title: Continuous Flow Deformability-Based Separation of Circulating Tumor Cells Using Microfluidic Ratchets.
abstract: Circulating tumor cells (CTCs) offer tremendous potential for the detection and characterization of cancer. A key challenge for their isolation and subsequent analysis is the extreme rarity of these cells in circulation. Here, a novel label-free method is described to enrich viable CTCs directly from whole blood based on their distinct deformability relative to hematological cells. This mechanism leverages the deformation of single cells through tapered micrometer scale constrictions using oscillatory flow in order to generate a ratcheting effect that produces distinct flow paths for CTCs, leukocytes, and erythrocytes. A label-free separation of circulating tumor cells from whole blood is demonstrated, where target cells can be separated from background cells based on deformability despite their nearly identical size. In doping experiments, this microfluidic device is able to capture >90% of cancer cells from unprocessed whole blood to achieve 10(4) -fold enrichment of target cells relative to leukocytes. In patients with metastatic castration-resistant prostate cancer, where CTCs are not significantly larger than leukocytes, CTCs can be captured based on deformability at 25× greater yield than with the conventional CellSearch system. Finally, the CTCs separated using this approach are collected in suspension and are available for downstream molecular characterization.
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Park
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Chao
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Quan
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Ang
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Duffy
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Kerryn
authors.initials: K
authors.lastname: Matthews
authors.affiliation: BC Cancer Agency-Vancouver Cancer Centre, 600 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada.
authors.forename: Arun
authors.initials: A
authors.lastname: Azad
authors.affiliation: Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Abdi
authors.affiliation: Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
authors.affiliation: Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Jenny
authors.initials: J
authors.lastname: Bazov
authors.affiliation: BC Cancer Agency-Vancouver Cancer Centre, 600 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada.|Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
authors.affiliation: Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Black
authors.affiliation: Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada.|Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
authors.forename: Hongshen
authors.initials: H
authors.lastname: Ma
mesh_terms: D006801:Humans; D044085:Microfluidics / Q000295:instrumentation*; D009360:Neoplastic Cells, Circulating
keywords: cell deformability; cell separation; circulating tumor cells; microfluidic ratchets; prostate cancer