Biomedical Microdevices

, Volume 13, Issue 1, pp 159–167 | Cite as

Asymmetry of blood flow and cancer cell adhesion in a microchannel with symmetric bifurcation and confluence

  • Takuji IshikawaEmail author
  • Hiroki Fujiwara
  • Noriaki Matsuki
  • Takefumi Yoshimoto
  • Yohsuke Imai
  • Hironori Ueno
  • Takami Yamaguchi


Bifurcations and confluences are very common geometries in biomedical microdevices. Blood flow at microchannel bifurcations has different characteristics from that at confluences because of the multiphase properties of blood. Using a confocal micro-PIV system, we investigated the behaviour of red blood cells (RBCs) and cancer cells in microchannels with geometrically symmetric bifurcations and confluences. The behaviour of RBCs and cancer cells was strongly asymmetric at bifurcations and confluences whilst the trajectories of tracer particles in pure water were almost symmetric. The cell-free layer disappeared on the inner wall of the bifurcation but increased in size on the inner wall of the confluence. Cancer cells frequently adhered to the inner wall of the bifurcation but rarely to other locations. Because the wall surface coating and the wall shear stress were almost symmetric for the bifurcation and the confluence, the result indicates that not only chemical mediation and wall shear stress but also microscale haemodynamics play important roles in the adhesion of cancer cells to the microchannel walls. These results provide the fundamental basis for a better understanding of blood flow and cell adhesion in biomedical microdevices.


Microchannel Blood flow Red blood cells Cancer cells Bifurcation Confluence 



The authors are grateful for helpful discussions with Dr. R. Lima in Braganca Polytechnic Institute, and Prof. C. T. Lim in National University of Singapore. This study was supported by Grant-in-Aid for Scientific Research (S) from the Japan Society for the Promotion of Science (JSPS; No. 19100008) and by a Grant-in-Aid for Young Scientists (A) from the JSPS (No. 19686016). We also acknowledge the support from the 2007 Global COE Program “Global Nano-Biomedical Engineering Education and Research Network Centre”.

Supplementary material

Movie 1

Distribution of RBCs and cell-free layers around the bifurcation. The movie is taken by a standard halogen light, and hematocrit is about 10%. (MOV 1345 kb)

Movie 2

Distribution of RBCs and cell-free layers around the confluence. The movie is taken by a standard halogen light, and hematocrit is about 10%. (MOV 1355 kb)


