Modulation of rotation-induced lift force for cell filtration in a low aspect ratio microchannel

Abstract

Cell filtration is a critical step in sample preparation in many bioapplications. Herein, we report on a simple, filter-free, microfluidic platform based on hydrodynamic inertial migration. Our approach builds on the concept of two-stage inertial migration which permits precise prediction of microparticle position within the microchannel. Our design manipulates equilibrium positions of larger microparticles by modulating rotation-induced lift force in a low aspect ratio microchannel. Here, we demonstrate filtration of microparticles with extreme efficiency (>99%). Using multiple prostate cell lines (LNCaP and human prostate epithelial tumor cells), we show filtration from spiked blood, with 3-fold concentration and >83% viability. Results of a proliferation assay show normal cell division and suggest no negative effects on intrinsic properties. Considering the planar low-aspect-ratio structure and predictable focusing, we envision promising applications and easy integration with existing lab-on-a-chip systems. V C 2014 AIP Publishing LLC.

Microfluidic Platform for Cell Isolation and Manipulation Based on Cell Properties

“…Following this, Papautsky and Bhagat invented several spiral architectures for continuous multi-particle separation [ 83 , 94 , 95 , 96 , 97 , 98 ] operating at higher flow rates of up to 3 mL/min. They invented a two-stage separation technique to separate a range of different cell types including blood and tumor cell.…”

Investigation of particle movement in irregularly shaped channels in inertial fluidics for scale up applications in bioprocessing

“…Increasing the AR of rectangular channel greater than ~5.6 with a blunt velocity profile along the channel width caused widening of particle streaks around the mid plane as a result of weakened wall-induced lift force [32]. Based on their two-stage particle migration in a rectangular channel [36], Zhou et al designed different straight channels for filtration [37,38,99], separation [36,100] and particle ordering cell/particle filtration. Bigger particles migrated faster towards the midplane because migration velocity scales as ∝ , whereas smaller particles remained unfocused and were collected from side outlets (Figure 2-12a) [99].…”

“…Based on their two-stage particle migration in a rectangular channel [36], Zhou et al designed different straight channels for filtration [37,38,99], separation [36,100] and particle ordering cell/particle filtration. Bigger particles migrated faster towards the midplane because migration velocity scales as ∝ , whereas smaller particles remained unfocused and were collected from side outlets (Figure 2-12a) [99]. A channel cross-section consisted of low AR and high AR was fine-tuned along the length for separating cells or particles based on their sizes (Figure 2-12b).…”

“…the trapezoidal channel developed here can focus and filter ~15-µm particle or greater in contrast to smaller particle size of 10 µm or less dispersed. Also, the 1.5-fold concentration of the trapezoidal straight channel can potentially increase to 2-fold by simply cascading two channels, while the whole unit has only one inlet and two outlets, relatively easier than that of the rectangular channels with trifurcation used for filtration [38,99,104]. In a recent work, a rectangular channel with AR=2 (W>H) with higher concentration of 3-fold to filter K~0.4 particles/cells from the center outlet was used [99]; nonetheless, the particle clogging ratio could not exceed K~0.5…”

“…Mainly two equilibrium positions inside a rectangular microchannel, adjacent to the longer walls has been utilized for particle filtration [38,99], fractionation [36], and flow cytometry [134,178] when the AR varies considerably from unity. Recently experimental results demonstrated that the higher the clogging ratio K (0.3≤K<0.4), the higher the AR (2≤AR<5) will be to obtain two strong focusing streaks, i.e.…”