneous, covering a range of sizes and expressing different molecular receptors. Filtration has emerged as a simple and powerful method to enrich CTCs but only captures cells above a certain size regardless of molecular characteristics. Here, we introduce antibody-functionalized microfilters to isolate CTCs based on both size and surface receptor expression. We present a 3D printed filtration cartridge with microfabricated polymer filters with 8, 10, 12, 15, or 20 μm-diameter pores. Pristine filters were used to optimize sample dilution, rinsing protocol, flow rate, and pore size, leading to >80% for the recovery of spiked cancer cells with very low white blood cell contamination (<1000). Then, filters were functionalized with antibodies against either epithelial cell adhesion molecule (EpCAM) or epidermal growth factor receptor (EGFR) and the cartridges were used to enrich breast (MDA-MB-231, MCF-7) and renal (786-O, A-498) cancer cells expressing various levels of EpCAM and EGFR. Cancer cells were spiked into human blood, and when using filters with antibodies specific to a molecular receptor expressed on a cell, efficiency was increased to >96%. These results suggest that filtration can be optimized to target specific CTC characteristics such as size and receptor expression and that a diverse range of CTCs may be captured using particular combinations of pore size, filtration parameters, and antibody functionalization.
Publication date
LanguageEnglish
AffiliationMedical Devices; National Research Council Canada
Peer reviewedYes
NPARC number23001205
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Record identifierb5eb2c97-14cf-41f7-8e9e-9c075fcd6d60
Record created2017-01-05
Record modified2017-01-05
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