Fully automated circulating tumor cell isolation platform with large-volume capacity based on lab-on-a-disc

Jong Myeon Park, Minseok S. Kim, Hui Sung Moon, Chang Eun Yoo, Donghyun Park, Yeon Jeong Kim, Kyung Yeon Han, June Young Lee, Jin Ho Oh, Sun Soo Kim, Woong Yang Park, Won Yong Lee, Nam Huh

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33 Citations (Scopus)

Abstract

Full automation with high purity for circulating tumor cell (CTC) isolation has been regarded as a key goal to make CTC analysis a "bench-to- bedside" technology. Here, we have developed a novel centrifugal microfluidic platform that can isolate the rare cells from a large volume of whole blood. To isolate CTCs from whole blood, we introduce a disc device having the biggest sample capacity as well as manipulating blood cells for the first time. The fully automated disc platform could handle 5 mL of blood by designing the blood chamber having a triangular obstacle structure (TOS) with lateral direction. To guarantee high purity that enables molecular analysis with the rare cells, CTCs were bound to the microbeads covered with anti-EpCAM to discriminate density between CTCs and blood cells and the CTCs being heavier than blood cells were only settled under a density gradient medium (DGM) layer. To understand the movement of CTCs under centrifugal force, we performed computational fluid dynamics simulation and found that their major trajectories were the boundary walls of the DGM chamber, thereby optimizing the chamber design. After whole blood was inserted into the blood chamber of the disc platform, size- and density-amplified cancer cells were isolated within 78 min, with minimal contamination as much as approximately 12 leukocytes per milliliter. As a model of molecular analysis toward personalized cancer treatment, we performed epidermal growth factor receptor (EGFR) mutation analysis with HCC827 lung cancer cells and the isolated cells were then successfully detected for the mutation by PCR clamping and direct sequencing.

Original languageEnglish
Pages (from-to)3735-3742
Number of pages8
JournalAnalytical Chemistry
Volume86
Issue number8
DOIs
Publication statusPublished - 2014 Apr 15

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry

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    Park, J. M., Kim, M. S., Moon, H. S., Yoo, C. E., Park, D., Kim, Y. J., Han, K. Y., Lee, J. Y., Oh, J. H., Kim, S. S., Park, W. Y., Lee, W. Y., & Huh, N. (2014). Fully automated circulating tumor cell isolation platform with large-volume capacity based on lab-on-a-disc. Analytical Chemistry, 86(8), 3735-3742. https://doi.org/10.1021/ac403456t