Research Papers

Internal Viscosity-Dependent Margination of Red Blood Cells in Microfluidic Channels

[+] Author and Article Information
Faisal Ahmed

Wallace H. Coulter Department
of Biomedical Engineering,
Georgia Institute of Technology,
Atlanta, GA 30332
e-mail: faisal.ahmedbd@gmail.com

Marmar Mehrabadi

George W. Woodruff School
of Mechanical Engineering,
801 Ferst Drive,
Atlanta, GA 30332
e-mail: marmar@gatech.edu

Zixiang Liu

George W. Woodruff School
of Mechanical Engineering,
801 Ferst Drive,
Atlanta, GA 30332
e-mail: zxliu@gatech.edu

Gilda A. Barabino

Grove School of Engineering,
The City College of New York,
Steinman Hall, Suite 142,
160 Convent Avenue,
New York, NY 10031
e-mail: gbarabino@ccny.cuny.edu

Cyrus K. Aidun

George W. Woodruff School
of Mechanical Engineering,
Parker H. Petit Institute for
Bioengineering and Bioscience,
Georgia Institute of Technology,
Love Building, Room 320,
801 Ferst Drive,
Atlanta, GA 30332
e-mail: cyrus.aidun@me.gatech.edu

1Corresponding author.

Manuscript received June 9, 2017; final manuscript received February 6, 2018; published online April 30, 2018. Assoc. Editor: Nathan Sniadecki.

J Biomech Eng 140(6), 061013 (Apr 30, 2018) (7 pages) Paper No: BIO-17-1250; doi: 10.1115/1.4039897 History: Received June 09, 2017; Revised February 06, 2018

Cytoplasmic viscosity-dependent margination of red blood cells (RBC) for flow inside microchannels was studied using numerical simulations, and the results were verified with microfluidic experiments. Wide range of suspension volume fractions or hematocrits was considered in this study. Lattice Boltzmann method for fluid-phase coupled with spectrin-link method for RBC membrane deformation was used for accurate analysis of cell margination. RBC margination behavior shows strong dependence on the internal viscosity of the RBCs. At equilibrium, RBCs with higher internal viscosity marginate closer to the channel wall and the RBCs with normal internal viscosity migrate to the central core of the channel. Same margination pattern has been verified through experiments conducted with straight channel microfluidic devices. Segregation between RBCs of different internal viscosity is enhanced as the shear rate and the hematocrit increases. Stronger separation between normal RBCs and RBCs with high internal viscosity is obtained as the width of a high aspect ratio channel is reduced. Overall, the margination behavior of RBCs with different internal viscosities resembles with the margination behavior of RBCs with different levels of deformability. Observations from this work will be useful in designing microfluidic devices for separating the subpopulations of RBCs with different levels of deformability that appear in many hematologic diseases such as sickle cell disease (SCD), malaria, or cancer.

