Continuous blood cell separation by hydrophoretic filtration

Abstract

We propose a new hydrophoretic method for continuous blood cell separation using a microfluidic device composed of slanted obstacles and filtration obstacles. The slanted obstacles have a larger height and gap than the particles in order to focus them to a sidewall by hydrophoresis. In the successive structure, the height and gap of the filtration obstacles with a filtration pore are set between the diameters of small and large particles, which defines the critical separation diameter. Accordingly, the particles smaller than the criterion freely pass through the gap and keep their focused position. In contrast, the particles larger than the criterion collide against the filtration obstacle and move into the filtration pore. The microfluidic device was characterized with polystyrene beads with a minimum diameter difference of 7.3%. We completely separated polystyrene microbeads of 9 and 12 microm diameter with a separation resolution of approximately 6.2. This resolution is increased by 6.4-fold compared with our previous separation method based on hydrophoresis (S. Choi and J.-K. Park, Lab Chip, 2007, 7, 890, ref. 1). In the isolation of white blood cells (WBCs) from red blood cells (RBCs), the microfluidic device isolated WBCs with 210-fold enrichment within a short filtration time of approximately 0.3 s. These results show that the device can be useful for the binary separation of a wide range of biological particles by size. The hydrophoretic filtration as a sample preparation unit offers potential for a power-free cell sorter to be integrated into disposable lab-on-a-chip devices.

A method for reducing pressure-induced deformation in silicone microfluidics

“…17 It is also relevant to other particle separation approaches that use obstacles and to microfluidic sheathing in PDMS. [18][19][20] Limitations to this technique include more difficult input and output connections and the need for a clean, flat surface.…”

Hydrodynamic mechanisms of cell and particle trapping in microfluidics

“…18 The controlling mechanism in the aforementioned handling techniques can be classified in two categories: active methods based on the application of external force fields and passive methods where their functionality is established by harnessing microchannel geometrical effects and nonlinear hydrodynamic forces. In the past decade, extensive investigations have been conducted in order to trap and sort cells and particles using either innovative active techniques, such as dielectrophoresis (DEP), [19][20][21][22] magnetophoresis, 23 acoustophoresis, 24 and optical tweezers, 25 or novel passive approaches, including pinched flow fractionation (PFF), 26 hydrodynamic filtration, 27 biomimetic methods, 28 hydrophoretic focusing, 29 deterministic lateral displacement (DLD), 30 and surface acoustic wave (SAW)-induced streaming. 31 Each of these methods is associated with some advantages and deficiencies which make them preferable in certain applications.…”

Microfluidic bio-particle manipulation for biotechnology

“…The presence of slanted or anisotropic obstacles within the microchannel can also induce size-based motion of the particles due to the particle-obstacle interaction induced rotational flows, which is known as hydrophoresis (see Fig. 1b) and can be implemented for bio-particle separation, sorting and focusing [21][22][23][24][25][26]. With the introduction of contraction/expansion (pinch segment) within the microchannel network together with the laminar flow profile, bioparticles can also be manipulated to flow at different streamlines, which is known as pinch-flow fractionation (PFF) (see Fig 1c) and can be implemented for bio-particle separation, sorting and focusing [27][28][29][30][31].…”

“…Separation by size includes (i) enrichment of low-concentrated cancer cells from the peritoneal wash [114], separation of plasma from whole blood [115] using filtration, (ii) separation of white blood cells (WBCs) and RBCs [17], separation of plasma from whole blood [17], separation of parasites from human blood [19], capturing of circulating tumor cells (assisted by affinity-based cell culture) using DLD, (iii) separation of RBCs and WBCs [22] and separation of U937 (human leukemic monocyte lymphoma cell line) cells at different phase using hydrophoresis, (iv) enrichment of leukocyte [30] using PFF, and (v) separation of Escherichia coli from RBCs, separation of WBCs, MCF-7 and MDA-MB-231 breast cancer cells [116], focusing of Jurkat and MCF7 (a breast carcinoma cell line) [38], separation of HeLa and MCF cells [34], focusing of HeLa and Jurkat cells [39], separation of plasma from whole blood [117] using inertial microfluidics. Separation by shape includes (i) separation of parasites from human blood [19], filtration of budding yeast cells [18], separation of RBCs [20] using DLD, (ii) separation of RBCs from whole blood [28] using PFF, (iii) focusing and separation of Saccharomyces cerevisiae yeast cells [40] using inertial microfluidics.…”