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

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.

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References

  1. G.C. Agbangla, É. Climent, P. Bacchin, Sep. Purif. Technol. 101, 42–48 (2012)

    Article  Google Scholar 

  2. E.L. Bradley, L. Bernard, P. Thomas, J. Brian, J. Micromech. Microeng. 22, 025009 (2012)

    Article  Google Scholar 

  3. X. Chen, D. Cui, C. Liu, H. Li, J. Chen, Anal. Chim. Acta 584, 237–243 (2007)

    Article  Google Scholar 

  4. X. Chen, D.F. Cui, C.C. Liu, H. Li, Sens. Actuators B Chem. 130, 216–221 (2008)

    Article  Google 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)

    Article  Google Scholar 

  6. V. Faustino, D. Pinho, T. Yaginuma, R. Calhelha, I.F.R. Ferreira, R. Lima, BioChip J. 8, 42–47 (2014)

    Article  Google 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)

    Article  Google Scholar 

  8. J. Fu, B.E. Sha, L.L. Thomas, J. Acquir. Immune Defic. Syndr. 56, 16–25 (2011)

    Article  Google Scholar 

  9. K. Georgieva, D.J. Dijkstra, H. Fricke, N. Willenbacher, J. Colloid Interface Sci. 352, 265–277 (2010)

    Article  Google 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)

    Article  Google 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)

    Article  Google 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)

    Article  Google Scholar 

  13. H.M. Ji, V. Samper, Y. Chen, C.K. Heng, T.M. Lim, L. Yobas, Biomed. Microdevices 10, 251–257 (2008)

    Article  Google Scholar 

  14. Z. Jinlong, G. Qiuquan, L. Mei, Y. Jun, J. Micromech. Microeng. 18, 125025 (2008)

    Article  Google 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. 47–111

    Google Scholar 

  16. M. Kim, S. Mo Jung, K.H. Lee, Y. Jun Kang, S. Yang, Artif. Organs 34, 996–1002 (2010)

    Article  Google Scholar 

  17. V. Leble, R. Lima, R. Dias, C. Fernandes, T. Ishikawa, Y. Imai, T. Yamaguchi, Biomicrofluidics 5, 044120-044120-044115 (2011)

  18. S. Lee, Y. Yim, K. Ahn, S. Lee, Biomed. Microdevices 11, 1021–1027 (2009)

    Article  Google Scholar 

  19. R. Lima, S. Wada, S. Tanaka, M. Takeda, T. Ishikawa, K. Tsubota, Y. Imai, T. Yamaguchi, Biomed. Microdevices 10, 153–167 (2008)

    Article  Google Scholar 

  20. X.H. Liu, X. Wang, J. Biomech. 37, 1079–1085 (2004)

    Article  Google 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)

    Article  Google Scholar 

  23. E. Meijering, I. Smal, G. Danuser, IEEE Signal Process. Mag. 23, 46–53 (2006)

    Article  Google Scholar 

  24. S. Metz, C. Trautmann, A. Bertsch, R. Ph, J. Micromech. Microeng. 14, 324 (2004)

    Article  Google Scholar 

  25. S.K. Murthy, P. Sethu, G. Vunjak-Novakovic, M. Toner, M. Radisic, Biomed. Microdevices 8, 231–237 (2006)

    Article  Google Scholar 

  26. E. Ortega, R. Gilabert, I. Nuñez, M. Cofán, A. Sala-Vila, E. de Groot, E. Ros, Atherosclerosis 221, 275–281 (2012)

    Article  Google 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)

    Article  Google 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)

    Article  Google Scholar 

  31. Sigma-Aldrich, Histopaque-1077: product information. St. Louis, MO, USA, (2011)

  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)

    Article  Google Scholar 

  33. K. Tae Goo, Y. Yong-Jin, J. Hongmiao, L. Pei Yi, C. Yu, J. Micromech. Microeng. 24, 087001 (2014)

    Article  Google 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)

    Article  Google Scholar 

  35. V. VanDelinder, A. Groisman, Anal. Chem. 78, 3765–3771 (2006)

    Article  Google Scholar 

  36. V. VanDelinder, A. Groisman, Anal. Chem. 79, 2023–2030 (2007)

    Article  Google Scholar 

  37. T. Yaginuma, M.S.N. Oliveira, R. Lima, T. Ishikawa, T. Yamaguchi, Biomicrofluidics 7, 054110 (2013)

    Article  Google Scholar 

  38. X. Yang, J.M. Yang, Y.-C. Tai, C.-M. Ho, Sensors Actuators A Phys. 73, 184–191 (1999)

    Article  Google 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)

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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.

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Correspondence to Rui Lima.

Electronic supplementary material

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)

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Rodrigues, R.O., Pinho, D., Faustino, V. et al. A simple microfluidic device for the deformability assessment of blood cells in a continuous flow. Biomed Microdevices 17, 108 (2015). https://doi.org/10.1007/s10544-015-0014-2

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Keywords

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