Abstract
Microfluidic cell adhesion assays have emerged as a means to increase throughput as well as reduce the amount of costly reagents. However as dimensions of the flow chamber are reduced and approach the diameter of a cell (Dc), theoretical models have predicted that mechanical stress, force, and torque on a cell will be amplified. We fabricated a series of microfluidic devices that have a constant width:height ratio (10:1) but with varying heights. The smallest microfluidic device (200 μm ×20 μm) requires perfusion rates as low as 40 nL/min to generate wall shear stresses of 0.5 dynes/cm2. When neutrophils were perfused through P-selectin coated chambers at equivalent wall shear stress, rolling velocities decreased by approximately 70 % as the ratio of cell diameter to chamber height (Dc/H) increased from 0.08 (H = 100 μm) to 0.40 (H = 20 μm). Three-dimensional numerical simulations of neutrophil rolling in channels of different heights showed a similar trend. Complementary studies with PSGL-1 coated microspheres and paraformaldehyde-fixed neutrophils suggested that changes in rolling velocity were related to cell deformability. Using interference reflection microscopy, we observed increases in neutrophil contact area with increasing chamber height (9–33 %) and increasing wall shear stress (28–56 %). Our results suggest that rolling velocity is dependent not only on wall shear stress but also on the shear stress gradient experienced by the rolling cell. These results point to the Dc/H ratio as an important design parameter of leukocyte microfluidic assays, and should be applicable to rolling assays that involve other cell types such as platelets or cancer cells.
Similar content being viewed by others
References
S. Aigner, C.L. Ramos, A. Hafezi-Moghadam, M.B. Lawrence, J. Friederichs, P. Altevogt, K. Ley, FASEB J. 12, 1241 (1998)
R. Alon, D.A. Hammer, T.A. Springer, Nature 374, 539 (1995)
R. Baetta, A. Corsini, Atherosclerosis 210, 1 (2010)
G.I. Bell, Science 200, 618 (1978)
S.B. Brooks, A. Tozeren, Computers & Fluids 25, 741 (1996)
R.E. Bruehl, T.A. Springer, D.F. Bainton, J. Histochem. Cytochem. 44, 835 (1996)
G. Chapman, G. Cokelet, Biorheology 33, 119 (1996)
G.B. Chapman, G.R. Cokelet, Biorheology 34, 37 (1997)
G.B. Chapman, G.R. Cokelet, Biophys. J. 74, 3292 (1998)
S.Q. Chen, T.A. Springer, Proc. Nat. Acad. Sci. U.S.A. 98, 950 (2001)
C. Christophis, I. Taubert, G.R. Meseck, M. Schubert, M. Grunze, A.D. Ho, A. Rosenhahn, Biophys. J. 101, 585 (2011)
B.J. Chung, A.M. Robertson, D.G. Peters, Comput. Struct. 81, 535 (2003)
E.R. Damiano, J. Westheider, A. Tozeren, K. Ley, Circ. Res. 79, 1122 (1996)
C. Dong, X.X. Lei, J. Biomech. 33, 35 (2000)
C. Dong, J. Cao, E.J. Struble, H.W. Lipowsky, Ann. Biomed. Eng. 27, 298 (1999)
C. Edington, H. Murata, R. Koepsel, J. Andersen, S. Eom, T. Kanade, A.C. Balazs, G. Kolmakov, C. Kline, D. McKeel et al., Langmuir 27, 15345 (2011)
M.J. Eppihimer, H.H. Lipowsky, Am. J. Physiol. 267, H1122 (1994)
E.B. Finger, R.E. Bruehl, D.F. Bainton, T.A. Springer, J. Immunol. 157, 5085 (1996)
J. Fritz, A.G. Katopodis, F. Kolbinger, D. Anselmetti, Proc Nat Acad Sci, U.S.A 95, 12283 (1998)
D.P. Gaver, S.M. Kute, Biophys. J. 75, 721 (1998)
A.J. Goldman, R.G. Cox, H. Brenner, Chem. Eng. Sci. 22, 653 (1967)
E. Gutierrez, A. Groisman, Anal. Chem. 79, 2249 (2007)
S.D. House, H.H. Lipowsky, Circ. Res. 63, 658 (1988)
S. Jadhav, C.D. Eggleton, K. Konstantopoulos, Biophys. J. 88, 96 (2005)
R.A. Jannat, G.P. Robbins, B.G. Ricart, M. Dembo, D.A. Hammer, J. Phys. Condens. Matter 22, 194117 (2010)
N.L. Jeon, H. Baskaran, S.K.W. Dertinger, G.M. Whitesides, L. Van de Water, M. Toner, Nature Biotechnol 20, 826 (2002)
D.B. Khismatullin, G.A. Truskey, Microvasc. Res. 68, 188 (2004)
D.B. Khismatullin, G.A. Truskey, Phys Fluids 17, 031505 (2005)
D.B. Khismatullin, G.A. Truskey, Biophys. J. 102, 1757 (2012)
P.M. Kochanek, J.M. Hallenbeck, Stroke 23, 1367 (1992)