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Hou, H. W. , Bhagat, A. A. S. , Chong, A. G. L. , Mao, P. , Tan, K. S. W. , Han, J. , and Lim, C. T. , 2010, “ Deformability Based Cell Margination—A Simple Microfluidic Design for Malaria-Infected Erythrocyte Separation,” Lab Chip, 10(19), pp. 2605–2613. [CrossRef] [PubMed]
Hur, S. C. , Henderson-MacLennan, N. K. , McCabe, E. R. B. , and Di Carlo, D. , 2011, “ Deformability-Based Cell Classification and Enrichment Using Inertial Microfluidics,” Lab Chip, 11(5), pp. 912–920. [CrossRef] [PubMed]
Wang, G. , Mao, W. , Byler, R. , Patel, K. , Henegar, C. , Alexeev, A. , and Sulchek, T. , 2013, “ Stiffness Dependent Separation of Cells in a Microfluidic Device,” PLoS ONE, 8(10), p. e75901.
Segré, G. , and Silberberg, A. , 1961, “ Radial Particle Displacements in Poiseuille Flow of Suspensions,” Nature, 189(4760), pp. 209–210. [CrossRef]
Segré, G. , and Silberberg, A. , 1962, “ Behavior of Macroscopic Rigid Spheres in Poiseuille Flow—Part 2: Experimental Results and Interpretation,” J. Fluid Mech., 14(01), pp. 136–157. [CrossRef]
Matas, J. P. , Morris, J. F. , and Guazzelli, E. , 2004, “ Lateral Forces on a Sphere,” Oil Gas Sci. Technol., 59(1), pp. 59–70. [CrossRef]
Mortazavi, S. , and Tryggvason, G. , 2000, “ A Numerical Study of the Motion of Drops in Poiseuille Flow—Part 1: Lateral Migration of One Drop,” J. Fluid Mech., 411, pp. 325–350. [CrossRef]
Tam, C. K. W. , and Hyman, W. A. , 1973, “ Transverse Motion of an Elastic Sphere in a Shear Field,” J. Fluid Mech., 59(1), pp. 177–185. [CrossRef]
Feng, J. , Hu, H. H. , and Joseph, D. D. , 1994, “ Direct Simulation of Initial Value Problems for the Motion of Solid Bodies in a Newtonian Fluid—Part 2: Couette and Poiseuille Flows,” J. Fluid Mech., 277(1), pp. 271–301. [CrossRef]
Magnaudet, J. , Takagi, S. H. U. , and Legendre, D. , 2003, “ Drag, Deformation and Lateral Migration of a Buoyant Drop Moving Near a Wall,” J. Fluid Mech., 476, pp. 115–157. [CrossRef]
Abkarian, M. , and Viallat, A. , 2005, “ Dynamics of Vesciles in a Wall-Bounded Shear Flow,” Biophys. J., 89(2), pp. 1055–1066. [CrossRef] [PubMed]
McLaughlin, J. B. , 1993, “ The Lift on a Small Sphere in Wall-Bounded Linear Shear Flows,” J. Fluid Mech., 246(1), pp. 249–265. [CrossRef]
Hogg, A. J. , 1994, “ The Inertial Migration of Non-Neutrally Buoyant Spherical Particles in Two-Dimensional Shear Flows,” J. Fluid Mech., 272(1), pp. 285–318. [CrossRef]
Zeng, L. Y. , Balachandar, S. , and Fischer, P. , 2005, “ Wall-Induced Forces on a Rigid Sphere at Finite Reynolds Number,” J. Fluid Mech., 536, pp. 1–25. [CrossRef]
Asmolov, E. S. , 1999, “ The Inertial Lift on a Spherical Particle in a Plane Poiseuille Flow at Large Channel Reynolds Number,” J. Fluid Mech., 381, pp. 63–87. [CrossRef]
Coupier, G. , Kaoui, B. , Podgorski, T. , and Misbah, C. , 2008, “ Noninertial Lateral Migration of Vesicles in Bounded Poiseuille Flow,” Phys. Fluids, 20(11), p. 111702. [CrossRef]
Doddi, S. K. , and Bagchi, P. , 2008, “ Lateral Migration of Capsule in Plane Poiseuille Flow in a Channel,” Int. J. Multiphase Flow, 34(10), pp. 966–986. [CrossRef]
Danker, G. , Vlahovska, P. M. , and Misbah, C. , 2009, “ Vesicles in Poiseuille Flow,” Phys. Rev. Lett., 102(14), p. 148102. [CrossRef] [PubMed]
Chan, P. C.-H. , and Leal, L. G. , 1979, “ The Motion of a Deformable Drop in a Second-Order Fluid,” J. Fluid Mech., 92(01), pp. 131–170. [CrossRef]
Zhou, H. , and Pozrikidis, C. , 1994, “ Pressure-Driven Flow of Suspensions of Liquid Drops,” Phys. Fluids, 6(1), pp. 80–94. [CrossRef]
Karnis, A. , and Mason, S. G. , 1967, “ Particle Motions in Sheared Suspension—XXIII: Wall Migration of Fluid Drops,” J. Colloid Interface Sci., 24(2), pp. 164–169. [CrossRef]
Hiller, W. , and Kowalewski, T. A. , 1986, “ An Experimental Study of the Lateral Migration of a Droplet in a Creeping Flow,” Exp. Fluids, 5(1), pp. 43–48. [CrossRef]
