Hydrodynamic mechanisms of cell and particle trapping in microfluidics

Viscoelasticity-induced particle migration has recently received increasing attention due to its ability to obtain high-quality focusing over a wide range of flow rates. However, its application is limited to low throughput regime since the particles can defocus as flow rate increases. Using an engineered carrier medium with constant and low viscosity and strong elasticity, the sample flow rates are improved to be one order of magnitude higher than those in existing studies. Utilizing differential focusing of particles of different sizes, here we present sheathless particle/cell separation in simple straight microchannels that possess excellent parallelizability for further throughput enhancement. The present method can be implemented over a wide range of particle/cell sizes and flow rates. We successfully separate small particles from larger particles, MCF-7 cells from red blood cells (RBCs), and Escherichia coli (E. coli) bacteria from RBCs in different straight microchannels. The proposed method could broaden the applications of viscoelastic microfluidic devices to particle/cell separation due to the enhanced sample throughput and simple channel design.Continuous manipulation and separation of particles and cells is important for a wide range of applications in biology, 1,2 medicine, 2,3 and industry. [4][5][6] Microfluidic systems have been proven to be promising tools for particle/cell manipulation with higher sensitivity and accuracy than their macroscale counterparts. The last decade has seen extensive development of microfluidic approaches for particle/cell manipulation that resort to immunocapture, 7 externally applied physical fields, [8][9][10][11][12][13][14][15][16][17][18] microfiltration, 19,20 gravitational sedimentation, 21 or deterministic lateral migration. 22,23 More recently, cross-streamline migration induced by the hydrodynamic effects of carrier media, such as inertia 24,25 and viscoelasticity, 26,27 has shown its promise for effective particle/cell manipulation without need of labeling and external force fields. Particles and cells can be separated based on the size-dependent nature of hydrodynamic forces. Briefly, the inertial lift scales as F a ∝ , where a is the particle diameter. There are several cell types of biological and clinical interest with separable size ranges: epithelial tumor cells (15-25 µm in diameter), blood cells (erythrocytes are 6-8 µm biconcave disks and peripheral blood lymphocytes are 7-10 µm in diameter), and bacteria (1-3 µm). Inertial migration in Newtonian fluids has been intensively studied and implemented in high-throughput label-free separation devices for cell separation. [28][29][30][31][32][33][34] Recently, particle migration induced by viscoelasticity has begun to attract increasing attention due to its simple focusing pattern and potential for achieving efficient focusing over a wide range of flow rates. 35,36 In a viscoelastic medium, elasticity coupled with non-negligible inertia will drive particles towards the channel centerline, whic...

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“…46 The elastic lift e F on a particle arises from the imbalance of 1 N over the particle, and can be expressed as: 27…”

Section: Design Principlesmentioning

confidence: 99%

Size-Based Separation of Particles and Cells Utilizing Viscoelastic Effects in Straight Microchannels

et al. 2015

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“…By properly designing the geometry of apparatus, the cross streamline migration can be used in cell and particle focusing, sorting, separation, filtration, enrichment and trapping. Review articles by Di and Karimi et al (2013) provide a comprehensive discussion of the progress and future directions in this area.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of particle migration in channel flow of viscoelastic fluids

2015

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The migration of a sphere in the pressure-driven channel flow of a viscoelastic fluid is studied numerically. The effects of inertia, elasticity, shear-thinning viscosity, secondary flows and the blockage ratio are considered by conducting fully resolved direct numerical simulations over a wide range of parameters. In a Newtonian fluid in the presence of inertial effects, the particle moves away from the channel centreline. The elastic effects, however, drive the particle towards the channel centreline. The equilibrium position depends on the interplay between the elastic and inertial effects. Particle focusing at the centreline occurs in flows with strong elasticity and weak inertia. Both shear-thinning effects and secondary flows tend to move the particle away from the channel centreline. The effect is more pronounced as inertia and elasticity effects increase. A scaling analysis is used to explain these different effects. Besides the particle migration, particle-induced fluid transport and particle migration during flow start-up are also considered. Inertia effects, shear-thinning behaviour, and secondary flows are all found to enhance the effective fluid transport normal to the flow direction. Due to the oscillation in fluid velocity and strong normal stress differences that develop during flow start-up, the particle has a larger transient migration velocity, which may be potentially used to accelerate the particle-focusing.

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“…5,6,[15][16][17][18][19] We 24,38 and others 16,17,33,38,42 used straight channels to order cells into multiple equilibration positions for size-based separations and flow cytometry. Although straight rectangular channels can be used to sort multiple cell types in single pass, separating more than two cell types causes drastic reduction in sorting efficiency and throughput, especially in high aspect ratio channels.…”

Section: Introductionmentioning

confidence: 99%

Continuous separation of blood cells in spiral microfluidic devices

2013

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Blood cell sorting is critical to sample preparation for both clinical diagnosis and therapeutic research. The spiral inertial microfluidic devices can achieve label-free, continuous separation of cell mixtures with high throughput and efficiency. The devices utilize hydrodynamic forces acting on cells within laminar flow, coupled with rotational Dean drag due to curvilinear microchannel geometry. Here, we report on optimized Archimedean spiral devices to achieve cell separation in less than 8 cm of downstream focusing length. These improved devices are small in size (<1 in. 2 ), exhibit high separation efficiency ($95%), and high throughput with rates up to 1 Â 10 6 cells per minute. These device concepts offer a path towards possible development of a lab-on-chip for point-of-care blood analysis with high efficiency, low cost, and reduced analysis time. V C 2013 AIP Publishing LLC.

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Hydrodynamic mechanisms of cell and particle trapping in microfluidics

Cited by 347 publications

References 177 publications

Size-Based Separation of Particles and Cells Utilizing Viscoelastic Effects in Straight Microchannels

Size-Based Separation of Particles and Cells Utilizing Viscoelastic Effects in Straight Microchannels

Dynamics of particle migration in channel flow of viscoelastic fluids

Continuous separation of blood cells in spiral microfluidic devices

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