Microsystems for Whole Blood Purification and Electrophysiological Analysis

  • Han, Arum (School of Electrical and Computer Engineering Georgia Institute of Technology) ;
  • Han, Ki-Ho (School of Electrical and Computer Engineering Georgia Institute of Technology) ;
  • Mohanty Swomitra K. (School of Electrical and Computer Engineering Georgia Institute of Technology) ;
  • Frazier A. Bruno (School of Electrical and Computer Engineering Georgia Institute of Technology)
  • Published : 2005.03.31

Abstract

This paper presents the development of a microsystem for whole blood purification and electrophysiological analysis of the purified cells. Magnetophoresis using continuous diamagnetic capture (DMC) was utilized for whole cell purification and electrical impedance spectroscopy (EIS) was utilized for electrophysiological analysis of the purified cells. The system was developed on silicon and plastic substrates utilizing conventional microfabrication technologies and plastic microfabrication technologies. Using the magnetophoretic microseparator, white blood cells were purified from a sample of whole blood. The experimental results of the DMC microseparator show that 89.7% of the red blood cells (RBCs) and 72.7% of the white blood cells (WBCs) could be continuously separated out from a whole blood using an external magnetic flux of 0.2 T. EIS was used as a downstream whole cell analysis tool to study the electrophysiological characteristics of purified cells. In this work, primary cultured bovine chromaffin cells and human red blood cells were characterized using EIS. Further analysis capabilities of the EIS were demonstrated by successfully obtaining unique impedance signatures for chromaffin cells based on the whole cell ion channel activity.

