Skip to main content
SpringerLink
Log in

Six-stage cascade paramagnetic mode magnetophoretic separation system for human blood samples

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

This paper is focused on the development of a six-stage cascade paramagnetic mode magnetophoretic separation (PMMS) system for separating suspended cells in blood based on their native magnetic properties. The design and fabrication of a PMMS system are presented and the microfluidic separation system is characterized experimentally using human whole blood as the case study. The PMMS system can separate blood cells types continuously using the magnetophoretic force produced from a high magnetic field gradient without magnetic or fluorescent tagging. Experimental results demonstrated that red blood cell separation in the PMMS system at a volumetric flow rate of 28.8 μL / hr, resulting in a separation time of 10.4 min for a 5.0 μL blood sample with a separation efficiency of 89.5 ± 0.20%. The PMMS system was tested at higher volumetric flow rates of 50.4 μL / hr and 72.0 μL / hr. The measured separation efficiencies were 86.2 ± 1.60% and 59.9 ± 6.06% respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • J.D. Adams, U. Kim, H.T. Soh, Multitarget magnetic activated cell sorter. Proc. Natl. Acad. Sci. U.S.A. 105, 18165–18170 (2008)

    Article  Google Scholar 

  • R.W. Applegate, J. Squier, T. Vestad, J. Oakey, D.W.M. Marr, Optical trapping, manipulation, and sorting of cells and colloids in microfluidic systems with diode laser bars. Opt. Express 12, 4390–4398 (2004)

    Article  Google Scholar 

  • F.F. Becker, X.B. Wang, Y. Huang, R. Pethig, J. Vykoukal, P.R.C. Gascoyne, Separation of human breast-cancer cells from blood by differential dielectric affinity. Proc. Natl. Acad. Sci. U.S.A. 92, 860–864 (1995)

    Article  Google Scholar 

  • H.T. Chen, A.D. Ebner, A.J. Rosengart, M.D. Kaminski, J.A. Ritter, Analysis of magnetic drug carrier particle capture by a magnetizable intravascular stent: 1. Parametric study with single wire correlation. J. Magn. Magn. Mater. 284, 181–194 (2004)

    Article  Google Scholar 

  • X. Chen, D.F. Cui, C.C. Liu, H. Li, Microfluidic chip for blood cell separation and collection based on crossflow filtration. Sens. Actuators, B, Chem. 130, 216–221 (2008)

    Article  Google Scholar 

  • I.F. Cheng, H.C. Chang, D. Hou, H.C. Chang, An integrated dielectrophoretic chip for continuous bioparticle filtering, focusing, sorting, trapping, and detecting. Biomicrofluidics 1, 15 (2007)

    Article  Google Scholar 

  • S. Choi, J.K. Park, Continuous hydrophoretic separation and sizing of microparticles using slanted obstacles in a microchannel. Lab Chip 7, 890–897 (2007)

    Article  Google Scholar 

  • D.A. Colling, Intrinsic magnetization of Fe-Ni-Mn alloys. J. Appl. Physi. 40, 1379–1381 (1969)

    Article  Google Scholar 

  • K. Dholakia, M.P. MacDonald, P. Zemanek, T. Cizmar, Cellular and colloidal separation using optical forces. Laser Manipulation of Cells and Tissues 82, 467–495 (2007)

    Article  Google Scholar 

  • A. Ditsch, J. Yin, P.E. Laibinis, D.I.C. Wang, T.A. Hatton, Ion-exchange purification of proteins using magnetic nanoclusters. Biotechnol. Prog. 22, 1153–1162 (2006)

    Article  Google Scholar 

  • A.D. Ebner, J.A. Ritter, L. Nunez, High-gradient magnetic separation for the treatment of high-level radioactive wastes. Sep. Sci. Technol. 34, 1333–1350 (1999)

    Google Scholar 

  • A.B. Frazier, Metallic microstructures fabricated using photosensitive polyimide electroplating molds. J. Microelectromech. Syst. 2, 87–94 (1993)

    Article  Google Scholar 

  • P.R.C. Gascoyne, J. Vykoukal, Particle separation by dielectrophoresis. Electrophoresis 23, 1973–1983 (2002)

    Article  Google Scholar 

  • K.H. Han, A.B. Frazier, Continuous magnetophoretic separation of blood cells in microdevice format. J. Appl. Physi. 96, 5797–5802 (2004)

    Article  Google Scholar 

  • K.H. Han, A.B. Frazier, Diamagnetic capture mode magnetophoretic microseparator for blood cells. J. Microelectromech. Syst. 14, 1422–1431 (2005a)

