Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-28T09:57:56.993Z Has data issue: false hasContentIssue false
  • English
  • Français

Sorting same-size red blood cells in deep deterministic lateral displacement devices

Published online by Cambridge University Press:  19 November 2018

Gökberk Kabacaoğlu Open the ORCID record for Gökberk Kabacaoğlu [Opens in a new window]  and
George Biros
Gökberk Kabacaoğlu*
Affiliation:
Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
George Biros
Affiliation:
Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712, USA Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX 78712, USA
*
†Email address for correspondence: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Microfluidic sorting of deformable particles finds many applications, for example, medical devices for cells. Deterministic lateral displacement (DLD) is one of them. Particle sorting via DLD relies only on hydrodynamic forces. For rigid spherical particles, this separation is to a great extent understood and can be attributed to size differences: large particles displace in the lateral direction with respect to the flow while small particles travel in the flow direction with negligible lateral displacement. However, the separation of non-spherical deformable particles such as red blood cells (RBCs) is more complicated than that of rigid particles. For example, is it possible to separate deformable particles that have the same size but different mechanical properties? We study deformability-based sorting of same-size RBCs via DLD using an in-house integral equation solver for vesicle flows in two dimensions. Our goal is to quantitatively characterize the physical mechanisms that enable the cell separation. To this end, we systematically investigate the effects of the interior fluid viscosity and membrane elasticity of a cell on its behaviour. In particular, we consider deep devices in which a cell can show rich dynamics such as taking a particular angular orientation depending on its mechanical properties. We have found out that cells moving with a sufficiently high positive inclination angle with respect to the flow direction displace laterally while those with smaller angles travel with the flow streamlines. Thereby, deformability-based cell sorting is possible. The underlying mechanism here is cell migration due to the cell’s positive inclination and the shear gradient. The higher the inclination is, the farther the cell can travel laterally. We also assess the efficiency of the technique for dense suspensions. It turns out that most of the cells in dense suspensions do not displace in the lateral direction no matter what their deformability is. As a result, separating cells using a DLD device becomes harder.

JFM classification

Biological Fluid Dynamics: Blood flow Low-Reynolds-number flows: Boundary integral methods Micro-/Nano-fluid dynamics: Microfluidics
Type
JFM Papers
Information
Journal of Fluid Mechanics , Volume 859 , 25 January 2019 , pp. 433 - 475
Copyright
© 2018 Cambridge University Press 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aouane, O., Thiebaud, M., Benyoussef, A., Wagner, C. & Misbah, C. 2014 Vesicle dynamics in a confined Poiseuille flow: from steady state to chaos. Phys. Rev. E 90 (3), 033011.Google Scholar
Autebert, J., Coudert, B., Bidard, F.-C., Pierga, J.-Y., Descroix, S., Malaquin, L. & Viovy, J.-L. 2012 Microfluidic: an innovative tool for efficient cell sorting. Methods 57, 297–307.Google Scholar
Barabino, G. A. 2010 Sickle cell biomechanics. Annu. Rev. Biomed. Engng 12, 345–367.Google Scholar
Beaucourt, J., Rioual, F., Séon, T., Biben, T. & Misbah, C. 2004 Steady to unsteady dynamics of a vesicle in a flow. Phys. Rev. Lett. E 69 (1), 011906.Google Scholar
