title: Microcavity array system for size-based enrichment of circulating tumor cells from the blood of patients with small-cell lung cancer.
abstract: In this study, we present a method for efficient enrichment of small-sized circulating tumor cells (CTCs) such as those found in the blood of small-cell lung cancer (SCLC) patients using a microcavity array (MCA) system. To enrich CTCs from whole blood, a microfabricated nickel filter with a rectangular MCA (10(4) cavities/filter) was integrated with a miniaturized device, allowing for the isolation of tumor cells based on differences in size and deformability between tumor and blood cells. The shape and porosity of the MCA were optimized to efficiently capture small tumor cells on the microcavities under low flow resistance conditions, while allowing other blood cells to effectively pass through. Under optimized conditions, approximately 80% of SCLC (NCI-H69 and NCI-H82) cells spiked in 1 mL of whole blood were successfully recovered. In clinical samples, CTCs were detectable in 16 of 16 SCLC patients. In addition, the number of leukocytes captured on the rectangular MCA was significantly lower than that on the circular MCA (p < 0.001), suggesting that the use of the rectangular MCA diminishes a considerable number of carryover leukocytes. Therefore, our system has potential as a tool for the detection of CTCs in small cell-type tumors and detailed molecular analyses of CTCs.
authors.affiliation: Division of Biotechnology and Life Science, Institute of Engineering, Tokyo University of Agriculture and Technology, Koganei, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Negishi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshino
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.forename: Tateaki
authors.initials: T
authors.lastname: Naito
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kikuhara
authors.forename: Hisashige
authors.initials: H
authors.lastname: Kanbara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsunaga
mesh_terms: D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D048429:Cell Size; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D055752:Small Cell Lung Carcinoma / Q000097:blood* / Q000175:diagnosis