BioChip Journal

, Volume 10, Issue 1, pp 9–15 | Cite as

In vitro blood flow and cell-free layer in hyperbolic microchannels: Visualizations and measurements

  • Raquel O. Rodrigues
  • Raquel Lopes
  • Diana Pinho
  • Ana I. Pereira
  • Valdemar Garcia
  • Stefan Gassmann
  • Patrícia C. Sousa
  • Rui LimaEmail author
Original Article


Red blood cells (RBCs) in microchannels has tendency to undergo axial migration due to the parabolic velocity profile, which results in a high shear stress around wall that forces the RBC to move towards the centre induced by the tank treading motion of the RBC membrane. As a result there is a formation of a cell free layer (CFL) with extremely low concentration of cells. Based on this phenomenon, several works have proposed microfluidic designs to separate the suspending physiological fluid from whole in vitro blood. This study aims to characterize the CFL in hyperbolic-shaped microchannels to separate RBCs from plasma. For this purpose, we have investigated the effect of hyperbolic contractions on the CFL by using not only different Hencky strains but also varying the series of contractions. The results show that the hyperbolic contractions with a Hencky strain of 3 and higher, substantially increase the CFL downstream of the contraction region in contrast with the microchannels with a Hencky strain of 2, where the effect is insignificant. Although, the highest CFL thickness occur at microchannels with a Hencky strain of 3.6 and 4.2 the experiments have also shown that cells blockage are more likely to occur at this kind of microchannels. Hence, the most appropriate hyperbolic-shaped microchannels to separate RBCs from plasma is the one with a Hencky strain of 3.


Blood Cell-free layer Hyperbolic microchannels Hencky strain Microcirculation Microfluidic systems Red blood cells 