Lan, H. , and Khismatullin, D. B. , 2012, “ A Numerical Study of the Lateral Migration and Deformation of Drops and Leukocytes in a Rectangular Microchannel,” Int. J. Multiphase Flow, 47, pp. 73–84. [CrossRef]
Kilimnik, A. , Mao, W. , and Alexeev, A. , 2011, “ Inertial Migration of Deformable Capsules in Channel Flow,” Phys. Fluids, 23(12), p. 123302. [CrossRef]
Nourbakhsh, A. , Mortazavi, S. , and Afshar, Y. , 2011, “ Three-Dimensional Numerical Simulation of Drops Suspended in Poiseuille Flow at Non-Zero Reynolds Numbers,” Phys. Fluids, 23(12), p. 123303. [CrossRef]
Krüger, T. , Kaoui, B. , and Harting, J. , 2014, “ Interplay of Inertia and Deformability on Rheological Properties of a Suspension of Capsules,” J. Fluid Mech., 751, pp. 725–745. [CrossRef]
Goldsmith, H. L. , and Marlow, J. , 1972, “ Flow Behavior of Erythrocytes. I. Rotation and Deformation in Dilute Suspensions,” Proc. R. Soc. London B, 182(1068), pp. 351–384. [CrossRef]
Dupin, M. M. , Halliday, I. , Care, C. M. , Alboul, L. , and Munn, L. L. , 2007, “ Modeling the Flow of Dense Suspensions of Deformable Particles in Three Dimensions,” Phys. Rev. E, 75(6), p. 066707. [CrossRef]
Goldsmith, H. L. , and Marlow, J. , 1979, “ Flow Behavior of Erythrocytes—II: Particle Motions in Concentrated Suspensions of Ghost Cells,” J. Colloid Interface Sci., 71(2), pp. 383–407. [CrossRef]
Reasor , D. A., Jr. , Clausen, J. R. , and Aidun, C. K. , 2012, “ Coupling the Lattice-Boltzmann and Spectrin-Link Methods for the Direct Numerical Simulation of Cellular Blood Flow,” Int. J. Numer. Meth. Fluids, 68(6), pp. 767–781. [CrossRef]
Reasor , D. A., Jr. , Clausen, J. R. , and Aidun, C. K. , 2013, “ Rheological Characterization of Cellular Blood in Shear,” J. Fluid Mech., 726, pp. 497–516. [CrossRef]
Tsukada, K. , Sekizuka, E. , Oshio, C. , and Minamitani, H. , 2001, “ Direct Measurement of Erythrocyte Deformability in Diabetes Mellitus With a Transparent Microchannel Capillary Model and High-Speed Video Camera System,” Microvasc. Res., 61(3), pp. 231–239. [CrossRef] [PubMed]
Mehrabadi, M. , Aidun, C. K. , and Ku, D. N. , 2013, “ Effects of Channel Size and Shear Rate on Platelet Margination,” ASME Paper No. SBC2013-14599.
Mehrabadi, M. , 2014, “ Effects of red Blood Cells and Shear Rate on Thrombus Growth,” Ph.D. dissertation, Georgia Institute of Technology, Atlanta, GA, p. 8.
Mehrabadi, M. , Ku, D. N. , and Aidun, C. K. , 2016, “ Effects of Shear Rate, Confinement, and Particle Parameters on Margination in Blood Flow,” Phys. Rev. E, 93(2), p. 023109. [CrossRef] [PubMed]
Papautsky, I. , and Zhou, J. , 2013, “ Fundamentals of Inertial Focusing in Microchannels,” Lab Chip, 13(6), pp. 1121–1132. [CrossRef] [PubMed]
Byun, H. , Hillman, T. R. , Higgins, J. M. , Diez-Silva, M. , Peng, Z. , Dao, M. , Dasari, R. R. , Suresh, S. , and Park, Y. , 2012, “ Optical Measurement of Biomechanical Properties of Individual Erythrocytes From a Sickle Cell Patient,” Acta Biomater., 8(11), pp. 4130–4138. [CrossRef] [PubMed]
Barabino, G. A. , Platt, M. O. , and Kaul, D. K. , 2010, “ Sickle Cell Biomechanics,” Annu. Rev. Biomed. Eng., 12, pp. 345–367. [CrossRef] [PubMed]
Fedosov, D. A. , Caswell, B. , and Karniadakis, G. E. , 2010, “ Systematic Coarse-Graining of Spectrin-Level Red Blood Cell Models,” Comput. Methods Appl. Mech. Eng., 199(29–32), pp. 1937–1948. [CrossRef]
Marina, K. , Wu, Z. J. , Uraysh, A. , Repko, B. , Litwak, K. N. , Billiar, T. R. , Fink, M. P. , Simmons, R. L. , Griffith, B. P. , and Borovetz, H. , 2004, “ Blood Soluble Drag-Reducing Polymers Prevent Lethality From Hemorrhagic Shock in Acute Animal Experiments,” Biorheology, 41(1), pp. 53–64. [PubMed]
Goldsmith, H. L. , and Mason, S. G. , 1962, “ The Flow of Suspensions Through Tubes—I: Single Spheres, Rods and Discs,” J. Colloid Sci., 17(5), pp. 448–476. [CrossRef]
Schonberg, J. A. , and Hinch, E. J. , 1989, “ Inertial Migration of a Sphere in Poiseuille Flow,” J. Fluid Mech., 203, pp. 517–524. [CrossRef]