    Article  Google Scholar 

  • K.H. Han, A.B. Frazier, Reliability aspects of packaging and integration technology for microfluidic systems. IEEE Transactions on Device and Materials Reliability 5, 452–457 (2005b)

    Article  Google Scholar 

  • K.H. Han, A.B. Frazier, Paramagnetic capture mode magnetophoretic microseparator for blood cells. IEE Proc. Nanobiotechnol. 153, 67–73 (2006a)

    Article  Google Scholar 

  • K.H. Han, A.B. Frazier, Paramagnetic capture mode magnetophoretic microseparator for high efficiency blood cell separations. Lab Chip 6, 265–273 (2006b)

    Article  Google Scholar 

  • K.H. Han, A.B. Frazier, Lateral-driven continuous dielectrophoretic microseparators for blood cells suspended in a highly conductive medium. Lab Chip 8, 1079–1086 (2008)

    Article  Google Scholar 

  • L.A. Herzenberg, D. Parks, B. Sahaf, O. Perez, M. Roederer, L.A. Herzenberg, The history and future of the fluorescence activated cell sorter and flow cytometry: A view from Stanford. Clin. Chem. 48, 1819–1827 (2002)

    Google Scholar 

  • Y. Kakihara, T. Fukunishi, S. Takeda, S. Nishijima, A. Nakahira, Superconducting high gradient magnetic separation for purification of wastewater from paper factory. IEEE Trans. Appl. Supercond. 14, 1565–1567 (2004)

    Article  Google Scholar 

  • M.P. MacDonald, G.C. Spalding, K. Dholakia, Microfluidic sorting in an optical lattice. Nature 426, 421–424 (2003)

    Article  Google Scholar 

  • M.P. MacDonald, S. Neale, L. Paterson, A. Richies, K. Dholakia, G.C. Spalding, Cell cytometry with a light touch: Sorting microscopic matter with an optical lattice. J. Biol. Regul. Homeost. Agents 18, 200–205 (2004)

    Google Scholar 

  • H. Maenaka, M. Yamada, M. Yasuda, M. Seki, Continuous and size-dependent sorting of emulsion droplets using hydrodynamics in pinched microchannels. Langmuir 24, 4405–4410 (2008)

    Article  Google Scholar 

  • D. Melville, F. Paul, S. Roath, High gradient magnetic separation of red-cells from whole-blood. IEEE Trans. Magn. 11, 1701–1704 (1975)

    Article  Google Scholar 

  • S. Miltenyi, W. Muller, W. Weichel, A. Radbruch, High-gradient magnetic cell-separation with MACS. Cytometry 11, 231–238 (1990)

    Article  Google Scholar 

  • G.D. Moeser, K.A. Roach, W.H. Green, P.E. Laibinis, T.A. Hatton, Water-based magnetic fluids as extractants for synthetic organic compounds. Ind. Eng. Chem. Res. 41, 4739–4749 (2002)

    Article  Google Scholar 

  • A.F. Ngomsik, A. Bee, M. Draye, G. Cote, V. Cabuil, Magnetic nano- and microparticles for metal removal and environmental applications: a review. Comptes Rendus Chimie 8, 963–970 (2005)

    Article  Google Scholar 

  • M. Ozkan, M. Wang, C. Ozkan, R. Flynn, A. Birkbeck, S. Esener, Optical manipulation of objects and biological cells in microfluidic devices. Biomed. Microdevices 5, 61–67 (2003)

    Article  Google Scholar 

  • N. Pamme, C. Wilhelm, Continuous sorting of magnetic cells via on-chip free-flow magnetophoresis. Lab Chip 6, 974–980 (2006)

    Article  Google Scholar 

  • N. Pamme, J.C.T. Eijkel, A. Manz, On-chip free-flow magnetophoresis: Separation and detection of mixtures of magnetic particles in continuous flow. J. Magn. Magn. Mater. 307, 237–244 (2006)

    Article  Google Scholar 

  • M.S. Pommer, Y.T. Zhang, N. Keerthi, D. Chen, J.A. Thomson, C.D. Meinhart, H.T. Soh, Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels. Electrophoresis 29, 1213–1218 (2008)

    Article  Google Scholar 

  • A.J. Richards, O.S. Roath, R.J.S. Smith, J.H.P. Watson, The mechanisms of high gradient magnetic separation of human blood and bone marrow. IEEE Trans. Magn. 32, 459–470 (1996)

    Article  Google Scholar 

  • J.A. Ritter, A.D. Ebner, K.D. Daniel, K.L. Stewart, Application of high gradient magnetic separation principles to magnetic drug targeting. J. Magn. Magn. Mater. 280, 184–201 (2004)