Beech, J. P., Holm, S. H., Adolfsson, K. & Tegenfeldt, J. O. 2012 Sorting cells by size, shape and deformability. Lab on a Chip 12, 1048–1051.Google Scholar
Bhagat, A. S., Bow, H., Houd, H. W., Tan, S. J., Han, J. & Lim, C. T. 2010 Microfluidics for cell separation. Med. Biol. Engng Comput. 49, 999–1014.Google Scholar
Buys, A. V., Van Rooy, M.-J., Soma, P., Van Papendorp, D., Lipinski, B. & Pretorius, E. 2013 Changes in red blood cell membrane struture in type 2 diabetes: a scanning electron and atomic force microscopy study. Cardiovasc. Diabetol. 12 (1), 25.Google Scholar
Chien, S. 1987 Red cell deformability and its relevance to blood flow. Ann. Rev. Physiol. 49, 177–192.Google Scholar
Coupier, G., Kaoui, B., Podgorski, T. & Misbah, C. 2008 Noninertial lateral migration of vesicles in bounded Poiseuille flow. Phys. Fluids 20, 111702.Google Scholar
Danker, G., Vlahovska, P. M. & Misbah, C. 2009 Vesicles in Poiseuille flow. Phys. Rev. Lett. 102, 148102.Google Scholar
D’Avino, G. 2013 Non-Newtonian deterministic lateral displacement separator: theory and simulations. Rheol. Acta 52, 221–236.Google Scholar
Davis, J. A.2008 Microfluidic separation of blood components through deterministic lateral displacement. PhD thesis, Princeton University, USA.Google Scholar
Davis, J. A., Inglis, D. W., Morton, K. J., Lawrence, D. A., Huang, L. R., Chou, S. Y., Sturm, J. C. & Austin, R. H. 2006 Deterministic hydrodynamics: taking blood apart. Proc. Natl Acad. Sci. USA 103 (40), 14779–14784.Google Scholar
Fedosov, D. A., Peltomäki, M. & Gompper, G. 2014 Deformation and dynamics of red blood cells in flow through cylindrical microchannels. Soft Matt. 10, 4258–4267.Google Scholar
Freund, J. B. 2007 Leukocyte margination in a model microvessel. Phys. Fluids 19 (2), 023301.Google Scholar
Freund, J. B. 2014 Numerical simulation of flowing blood cells. Annu. Rev. Fluid Mech. 46:1, 67–95.Google Scholar
Freund, J. B. & Orescanin, M. M. 2011 Cellular flow in a small blood vessel. J. Fluid Mech. 671, 466–490.Google Scholar
Freund, J. B. & Zhao, H. 2010 A High-Resolution Fast Boundary-Integral Method for Multiple Blood Cells, chap. 3, pp. 71–111. CRC Press.Google Scholar
Ghigliotti, G., Biben, T. & Misbah, C. 2010 Rheology of a dilute two-dimensional suspension of vesicles. J. Fluid Mech. 653, 489–518.Google Scholar
Ghigliotti, G., Rahimian, A., Biros, G. & Misbah, C. 2011 Vesicle migration and spatial organization driven by flow line curvature. Phys. Rev. Lett. 106, 028101.Google Scholar
Goldsmith, H. L. & Mason, S. G. 1961 Axial migration of particles in Poiseuille flow. Nature 4781, 1095–1096.Google Scholar
Guck, J., Schinkinger, S., Lincoln, B., Wottawah, F., Ebert, S., Romeyke, M., Lenz, D., Erickson, H. M., Ananthakrishnan, R. & Mitchell, D. 2005 Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88 (5), 3689–3698.Google Scholar
Henry, E., Holm, S. H., Zhang, Z., Beech, J. P., Tegenfeldt, J. O., Fedosov, D. A. & Gompper, G. 2016 Sorting cells by their dynamical properties. Sci. Rep. 6, 34375.Google Scholar
Holm, S. H., Beech, J. P., Barret, M. P. & Tegenfeldt, J. O. 2011 Separation of parasites from human blood using deterministic lateral displacement. Lab on a Chip 11, 1326–1332.Google Scholar
Huang, L. R., Cox, E. C., Austin, R. H. & Sturm, J. C. 2004 Continuous particle separation through deterministic lateral displacement. Science 304 (5673), 987–990.Google Scholar
Inglis, D. W., Davis, J. A., Austin, R. H. & Sturm, J. C. 2006 Critical particle size for fractionation by deterministic lateral displacement. Lab on a Chip 6, 655–658.Google Scholar
Inglis, D. W., Lord, M. & Nordon, R. E. 2011 Scaling deterministic lateral displacement arrays for high throughput and dilution-free enrichment of leukocytes. J. Micromech. Microengng 21 (5), 054024.Google Scholar
