Cell electrophoresis on a chip: what can we know from the changes in electrophoretic mobility?



An overview of both experimental and theoretical studies of cell electrophoresis mobility (EPM) over the past fifty years and the relevance of cell EPM measurement are presented and discussed from the viewpoint of exploring the potential use of cell EPM as an index of the biological condition of cells. Physical measurements of the optical and/or electrical properties of cells have been attracting considerable attention as noninvasive cell-evaluation methods that are essential for the future of cell-based application technologies such as cell-based drug screening and cell therapy. Cell EPM, which can be measured in a noninvasive manner by cell electrophoresis, reflects the electrical and mechanical properties of the cell surface. Although the importance of cell EPM has been underestimated for a long time, mostly owing to the technical difficulties associated with its measurement, recent improvements in measurement technology using microcapillary chips have been changing the situation: cell EPM measurement has become more reliable and faster. Recent studies using the automated microcapillary cell electrophoresis system have revealed the close correlation between cell EPM and important biological phenomena including cell cycle, apoptosis, enzymatic treatment, and immune reaction. In particular, the converged EPM distribution observed for synchronized cells has altered the conventional belief that cell EPMs vary considerably. Finding a new significance of cell EPM is likely to lead to noninvasive cell evaluation methods essential for the next-generation of cell engineering.


Cell analysis Microcapillary electrophoresis chip Electrophoretic mobility Quality control Cell cycle Apoptosis Immunity 



This work was supported by the Precursory Research for Embryonic Science and Technology (PRESTO) program of the Japan Science and Technology Agency (JST) and a Grant-in-Aid for Young Scientists (B) (T.A., 19710113) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.


  1. 1.
    Jones JO, Diamond MI (2007) Acs Chemical Biology 2:718–724Google Scholar
  2. 2.
    Weaver CV, Garry DJ (2008) Regen Med 3:63–82Google Scholar
  3. 3.
    Hopkins AL (2007) Nat Biotechnol 25:1110–1111Google Scholar
  4. 4.
    Hood L, Perlmutter RM (2004) Nat Biotechnol 22:1215–1217Google Scholar
  5. 5.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Cell 131:861–872Google Scholar
  6. 6.
    Bordignon C (2006) Nature 441:1100–1102Google Scholar
  7. 7.
    Srivastava D, Ivey KN (2006) Nature 441:1097–1099Google Scholar
  8. 8.
    Lindvall O, Kokaia Z (2006) Nature 441:1094–1096Google Scholar
  9. 9.
    Templeton N (2003) Gene and cell therapy: therapeutic mechanisms and strategies. Marcel Dekker, New York, USAGoogle Scholar
  10. 10.
    Battler A, Leor J (2007) Stem cell and gene-based therapy: frontiers in regenerative medicine. Springer, Berlin, GermanyGoogle Scholar
  11. 11.
    Mason C, Hoare M (2007) Tissue Eng 13:301–311Google Scholar
  12. 12.
    Burger SR (2000) Cytotherapy 2:111–122Google Scholar
  13. 13.
    CBER/FDA (2004) Fed Regist 69:68611–68688Google Scholar
  14. 14.
    Sawada R, Ito T, Tsuchiya T (2006) J Artif Organs 9:179–184Google Scholar
  15. 15.
    McGuinness R (2007) Curr Opin Pharmacol 7:535–540Google Scholar
  16. 16.
    Atienza JM, Yu NC, Kirstein SL, Xi B, Wang XB, Xu X, Abassi YA (2006) Assay Drug Dev Technol 4:597–607Google Scholar
  17. 17.
    Verdonk E, Johnson K, McGuinness R, Leung G, Chen YW, Tang HR, Michelotti JM, Liu VF (2006) Assay Drug Dev Technol 4:609–619Google Scholar
  18. 18.
    Notingher L, Jell G, Notingher PL, Bisson I, Tsigkou O, Polak JM, Stevens MM, Hench LL (2005) J Mol Struct 744:179–185Google Scholar
  19. 19.