    Article  Google Scholar 

  • M. Sarikaya, T. Abbasov, M. Erdemoglu, Some aspects of magnetic filtration theory for removal of fine particles from aqueous suspensions. J. Dispers. Sci. Technol. 27, 193–198 (2006)

    Article  Google Scholar 

  • T. Schneider, L.R. Moore, Y. Jing, S. Haam, P.S. Williams, A.J. Fleischman, S. Roy, J.J. Chalmers, M. Zborowski, Continuous flow magnetic cell fractionation based on antigen expression level. J. Biochem. Biophys. Methods 68, 1–21 (2006)

    Article  Google Scholar 

  • Y.Y. Sun, X.C. Yuan, L.S. Ong, J. Bu, S.W. Zhu, R. Liu, Large-scale optical traps on a chip for optical sorting. Appl. Phys. Lett. 90, (2007)

  • M. Takayasu, D.R. Kelland, J.V. Minervini, Continuous magnetic separation of blood components from whole blood. IEEE Trans. Appl. Supercond. 10, 927–930 (2000)

    Article  Google Scholar 

  • A. Thiel, A. Scheffold, A. Radbruch, Immunomagnetic cell sorting—pushing the limits. Immunotechnology 4, 89–96 (1998)

    Article  Google Scholar 

  • T.E. Thomas, S.J.R. Abraham, A.J. Otter, E.W. Blackmore, P.M. Lansdorp, High-gradient magnetic separation of cells on the basis of expression levels of cell-surface antigens. J. Immunol. Methods 154, 245–252 (1992)

    Article  Google Scholar 

  • M. Toner, D. Irimia, Blood-on-a-chip. Annu. Rev. Biomed. Eng. 7, 77–103 (2005)

    Article  Google Scholar 

  • S. Vankrunkelsven, D. Clicq, K. Pappaert, W. Ranson, C. De Tandt, H. Ottevaere, H. Thienpont, G.V. Baron, G. Desmet, A novel microstep device for the size separation of cells. Electrophoresis 25, 1714–1722 (2004)

    Article  Google Scholar 

  • M.M. Wang, E. Tu, D.E. Raymond, J.M. Yang, H.C. Zhang, N. Hagen, B. Dees, E.M. Mercer, A.H. Forster, I. Kariv, P.J. Marchand, W.F. Butler, Microfluidic sorting of mammalian cells by optical force switching. Nat. Biotechnol. 23, 83–87 (2005)

    Article  Google Scholar 

  • N. Xia, T.P. Hunt, B.T. Mayers, E. Alsberg, G.M. Whitesides, R.M. Westervelt, D.E. Ingber, Combined microfluidic-micromagnetic separation of living cells in continuous flow. Biomed. Microdevices 8, 299–308 (2006)

    Article  Google Scholar 

  • M. Yamada, M. Seki, Microfluidic particle sorter employing flow splitting and recombining. Anal. Chem. 78, 1357–1362 (2006)

    Article  Google Scholar 

  • B.B. Yellen, Z.G. Forbes, D.S. Halverson, G. Fridman, K.A. Barbee, M. Chorny, R. Levy, G. Friedman, Targeted drug delivery to magnetic implants for therapeutic applications. J. Magn. Magn. Mater. 293, 647–654 (2005)

    Article  Google Scholar 

  • M. Zborowski, G.R. Ostera, L.R. Moore, S. Milliron, J.J. Chalmers, A.N. Schechter, Red blood cell magnetophoresis. Biophys. J. 84, 2638–2645 (2003)

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Institutes of Health (NIH) under Grant Number ES10846.

Authorships

Contributions: Youngdo Jung designed the research, carried out fabrication and experiments, analyzed data, and wrote the paper. Yoonsu Choi carried out fabrication. Ki-Ho Han provided theoretical background for the research. A. Bruno Frazier managed overall research and edited the paper.

Conflict-of-interest disclosure

The authors declare no competing financial interests.

Author information

Authors and Affiliations

  1. School of Electrical and Computer Engineering, Georgia Institute of Technology, 777 Atlantic Drive, Atlanta, GA, 30332-0250, USA

    Youngdo Jung, Yoonsu Choi & A. Bruno Frazier

  2. School of Nano Engineering, Inje University, 607 Obang-dong, Gimhae, Gyongnam, 621-749, Republic of Korea

    Ki-Ho Han

Authors
  1. Youngdo Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoonsu Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ki-Ho Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Bruno Frazier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Bruno Frazier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jung, Y., Choi, Y., Han, KH. et al. Six-stage cascade paramagnetic mode magnetophoretic separation system for human blood samples. Biomed Microdevices 12, 637–645 (2010). https://doi.org/10.1007/s10544-010-9416-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-010-9416-3

Keywords

Search

Navigation