Abstract

We herein propose a new hydrodynamic mechanism of particle separation using dual-depth, lattice-patterned asymmetric microchannel networks. This mechanism utilizes three-dimensional (3D) laminar flow profiles formed at intersections of lattice channels. Large particles, primarily flowing near the bottom surface, frequently enter the shallower channels (separation channels), whereas smaller particles flowing near the microchannel ceiling primarily flow along the deeper channels (main channels). Consequently, size-based continuous particle separation was achieved in the lateral direction in the lattice area. We confirmed that the depth of the main channel was a critical factor dominating the particle separation efficiencies, and the combination of 15-μm-deep separation channels and 40-μm-deep main channels demonstrated the good separation ability for 3–10-μm particles. We prepared several types of microchannels and successfully tuned the particle separation size. Furthermore, the input position of the particle suspension was controlled by adjusting the input flow rates and/or using a Y-shaped inlet connector that resulted in a significant improvement in the separation precision. The presented concept is a good example of a new type of microfluidic particle separation mechanism using 3D flows and may potentially be applicable to the sorting of various types of micrometer-sized objects, including living cells and synthetic microparticles.

Highlights

  • The need to separate micrometer-sized particles precisely, especially mammalian cells of specific phenotypes, is increasing with the recent progress in cell-based liquid biopsy technologies and stem cell engineering [1,2,3]

  • The 3.0- and 4.8-μm particles were separated, indicating that the separation resolution had improved. This result indicated that the small particles were likely to selectively flow near the ceiling of the main channel, whereas the large particles, flowing near the bottom, frequently entered the separation channels (Figure 8e)

  • The separation resolution of the 3.0- and 4.8-μm particles was not high in these experiments, possibly because these particles are relatively small compared to the critical separation size of the presented microfluidic device

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Summary

Introduction

The need to separate micrometer-sized particles precisely, especially mammalian cells of specific phenotypes, is increasing with the recent progress in cell-based liquid biopsy technologies and stem cell engineering [1,2,3]. Representative examples of particle sorting mechanisms that do not necessitate the application of outer forces include deterministic lateral displacement (DLD) [7,8,9], pinched-flow fractionation (PFF) [10,11], hydrodynamic filtration [12,13,14], Dean-flow fractionation [15,16,17], hydrophoresis [18,19,20], inertial microfluidics [21,22], and multi-orifice fractionation [23,24] Most of these techniques utilize precisely controlled flow profiles in a quasi-two-dimensional microchannel, i.e., laminar flow patterns in microchannels with a uniform depth, neglecting the flow rate distribution in the z (depth) direction. We expect that unprecedented but efficient microfluidic mechanisms for particle separation can be developed using three-dimensional (3D) flow profiles in microfluidic channels with non-uniform depths

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