Determinants of Leukocyte Margination in Rectangular Microchannels

Microfabrication of polydimethylsiloxane (PDMS) devices has provided a new set of tools for studying fluid dynamics of blood at the scale of real microvessels. However, we are only starting to understand the power and limitations of this technology. To determine the applicability of PDMS microchannels for blood flow analysis, we studied white blood cell (WBC) margination in channels of various geometries and blood compositions. We found that WBCs prefer to marginate downstream of sudden expansions, and that red blood cell (RBC) aggregation facilitates the process. In contrast to tubes, WBC margination was restricted to the sidewalls in our low aspect ratio, pseudo-2D rectangular channels and consequently, margination efficiencies of more than 95% were achieved in a variety of channel geometries. In these pseudo-2D channels blood rheology and cell integrity were preserved over a range of flow rates, with the upper range limited by the shear in the vertical direction. We conclude that, with certain limitations, rectangular PDMS microfluidic channels are useful tools for quantitative studies of blood rheology.

[1]  Sergey S Shevkoplyas,et al.  Biomimetic autoseparation of leukocytes from whole blood in a microfluidic device. , 2005, Analytical chemistry.

[2]  C. Thornton,et al.  Red cell aggregation as a factor influencing margination and adhesion of leukocytes and platelets. , 2008, Clinical hemorheology and microcirculation.

[3]  R. Karlsson,et al.  Maintenance of white blood cell margination at the passage through small venular junctions. , 1980, Microvascular research.

[4]  Sergey S Shevkoplyas,et al.  Direct measurement of the impact of impaired erythrocyte deformability on microvascular network perfusion in a microfluidic device. , 2006, Lab on a chip.

[5]  Aleksander S Popel,et al.  Aggregate formation of erythrocytes in postcapillary venules. , 2005, American journal of physiology. Heart and circulatory physiology.

[6]  R. Shah Laminar Flow Forced convection in ducts , 1978 .

[7]  R. Sasisekharan,et al.  Heparanase, heparin and the coagulation system in cancer progression. , 2007, Thrombosis research.

[8]  G. Cokelet,et al.  Prediction of blood flow in tubes with diameters as small as 29 microns. , 1971, Microvascular research.

[9]  Dafu Cui,et al.  Microfluidic devices for sample pretreatment and applications , 2009 .

[10]  R. Jain,et al.  Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions. , 1991, Cancer research.

[11]  G. Whitesides,et al.  Applications of microfluidics in chemical biology. , 2006, Current opinion in chemical biology.

[12]  L. Munn,et al.  Particulate nature of blood determines macroscopic rheology: a 2-D lattice Boltzmann analysis. , 2005, Biophysical journal.

[13]  H Schmid-Schönbein,et al.  On the shear rate dependence of red cell aggregation in vitro. , 1968, The Journal of clinical investigation.

[14]  H. Goldsmith,et al.  Radial distribution of white cells in tube flow. , 1984, Kroc Foundation series.

[15]  S. Shevkoplyas,et al.  Prototype of an in vitro model of the microcirculation. , 2003, Microvascular research.

[16]  S. Deitcher Cancer and Thrombosis: Mechanisms and Treatment , 2003, Journal of Thrombosis and Thrombolysis.

[17]  A. Popel,et al.  Contributions of collision rate and collision efficiency to erythrocyte aggregation in postcapillary venules at low flow rates. , 2007, American journal of physiology. Heart and circulatory physiology.

[18]  Pablo Engel,et al.  The selecting: vascular adhesion molecules , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  R. Jäggi,et al.  Microfluidic depletion of red blood cells from whole blood in high-aspect-ratio microchannels , 2006 .

[20]  G. Schmid-Schönbein,et al.  Analysis of inflammation. , 2006, Annual review of biomedical engineering.

[21]  R K Jain,et al.  Role of erythrocytes in leukocyte-endothelial interactions: mathematical model and experimental validation. , 1996, Biophysical journal.

[22]  M. Pearson,et al.  Effect of Fibrinogen on Leukocyte Margination and Adhesion in Postcapillary Venules , 2004, Microcirculation.

[23]  Andreas Manz,et al.  Micro total analysis systems: latest achievements. , 2008, Analytical chemistry.

[24]  Mehmet Toner,et al.  Blood-on-a-chip. , 2005, Annual review of biomedical engineering.

[25]  L Mahadevan,et al.  Sickle cell vasoocclusion and rescue in a microfluidic device , 2007, Proceedings of the National Academy of Sciences.

[26]  Bernhard Weigl,et al.  Towards non- and minimally instrumented, microfluidics-based diagnostic devices. , 2008, Lab on a chip.

[27]  G. Whitesides,et al.  Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). , 1998, Analytical chemistry.

[28]  Eleanor A. M. Graham Lab-on-a-chip technology , 2005, Forensic science, medicine, and pathology.

[29]  A. Manz,et al.  Micro total analysis systems. Latest advancements and trends. , 2006, Analytical chemistry.

[30]  G. Segré,et al.  Behaviour of macroscopic rigid spheres in Poiseuille flow Part 2. Experimental results and interpretation , 1962, Journal of Fluid Mechanics.

