title: Dual-patterned immunofiltration (DIF) device for the rapid efficient negative selection of heterogeneous circulating tumor cells.
abstract: The analysis of circulating tumor cells (CTCs) is an emerging field for estimating the metastatic relapse and tumor burden of cancer patients. However, the isolation of CTCs is still challenging due to their ambiguity, rarity, and heterogeneity. Here, we present an anti-CD45 antibody based dual-patterned immunofiltration (DIF) device for the enrichment of heterogeneous CTC subtypes by effective elimination of leukocytes. Our uniquely designed dual-patterned layers significantly enhance the binding chance between immuno-patterns and leukocytes due to the fluidic whirling and the increased binding sites, thus achieving superior negative selection in terms of high-throughput and high purity. From the experiments using lung cancer cells, 97.07 ± 2.79% of leukocytes were eliminated with less than 10% loss of cancerous cells at the flow rate of 1 mL h-1. To verify the device as a potential diagnostic tool, CTCs were collected from 11 cancer patients' blood and an average of 283.3 CTC-like cells were identified while less than 1 CTC-like cells were found from healthy donors. The samples were also analyzed by immunohistochemistry and the reverse transcription polymerase chain reaction to identify their heterogeneous characteristics. These remarkable results demonstrate that the present device could help to understand the unknown properties or undiscovered roles of CTCs with a non-biased view.
authors.affiliation: Cell Bench Research Center, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea. nanosys@kaist.ac.kr.
authors.forename: Jiyoon
authors.initials: J
authors.lastname: Bu
authors.affiliation: Cell Bench Research Center, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea. nanosys@kaist.ac.kr.
authors.forename: Yoon-Tae
authors.initials: YT
authors.lastname: Kang
authors.affiliation: Cell Bench Research Center, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea. nanosys@kaist.ac.kr.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Cell Bench Research Center, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea. nanosys@kaist.ac.kr.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Sungkyunkwan University School of Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
authors.forename: Hojoong
authors.initials: H
authors.lastname: Kim
authors.affiliation: College of Medicine, Ewha Womans University and Ewha Medical Research Institute, 911-1, MokDong, YangCheon-Ku, Seoul, 07985, Republic of Korea.
authors.forename: Byung-In
authors.initials: BI
authors.lastname: Moon
authors.affiliation: Catholic University of Daegu School of Medicine, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu, 42472, Republic of Korea.
authors.forename: Ho Gak
authors.initials: HG
authors.lastname: Kim
mesh_terms: D055910:Antibodies, Immobilized / Q000276:immunology; D002469:Cell Separation / Q000295:instrumentation*; D004867:Equipment Design; D005374:Filtration / Q000295:instrumentation*; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000276:immunology* / Q000473:pathology*; D013997:Time Factors
chemical_list: D055910:Antibodies, Immobilized