A microchip filter device incorporating slit arrays and 3-D flow for detection of circulating tumor cells using CAV1-EpCAM conjugated microbeads

Yeon Jeong Kim, Gi Bang Koo, June Young Lee, Hui Sung Moon, Dong Gun Kim, Da Gyum Lee, Ju Yeon Lee, Jin Ho Oh, Jong Myeon Park, Minseok S. Kim, Hyun Goo Woo, Seung Il Kim, Pilsung Kang, Wonshik Choi, Tae Seok Sim, Woong Yang Park, Jeong Gun Lee, You Sun Kim

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Circulating tumor cells (CTCs) are rare cells and the presence of these cells may indicate a poor prognosis and a high potential for metastasis. Despite highly promising clinical applications, CTCs have not been investigated thoroughly, due to many technical limitations faced in their isolation and identification. Current CTC detection techniques mostly take the epithelial marker epithelial cell adhesion molecule (EpCAM), however, accumulating evidence suggests that CTCs show heterogeneous EpCAM expression due to the epithelial-to-mesenchymal transition (EMT). In this study, we report that a microchip filter device incorporating slit arrays and 3-dimensional flow that can separate heterogeneous population of cells with marker for CTCs. To select target we cultured breast cancer cells under prolonged mammosphere culture conditions which induced EMT phenotype. Under these conditions, cells show upregulation of caveolin1 (CAV1) but down-regulation of EpCAM expression. The proposed device which contains CAV1-EpCAM conjugated bead has several tens of times increased throughput. More importantly, this platform enables the enhanced capture yield from metastatic breast cancer patients and obtained cells that expressed various EMT markers. Further understanding of these EMT-related phenotypes will lead to improved detection techniques and may provide an opportunity to develop therapeutic strategies for effective treatment and prevention of cancer metastasis.

Original languageEnglish
Pages (from-to)7501-7510
Number of pages10
JournalBiomaterials
Volume35
Issue number26
DOIs
Publication statusPublished - 2014 Jan 1

    Fingerprint

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Kim, Y. J., Koo, G. B., Lee, J. Y., Moon, H. S., Kim, D. G., Lee, D. G., Lee, J. Y., Oh, J. H., Park, J. M., Kim, M. S., Woo, H. G., Kim, S. I., Kang, P., Choi, W., Sim, T. S., Park, W. Y., Lee, J. G., & Kim, Y. S. (2014). A microchip filter device incorporating slit arrays and 3-D flow for detection of circulating tumor cells using CAV1-EpCAM conjugated microbeads. Biomaterials, 35(26), 7501-7510. https://doi.org/10.1016/j.biomaterials.2014.05.039