    Koga H, Kyo M, Usui-Aoki K, Inamori K (2006) Electrophoresis 27:3676–3683Google Scholar
  20. 20.
    Fang Y (2006) Assay Drug Dev Technol 4:583–595Google Scholar
  21. 21.
    Proll G, Steinle L, Proll F, Kumpf M, Moehrle B, Mehlmann M, Gauglitz G (2007) J Chromatogr A 1161:2–8Google Scholar
  22. 22.
    Sakata T, Miyahara Y (2008) Anal Chem 80:1493–1496Google Scholar
  23. 23.
    Mehrishi JN, Bauer J (2002) Electrophoresis 23:1984–1994Google Scholar
  24. 24.
    Hsu JP, Hsieh TS, Young TH, Tseng S (2003) Electrophoresis 24:1338–1346Google Scholar
  25. 25.
    Kremser L, Blaas D, Kenndler E (2004) Electrophoresis 25:2282–2291Google Scholar
  26. 26.
    Slivinsky GG, Hymer WC, Bauer J, Morrison DR (1997) Electrophoresis 18:1109–1119Google Scholar
  27. 27.
    Korohoda W, Wilk A (2008) Cell Mol Biol Lett 13:312–326Google Scholar
  28. 28.
    Baskurt OK, Tugral E, Neu B, Meiselman HJ (2002) Electrophoresis 23:2103–2109Google Scholar
  29. 29.
    Yamada T, Takaoka T, Katsuta H, Namba M, Sato J (1972) Jpn J Exp Med 42:377–388Google Scholar
  30. 30.
    Yamada T, Takaoka T, Katsuta H (1974) Jpn J Exp Med 44:199–210Google Scholar
  31. 31.
    Yamada T, Takaoka T, Katsuta H (1976) Jpn J Exp Med 46:223–233Google Scholar
  32. 32.
    Makino K, Taki T, Ogura M, Handa S, Nakajima M, Kondo T, Ohshima H (1993) Biophys Chem 47:261–265Google Scholar
  33. 33.
    Hayry P, Saxen L (1965) Nature 205:1105–1106Google Scholar
  34. 34.
    Haydon DA, Seaman GV (1967) Arch Biochem Biophys 122:126–136Google Scholar
  35. 35.
    Mironov SL, Dolgaya EV (1985) J Membr Biol 86:197–202Google Scholar
  36. 36.
    Young TH, Hung CH (2003) J Biomed Mater Res A 67:1238–1244Google Scholar
  37. 37.
    Wang CC, Lu JN, Young TH (2007) Biomaterials 28:625–631Google Scholar
  38. 38.
    Baskurt OK, Tugral E, Neu B, Meiselman HJ (2002) Electrophoresis 23:2103–2109Google Scholar
  39. 39.
    Young TH, Hung CH, Huang SW, Hsieh TS, Hsu JP (2005) J Colloid Interface Sci 285:557–561Google Scholar
  40. 40.
    Kuo YC, Chen IC (2007) J Phys Chem B 111:11228–11236Google Scholar
  41. 41.
    Masui M, Takata H, Kominami T (2002) Electrophoresis 23:2087–2095Google Scholar
  42. 42.
    Yu L, Shen Z, Mo J, Dong X, Qin J, Lin B (2007) Electrophoresis 28:4741–4747Google Scholar
  43. 43.
    Rodriguez VV, Busscher HJ, Norde W, van der Mei HC (2002) Electrophoresis 23:2007–2011Google Scholar
  44. 44.
    Ujiie T, Kikuchi T, Ichiki T, Horiike Y (2000) Jpn J Appl Phys 39:3677–3682Google Scholar
  45. 45.
    Akagi T, Minamino A, Ichiki T (2006) IEEJ Trans EIS 126:730–735Google Scholar
  46. 46.
    Akagi T, Suzuki M, Ichiki T (2006) Jpn J Appl Phys 45:L1106–L1109Google Scholar
  47. 47.
    Akagi T, Suzuki M, Sato T, Ichiki T (2007) Jpn J Appl Phys 46:6404–6409Google Scholar
  48. 48.