[31]  H. Brenner The slow motion of a sphere through a viscous fluid towards a plane surface , 1961 .

[32]  G. Whitesides,et al.  Soft lithography in biology and biochemistry. , 2001, Annual review of biomedical engineering.

[33]  H. Goldsmith,et al.  Margination of leukocytes in blood flow through small tubes. , 1984, Microvascular research.

[34]  T. Ishikawa,et al.  In vitro blood flow in a rectangular PDMS microchannel: experimental observations using a confocal micro-PIV system , 2008, Biomedical microdevices.

[35]  H. Stone,et al.  Geometrical focusing of cells in a microfluidic device: an approach to separate blood plasma. , 2006, Biorheology.

[36]  D. Hammer,et al.  Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow , 1995, Nature.

[37]  Goldsmith Hl,et al.  Red cell motions and wall interactions in tube flow. , 1971 .

[38]  A. Pries,et al.  Radial distribution of white cells during blood flow in small tubes. , 1985, Microvascular research.

[39]  Howard A Stone,et al.  Dynamics of shear-induced ATP release from red blood cells , 2008, Proceedings of the National Academy of Sciences.

[40]  M P Bevilacqua,et al.  Endothelial-leukocyte adhesion molecules. , 1993, Annual review of immunology.

[41]  Lance L. Munn,et al.  Influence of erythrocyte aggregation on leukocyte margination in postcapillary expansions: A lattice Boltzmann analysis , 2006 .

[42]  H. Goldsmith,et al.  Deformation of human red cells in tube flow. , 1971, Biorheology.

[43]  J. Sturm,et al.  Deterministic hydrodynamics: Taking blood apart , 2006, Proceedings of the National Academy of Sciences.

[44]  L V McIntire,et al.  Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion. , 1987, Blood.

[45]  R K Jain,et al.  Analysis of cell flux in the parallel plate flow chamber: implications for cell capture studies. , 1994, Biophysical journal.

[46]  Daniel A Fletcher,et al.  Analyzing cell mechanics in hematologic diseases with microfluidic biophysical flow cytometry. , 2008, Lab on a chip.

[47]  M J Pearson,et al.  Influence of erythrocyte aggregation on leukocyte margination in postcapillary venules of rat mesentery. , 2000, American journal of physiology. Heart and circulatory physiology.

[48]  T. Secomb,et al.  Microangiectasias: Structural regulators of lymphocyte transmigration , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[49]  J. Williamson,et al.  Electron microscopy of leukocytic margination and emigration in acute inflammation in dog pancreas. , 1961, The American journal of pathology.

[50]  G. Nash,et al.  Rheological properties of the blood influencing selectin-mediated adhesion of flowing leukocytes. , 2003, American journal of physiology. Heart and circulatory physiology.

[51]  J. Geng,et al.  P-selectin primes leukocyte integrin activation during inflammation , 2007, Nature Immunology.

[52]  R. Phibbs Distribution of leukocytes in blood flowing through arteries. , 1966, The American journal of physiology.

[53]  K. Ley,et al.  Molecular mechanisms of leukocyte recruitment in the inflammatory process. , 1996, Cardiovascular research.

[54]  H. Goldsmith,et al.  Red cell motions and wall interactions in tube flow. , 1971, Federation proceedings.

[55]  H. H. Lipowsky,et al.  Leukocyte margination and deformation in mesenteric venules of rat. , 1989, The American journal of physiology.

[56]  U. Bagge,et al.  The initiation of post-capillary margination of leukocytes: studies in vitro on the influence of erythrocyte concentration and flow velocity. , 1983, International journal of microcirculation, clinical and experimental.

[57]  Wei Du,et al.  Microfluidic chips for cell sorting. , 2008, Frontiers in bioscience : a journal and virtual library.

[58]  S. Shoji Micro Total Analysis Systems , 1999 .

[59]  V. Vandelinder,et al.  Perfusion in microfluidic cross-flow: separation of white blood cells from whole blood and exchange of medium in a continuous flow. , 2007, Analytical chemistry.

[60]  H. Meiselman,et al.  Effects of dextran molecular weight on red blood cell aggregation. , 2008, Biophysical journal.

[61]  S Chien,et al.  The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels. , 1980, Microvascular research.

[62]  H. Andersson,et al.  Microfluidic devices for cellomics: a review , 2003 .

[63]  L. Munn,et al.  Red blood cells initiate leukocyte rolling in postcapillary expansions: a lattice Boltzmann analysis. , 2003, Biophysical journal.

[64]  G. Cokelet,et al.  The Fahraeus effect. , 1971, Microvascular research.

[65]  R S Reneman,et al.  Wall shear rate in arterioles in vivo: least estimates from platelet velocity profiles. , 1988, The American journal of physiology.

[66]  I. Colditz Margination and emigration of leucocytes. , 1985, Survey and synthesis of pathology research.

[67]  K. Matsumoto,et al.  Constitutive expression of ICAM-1 in rat microvascular systems analyzed by laser confocal microscopy. , 1997, The American journal of physiology.

[68]  Kenneth E. Newhouse,et al.  Handbook of Bioengineering , 1987, The Yale Journal of Biology and Medicine.