Biomedical Microdevices

, Volume 12, Issue 3, pp 485–497 | Cite as

Fast and continuous plasma extraction from whole human blood based on expanding cell-free layer devices

  • Elodie Sollier
  • Myriam Cubizolles
  • Yves Fouillet
  • Jean-Luc Achard


This paper presents promising microfluidic devices designed for continuous and passive extraction of plasma from whole human blood. These designs are based on red cells lateral migration and the resulting cell-free layer locally expanded by geometric singularities such as an enlargement of the channel or a cavity adjacent to the channel. After an explanation of flow patterns, different tests are described that confirm the advantages of both proposed singularities, providing a 1.5 and 2X increase in extraction yield compared to a reference device, for 1:20 diluted blood at 100 µL/min. Devices have also been successively optimized, with extraction yields up to 17.8%, and biologically validated for plasma extraction, with no protein loss or denaturation, no hemolysis and with excellent cell purity. Finally, the dilution effect has been experimentally investigated.


Plasma extraction Cell-free layer Singularities Recirculation flows Blood 


  1. M. Abkarian, A. Viallat, Biophys. J. 89, 1055–1066 (2005)CrossRefGoogle Scholar
  2. N. Alleborn, K. Nandakumar, H. Raszillier, F. Durst, J. Fluid. Mech. 330, 169–188 (1997)MATHCrossRefGoogle Scholar
  3. D.R. Arifin, L.Y. Yeo, J.R. Friend, Biomicrofluidics 1(014103), 1–13 (2007)Google Scholar
  4. E.S. Asmolov, J. Fluid Mech. 381, 63–87 (1999)MATHCrossRefGoogle Scholar
  5. S.A. Bergern, L. Talbot, L.S. Yao, Annu. Rev. Fluid Mech. 15, 461–512 (1983)CrossRefGoogle Scholar
  6. A.A.S. Bhagat, S.S. Kuntaegowdanahalli, I. Papautsky, Microfluid. Nanofluid. 7, 217–226 (2009)CrossRefGoogle Scholar
  7. C. Blattert, R. Jurischka, I. Tahhan, A. Schoth, H. Reinecke, Proc. µTAS, Tokyo, Japan, 359–361 (2006)Google Scholar
  8. X. Chen, D.F. Cui, C.C. Liu, H. Li, Sens. Actuators, B 130, 216–221 (2008)CrossRefGoogle Scholar
  9. X. Cheng, D. Irimia, M. Dixon, J.C. Ziperstein, U. Demirci, L. Zamir, R.G. Tompkins, M. Toner, W.R. Rodriguez, JAIDS 45(3), 257–261 (2007)Google Scholar
  10. D.T. Chiu, Anal. Bioanal. Chem. 387, 17–20 (2007)CrossRefGoogle Scholar
  11. S. Choi, JK Park (Proc. µTAS, Paris, France, 2007), pp. 1486–1488Google Scholar
  12. C.M. Cripps, J. Clin. Pathol. 21, 110 (1968)CrossRefGoogle Scholar
  13. T.A. Crowley, V. Pizziconi, Lab Chip 5, 922–929 (2005)CrossRefGoogle Scholar
  14. J.A. Davis, D.W. Inglis, K.J. Morton, D.A. Lawrence, L.R. Huang, S.Y. Chou, J.C. Sturm, R.H. Austin, PNAS 103(40), 14779–14784 (2006)CrossRefGoogle Scholar
  15. D. Di Carlo, J.F. Edd, D. Irimia, R.G. Tompkins, M. Toner, Anal. Chem. 80, 2204–2211 (2008)CrossRefGoogle Scholar
  16. D. Di Carlo, J.F. Edd, K.J. Humphry, H.A. Stone, M. Toner, Phys. Rev. Lett. 102, 094503 (2009)CrossRefGoogle Scholar
  17. M. Faivre, M. Abkarian, K. Bickraj, H. Stone, Biorheology 43, 147–159 (2006)Google Scholar
  18. E.P. Furlani, J. Phys. D: Appl. Phys. 40, 1313–1319 (2007)CrossRefGoogle Scholar
  19. I. Gregoratto, C.J. McNeil, M.W. Reeks, Proc (Nanotech, Montreux, Switzerland, 2006)Google Scholar
