Biomedical Microdevices

, 17:95 | Cite as

Acoustophoretic removal of proteins from blood components

  • Maria Tenje
  • Maria N. Lundgren
  • Ann-Margret Swärd-Nilsson
  • Jens Kjeldsen-Kragh
  • Lena Lyxe
  • Andreas Lenshof


This work presents the development of a miniaturized system for removing plasma proteins and other low-molecular-weight compounds from red blood cell (RBC) concentrate in a simple one-step-process using integrated ultrasound. The technology utilizes the principles of acoustophoresis to transfer the RBCs from the original plasma-containing solution into a protein-free SAG-M additive solution in a continuous flow process. The preparation of protein free RBC concentrate is important for blood transfusion to patients suffering from immunoglobulin A (IgA)-deficiency and developing antibodies against IgA. We show a nearly complete removal of both albumin and IgA from concentrated RBCs via this one-step-processes in samples obtained from RBC concentrate. The cell recovery of our technology is close to 97 %, compared to just above 90 % of the current procedure of repeated dilution and centrifugation steps. This work clearly shows the potential of integrated acoustophoresis in a miniaturized system for clinical applications.


Acoustophoresis Blood component preparation IgA deficiency 



We gratefully thank Sandra Pettersson at the Department of Transfusion Medicine, Skånes University Hospital, Lund, Sweden for providing the RBC concentrate samples. Financial support for this work has been provided by The Swedish Governmental Agency for Innovation Systems, VINNOVA, the project “CellCARE” (grant no. 2009–00236) and the Swedish Research Council FORMAS through the Strong Research Environments project “BioBridges” (project no. 221-2011-1692).


  1. P. Augustsson et al., Decomplexing biofluids using microchip based acoustophoresis. Lab Chip 9(6), 810–818 (2009)CrossRefGoogle Scholar
  2. P. Augustsson et al., Microfluidic, label-free enrichment of prostate cancer cells in blood based on acoustophoresis. Anal. Chem. 84(18), 7954–7962 (2012)CrossRefGoogle Scholar
  3. R. Barnkob et al., Acoustic radiation- and streaming-induced microparticle velocities determined by microparticle image velocimetry in an ultrasound symmetry plane. Phys. Rev. E 86(5), 056307 (2012)CrossRefGoogle Scholar
  4. H. Bruus, Acoustofluidics 1: Governing equations in microfluidics. Lab Chip 11(22), 3742–3751 (2011)CrossRefGoogle Scholar
  5. H. Bruus, Acoustofluidics 7: The acoustic radiation force on small particles. Lab Chip 12(6), 1014–1021 (2012)CrossRefGoogle Scholar
  6. M.A. Burguillos et al., Microchannel acoustophoresis does not impact survival or function of microglia, leukocytes or tumor cells. PLoS One 8(5), e64233 (2013)CrossRefGoogle Scholar
  7. C. Cunningham-Rundles, Physiology of IgA and IgA deficiency. J. Clin. Immunol. 21(5), 303–309 (2001)CrossRefGoogle Scholar
  8. S. Deshmukh et al., Acoustic radiation forces at liquid interfaces impact the performance of acoustophoresis. Lab Chip 14(17), 3394–3400 (2014)CrossRefGoogle Scholar
  9. J. Dykes et al., Efficient removal of platelets from peripheral blood progenitor cell products using a novel micro-chip based acoustophoretic platform. PLoS One 6(8), e23074 (2011). 10 pp CrossRefGoogle Scholar
  10. S.K. Harm et al., Haemolysis and sublethal injury of RBCs after routine blood bank manipulations. Transfus. Med. 22(3), 181–185 (2012)CrossRefGoogle Scholar
  11. J.J. Hawkes et al., Continuous cell washing and mixing drvien by an ultrasound standing wave within a microfluidic channel. Lab Chip 4, 446–452 (2004)CrossRefGoogle Scholar
  12. European Directorate For The Quality Of Medicines And Healthcare. Guide for the preparation, use and quality assurance of blood components. Brussels: Council of Europe 2013Google Scholar
  13. M. Holmberg, X. Hou, Competitive protein adsorption - multilayer adsorption and surface induced protein aggregation. Langmuir 25, 2081–2089 (2009)CrossRefGoogle Scholar
  14. M. Janzi et al., Selective IgA deficiency in early life: association to infections and allergic diseases during childhood. Clin. Immunol. 133(1), 78–85 (2009)CrossRefGoogle Scholar
  15. H. Jonsson et al., Particle separation using ultrasound can radically reduce embolic load to brain after cardiac surgery. Ann. Thorac. Surg. 78(5), 1572–1577 (2004)CrossRefGoogle Scholar
  16. A. Lenshof, T. Laurell, Emerging clinical applications of microchip-based acoustophoresis. J. Lab. Autom. 16(6), 443–449 (2011)CrossRefGoogle Scholar
  17. A. Lenshof et al., Acoustic whole blood plasmapheresis chip for prostate specific antigen microarray diagnostics. Anal. Chem. 81, 6030–6037 (2009)CrossRefGoogle Scholar
  18. J.F. Ludvigsson et al., IgA deficiency and risk of cancer: a population-based matched cohort study. J. Clin. Immunol. 35(2), 182–188 (2015)CrossRefGoogle Scholar
  19. A. Nilsson et al., Acoustic control of suspended particles in micro fluidic chips. Lab Chip 4(2), 131–135 (2004)CrossRefGoogle Scholar
  20. S. Oltean et al., Detection of anti-IgA antibodies using the particle gel immunoassay: a rapid test for increased patient safety. Blood Transfus. 12(3), 334–339 (2014)MathSciNetGoogle Scholar
  21. S.V. Rudmann, Textbook of blood banking and transfusion medicine (Elsevier, Philadelphia, 2005)Google Scholar
  22. S.G. Sandler, N.D. Zantek, Review: IgA anaphylactic transfusion reactions. Part II. Clinical diagnosis and bedside management. Immunohematology 20(4), 234–238 (2004)Google Scholar
  23. R.L. Sunheimer, L. Graves, Clinical Laboratory Chemistry (Pearson, Upper Saddle River, 2010)Google Scholar
  24. R.R. Vassallo, Review: IgA anaphylactic transfusion reactions. Part I. Laboratory diagnosis, incidence, and supply of IgA-deficient products. Immunohematology 20(4), 226–233 (2004)Google Scholar
  25. L. Yel, Selective IgA deficiency. J. Clin. Immunol. 30(1), 10–16 (2010)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Maria Tenje
    • 1
    • 2
  • Maria N. Lundgren
    • 3
  • Ann-Margret Swärd-Nilsson
    • 3
  • Jens Kjeldsen-Kragh
    • 3
  • Lena Lyxe
    • 4
  • Andreas Lenshof
    • 1
  1. 1.Department of Biomedical EngineeringLund UniversityLundSweden
  2. 2.Department of Engineering Sciences, Science for Life LaboratoryUppsala UniversityUppsalaSweden
  3. 3.Department of Clinical Immunology and Transfusion MedicineSkåne University HospitalLundSweden
  4. 4.Sahlgrenska University HospitalGöteborgSweden

Personalised recommendations