Microbubble moving in blood flow in microchannels: effect on the cell-free layer and cell local concentration

  • David Bento
  • Lúcia Sousa
  • Tomoko Yaginuma
  • Valdemar Garcia
  • Rui Lima
  • João M. Miranda


Gas embolisms can hinder blood flow and lead to occlusion of the vessels and ischemia. Bubbles in microvessels circulate as tubular bubbles (Taylor bubbles) and can be trapped, blocking the normal flow of blood. To understand how Taylor bubbles flow in microcirculation, in particular, how bubbles disturb the blood flow at the scale of blood cells, experiments were performed in microchannels at a low Capillary number. Bubbles moving with a stream of in vitro blood were filmed with the help of a high-speed camera. Cell-free layers (CFLs) were observed downstream of the bubble, near the microchannel walls and along the centerline, and their thicknesses were quantified. Upstream to the bubble, the cell concentration is higher and CFLs are less clear. While just upstream of the bubble the maximum RBC concentration happens at positions closest to the wall, downstream the maximum is in an intermediate region between the centerline and the wall. Bubbles within microchannels promote complex spatio-temporal variations of the CFL thickness along the microchannel with significant relevance for local rheology and transport processes. The phenomenon is explained by the flow pattern characteristic of low Capillary number flows. Spatio-temporal variations of blood rheology may have an important role in bubble trapping and dislodging.


Microfluidics Gas embolism Cell-free layer Red blood cells In vitro blood Micro bubble 



The authors acknowledge the financial support provided by PTDC/SAU-BEB/105650/2008, PTDC/SAU-ENB/116929/2010, EXPL/EMS-SIS/2215/2013 and PTDC/QEQ-FTT/4287/2014 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER).

Supplementary material

10544_2016_138_MOESM1_ESM.avi (869 kb)
ESM 1 (AVI 869 kb)
10544_2016_138_MOESM2_ESM.avi (5.2 mb)
ESM 2 (AVI 5335 kb)