Keywords

References

  1. E. Racila, D. Euhus, A. J. Weiss, C. Rao, J. McConnell, L. W. M. M. Terstappen, and J. W. Uhr, Proceedings of the National Academy of Sciences of the United States of America, vol. 95, pp. 4589-4594, 1998 https://doi.org/10.1073/pnas.95.8.4589
  2. M. Cristofanilli and et.al, New England Journal of Medicine, vol. 351, pp. 781-7991, 2004 https://doi.org/10.1056/NEJMoa040766
  3. R. Pethig, Critical Reviews in Biotechnology, vol. 16, pp. 331-348, 1996 https://doi.org/10.3109/07388559609147425
  4. J. Oberteuffer, IEEE Transactions on Magnetics, vol. 10, pp. 223-238, 1974 https://doi.org/10.1109/TMAG.1974.1058315
  5. H. Kolm, J. Oberteuffer, and D. Kelland. Scientific American, vol. 11, pp. 46-54, 1975
  6. M. R. Parker, Physics in Technology, vol. 12, pp. 263-268, 1981 https://doi.org/10.1088/0305-4624/12/6/I03
  7. D. Melville, F. Paul, and S. Roath, Nature, vol. 255, pp. 706, 1975 https://doi.org/10.1038/255706a0
  8. D. Melville, F. Paul, and S. Roath, IEEE Transactions on Magnetics, vol. MAG-11, pp. 1701-1704, 1975 https://doi.org/10.1109/TMAG.1975.1058970
  9. D. Melville, F. Paul, and S. Roath, IEEE Transactions on Magnetics, vol. MAG-18, pp. 1680-1685, 1982 https://doi.org/10.1109/TMAG.1982.1062171
  10. M. D. Graham, Journal of Applied Physics, vol. 52, pp. 2578-2580, 1981 https://doi.org/10.1063/1.329003
  11. A. S. Bahaj, J. H. P. Watson, and D. C. Ellwood, IEEE Transactions on Magnetics, vol. 25, pp. 3809-3811, 1989 https://doi.org/10.1109/20.42440
  12. J. Svobada, Journal of Magnetism and Magnetic Materials, vol. 220, pp. L103-105, 2000 https://doi.org/10.1016/S0304-8853(00)00479-0
  13. M. Zborowski, G. R. Ostera, L. Moore, S. Milliron, J. J. Chalmers, and A. N. Schechter, Biophysical Journal, vol. 84, pp. 2638-2645, 2003 https://doi.org/10.1016/S0006-3495(03)75069-3
  14. M. Takayasu, N. Duske, S. R. Ash, and F. J. Friedlaender, IEEE Transactions on Magnetics, vol. MAG-18, pp. 1520-1522, 1982 https://doi.org/10.1109/TMAG.1982.1062072
  15. M. Takaysau, D. R. Kelland, and J. V. Minervini, IEEE Transactions on Applied Superconductivity, vol. 10, pp. 927-930, 2000 https://doi.org/10.1109/77.828383
  16. K.-H. Han and A. B. Frazier, Journal of Applied Physics, vol. 96, pp. 5797-5802, 2004 https://doi.org/10.1063/1.1803628
  17. J. Morucci, M. E. Valentinuzzi, B. Rigaud, C. J. Felice, N. Chauveau, and P. Marsili, Critical Reviews in Biomedical Engineering, vol. 24, pp. 257-351, 1996
  18. R. Pethig, Dielectric and Electronic Properties of Biological Materials: John Wiley & Sons, 1979
  19. M. E. Valentinuzzi, J. Morucci, and C. J. Felice, Critical Reviews in Biomedical Engineering, vol. 24, pp. 353-466, 1996
  20. H. E. Ayliffe, A. B. Frazier, and R. D. Rabbitt, IEEE Journal of Microelectromechanical Systems, vol. 8, pp. 50-57, 1999 https://doi.org/10.1109/84.749402
  21. S. Gawad, M. Wuthrich, L. Schild, O. Dubochet, and P. Renaud, The 11th International Conference on Solid-State Sensors and Actuators (Transducers 2001), Munich, Germany, pp. 1190-1193, 2001
  22. S. Gawad, S. Metz, L. Schild, and P. Renaud, Micro Total Analysis Systems 2001, pp. 253-255, 2001
  23. Y. Huang, N. Chen, J. Borninski, and B. Rubinsky, The 16th Annual International Conference on Microelectromechanical Systems (MEMS 2003), pp. 403-406, 2003
  24. S. K. Mohanty, S. K. Ravula, K. Engisch, and A. B. Frazier, Micro Total Analysis Systems, pp. 838-840, 2002
  25. P. V. Gerwen, W. Laureys, G. Huyberechts, M. O. D. Beeck, and K. Baert, The 9th International Conference on Solid-State Sensors and Actuators (Transducers 97), pp. 907-910, 1997
  26. G. R. Langereis, W. Olthuis, and P. Bergveld, The 9th International Conference on Solid-State Sensors and Actuators (Transducers 97), pp. 543-546, 1997
  27. R. Gomez, R. Bashir, A. Sarikaya, M. R. Ladisch, J. Sturgis, J. P. Robinson, T. Geng, A. K. Bhunia, H. L. Apple, and S. Wereley, Biomedical Microdevices, vol. 3, pp. 201-209, 2001 https://doi.org/10.1023/A:1011403112850
  28. R. Gomez, M. R. Ladisch, A. K. Bhunia, and R. Bashir, Mat. Res. Soc. Symp. Proc., pp. U461-U466, 2002
  29. K.-H. Han, R. D. McConnell, J. P. Ferrance, J. P. Landers, and A. B. Frazier, Tech. Dig. of Solid-State Sensor and Actuator, pp. 180-183, 2004
  30. K. Ikuta, K. Hirowatari, and T. Ogata, The 7th Annual International Conference on MicroElectro Mechanical Systems (MEMS 94), pp. 1-6, 1994
  31. E. Kelemen, Physiopathology and Therapy of Human Blood Diseases (International Series of Monographs in Pure and Applied Biology. Division: Modern Trends in Physiological Sciences, Vol. 30): Pergamon Press Ltd., 1969