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The detection and study of circulating tumor cells (CTCs) are quite important while also challenging because of the rarity and heterogeneity of CTCs in peripheral blood. Despite the advances of microfluidic techniques improve the capture sensitivity to a certain extent, selectively isolating CTCs with a bias of metastatic potential remains a challenge. Here, aptamer-conjugated magnetic nanoparticles (MNPs) combining a microfluidic platform for selective capture and release of CTCs is demonstrated. The nucleic acid aptamers, which have been screened to target high metastatic hepatocellular carcinoma (HCC) cell line, are conjugated to iron oxide MNPs as capture probe, and the microfluidic chip capable of chaotic mixing and dynamically magnetic separation reaches a final capture efficiency of >60 % toward simulated CTCs spiked in whole blood even at low concentrations. By exonuclease treatment, the isolated HCC cells are further released from the attached MNPs, enabling negligible disruption to cell viability and proliferating functions. Interestingly, the RT-PCR analysis shows relatively higher mRNA expression of cytokeratin 19 toward captured HCC cells than escaped HCC cells, indicating the higher metastatic potential. |
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Keywords:circulating tumor cells; microfluidics; aptamers; magnetic nanoparticles |
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