  20. S. Haeberle, T. Brenner, R. Zengerle, J. Ducrée, Lab Chip 6, 776–781 (2006)CrossRefGoogle Scholar
  21. B.S. Hardy, K. Uechi, J. Zhen, H.P. Kavehpour, Lab Chip 9, 935–938 (2009)CrossRefGoogle Scholar
  22. R.D. Jäggi, R. Sandoz, C.S. Effenhauser, Microfluid. Nanofluid. 3, 47–53 (2007)CrossRefGoogle Scholar
  23. H.M. Ji, V. Samper, Y. Chen, C.K. Heng, T.M. Lim, L. Yobas, Biomed Microdevices 10, 251–257 (2008)CrossRefGoogle Scholar
  24. M. Kersaudy-Kerhoas, R.S. Dhariwal, M.P.Y. Desmulliez, IET Nanobiotechnol 2(1), 1–13 (2008)CrossRefGoogle Scholar
  25. M. Kersaudy-Kerhoas, R.S. Dhariwal, M.P.Y. Desmulliez, L. Jouvet, International Journal of Microfluidics and Nanofluidics, 1–10 (2009)Google Scholar
  26. A. Lenshof, A. Ahmad-Tajudin, K. Järas, A.M. Swärd-Nilsson, L. Aberg, G. Marko-Varga, J. Malm, H. Lilja, T. Laurell, Anal. Chem. 81, 6030–6037 (2009)Google Scholar
  27. H.K. Moffatt, J. Fluid Mech. 18, 1–18 (1967)CrossRefGoogle Scholar
  28. Y. Nakashima, T. Yasuda, Proc. µTAS, Paris, France 706–708 (2007)Google Scholar
  29. A. Nilsson, F. Petersson, T. Laurell, Proc. µTAS, Tokyo, Japan 314–316 (2006)Google Scholar
  30. P. Olla, J. Phys. France II, 7, 1533–1540 (1997)Google Scholar
  31. S. Ookawara, R. Higashi, D. Street, K. Ogawa, Chemical Engineering Journal 101, 171–178 (2004)CrossRefGoogle Scholar
  32. N. Pamme, Lab Chip 7, 1644–1659 (2007)CrossRefGoogle Scholar
  33. J. Park, K. Cho, C. Chung, D.C. Han, J.K. Chang, Proc. IEEE EMBS, Kahuku, Oahu, Hawaii (2005)Google Scholar
  34. J.S. Park, S.H. Song, H.I. Jung, Lab Chip 9, 939–948 (2009)CrossRefGoogle Scholar
  35. J.A. Schonberg, E.J. Hinch, J. Fluid Mech. 203, 517–524 (1989)MATHCrossRefMathSciNetGoogle Scholar
  36. G. Segre, A. Silberberg, J. Fluid Mech. 14, 136–57 (1962)CrossRefGoogle Scholar
  37. M. Seki, Proc. µTAS, Paris, France 1228–1230 (2007)Google Scholar
  38. P. Sethu, L.L. Moldawer, M.N. Mindrinos, P.O. Scumpia, C.L. Tannahill, J. Wilhelmy, P.A. Efron, B.H. Brownstein, R.G. Tompkins, M. Toner, Anal. Chem. 78(15), 5453–5461 (2006)CrossRefGoogle Scholar
  39. E. Sollier, H. Rostaing, P. Pouteau, Y. Fouillet, J.L. Achard, Sens Actuators B. 141(2), 617–624 (2009)Google Scholar
  40. S. Thorshund, O. Klett, F. Nikolajeff, K. Markides, J. Bergquist, Biomed Microdevices 8, 73–79 (2006)CrossRefGoogle Scholar
  41. G. Thurston, Biorheology 26, 199–214 (1989)Google Scholar
  42. M. Toner, D. Irimia, Annu. Rev. Biomed. Eng. 7, 77–103 (2005)CrossRefGoogle Scholar
  43. V. VanDeLinder, A. Groisman, Anal. Chem. 78, 3765–3771 (2006)CrossRefGoogle Scholar
  44. W. Wang, D. Xu, Z. Li, Proc. µTAS, Tokyo, Japan 543–545 (2006)Google Scholar
  45. M. Yamada, M. Seki, Lab Chip 5, 1233–1239 (2005)CrossRefGoogle Scholar
  46. S. Yang, A. Ündar, J.D. Zahn, Lab Chip 6, 871–880 (2006)CrossRefGoogle Scholar
  47. S.Y. Yoon, S. Yang, J.H. Moon, K.C. Kim, Proc. µTAS, Tokyo, Japan 1154–1156 (2006)Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Elodie Sollier
    • 1
  • Myriam Cubizolles
    • 1
  • Yves Fouillet
    • 1
  • Jean-Luc Achard
    • 2
  1. 1.Department of Technology for Biology and HealthCEA-LETI-MinatecGrenoble Cedex 9France
  2. 2.LEGI, Laboratoire des Ecoulements Géophysiques et IndustrielsDomaine UniversitaireGrenoble Cedex 9France

Personalised recommendations