Advertisement

Biomedical Microdevices

, 17:108 | Cite as

A simple microfluidic device for the deformability assessment of blood cells in a continuous flow

  • Raquel O. Rodrigues
  • Diana Pinho
  • Vera Faustino
  • Rui Lima
Article

Abstract

Blood flow presents several interesting phenomena in microcirculation that can be used to develop microfluidic devices capable to promote blood cells separation and analysis in continuous flow. In the last decade there have been numerous microfluidic studies focused on the deformation of red blood cells (RBCs) flowing through geometries mimicking microvessels. In contrast, studies focusing on the deformation of white blood cells (WBCs) are scarce despite this phenomenon often happens in the microcirculation. In this work, we present a novel integrative microfluidic device able to perform continuous separation of a desired amount of blood cells, without clogging or jamming, and at the same time, capable to assess the deformation index (DI) of both WBCs and RBCs. To determine the DI of both WBCs and RBCs, a hyperbolic converging microchannel was used, as well as a suitable image analysis technique to measure the DIs of these blood cells along the regions of interest. The results show that the WBCs have a much lower deformability than RBCs when subjected to the same in vitro flow conditions, which is directly related to their cytoskeleton and nucleus contents. The proposed strategy can be easily transformed into a simple and inexpensive diagnostic microfluidic system to simultaneously separate and assess blood cells deformability.

Keywords

Microfluidic devices Cell separation and deformability Hyperbolic microchannel Blood on chips RBC WBC 

Notes

Acknowledgments

The authors acknowledge the financial support provided by PTDC/SAU-ENB/116929/2010 and EXPL/EMS-SIS/2215/2013 from FCT (Fundação para a Ciência e a Tecnologia), COMPETE, QREN and European Union (FEDER). R. O. Rodrigues, D. Pinho and V. Faustino acknowledge respectively, the PhD scholarships SFRH/BD/97658/2013, SFRH/BD/89077/2012 and SFRH/BD/99696/2014 granted by FCT. The authors would also like to thank Dr. Ângela Fernandes for providing the blood samples and Dr. Ricardo Calhelha for supplying the tissue culture medium used in this work.

Supplementary material

10544_2015_14_MOESM1_ESM.avi (8.7 mb)
supplementary video 1 Trajectories of both RBC and PBMC flowing around the cross-flow pillars. RBCs deform and pass through the pillars into the branch channel whereas a PBMC rolls along the pillars in the direction of the primary flow. (AVI 8910 kb)

