Multivalent Binding, Cell Rolling, and Micropatterning for Enhanced Detection of Circulating Tumor Cells

Circulating tumor cells (CTCs) in the blood of cancer patients are related to cancer progress and metastasis. CTCs can be isolated from non-epithelial, hematological cells using one of antibodies against epithelial cell surface markers called epithelial-cell-adhesion-molecule (EpCAM), human-epidermal-growth-factor- receptor-2 (HER-2), and prostate-specific-antigen (PSA). However, the effective detection of CTCs has a challenge coming from the extreme rarity of CTCs (approximately one tumor cell in the background of one million - one billion blood cells). Recently, we have developed a novel surface system that is programmed to mimic two naturally occurring processes to detect these rare cells at great sensitivity and selectivity: i) E-selectin- mediated cancer cell rolling and ii) the multivalent binding through multiple antibodies immobilized on a dendrimer. A poly(amidoamine) dendrimer, a spherical polymer with multiple reactive groups on its surface, was used to mediate the multivalent binding effect. The biomimetic combination of E-selectin and antibody- dendrimer conjugate was micropatterned on a multifunctional surface using a gasket for effective recruitment and specific isolation of tumor cells, respectively. With in vitro spiked cancer cells in culture media or human blood, the multifunctional surfaces resulted in a significantly enhanced tumor cell detection by ~39-fold at maximum with higher binding stability than the control surfaces. This study demonstrates a novel surface engineering approach to exploiting the E-selectin-mediated cell rolling and strong multivalent binding, which has great potential for clinically significant detection of CTCs.