    Ichiki T, Shinbashi S, Ujiie T, Horiike Y (2002) J Photopolymer Sci Technol 15:487–492Google Scholar
  49. 49.
    Ichiki T, Ujiie T, Shinbashi S, Okuda T, Horiike Y (2002) Electrophoresis 23:2029–2034Google Scholar
  50. 50.
    Omasu F, Nakano Y, Ichiki T (2005) Electrophoresis 26:1163–1167Google Scholar
  51. 51.
    Akagi T, Ichiki T (2007) In: Viovy JL, Tabeling P, Descroix S, Malaquin L (eds) Micro total analysis systems 2007. CBMS, San Diego USA, pp 1330–1332Google Scholar
  52. 52.
    Akagi T, Suzuki M, Ichiki T (2006) In: Kitamori T, Fujita H, Hasebe S (eds) Micro total analysis systems 2006. CHEMINAS, Japan, pp 413–415Google Scholar
  53. 53.
    Dukhin SS, Derjaguin BV (1974) Electrokinetic phenomena. In: Matijevic E (ed) Surface and Colloid Science. Wiley, New York, USAGoogle Scholar
  54. 54.
    Hunter RJ (1981) Zeta potential in colloid science. Academic Press, New YorkGoogle Scholar
  55. 55.
    van der Ven TGM (1989) Colloid hydrodynamics. Academic Press, New YorkGoogle Scholar
  56. 56.
    Dukhin SS (1993) Adv Colloid Interface Sci 44:1–134Google Scholar
  57. 57.
    Smoluchowski MV (1917) Z Phys Chem 92:129–168Google Scholar
  58. 58.
    Ohshima H (2006) Theory of colloid and interfacial electric phenomena. Academic, Oxford, UKGoogle Scholar
  59. 59.
    Ohshima H (2007) Colloid Polym Sci 285:1411–1421Google Scholar
  60. 60.
    Stigter D (1978) J Phys Chem 82:1424–1429Google Scholar
  61. 61.
    Dekeizer A, Vanderdrift WPJT, Overbeek JTG (1975) Biophys Chem 3:107–108Google Scholar
  62. 62.
    Ohshima H (1996) J Colloid Interface Sci 180:299–301Google Scholar
  63. 63.
    Morita K, Muramatsu N, Ohshima H, Kondo T (1991) J Colloid Interface Sci 147:457–461Google Scholar
  64. 64.
    Levine S, Levine M, Sharp KA, Brooks DE (1983) Biophys J 42:127–135CrossRefGoogle Scholar
  65. 65.
    Vargas FF (1994) In: Bauer J (ed) Cell electrophoresis. CRC Press, Boca Raton, USAGoogle Scholar
  66. 66.
    Ohshima H, Kondo T (1989) J Colloid Interface Sci 130:281–282Google Scholar
  67. 67.
    Dukhin S, Zimmermann R, Werner C (2006) Adv Colloid Interface Sci 122:93–105Google Scholar
  68. 68.
    Ohshima H, Kondo T (1987) J Colloid Interface Sci 116:305–311Google Scholar
  69. 69.
    Takashima S, Morisaki H (1997) Colloids Surf B 9:205–212Google Scholar
  70. 70.
    Bos R, van der Mei HC, Busscher HJ (1998) Biophys Chem 74:251–255Google Scholar
  71. 71.
    Morisaki H, Nagai S, Ohshima H, Ikemoto E, Kogure K (1999) Microbiology 145:2797–2802Google Scholar
  72. 72.
    Hayashi H, Tsuneda S, Hirata A, Sasaki H (2001) Colloids Surf B 22:149–157Google Scholar
  73. 73.
    Kiers PJM, Bos R, van der Mei HC, Busscher HJ (2001) Microbiology 147:757–762Google Scholar
  74. 74.
    Mazda T, Makino K, Ohshima H (1995) Colloids Surf B 5:75–80Google Scholar
  75. 75.