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Fig. 1

Microchannel configuration

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Fig. 2

Single cell simulation cases: (a) snapshots at initial time-step for both  Rec=4  and  Rec=8  cases; (b) snapshot at a time-step after the cells have reached their equilibrium time-step for the  Rec=4  case; (c) snapshot at a time-step after the cells have reached their equilibrium time-step for the  Rec=8  case. N1, normal 1; N2, normal 2; S1, sickle 1; S2, sickle 2.

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Fig. 3

Parachuting of RBC in microcapillary flow: (a) snapshots of RBC shape at three timepoints and (b) variation of RBC deformation with flow velocity

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Fig. 4

Nondimensional lateral trajectories of individual cells: (a) for  Rec=4  and (b) for  Rec=8

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Fig. 5

Internal viscosity-dependent margination of RBCs for the case of  60 μm×60 μm×30 μm  and   Rec=10

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Fig. 6

Effects of wall shear rate  (γ˙w)  and RBC capillary number  (CaG)  on cell-free layer thickness

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Fig. 7

Effects of confinement ratio on margination: (a) shows average nondimensional lateral displacement of cells and (b) shows distance between lateral displacement of sickle and normal cells

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Fig. 8

Effects of shear rate on cell margination: (a) shows average nondimensional lateral displacement of RBCs and (b) shows distance between average trajectories of sickle and normal RBCs

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Fig. 9

Effects of volume fraction on cell margination: (a) shows average nondimensional lateral displacement of RBCs and (b) shows distance between average trajectories of sickle and normal RBCs

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Fig. 10

Cell population distribution (PD %) across the width of channel at a specific lengthwise location. The width is divided in three segments (outlet 1, outlet 2a, and outlet 2b) by two partitions, one located at 12 μm and another located at 28 μm. In each segment, the numbers represent the percentage of cell population of each cell type in that segment.

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Fig. 11

Variation of  ERstiff with Rec compared between simulations and experiments for volume fraction of  φ=10% 



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