References

  1. G.C. Agbangla, É. Climent, P. Bacchin, Sep. Purif. Technol. 101, 42–48 (2012)CrossRefGoogle Scholar
  2. E.L. Bradley, L. Bernard, P. Thomas, J. Brian, J. Micromech. Microeng. 22, 025009 (2012)CrossRefGoogle Scholar
  3. X. Chen, D. Cui, C. Liu, H. Li, J. Chen, Anal. Chim. Acta 584, 237–243 (2007)CrossRefGoogle Scholar
  4. X. Chen, D.F. Cui, C.C. Liu, H. Li, Sens. Actuators B Chem. 130, 216–221 (2008)CrossRefGoogle Scholar
  5. R. Covar, M. Gleason, B. Macomber, L. Stewart, P. Szefler, K. Engelhardt, J. Murphy, A. Liu, S. Wood, S. DeMichele, E.W. Gelfand, S.J. Szefler, Clin. Exp. Allergy 40, 1163–1174 (2010)CrossRefGoogle Scholar
  6. V. Faustino, D. Pinho, T. Yaginuma, R. Calhelha, I.F.R. Ferreira, R. Lima, BioChip J. 8, 42–47 (2014)CrossRefGoogle Scholar
  7. A.E. Frampton, C.E. Fletcher, T.M. Gall, L. Castellano, C.L. Bevan, J. Stebbing, J. Krell, Expert. Rev. Mol. Diagn. 13, 425–430 (2013)CrossRefGoogle Scholar
  8. J. Fu, B.E. Sha, L.L. Thomas, J. Acquir. Immune Defic. Syndr. 56, 16–25 (2011)CrossRefGoogle Scholar
  9. K. Georgieva, D.J. Dijkstra, H. Fricke, N. Willenbacher, J. Colloid Interface Sci. 352, 265–277 (2010)CrossRefGoogle Scholar
  10. D.R. Gossett, W.M. Weaver, A.J. Mach, S.C. Hur, H.T. Tse, W. Lee, H. Amini, D. Di Carlo, Anal. Bioanal. Chem. 397, 3249–3267 (2010)CrossRefGoogle Scholar
  11. D.R. Gossett, H.T.K. Tse, S.A. Lee, Y. Ying, A.G. Lindgren, O.O. Yang, J. Rao, A.T. Clark, D. Di Carlo, Proc. Natl. Acad. Sci. U. S. A. 109, 7630–7635 (2012)CrossRefGoogle Scholar
  12. H.W. Hou, A.A. Bhagat, A.G. Chong, P. Mao, K.S. Tan, J. Han, C.T. Lim, Lab Chip 10, 2605–2613 (2010)CrossRefGoogle Scholar
  13. H.M. Ji, V. Samper, Y. Chen, C.K. Heng, T.M. Lim, L. Yobas, Biomed. Microdevices 10, 251–257 (2008)CrossRefGoogle Scholar
  14. Z. Jinlong, G. Qiuquan, L. Mei, Y. Jun, J. Micromech. Microeng. 18, 125025 (2008)CrossRefGoogle Scholar
  15. D.B. Khismatullin, in Leukocyte rolling and adhesion: Current topics in membranes, ed. by K. Ley, vol. 64 (Academic, New York, 2009), pp. 47–111Google Scholar
  16. M. Kim, S. Mo Jung, K.H. Lee, Y. Jun Kang, S. Yang, Artif. Organs 34, 996–1002 (2010)CrossRefGoogle Scholar
  17. V. Leble, R. Lima, R. Dias, C. Fernandes, T. Ishikawa, Y. Imai, T. Yamaguchi, Biomicrofluidics 5, 044120-044120-044115 (2011)Google Scholar
  18. S. Lee, Y. Yim, K. Ahn, S. Lee, Biomed. Microdevices 11, 1021–1027 (2009)CrossRefGoogle Scholar
  19. R. Lima, S. Wada, S. Tanaka, M. Takeda, T. Ishikawa, K. Tsubota, Y. Imai, T. Yamaguchi, Biomed. Microdevices 10, 153–167 (2008)CrossRefGoogle Scholar
  20. X.H. Liu, X. Wang, J. Biomech. 37, 1079–1085 (2004)CrossRefGoogle Scholar
  21. W. Luttmann, K. Bratke, M. Kupper, D. Myrtek, Immunology, vol. 1 (Elsevier, Philadelphia, 2006)Google Scholar
  22. E. Maes, B. Landuyt, I. Mertens, L. Schoofs, PLoS One 8, e61933 (2013)CrossRefGoogle Scholar
  23. E. Meijering, I. Smal, G. Danuser, IEEE Signal Process. Mag. 23, 46–53 (2006)CrossRefGoogle Scholar
  24. S. Metz, C. Trautmann, A. Bertsch, R. Ph, J. Micromech. Microeng. 14, 324 (2004)CrossRefGoogle Scholar
  25. S.K. Murthy, P. Sethu, G. Vunjak-Novakovic, M. Toner, M. Radisic, Biomed. Microdevices 8, 231–237 (2006)CrossRefGoogle Scholar
  26. E. Ortega, R. Gilabert, I. Nuñez, M. Cofán, A. Sala-Vila, E. de Groot, E. Ros, Atherosclerosis 221, 275–281 (2012)CrossRefGoogle Scholar
  27. T.G. Papaioannou, C. Stefanadis, Hellenic J. Cardiol. 46, 9–15 (2005)Google Scholar
  28. D. Pinho, T. Yaginuma, R. Lima, BioChip J. 7, 367–374 (2013)CrossRefGoogle Scholar
  29. A. Sabo, V. Jakovljevic, M. Stanulovic, L. Lepsanovic, D. Pejin, Int. J. Clin. Pharmacol. Ther. Toxicol. 31, 1–5 (1993)Google Scholar
  30. S.S. Shevkoplyas, T. Yoshida, L.L. Munn, M.W. Bitensky, Anal. Chem. 77, 933–937 (2005)CrossRefGoogle Scholar
  31. Sigma-Aldrich, Histopaque-1077: product information. St. Louis, MO, USA, (2011)Google Scholar
  32. R. Suwanarusk, B.M. Cooke, A.M. Dondorp, K. Silamut, J. Sattabongkot, N.J. White, R. Udomsangpetch, J. Infect. Dis. 189, 190–194 (2004)CrossRefGoogle Scholar
  33. K. Tae Goo, Y. Yong-Jin, J. Hongmiao, L. Pei Yi, C. Yu, J. Micromech. Microeng. 24, 087001 (2014)CrossRefGoogle Scholar
  34. M. Tanino, R. Matoba, S. Nakamura, H. Kameda, K. Amano, T. Okayama, H. Nagasawa, K. Suzuki, K. Matsubara, T. Takeuchi, Biochem. Biophys. Res. Commun. 387, 261–265 (2009)CrossRefGoogle Scholar
  35. V. VanDelinder, A. Groisman, Anal. Chem. 78, 3765–3771 (2006)CrossRefGoogle Scholar
  36. V. VanDelinder, A. Groisman, Anal. Chem. 79, 2023–2030 (2007)CrossRefGoogle Scholar
  37. T. Yaginuma, M.S.N. Oliveira, R. Lima, T. Ishikawa, T. Yamaguchi, Biomicrofluidics 7, 054110 (2013)CrossRefGoogle Scholar
  38. X. Yang, J.M. Yang, Y.-C. Tai, C.-M. Ho, Sensors Actuators A Phys. 73, 184–191 (1999)CrossRefGoogle Scholar
  39. Y.T. Yaylali, I. Susam, E. Demir, M. Bor-Kucukatay, B. Uludag, E. Kilic-Toprak, G. Erken, D. Dursunoglu, J. Coron. Artery Dis. 24, 11–15 (2013)Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Raquel O. Rodrigues
    • 1
    • 2
  • Diana Pinho
    • 2
    • 3
  • Vera Faustino
    • 2
    • 4
  • Rui Lima
    • 2
    • 3
    • 5
  1. 1.LCM – Laboratory of Catalysis and Materials – Associate Laboratory LSRE/LCM, Faculdade de Engenhariada Universidade do Porto (FEUP)PortoPortugal
  2. 2.Polytechnic Institute of Bragança, ESTiG/IPBBragançaPortugal
  3. 3.CEFTFaculdade de Engenharia da Universidade do Porto (FEUP)PortoPortugal
  4. 4.Center for MicroElectromechanical Systems (CMEMS-UMinho)University of MinhoGuimarãesPortugal
  5. 5.Mechanical Engineering DepartmentUniversity of MinhoGuimarãesPortugal

Personalised recommendations