High-Throughput White Blood Cell (Leukocyte) Enrichment from Whole Blood Using Hydrodynamic and Inertial Forces

Lombodorj, Batzorig; Tseng, H.; Chang, Hwan‐You; Lu, Yen‐Wen; Tumurpurev, Namnan; Lee, Chun-Wei; Batdemberel, G.; Wu, Ren-Guei; Tseng, Fan‐Gang

doi:10.3390/mi11030275

Cited by 14 publications

(11 citation statements)

References 37 publications

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“…In a curvilinear channel, the pressure gradient difference in the radial direction will induce a cross sectional secondary flow, consisting of counter-rotating vortices (Dean vortices) above and below the plane of symmetry of the channel, thereby satisfying the mass balance across the inner and outer wall region. The dominating inertial lift forces and the Dean drag force causes particles to migrate and find its equilibrium positions [27][28][29] number of spiral cell-sorting devices have been reported for cell separation according to their size 11,15,16,[30][31][32][33][34] . Despite extremely high volumetric flow rates can obtained in inertial microfluidics, separation of smaller particles is challenging.…”

Section: High Throughput Viscoelastic Particle Focusing and Separation In Spiral Microchannelsmentioning

confidence: 99%

“…The dominating inertial lift forces and the Dean drag force causes particles to migrate and find its equilibrium positions 27 – 29 . A number of spiral cell-sorting devices have been reported for cell separation according to their size 11 , 15 , 16 , 30 – 34 . Despite extremely high volumetric flow rates can obtained in inertial microfluidics, separation of smaller particles is challenging.…”

Section: Introductionmentioning

confidence: 99%

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High throughput viscoelastic particle focusing and separation in spiral microchannels

Kumar

Ramachandraiah

Iyengar

et al. 2021

Sci Rep

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Passive particle manipulation using inertial and elasto-inertial microfluidics have received substantial interest in recent years and have found various applications in high throughput particle sorting and separation. For separation applications, elasto-inertial microfluidics has thus far been applied at substantial lower flow rates as compared to inertial microfluidics. In this work, we explore viscoelastic particle focusing and separation in spiral channels at two orders of magnitude higher Reynolds numbers than previously reported. We show that the balance between dominant inertial lift force, dean drag force and elastic force enables stable 3D particle focusing at dynamically high Reynolds numbers. Using a two-turn spiral, we show that particles, initially pinched towards the inner wall using an elasticity enhancer, PEO (polyethylene oxide), as sheath migrate towards the outer wall strictly based on size and can be effectively separated with high precision. As a proof of principle for high resolution particle separation, 15 µm particles were effectively separated from 10 µm particles. A separation efficiency of 98% for the 10 µm and 97% for the 15 µm particles was achieved. Furthermore, we demonstrate sheath-less, high throughput, separation using a novel integrated two-spiral device and achieved a separation efficiency of 89% for the 10 µm and 99% for the 15 µm particles at a sample flow rate of 1 mL/min—a throughput previously only reported for inertial microfluidics. We anticipate the ability to precisely control particles in 3D at extremely high flow rates will open up several applications, including the development of ultra-high throughput microflow cytometers and high-resolution separation of rare cells for point of care diagnostics.

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Section: High Throughput Viscoelastic Particle Focusing and Separation In Spiral Microchannelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High throughput viscoelastic particle focusing and separation in spiral microchannels

Kumar

Ramachandraiah

Iyengar

et al. 2021

Sci Rep

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“…To purify total population of WBCs from whole blood, which contains a huge portion of red blood cells (RBCs), an indirect way of removing RBCs is an alternative. For example, in a recent study, suction of RBCs was used to remove the non-WBCs by adding a suction tube into inertial microfluidics [33]. However, due to the similarity between the size of RBCs and the minimum size of WBCs, it is not avoidable to lose a small portion of WBCs, which resulted in obtaining the recovery rate of 93%.…”

Section: Introductionmentioning

confidence: 99%

A low‐cost and high‐throughput benchtop cell sorter for isolating white blood cells from whole blood

Tayebi

2021

Electrophoresis

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The ability to isolate and purify white blood cells (WBCs) from mixed ensembles such as blood would benefit autologous cell-based therapeutics as well as diagnosis of WBC disorders. Current WBCs isolation methods have the limitations of low purity or requiring complex and expensive equipment. In addition, due to the overlap in size distribution between lymphocytes (i.e., a sub-population of WBCs) and red blood cells (RBCs), it is challenging to achieve isolation of entire WBCs populations. In this work, we developed an inertial microfluidics-based cell sorter, which enables size-based, high-throughput isolation, and enrichment of WBCs from RBC-lysed whole blood. Using the developed inertial microfluidic chip, the sorting resolution is sharpened within 2 μm, which achieved separation between 3 and 5 μm diameter particles. Thus, with the present cell sorter, a full population of WBCs can be isolated from RBC-lysed blood samples with recovery ratio of 92%, and merely 5% difference in the composition percentage of the three subpopulations of granulocytes, monocytes, and lymphocytes compared to the original sample. Furthermore, our cell sorter is designed to enable broad application of size-based inertial cell sorting by supplying a series of microchips with different sorting cutoff size. This strategy allows us to further enrich the lymphocytes population by twofold using another microchip with a cutoff size between 10 and 15 μm. With simplicity and efficiency, our cell sorter provides a powerful platform for isolating and sorting of WBCs and also envisions broad potential sorting applications for other cell types.

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“…Besides incorporating filters within the microfluidic device, a passive microfluidic chip driven by the inertial migration effect was also developed to separate and enrich leukocytes from whole blood. 177 The chip design incorporated 10 switchback curve channels bridged by straight channels for inducing inertial migration effects to concentrate the blood cells while the curved channels were integrated for inducing Dean flow -a secondary cross-sectional force field characterized by the two counter-rotating vortices perpendicular to the direction of the flow for further separation of cells based on their sizes. 178 This configuration led to the very high erythrocyte separation efficiency with almost no erythrocyte loss (B100% capture efficiency) while still recovering B93.2% of the leukocytes from whole blood.…”

Section: Microfluidic Devices For Erythrocytapheresismentioning

confidence: 99%

Blood apheresis technologies – a critical review on challenges towards efficient blood separation and treatment

et al. 2021

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High-Throughput White Blood Cell (Leukocyte) Enrichment from Whole Blood Using Hydrodynamic and Inertial Forces

Cited by 14 publications

References 37 publications

High throughput viscoelastic particle focusing and separation in spiral microchannels

High throughput viscoelastic particle focusing and separation in spiral microchannels

A low‐cost and high‐throughput benchtop cell sorter for isolating white blood cells from whole blood

Blood apheresis technologies – a critical review on challenges towards efficient blood separation and treatment

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