title: Continuous enrichment of circulating tumor cells using a microfluidic lateral flow filtration chip.
abstract: The isolation and characterization of circulating tumor cells (CTC) is of great importance in cancer diagnosis and prognosis. Highly sensitive detection of CTCs can be very difficult because they are extremely rare (i.e., 1-5 CTCs per 10(9) erythrocytes) in blood. Recently, various devices have been developed that exploit biochemical (affinity-based) and physical (size or density) methods. Antibody-based isolation has its own limitations, as the expression level of the epitopes for an antibody varies due to the heterogeneity of cancer cells. Harsh conditions associated with physical methods can cause the deformation and damage of CTCs during the isolation process. Here, we propose a microfluidic lateral flow filtration (μ-LaFF) chip in which lateral flow was combined with vertical flow into the filter to capture the CTCs gently. The CTCs experienced weak shear flow owing to the lateral flow and traveled alongside the filter channel until finally being captured. The vertical flow in the filter held the captured cells tightly and served as an exit for uncaptured hematological cells (white and red blood cells). From our μ-LaFF chip we obtained a high capture efficiency (95%) and purity (99%), minimizing any damage to the CTCs. Our μ-LaFF technology is expected to be useful in the diagnosis and prognosis of various cancers.
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul, Republic of Korea; Center for Biomicrosystems, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul, Republic of Korea.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hyun
authors.affiliation: College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Kim
authors.affiliation: Center for Biomicrosystems, Korea Institute of Science and Technology, Seoul, Republic of Korea. Electronic address: jykang67@gmail.com.
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Kang
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul, Republic of Korea. Electronic address: uridle7@yonsei.ac.kr.
authors.forename: Hyo-Il
authors.initials: HI
authors.lastname: Jung
mesh_terms: D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods; D005374:Filtration / Q000295:instrumentation; D006801:Humans; D044085:Microfluidics; D009360:Neoplastic Cells, Circulating / Q000378:metabolism
keywords: Circulating tumor cells(CTCs); Enrichment; Lateral flow filtration; Microfluidics