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  1. 1.
    Lima, R., Ishikawa, T., Imai, Y. & Yamaguchi, T. in In Single and two-Phase Flows on Chemical and Biomedical Engineering, edited by Ricardo Dias, Antonio A. Martins, Rui Lima and T.M. Mata (Bentham science, 2012), pp. 513–547.Google Scholar
  2. 2.
    Garcia, V., Dias, R. & Lima, R. in Applied Biological Engineering - Principles and Practice, edited by G. R. Naik (InTech, 2012), pp. 393–416.Google Scholar
  3. 3.
    Fedosov, D.A., Caswell, B., Popel, A.S. & Karniadakis, G.E. Blood flow and cell-free layer in microvessels. Microcirculation (New York, N.Y.: 1994) 17, 615–628 (2010).CrossRefGoogle Scholar
  4. 4.
    Kim, S., Ong, P.K., Yalcin, O., Intaglietta, M. & Johnson, P.C. The cell-free layer in microvascular blood flow. Biorheology 46, 181–189 (2009).Google Scholar
  5. 5.
    Namgung, B., Liang, L. & Kim, S. in Visualization and Simulation of Complex Flows in Biomedical Engineering, edited by R. Lima, Y. Imai, T. Ishikawa and M. S. N. Oliveira (Springer Netherlands, 2014), Vol. 12, pp. 75–87.CrossRefGoogle Scholar
  6. 6.
    Abkarian, M. et al. Cellular-scale hydrodynamics. Biomed. Mater. 3, 034011 (2008).CrossRefGoogle Scholar
  7. 7.
    Pinho, D., Yaginuma, T. & Lima, R. A microfluidic device for partial cell separation and deformability assessment. BioChip J. 7, 367–374 (2013).CrossRefGoogle Scholar
  8. 8.
    Lee, S.S., Yim, Y., Ahn, K.H. & Lee, S.J. Extensional flow-based assessment of red blood cell deformability using hyperbolic converging microchannel. Biomed Microdevices 11, 1021–1027 (2009).CrossRefGoogle Scholar
  9. 9.
    Faustino, V. et al. Extensional flow-based microfluidic device: deformability assessment of red blood cells in contact with tumor cells. BioChip J. 8, 42–47 (2014).CrossRefGoogle Scholar
  10. 10.
    Faustino, V. et al. in Visualization and Simulation of Complex Flows in Biomedical Engineering, edited by R. Lima, Y. Imai, T. Ishikawa and M. S. N. Oliveira (Springer Netherlands, 2014), Vol. 12, pp. 151–163.CrossRefGoogle Scholar
  11. 11.
    Yaginuma, T., Oliveira, M.S.N., Lima, R., Ishikawa, T. & Yamaguchi, T. Human red blood cell behavior under homogeneous extensional flow in a hyperbolic-shaped microchannel. Biomicrofluidics 7, 054110 (2013).CrossRefGoogle Scholar
  12. 12.
    Sousa, P.C., Pinho, F.T., Oliveira, M.S. & Alves, M.A. Extensional flow of blood analog solutions in microfluidic devices. Biomicrofluidics 5, 14108 (2011).CrossRefGoogle Scholar
  13. 13.
    James, D.F., Chandler, G.M. & Armour, S.J. Measurement of the extensional viscosity of M1 in a converging channel rheometer. J. Nonnewton. Fluid. Mech. 35, 445–458 (1990).CrossRefGoogle Scholar
  14. 14.
    Oliveira, M.N., Alves, M., Pinho, F. & McKinley, G. Viscous flow through microfabricated hyperbolic contractions. Exp. Fluids 43, 437–451 (2007).CrossRefGoogle Scholar
  15. 15.
    Brust, M. et al. Rheology of Human Blood Plasma: Viscoelastic Versus Newtonian Behavior. Phys. Rev. Lett. 110, 078305 (2013).CrossRefGoogle Scholar
  16. 16.
    Sousa, P.C., Pinho, F.T., Oliveira, M.S.N. & Alves, M.A. Efficient microfluidic rectifiers for viscoelastic fluid flow. J. Nonnewton. Fluid. Mech. 165, 652–671 (2010).CrossRefGoogle Scholar
  17. 17.
    Lopes, A. The study of the effect of microcontractions in the separation of blood cells: soft lithography and micromilling. Polytechnic Institute of Bragança (2014).Google Scholar
  18. 18.
    Pinto, E. et al. A rapid and low-cost nonlithographic method to fabricate biomedical microdevices for blood flow analysis. Micromachines 6, 121–135 (2015).CrossRefGoogle Scholar
  19. 19.
    Pinho, D., Lima, R., Pereira, A.I. & Gayubo, F. Automatic tracking of labeled red blood cells in microchannels. Int. J. Numer. Method Biomed. Eng. 29, 977–987 (2013).CrossRefGoogle Scholar

Copyright information

© The Korean BioChip Society and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Raquel O. Rodrigues
    • 1
    • 2
  • Raquel Lopes
    • 2
  • Diana Pinho
    • 2
    • 3
  • Ana I. Pereira
    • 2
    • 4
  • Valdemar Garcia
    • 2
  • Stefan Gassmann
    • 5
  • Patrícia C. Sousa
    • 3
  • Rui Lima
    • 2
    • 3
    • 6
    Email author
  1. 1.LCM-Laboratory of Catalysis and Materials - Associate Laboratory LSRE-LCM, Faculdade de EngenhariaUniversidade do Porto (FEUP)PortoPortugal
  2. 2.Polytechnic Institute of BragançaESTiG/IPBBragançaPortugal
  3. 3.CEFT, Faculdade de Engenharia da Universidade do Porto (FEUP)PortoPortugal
  4. 4.Algoritmi R&D CentreUniversity of Minho, Campus de GualtarBragaPortugal
  5. 5.Jade University of Applied ScienceWilhelmshavenGermany
  6. 6.Mechanical Engineering DepartmentUniversity of Minho, Campus de AzurémGuimarãesPortugal

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