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 ml min 21 . The fraction of MCF7 cells was increased from 0.36 ¡ 0.04 to 0.83 ¡ 0.04 under these optimized conditions.

Cell-matrix adhesion characterization using multiple shear stress zones in single stepwise microchannel

“…The previous conventional macro-scale set-ups such as flow chamber [6][7][8][9] and rotating disk 10 were used to generate shear force to detach cells from the surface. Microfluidics has been also introduced into cell adhesion study [6][7][8][9][10][11][12][13][14][15][16][17][18][19] because it only requires simple setup and provides fast response. Previous microfluidic cell adhesion chip with single microchannel, 11 however, was incapable of analyzing the response of the cells simultaneously for multiple shear stresses.…”

Effect of a blind spot in a dielectrophoretic field on the separation of human breast cancer cells (MCF 7)

“…In the biomedical research field, microfabrication technology has provided various tools [1] for particle separation based on electric [2][3][4], magnetic [5][6][7], optical [8], hydrodynamic [9,10], ultrasonic force [11,12], and adhesion difference [13]. Nevertheless, most attempts at efficient manipulation of bioparticles in microchannels have proven to be more challenging.…”

Probing the mechanical properties of brain cancer cells using a microfluidic cell squeezer device

“…Our observation is consistent with a previous study that demonstrated that benign MCF10A breast epithelial cells can be differentiated from MCF7 breast cancer cells by their higher adhesion to label-free micro-patterned surfaces in microfluidic chips. 31 …”