  1. A.S. Ahuja, W.R. Hendee, P.L. Carson, Transport phenomena in laminar flow of blood. Phys. Med. Biol. 23, 928–936 (1978)CrossRefGoogle Scholar
  2. E. Bastida, L. Almirall, M.C. Bertomeu, A. Ordinas, Influence of shear stress on tumor-cell adhesion to endothelial-cell extracellular matrix and its modulation by fibronectin. Int. J. Cancer 43, 1174–1178 (1989)CrossRefGoogle Scholar
  3. J.G. Beeson, S.J. Rogerson, B.M. Cooke et al., Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria. Nat. Med. 6, 86–90 (2000)CrossRefGoogle Scholar
  4. N. Casson, Rheology of Disperse System (Pergamon, London, 1959)Google Scholar
  5. A.F. Chambers, A.C. Groom, I.C. MacDonald, Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2, 563–572 (2002)CrossRefGoogle Scholar
  6. X. Chen, D.F. Cui, C.C. Liu, H. Li, Microfluidic chip for blood cell separation and collection based on crossflow filtration. Sen. Actuators B 130, 216–221 (2008)CrossRefGoogle Scholar
  7. J.A. DiVietro, D.C. Brown, L.A. Sklar, R.S. Larson, M.B. Lawrence, Immobilized stromal cell-derived factor-1alpha triggers rapid VLA-4 affinity increases to stabilize lymphocyte tethers on VCAM-1 and subsequently initiate firm adhesion. J. Immunol. 178, 3903–3911 (2007)Google Scholar
  8. R. Fahraeus, T. Lindqvist, The viscosity of the blood in narrow capillary tubes. Am. J. Physiol. 96, 562–568 (1931)Google Scholar
  9. I.J. Fidler, The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat. Rev. Cancer 3, 453–458 (2003)CrossRefGoogle Scholar
  10. H. Fujiwara, T. Ishikawa, R. Lima, N. Matsuki, Y. Imai, H. Kaji, M. Nishizawa, T. Yamaguchi, Red blood cell motions in high-hematocrit blood flowing through a stenosed microchannel. J. Biomech. 42, 838–843 (2009)CrossRefGoogle Scholar
  11. O.V. Glinskii, V.H. Huxley, G.V. Glinsky et al., Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs. Neoplasia 7, 522–527 (2005)CrossRefGoogle Scholar
  12. J. Haier, G.L. Nicolson, Tumor cell adhesion under hydrodynamic conditions of fluid flow. Acta Pathol. Microbiol. Immunol. Scand. 109, 241–262 (2001)Google Scholar
  13. H.W. Hou, Q.S. Li, G.Y.H. Lee, A.P. Kumar, C.N. Ong, C.T. Lim, Deformability study of breast cancer cells using microfluidics. Biomed. Microdevices 11, 557–564 (2009)CrossRefGoogle Scholar
  14. J. Kitayama, N. Tsuno, E. Sunami, T. Osada, T. Muto, H. Nagawa, E-selectin can mediate the arrest type of adhesion of colon cancer cells under physiological shear flow. Eur. J. Cancer 36, 121–127 (2000)CrossRefGoogle Scholar
  15. S. Liang, M.J. Slattery, C. Dong, Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion. Exp. Cell Res. 310, 282–292 (2005)CrossRefGoogle Scholar
  16. S. Liang, M.J. Slattery, D. Wagner, S.I. Simon, C. Dong, Hydrodynamic shear rate regulates melanoma-leukocyte aggregation, melanoma adhesion to the endothelium, and subsequent extravasation. Ann. Biomed. Eng. 36, 661–671 (2008)CrossRefGoogle Scholar
  17. R. Lima, S. Wada, K. Tsubota, T. Yamaguchi, Confocal micro-PIV measurements of three-dimensional profiles of cell suspension flow in a square microchannel. Meas. Sci. Technol. 17, 797–808 (2006)CrossRefGoogle Scholar
  18. R. Lima, T. Ishikawa, Y. Imai, M. Takeda, S. Wada, T. Yamaguchi, Radial dispersion of red blood cells in blood flowing through glass capillaries: role of heamatocrit and geometry. J. Biomech. 41, 2188–2196 (2008)CrossRefGoogle Scholar
  19. R. Lima, T. Ishikawa, Y. Imai, M. Takeda, S. Wada, T. Yamaguchi, Measurement of individual red blood cell motions under high hematocrit conditions using a confocal micro-PTV system. Ann. Biomed. Eng. 37, 1546–1559 (2009)CrossRefGoogle Scholar
  20. E. Meijering, I. Smal, G. Danuser, Tracking in molecular bioimaging. IEEE Signal Process Mag. 23, 46–53 (2006)CrossRefGoogle Scholar
  21. F.L. Miles, F.L. Pruitt, K.L. van Golen, C.R. Cooper, Stepping out of the flow: capillary extravasation in cancer metastasis. Clin. Exp. Metastasis 25, 305–324 (2008)CrossRefGoogle Scholar
  22. S. Mine, T. Fujisaki, C. Kawahara et al., Hepatocyte growth factor enhances adhesion of breast cancer cells to endothelial cells in vitro through up-regulation of CD44. Exp. Cell Res. 288, 189–197 (2003)CrossRefGoogle Scholar
  23. H. Mohamed, M. Murray, J.N. Turner, M. Caggana, Isolation of tumor cells using size and deformation. J. Chromatogr. A 1216, 8289–8295 (2009)CrossRefGoogle Scholar
  24. M.S. Moss, B. Sisken, S. Zimmer, K.W. Anderson, Adhesion of nonmetastatic and highly metastatic breast cancer cells to endothelial cells exposed to shear stress. J. Biorheology 36, 359–371 (1999)Google Scholar
  25. S. Nagrath et al., Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450, 1235–1239 (2007)CrossRefGoogle Scholar
  26. G. Ostermann, K.S. Weber, A. Zernecke, A. Schroder, C. Weber, JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nat. Immunol. 3, 151–158 (2002)CrossRefGoogle Scholar
  27. A.S. Popel, P.C. Johnson, Microcirculation and hemorheology. Annu. Rev. Fluid Mech. 37, 43–69 (2005)CrossRefMathSciNetGoogle Scholar
  28. C. Scholander, C.J. Treutiger, K. Hultenby, M. Wahlgren, Novel fibrillar structure confers adhesive property to malaria?infected erythrocytes. Nat. Med. 2, 204–208 (1996)CrossRefGoogle Scholar
  29. S.J. Tan, L. Yobas, G.Y.H. Lee, C.N. Ong, C.T. Lim, Microdevice for the isolation and enumeration of cancer cells from blood. Biomed. Microdevices 11, 883–892 (2009)CrossRefGoogle Scholar
  30. V. Thamilselvan, A. Patel, J.V. Zyp, M.D. Basson, Colon cancer cell adhesion in response to Src Kinase activation and actin-cytoskeleton by non-laminar shear stress. J. Cell. Biochem. 92, 361–371 (2004)CrossRefGoogle Scholar
  31. P. Wilding, L.J. Kricka, J. Cheng, G. Hvichia, M.A. Shoffner, P. Fortina, Integrated cell isolation and polymerase chain reaction analysis using silicon microfilter chambers. Anal. Biochem. 257, 95–100 (1998)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Takuji Ishikawa
    • 1
    Email author
  • Hiroki Fujiwara
    • 1
  • Noriaki Matsuki
    • 2
  • Takefumi Yoshimoto
    • 1
  • Yohsuke Imai
    • 1
  • Hironori Ueno
    • 3
  • Takami Yamaguchi
    • 2
  1. 1.Department of Bioengineering and Robotics, Graduate School of EngineeringTohoku UniversitySendaiJapan
  2. 2.Department of Biomedical Engineering, Graduate School of Biomedical EngineeringTohoku UniversitySendaiJapan
  3. 3.International Advanced Research and Education OrganizationTohoku UniversitySendaiJapan

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