C.J. Ku, T. D’Amico Oblak, D.M. Spence, Anal. Chem. 80, 7543 (2008)
R.S. Kuczenski, H.C. Chang, A. Revzin, Biomicrofluidics 5, 032005 (2011)
Y. Kuwano, O. Spelten, H. Zhang, K. Ley, A. Zarbock, Blood 116, 617 (2010)
M.B. Lawrence, T.A. Springer, Cell 65, 859 (1991)
X. Lei, M.R. Lawrence, C. Dong, J. Biomech. Eng. 121, 636 (1999)
H. Lu, L.Y. Koo, W.C.M. Wang, D.A. Lauffenburger, L.G. Griffith, K.F. Jensen, Anal. Chem. 76, 5257 (2004)
R.P. McEver, Thromb. Haemost. 86, 746 (2001)
K.L. Moore, N.L. Stults, S. Diaz, D.F. Smith, R.D. Cummings, A. Varki, R.P. Mcever, J Cell Biol 118, 445 (1992)
S.K. Murthy, A. Sin, R.G. Tompkins, M. Toner, Langmuir 20, 11649 (2004)
D.D. Nalayanda, M. Kalukanimuttam, D.W. Schmidtke, Biomed. Microdev. 9, 207 (2007)
K.B. Neeves, S.F. Maloney, K.P. Fong, A.A. Schmaier, M.L. Kahn, L.F. Brass, S.L. Diamond, J. Thromb. Haemost. 6, 2193 (2008)
K.E. Norman, A.G. Katopodis, G. Thoma, F. Kolbinger, A.E. Hicks, M.J. Cotter, A.G. Pockley, P.G. Hellewell, Blood 96, 3585 (2000)
T. Palabrica, R. Lobb, B.C. Furie, M. Aronovitz, C. Benjamin, Y.M. Hsu, S.A. Sajer, B. Furie, Nature 359, 848 (1992)
V. Pappu, S.K. Doddi, P. Bagchi, J. Theor. Biol. 254, 483 (2008)
E.Y.H. Park, M.J. Smith, E.S. Stropp, K.R. Snapp, J.A. DiVietro, W.F. Walker, D.W. Schmidtke, S.L. Diamond, M.B. Lawrence, Biophys. J. 82, 1835 (2002)
K.D. Patel, M.U. Nollert, R.P. McEver, J Cell Biol 131, 1893 (1995)
A. Pierres, P. Eymeric, E. Baloche, D. Touchard, A.M. Benoliel, P. Bongrand, Biophys. J. 84, 2058 (2003)
C. Pozrikidis, Computers & Fluids 29, 617 (2000)
V. Ramachandran, M. Williams, T. Yago, D.W. Schmidtke, R.P. McEver, Proc Nat Acad Sci, U.S.A. 101, 13519 (2004)
L.J. Rinko, M.B. Lawrence, W.H. Guilford, Biophys. J. 86, 544 (2004)
S.D. Rodgers, R.T. Camphausen, D.A. Hammer, Biophys. J. 81, 2001 (2001)
M.J. Rosenbluth, W.A. Lam, D.A. Fletcher, Lab Chip 8, 1062 (2008)
D.P. Sarvepalli, D.W. Schmidtke, M.U. Nollert, Ann. Biomed. Eng. 37, 1331 (2009)
U.Y. Schaff, M.M.Q. Xing, K.K. Lin, N. Pan, N.L. Jeon, S.I. Simon, Lab Chip 7, 448 (2007)
U.Y. Schaff, I. Yamayoshi, T. Tse, D. Griffin, L. Kibathi, S.I. Simon, Ann. Biomed. Eng. 36, 632 (2008)
G.W. Schmid-Schonbein, K.L. Sung, H. Tozeren, R. Skalak, S. Chien, Biophys. J. 36, 243 (1981)
D.W. Schmidtke, S.L. Diamond, J Cell Biol 149, 719 (2000)
J.Y. Shao, H.P. Ting-Beall, R.M. Hochmuth, Proc Nat Acad Sci, U.S.A 95, 6797 (1998)
B.J. Shao, T. Yago, P.A. Coghill, A.G. Klopocki, P. Mehta-D’souza, D.W. Schmidtke, W. Rodgers, R.P. McEver, J. Biol. Chem. 287, 19585 (2012)
A. Sin, S.K. Murthy, A. Revzin, R.G. Tompkins, M. Toner, Biotechnol. Bioeng. 91, 816 (2005)
P. Sundd, E. Gutierrez, M.K. Pospieszalska, H. Zhang, A. Groisman, K. Ley, Nature Methods 7, 821 (2010)
Z.R. Taylor, J.C. Keay, E.S. Sanchez, M.B. Johnson, D.W. Schmidtke, Langmuir 28, 9656 (2012)
L.A. Tempelman, S. Park, D.A. Hammer, Biotechnol. Prog. 10, 97 (1994)
G.A. Truskey, J.S. Pirone, J. Biomed. Mater. Res. 24, 1333 (1990)
M.A. Tsai, R.S. Frank, R.E. Waugh, Biophys. J. 65, 2078 (1993)
Y. Tseng, J.S.H. Lee, T.P. Kole, I. Jiang, D. Wirtz, J Cell Sci 117, 2159 (2004)
T. Yago, A. Leppanen, H.Y. Qiu, W.D. Marcus, M.U. Nollert, C. Zhu, R.D. Cummings, R.P. McEver, J Cell Biol 158, 787 (2002)
A. Zarbock, C.A. Lowell, K. Ley, Immunity 26, 773 (2007)
D.V. Zhelev, D. Needham, R.M. Hochmuth, Biophys. J. 67, 696 (1994)
Acknowledgments
This work was supported by an Oklahoma Center for the Advancement of Science and Technology grant (HR06-102), a NSF-funded MRSEC (DMR-0520550), and a Louisiana Board of Regents grant LEQSF(2011-14)-RD-A-24 to D.B.K.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(DOC 39 kb)
Rights and permissions
About this article
Cite this article
Coghill, P.A., Kesselhuth, E.K., Shimp, E.A. et al. Effects of microfluidic channel geometry on leukocyte rolling assays. Biomed Microdevices 15, 183–193 (2013). https://doi.org/10.1007/s10544-012-9715-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10544-012-9715-y