  1. M. D. Abramoff, P. J. Magalhaes, S. J. Ram, Image processing with ImageJ. Biophoton. Int. 11(7), 36–42 (2004)Google Scholar
  2. Y. Abu-Omar, L. Balacumaraswami, D. W. Pigott, P. M. Matthews, D. P. Taggart, Solid and gaseous cerebral microembolization during off-pump, on-pump, and open cardiac surgery procedures. J. Thorac. Cardiovasc. Surg. 127(6), 1759–1765 (2004)CrossRefGoogle Scholar
  3. P. Angeli, A. Gavriilidis, Hydrodynamics of Taylor flow in small channels: a review. Proc. Inst. Mech. Eng. C J. Mech. Eng. Sci. 222(5), 737–751 (2008)CrossRefGoogle Scholar
  4. D. A. Bartholomeusz, R. W. Boutte, J. D. Andrade, Xurography: rapid prototyping of microstructures using a cutting plotter. J. Microelectromech. Syst. 14(6), 1364–1374 (2005)CrossRefGoogle Scholar
  5. M. D. Bischel, B. G. Scoles, J. G. Mohler, Evidence for pulmonary microembolization during hemodialysis. CHEST Journal 67(3), 335–337 (1975)CrossRefGoogle Scholar
  6. M. A. Borger, C. M. Peniston, R. D. Weisel, M. Vasiliou, R. E. A. Green, C. M. Feindel, Neuropsychologic impairment after coronary bypass surgery: effect of gaseous microemboli during perfusionist interventions. J. Thorac. Cardiovasc. Surg. 121(4), 743–749 (2001)CrossRefGoogle Scholar
  7. A. B. Branger, D. M. Eckmann, Accelerated arteriolar gas embolism reabsorption by an exogenous surfactant. Anesthesiology 96(4), 971–979 (2002)CrossRefGoogle Scholar
  8. N. Bumseok, H. L. Leo K. Sangho, Physiological significance of cell-free layer and experimental determination of its width in mi-crocirculatory vessels, in Visualization and simulation of complex flows in biomedical engineering, ed. by R. lima, T. Ishikawa, Y. Imai, M. S. N. Oliveira (Springer, Dordrecht, 2014), pp. 75–87Google Scholar
  9. A. J. Calderón, Y. S. Heo, D. Huh, N. Futai, S. Takayama, J. B. Fowlkes, J. L. Bull, Microfluidic model of bubble lodging in microvessel bifurcations, Appl. Phys. Lett. 89(24), 244103–3 (2006)Google Scholar
  10. G. Deklunder, M. Roussel, J.-L. Lecroart, A. Prat, C. Gautier, Microemboli in cerebral circulation and alteration of cognitive abilities in patients with mechanical prosthetic heart valves. Stroke 29(9), 1821–1826 (1998)CrossRefGoogle Scholar
  11. V. Doyeux, T. Podgorski, S. Peponas, M. Ismail, G. Coupier, Spheres in the vicinity of a bifurcation: elucidating the Zweifach–Fung effect. J. Fluid Mech. 674, 359–388 (2011)MathSciNetCrossRefMATHGoogle Scholar
  12. D. C. Duffy, J. C. McDonald, O. J. Schueller, G. M. Whitesides, Rapid prototyping of microfluidic systems in poly (dimethylsiloxane), Anal. Chem. 70(23), 4974–4984 (1998)Google Scholar
  13. D. M. Eckmann, J. I. E. Zhang, J. Lampe, P. S. Ayyaswamy, Gas embolism and surfactant-based intervention. Ann. N. Y. Acad. Sci. 1077(1), 256–269 (2006)CrossRefGoogle Scholar
  14. B. Eshpuniyani, J. B. Fowlkes, J. L. Bull, A bench top experimental model of bubble transport in multiple arteriole bifurcations. Int. J. Heat Fluid Flow 26(6), 865–872 (2005)CrossRefGoogle Scholar
  15. R. Fåhraeus, The suspension stability of the blood. Physiol. Rev. 9(2), 241–274 (1929)Google Scholar
  16. R. Fåhræus, T. Lindqvist, The viscosity of the blood in narrow capillary tubes. Am. J. Phys. 96(3), 562–568 (1931)Google Scholar
  17. M. Faivre, M. Abkarian, K. Bickraj, H. A. Stone, Geometrical focusing of cells in a microfluidic device: an approach to separate blood plasma. Biorheology 43(2), 147–159 (2006)Google Scholar
  18. V. Faustino, S. O. Catarino, R. Lima, G. Minas, Biomedical microfluidic devices by using low-cost fabrication techniques: a review. J. Biomech. 49(11), 2280–2292 (2016)CrossRefGoogle Scholar
  19. L. K. Fiddes, N. Raz, S. Srigunapalan, E. Tumarkan, C. A. Simmons, A. R. Wheeler, E. Kumacheva, A circular cross-section PDMS microfluidics system for replication of cardiovascular flow conditions. Biomaterials 31(13), 3459–3464 (2010)CrossRefGoogle Scholar
  20. P. P. Foster, B. D. Butler, Decompression to altitude: assumptions, experimental evidence, and future directions. J. Appl. Physiol. 106(2), 678–690 (2009)CrossRefGoogle Scholar
  21. Y.-C. Fung, Stochastic flow in capillary blood vessels. Microvasc. Res. 5(1), 34–48 (1973)MathSciNetCrossRefGoogle Scholar
  22. V. Garcia, R. Dias, R. Lima, In vitro blood flow behaviour in microchannels with simple and complex geometries, in Applied Biological Engineering – Principles and Practice, ed. by G. R. Naik (InTech, Rijeka, 2012), pp. 393–416Google Scholar
  23. T. Ishikawa, H. Fujiwara, N. Matsuki, T. Yoshimoto, Y. Imai, H. Ueno, T. Yamaguchi, Asymmetry of blood flow and cancer cell adhesion in a microchannel with symmetric bifurcation and confluence. Biomed. Microdevices 13(1), 159–167 (2011)CrossRefGoogle Scholar
  24. L. L. Karlsson, S. L. Blogg, P. Lindholm, M. Gennser, T. Hemmingsson, D. Linnarsson, Venous gas emboli and exhaled nitric oxide with simulated and actual extravehicular activity. Respir. Physiol. Neurobiol. 169, 315–322 (2009)CrossRefGoogle Scholar