    Kawahata S, Ohshima H, Muramatsu N, Kondo T (1990) J Colloid Interface Sci 138:182–186Google Scholar
  76. 76.
    Nakano Y, Makino K, Ohshima H, Kondo T (1994) Biophys Chem 50:249–254Google Scholar
  77. 77.
    Makino K, Ikekita M, Kondo T, Tanuma S, Ohshima H (1994) Colloid Polym Sci 272:487–492Google Scholar
  78. 78.
    Whitesides GM (2006) Nature 442:368–373Google Scholar
  79. 79.
    Ishihara K, Oshida H, Endo Y, Ueda T, Watanabe A, Nakabayashi N (1992) J Biomed Mater Res 26:1543–1552Google Scholar
  80. 80.
    Xu Y, Takai M, Konno T, Ishihara K (2007) Lab Chip 7:199–206Google Scholar
  81. 81.
    Hamada Y, Ono T, Akagi T, Ishihara K, Ichiki T (2007) J Photopolymer Sci Technol 20:245–249Google Scholar
  82. 82.
    Sanders JC, Breadmore MC, Kwok YC, Horsman KM, Landers JP (2003) Anal Chem 75:986–994Google Scholar
  83. 83.
    Yang C, El Rassi Z (1998) Electrophoresis 19:2278–2284Google Scholar
  84. 84.
    Levi F (2006) Cancer Causes Control 17:611–621Google Scholar
  85. 85.
    Akagi T, Ushinohama K, Kage Y, Ishizaki T, Makinosumi T, Yamauchi A, Taguchi Y, Inoue K, Yukawa E, Higuchi S, Ohdo S (2003) Life Sci 72:1183–1197Google Scholar
  86. 86.
    Smaaland R, Lote K, Sothern RB, Laerum OD (1993) Cancer Res 53:3129–3138Google Scholar
  87. 87.
    Kerr JF, Wyllie AH, Currie AR (1972) Br J Cancer 26:239–257Google Scholar
  88. 88.
    Jana S, Paliwal J (2007) Curr Med Chem 14:2369–2379Google Scholar
  89. 89.
    Demierre MF, Higgins PD, Gruber SB, Hawk E, Lippman SM (2005) Nat Rev Cancer 5:930–942Google Scholar
  90. 90.
    Becker JC, Kirkwood JM, Agarwala SS, Dummer R, Schrama D, Hauschild A (2006) Cancer 107:2317–2327Google Scholar
  91. 91.
    Marchetti S, Schellens JH (2007) Br J Cancer 97:577–581Google Scholar
  92. 92.
    Beretta GL, Zunino F (2007) Biochem Pharmacol 74:1437–1444Google Scholar
  93. 93.
    Mathijssen RH, Loos WJ, Verweij J, Sparreboom A (2002) Curr Cancer Drug Targets 2:103–123Google Scholar
  94. 94.
    Ohtsubo K, Marth JD (2006) Cell 126:855–867Google Scholar
  95. 95.
    Varki A (1993) Glycobiology 3:97–130Google Scholar
  96. 96.
    Smith ML, Long DS, Damiano ER, Ley K (2003) Biophys J 85:637–645Google Scholar
  97. 97.
    Chu VC, Whittaker GR (2004) Proc Natl Acad Sci USA 101:18153–18158Google Scholar
  98. 98.
    Freeze HH (2006) Nat Rev Genet 7:537–551Google Scholar
  99. 99.
    El-Ali J, Sorger PK, Jensen KF (2006) Nature 442:403–411Google Scholar
  100. 100.
    Ye N, Qin J, Shi W, Liu X, Lin B (2007) Lab Chip 7:1696–1704Google Scholar
  101. 101.
    Wu D, Qin J, Lin B (2008) J Chromatogr A 1184:542–559Google Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of Bioengineering, School of EngineeringThe University of TokyoBunkyo-kuJapan
  2. 2.Center for Nano-Bio IntegrationThe University of TokyoBunkyo-kuJapan
  3. 3.Institute of Engineering Innovation, School of EngineeringThe University of TokyoBunkyo-kuJapan

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