Double spiral microchannel for label-free tumor cell separation and enrichment

Sun, Jiashu; Li, Mengmeng; Liu, Chao; Zhang, Yi; Liu, Dingbin; Liu, Wenwen; Hu, Guoqing; Jiang, Xingyu

doi:10.1039/c2lc40679a

Cited by 267 publications

(223 citation statements)

References 51 publications

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“…The microfluidic device is fabricated using a standard soft lithography 14,30,31 technique by patterning SU8-2050 (MicroChem Corp., USA) on a silicon wafer (CapitalBio Corp., China). Polydimethylsiloxane (PDMS) mixed with the curing agent (Sylgrad184, Dow Corning Inc., USA) in a ratio of 10:1 is cast over the fabricated wafer and baked at 80 • C for 2 h after degassing.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our group designed double spiral microchannels to focus and separate particles and cells in a high-throughput manner. 14,15 For droplets, Hur et al 16 have experimentally studied the inertial migration of viscous oil droplets with various viscosities in a single straight microchannel with an aspect ratio of approximately 2.3. They determined that deformable droplets occupy equilibrium positions much closer to the channel centerline than do rigid particles.…”

Section: Introductionmentioning

confidence: 99%

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Inertial migration of deformable droplets in a microchannel

Chen

Xue

Zhang³

et al. 2014

Physics of Fluids

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The microfluidic inertial effect is an effective way of focusing and sorting droplets suspended in a carrier fluid in microchannels. To understand the flow dynamics of microscale droplet migration, we conduct numerical simulations on the droplet motion and deformation in a straight microchannel. The results are compared with preliminary experiments and theoretical analysis. In contrast to most existing literature, the present simulations are three-dimensional and full length in the streamwise direction and consider the confinement effects for a rectangular cross section. To thoroughly examine the effect of the velocity distribution, the release positions of single droplets are varied in a quarter of the channel cross section based on the geometrical symmetries. The migration dynamics and equilibrium positions of the droplets are obtained for different fluid velocities and droplet sizes. Droplets with diameters larger than half of the channel height migrate to the centerline in the height direction and two equilibrium positions are observed between the centerline and the wall in the width direction. In addition to the well-known Segré-Silberberg equilibrium positions, new equilibrium positions closer to the centerline are observed. This finding is validated by preliminary experiments that are designed to introduce droplets at different initial lateral positions. Small droplets also migrate to two equilibrium positions in the quarter of the channel cross section, but the coordinates in the width direction are between the centerline and the wall. The equilibrium positions move toward the centerlines with increasing Reynolds number due to increasing deformations of the droplets. The distributions of the lift forces, angular velocities, and the deformation parameters of droplets along the two confinement direction are investigated in detail. Comparisons are made with theoretical predictions to determine the fundamentals of droplet migration in microchannels. In addition, existence of the inner equilibrium position is linked to the quartic velocity distribution in the width direction through a simple model for the slip angular velocities of droplets.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inertial migration of deformable droplets in a microchannel

Chen

Xue

Zhang³

et al. 2014

Physics of Fluids

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“…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, which is more desirable for focusing and further manipulation compared to the pure inertial focusing.…”

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confidence: 99%

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

et al. 2015

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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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“…Moreover, introduction of asymmetrical channel structure can also produce lift forces in simple systems [20]. Curved structures like serpentine or spiral have been frequently employed to improve the performance of inertial manipulation of rigid particles [16,35,36]. For droplets in low Re flows, curved channels would also influence the migration behaviour, which is rarely addressed in existing studies.…”

Section: Introductionmentioning

confidence: 99%

Lateral migration of dual droplet trains in a double spiral microchannel

Xue

Chen

Liu

et al. 2016

Sci. China Phys. Mech. Astron.

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Microfluidic droplets have emerged as novel platforms for chemical and biological applications. Manipulation of droplets has thus attracted increasing attention. Different from solid particles, deformable droplets cannot be efficiently controlled by inertia-driven approaches. Here, we report a study on the lateral migration of dual droplet trains in a double spiral microchannel at low Reynolds numbers. The dominant driving mechanism is elucidated as wall effect originated from the droplet deformation. Three types of migration modes are observed with varying Reynolds numbers and the size-dependent mode is intensively investigated. We obtain empirical formulas by relating the migration to Reynolds numbers and droplet sizes. The effect of droplet deformability on the migration and the detailed migration behavior along the double spiral channel are discussed. Numerical simulations are also performed and yielded in qualitative agreement with the experiments. This proposed low Re approach based on lateral migration could be a promising alternative to existing inertia-driven approaches especially concerning deformable entities and susceptible bio-particles.

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Double spiral microchannel for label-free tumor cell separation and enrichment

Cited by 267 publications

References 51 publications

Inertial migration of deformable droplets in a microchannel

Inertial migration of deformable droplets in a microchannel

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

Lateral migration of dual droplet trains in a double spiral microchannel

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