Kabacaoğlu, G., Quaife, B. & Biros, G. 2017 Quantification of mixing in vesicle suspensions using numerical simulations in two dimensions. Phys. Fluids 29 (2), 021901.Google Scholar
Kabacaoğlu, G., Quaife, B. & Biros, G. 2018 Low-resolution simulations of vesicle suspensions in 2D. J. Comput. Phys. 357, 43–77.Google Scholar
Kantsler, V. & Steinberg, V. 2006 Transition to tumbling and two regimes of tumbling motion of a vesicle in shear flow. Phys. Rev. Lett. 96 (3), 036001.Google Scholar
Kaoui, B., Krüger, T. & Harting, J. 2012 How does confinement affect the dynamics of viscous vesicles and red blood cells? Soft Matt. 8, 9246–9252.Google Scholar
Kaoui, B., Tahiri, N., Biben, T., Ez-Zahraouy, H., Benyoussef, A., Biros, G. & Misbah, C. 2011 Complexity of vesicle microcirculation. Phys. Rev. E 84, 041906.Google Scholar
Karabacak, N. M., Spuhler, P. S., Fachin, F., Lim, E. J., Pai, V., Ozkumur, E., Martel, J. M., Kojic, N., Smith, K., Chen, P., Yang, J., Hwang, H., Morgan, B., Trautwein, J., Barber, T. A., Stott, S. L., Maheswaran, S., Kapur, R., Haber, D. A. & Toner, M. 2014 Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat. Prot. 9 (3), 694–710.Google Scholar
Krüger, T., Holmes, D. & Coveney, P. V. 2014 Deformability-based red blood cell separation in deterministic lateral displacement devices: a simulation study. Biomicrofluidics 8, 054114.Google Scholar
Kulrattanarak, T., van der Sman, R. G. M., Schröen, C. G. P. H. & Boom, R. M. 2011 Analysis of mixed motion in deterministic ratchets via experiment and particle simulation. Microfluid. Nanofluid. 10, 843–853.Google Scholar
Li, X., Vlahovska, P. & Karniadakis, G. E. 2013 Continuum- and particle-based modeling of shapes and dynamics of red blood cells in health and disease. Soft Matt. 9, 28–37.Google Scholar
Loutherback, K., D’Silva, J., Liu, L., Wu, A., Austin, R. H. & Sturm, J. C. 2012 Deterministic separation of cancer cells from blood at 10 mL min-1 . AIP Adv. 2 (4), 042107.Google Scholar
McGrath, J., Jimenez, M. & Bridle, H. 2014 Deterministic lateral displacement for particle separation: a review. Lab on a Chip 14, 4139–4158.Google Scholar
Messlinger, S., Schmidt, B., Noguchi, H. & Gompper, G. 2009 Dynamical regimes and hydrodynamic lift of viscous vesicles under shear. Phys. Rev. E 80, 011901.Google Scholar
Misbah, C. 2006 Vacillating breathing and tumbling of vesicles under shear flow. Phys. Rev. Lett. 96 (2), 028104.Google Scholar
Misbah, C. 2012 Vesicles, capsules and red blood cells under flow. J. Phys. Conf. Ser. 392, 012005.Google Scholar
Mohandas, N. & Gallagher, P. G. 2008 Red cell membrane: past, present, and future. Blood 112 (10), 3939–3948.Google Scholar
Müller, K., Fedosov, D. A. & Gompper, G. 2014 Margination of micro- and nano-particles in blood flow and its effect on drug delivery. Sci. Rep. 4, 4871.Google Scholar
Noguchi, H. & Gompper, D. G. 2005 Shape transitions of fluid vesicles and red blood cells in capillary flows. Proc. Natl Acad. Sci. USA 102, 14159–14164.Google Scholar
Olla, P. 1997 The lift on a tank-treading ellipsoidal cell in a shear flow. J. Phys. II, EDP Sci. 7 (10), 1533–1540.Google Scholar
Podgorski, T., Callens, N., Minetti, C., Coupier, G., Dubois, F. & Misbah, C. 2011 Dynamics of vesicle suspensions in shear flow between walls. Microgravity Sci. Technol. 23, 263–270.Google Scholar
Popel, A. S. & Johnson, P. C. 2005 Microcirculation and hemorheology. Annu. Rev. Fluid Mech. 37, 43–69.Google Scholar
Pozrikidis, C. 2001 Interfacial dynamics for Stokes flow. J. Comput. Phys. 169, 250–301.Google Scholar
Pozrikidis, C. 2003 Numerical simulation of the flow-induced deformation of red blood cells. Ann. Biomed. Engng 31 (10), 1194–1205.Google Scholar
