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

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

来源：Biomaterials, 2014, 35(26): 7501-7510.

DOI：10.1016/j.biomaterials.2014.05.039

• CTCs
• EMT
• Caveolin1
• 3D-flow path membrane filter

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.

• 出版日期2014-8