title: A microchip filter device incorporating slit arrays and 3-D flow for detection of circulating tumor cells using CAV1-EpCAM conjugated microbeads.
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.
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 135-710, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea.
authors.forename: Yeon Jeong
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-749, Korea.
authors.forename: Gi-Bang
authors.initials: GB
authors.lastname: Koo
authors.affiliation: Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Yongin 446-712, Korea.
authors.forename: June-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 135-710, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea.
authors.forename: Hui-Sung
authors.initials: HS
authors.lastname: Moon
authors.affiliation: Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-749, Korea.
authors.forename: Dong-Gun
authors.initials: DG
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-749, Korea.
authors.forename: Da-Gyum
authors.initials: DG
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-749, Korea.
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 135-710, Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Seoul 135-710, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea.
authors.forename: Jong-Myeon
authors.initials: JM
authors.lastname: Park
authors.affiliation: Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Yongin 446-712, Korea.
authors.forename: Minseok S
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon 443-749, Korea.
authors.forename: Hyun Goo
authors.initials: HG
authors.lastname: Woo
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Kim
authors.affiliation: Department of Physics, Korea University, Seoul 136-701, Korea.
authors.forename: Pilsung
authors.initials: P
authors.lastname: Kang
authors.affiliation: Department of Physics, Korea University, Seoul 136-701, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Choi
authors.affiliation: Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co. Ltd., Yongin 446-712, Korea.
authors.forename: Tae Seok
authors.initials: TS
authors.lastname: Sim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Advanced Device Team, DMC R&D center, Samsung Electronics Co. Ltd., Suwon 443-742, Korea. Electronic address: biogun.lee@samsung.com.
authors.forename: Jeong-Gun
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-749, Korea. Electronic address: yousunkim@ajou.ac.kr.
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D051242:Caveolin 1 / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation*; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition; D004867:Equipment Design; D005260:Female; D005374:Filtration / Q000295:instrumentation; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D051242:Caveolin 1; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D055767:Immobilized Proteins
keywords: 3D-flow path membrane filter; CTCs; Caveolin1; EMT