  25. V. Leble, R. Lima, R. Dias, C. Fernandes, T. Ishikawa, Y. Imai, T. Yamaguchi, Asymmetry of red blood cell motions in a microchannel with a diverging and converging bifurcation, Biomicrofluidics 5(4), 044120–15 (2011)Google Scholar
  26. R. Lima, M. Nakamura, T. Omori, T. Ishikawa, S. Wada, T. Yamaguchi, Microscale flow dynamics of red blood cells in microchannels: an experimental and numerical analysis, in Advances in Computational Vision and Medical Image Processing: Methods and Applications, ed. by T. a. Jorge (Springer, Dordrecht, 2009a), pp. 203–220Google Scholar
  27. R. Lima, M. S. Oliveira, T. Ishikawa, H. Kaji, S. Tanaka, M. Nishizawa, T. Yamaguchi, Axisymmetric polydimethysiloxane microchannels for in vitro hemodynamic studies, Biofabrication 1(3), 035005 (2009b)Google Scholar
  28. N. Maeda, Erythrocyte rheology in microcirculation. The Japanese Journal of Physiology 46(1), 1–14 (1996)MathSciNetCrossRefGoogle Scholar
  29. G. Mchedlishvili, N. Maeda, Blood flow structure related to red cell flow: determinant of blood fluidity in narrow microvessels. The Japanese Journal of Physiology 51(1), 19–30 (2001)CrossRefGoogle Scholar
  30. E. Meijering, O. Dzyubachyk, I. Smal, Methods for cell and particle tracking. Methods Enzymol. 504(9), 183–200 (2012)CrossRefGoogle Scholar
  31. S. Milo, E. Rambod, C. Gutfinger, M. Gharib, Mitral mechanical heart valves: in vitro studies of their closure, vortex and microbubble formation with possible medical implications. Eur. J. Cardiothorac. Surg. 24(3), 364–370 (2003)CrossRefGoogle Scholar
  32. C. M. Muth, E. S. Shank, Gas embolism. N. Engl. J. Med. 342, ‘ (2000)CrossRefGoogle Scholar
  33. V. Papadopoulou, R. J. Eckersley, C. Balestra, T. D. Karapantsios, M.-X. Tang, A critical review of physiological bubble formation in hyperbaric decompression. Adv. Colloid Interf. Sci. 191–192, 22–30 (2013)Google Scholar
  34. V. Papadopoulou, M. X. Tang, C. Balestra, R. J. Eckersley, T. D. Karapantsios, Circulatory bubble dynamics: from physical to biological aspects. Adv. Colloid Interf. Sci. 206, 239–249 (2014)Google Scholar
  35. D. Pinho, T. Yaginuma, R. Lima, A microfluidic device for partial cell separation and deformability assessment. Biochip Journal 7(4), 367–374 (2013)CrossRefGoogle Scholar
  36. E. Pinto, V. Faustino, R. Rodrigues, D. Pinho, V. Garcia, J. Miranda, R. Lima, A rapid and low-cost Nonlithographic method to fabricate biomedical microdevices for blood flow analysis. Micromachines 6(1), 121–135 (2015)CrossRefGoogle Scholar
  37. S. Samuel, A. Duprey, M. L. Fabiilli, J. L. Bull, J. Brian Fowlkes, In Vivo microscopy of targeted vessel occlusion employing acoustic droplet vaporization. Microcirculation 19(6), 501–509 (2012)CrossRefGoogle Scholar
  38. E. Sollier, M. Cubizolles, Y. Fouillet, J.-L. Achard, Fast and continuous plasma extraction from whole human blood based on expanding cell-free layer devices. Biomed. Microdevices 12(3), 485–497 (2010)CrossRefGoogle Scholar
  39. A. Suzuki, S. C. Armstead, D. M. Eckmann, Surfactant reduction in embolism bubble adhesion and endothelial damage. Anesthesiology 101(1), 97–103 (2004)CrossRefGoogle Scholar
  40. K. Svanes, B. W. Zweifach, Variations in small blood vessel hematocrits produced in hypothermic rats by micro-occlusion. Microvasc. Res. 1(2), 210–220 (1968)CrossRefGoogle Scholar
  41. T. Taha, Z. Cui, Hydrodynamics of slug flow inside capillaries. Chem. Eng. Sci. 59(6), 1181–1190 (2004)CrossRefGoogle Scholar
  42. T. Taha, Z. F. Cui, CFD modelling of slug flow inside square capillaries. Chem. Eng. Sci. 61(2), 665–675 (2006)CrossRefGoogle Scholar
  43. V. Talimi, Y. Muzychka, S. Kocabiyik, A review on numerical studies of slug flow hydrodynamics and heat transfer in microtubes and microchannels. Int. J. Multiphase Flow 39, 88–104 (2012)CrossRefGoogle Scholar
  44. T. Thulasidas, M. Abraham, R. Cerro, Flow patterns in liquid slugs during bubble-train flow inside capillaries. Chem. Eng. Sci. 52(17), 2947–2962 (1997)CrossRefGoogle Scholar
  45. D. Valassis, R. Dodde, B. Esphuniyani, J. B. Fowlkes, J. Bull, Microbubble transport through a bifurcating vessel network with pulsatile flow. Biomed. Microdevices 14(1), 131–143 (2012)CrossRefGoogle Scholar
  46. T. Yaginuma, M. S. Oliveira, R. Lima, T. Ishikawa, T. Yamaguchi, Human red blood cell behavior under homogeneous extensional flow in a hyperbolic-shaped microchannel. Biomicrofluidics 7(5), 054110–14 (2013)Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • David Bento
    • 1
    • 3
  • Lúcia Sousa
    • 1
  • Tomoko Yaginuma
    • 1
  • Valdemar Garcia
    • 1
  • Rui Lima
    • 2
    • 3
  • João M. Miranda
    • 3
  1. 1.School of Technology and Management (ESTiG)Polytechnic Institute of Bragança (IPB)BragançaPortugal
  2. 2.MEtRiS, Department of Mechanical EngineeringMinho UniversityGuimarãesPortugal
  3. 3.Transport Phenomena Research Center (CEFT), Department of Chemical Engineering, Engineering FacultyUniversity of PortoPortoPortugal

Personalised recommendations