Rapid isolation of cancer cells using microfluidic deterministic lateral displacement structure

Abstract

This work reports a microfluidic device with deterministic lateral displacement (DLD) arrays allowing rapid and label-free cancer cell separation and enrichment from diluted peripheral whole blood, by exploiting the size-dependent hydrodynamic forces. Experiment data and theoretical simulation are presented to evaluate the isolation efficiency of various types of cancer cells in the microfluidic DLD structure. We also demonstrated the use of both circular and triangular post arrays for cancer cell separation in cell solution and blood samples. The device was able to achieve high cancer cell isolation efficiency and enrichment factor with our optimized design. Therefore, this platform with DLD structure shows great potential on fundamental and clinical studies of circulating tumor cells.

Figure 1

Schematic illustration of the microfluidic DLD design for cancer cell isolation from blood. (a) Overview of the device. (b) Flow chamber with circular micropost array showing the trajectory of cancer cells, leukocytes, and erythrocytes. (c) Three outlet channels showing cancer cell isolation effect: cancer cells are collected by the middle narrow channel. (d)Triangular micropost array.

Figure 2

The fabricated cancer cell isolation chip. (a) Device overview. (b) The outlet portion of the device consists of a row of microposts with gradually decreasing gaps, as indicated in the blue circle.

Figure 3

Cell isolation efficiency of circular DLD array. (a) Images of MCF-7, KYSE150, A549, HEPG2, and MDAMB231 cells. (b) Image of cancer cells isolated and concentrated to the centre narrow channel at flow rate of 30 μl/min. (c) Isolation efficiency for MCF-7, KYSE150, MDAMB231, A549, and HEPG2 cell lines at flow rates of 30, 50, 100, 500, 1000, and 2000 μl/min. (d) Isolation efficiency at lower flow rates with error bars representing standard deviations (n = 3).

Figure 4

Cell isolation efficiency of triangular DLD array. Error bars show standard deviations (n = 3). (a) Cells were isolated and focused to the centre narrow channel at flow rate of 50 μl/min. (b) Isolation efficiency for MCF-7 and MDAMB231 cell lines at flow rates of 50, 100, 500, 1000, and 2000 μl/min. (c) Isolation efficiency for MCF-7 and MDAMB231 cell lines at flow rates of 100 and 1000 μl/min.

Figure 5

Comparison of cancer cell isolation efficiency between circular and triangular DLD arrays. Error bars show standard deviations (n = 3). (a) MCF-7 isolation efficiency. (b) MDAMB231 isolation efficiency.

Figure 6

Isolation of MCF-7 and MDAMB231 from spiked diluted blood sample with triangular DLD array. (a) Image of blood sample flowing through the microfluidic device. (b) MCF-7 and MDAMB231 isolation efficiency. (c) Image of MCF-7 cells in diluted blood sample before processing. MCF-7 cells were pre-stained by Vybrant^® DyeCycle™ Green. (d)Image of MCF-7 cells (green) in the collected solution of triangular micropost array. After flowing through the chip, the MCF-7 cells were significantly enriched.

Figure 7

Simulation of cell movement and experimental observation in DLD arrays. (a) and (b) Schematic illustration of cell movement and deformation in circular and triangular DLD arrays. Cells were added after simulation. (c) Cell deformation at flow rate 1000 μl/min in circular and triangular DLD arrays. Cells had significant deformation in circular DLD structure while there was no cell deformation in triangular DLD structure.