title: Label-free, microfluidic separation and enrichment of human breast cancer cells by adhesion difference.
abstract: A label-free microfluidic method for separation and enrichment of human breast cancer cells is presented using cell adhesion as a physical marker. To maximize the adhesion difference between normal epithelial and cancer cells, flat or nanostructured polymer surfaces (400 nm pillars, 400 nm perpendicular, or 400 nm parallel lines) were constructed on the bottom of polydimethylsiloxane (PDMS) microfluidic channels in a parallel fashion using a UV-assisted capillary moulding technique. The adhesion of human breast epithelial cells (MCF10A) and cancer cells (MCF7) on each channel was independently measured based on detachment assays where the adherent cells were counted with increasing flow rate after a pre-culture for a period of time (e.g., one, two, and four hours). It was found that MCF10A cells showed higher adhesion than MCF7 cells regardless of culture time and surface nanotopography at all flow rates, resulting in label-free separation and enrichment of cancer cells. For the cell types used in our study, an optimum separation was found for 2 hours pre-culture on the 400 nm perpendicular line pattern followed by flow-induced detachment at a flow rate of 200 microl min(-1). The fraction of MCF7 cells was increased from 0.36 +/- 0.04 to 0.83 +/- 0.04 under these optimized conditions.
authors.affiliation: School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Korea.
authors.forename: Keon Woo
authors.initials: KW
authors.lastname: Kwon
authors.forename: Sung Sik
authors.initials: SS
authors.lastname: Choi
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Byungkyu
authors.initials: B
authors.lastname: Kim
authors.forename: Se Na
authors.initials: SN
authors.lastname: Lee
authors.forename: Min Cheol
authors.initials: MC
authors.lastname: Park
authors.forename: Pilnam
authors.initials: P
authors.lastname: Kim
authors.forename: Se Yon
authors.initials: SY
authors.lastname: Hwang
authors.forename: Kahp Y
authors.initials: KY
authors.lastname: Suh
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D006801:Humans; D044085:Microfluidics / Q000379:methods*; D049329:Nanostructures