Quaife, B. & Biros, G. 2014 High-volume fraction simulations of two-dimensional vesicle suspensions. J. Comput. Phys. 274, 245–267.Google Scholar
Quaife, B. & Biros, G. 2015 High-order adaptive time stepping for vesicle suspensions with viscosity contrast. Proc. IUTAM 16, 89–98.Google Scholar
Quaife, B. & Biros, G. 2016 Adaptive time stepping for vesicle suspensions. J. Comput. Phys. 306, 478–499.Google Scholar
Quek, R., Le, D. V. & Chiam, K.-H. 2011 Separation of deformable particles in deterministic lateral displacement devices. Phys. Rev. E 83, 056301.Google Scholar
Rahimian, A., Veerapaneni, S. K. & Biros, G. 2010 Dynamic simulation of locally inextensible vesicles suspended in an arbitrary two-dimensional domain, a boundary integral method. J. Comput. Phys. 229, 6466–6484.Google Scholar
Ranjan, S., Zeming, K. K., Jureen, R., Fisher, D. & Zhang, Y. 2014 DLD pillar shape design for efficient separation of spherical and non-spherical bioparticles. Lab on a Chip 14, 4250–4262.Google Scholar
Rossinelli, D., Tang, Y.-H., Lykov, K., Alexeev, D., Bernaschi, M., Hadjidoukas, P., Bisson, M., Joubert, W., Conti, C., Karniadakis, G., Fatica, M., Pivkin, I. & Koumoutsakas, P. 2015 The in-silico lab-on-a-chip: petascale and high-throughput simulations of microfluidics at cell resolution. In Proceedings of the International Conference for High Performance Computing, Networking, Storage and Analysis: SC ’15, Austin, Texas, pp. 2:1–2:12. ACM.Google Scholar
Suresh, S., Spatz, J., Mills, J. P., Micoulet, A., Dao, M., Lim, C. T., Beil, M. & Seufferlein, T. 2005 Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomater. 1 (1), 15–30.Google Scholar
Tomaiuolo, G. 2014 Biomechanical properties of red blood cells in health and disease towards microfluidics. Biomicrofluidics 8, 051501.Google Scholar
Veerapaneni, S. K., Gueyffier, D., Zorin, D. & Biros, G. 2009 A boundary integral method for simulating the dynamics of inextensible vesicles suspended in a viscous fluid in 2D. J. Comput. Phys. 228 (7), 2334–2353.Google Scholar
Vernekar, R. & Krüger, T. 2015 Breakdown of deterministic lateral displacement efficiency for non-dilute suspensions: a numerical study. Med. Engng Phys. 37, 845–854.Google Scholar
Vernekar, R., Krüger, T., Loutherback, K., Morton, K. & Inglis, D. 2017 Anisotropic permeability in deterministic lateral displacement arrays. Lab on a Chip 17, 3318–3330.Google Scholar
Vlahovska, P. M. & Gracia, R. S. 2007 Dynamics of a viscous vesicle in linear flows. Phys. Rev. E 75, 016313.Google Scholar
Ye, S., Shao, X., Yu, Z. & Yu, W. 2014 Effects of the particle deformability on the critical separation diameter in the deterministic lateral displacement device. J. Fluid Mech. 743, 60–74.Google Scholar
Zeming, K. K., Ranjan, S. & Zhang, Y. 2013 Rotational separation of non-spherical bioparticles using I-shaped pillar arrays in a microfluidic device. Nature Commun. 4, 1625.Google Scholar
Zhang, Z., Henry, E., Gompper, G. & Fedosov, D. A. 2015 Behavior of rigid and deformable particles in deterministic lateral displacement devices with different post shapes. J. Chem. Phys. 143, 243145.Google Scholar
Zhao, H. & Shaqfeh, E. S. 2011a Shear-induced platelet margination in a microchannel. Phys. Rev. E 83, 061924.Google Scholar
Zhao, H. & Shaqfeh, E. S. G. 2011b The dynamics of a vesicle in simple shear flow. J. Fluid Mech. 674, 578–604.Google Scholar
Zhao, H. & Shaqfeh, E. S. G. 2013a The dynamics of a non-dilute vesicle suspension in simple shear flow. J. Fluid Mech. 725, 709–731.Google Scholar
Zhao, H. & Shaqfeh, E. S. G. 2013b The shape stability of a lipid vesicle in a uniaxial extensional flow. J. Fluid Mech. 719, 345–361.Google Scholar