Nanospheres for DNA separation chips


We report here a technology to carry out separations of a wide range of DNA fragments with high speed and high resolution. The approach uses a nanoparticle medium, core-shell type nanospheres, in conjunction with a pressurization technique during microchip electrophoresis. DNA fragments up to 15 kilobase pairs (kbp) were successfully analyzed within 100 s without observing any saturation in migration rates. DNA fragments migrate in the medium while maintaining their characteristic molecular structure. To guarantee effective DNA loading and electrofocusing in the nanosphere solution, we developed a double pressurization technique. Optimal pressure conditions and concentrations of packed nanospheres are critical to achieve improved DNA separations.

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Figure 1: The new system using nanospheres and a double pressurization technique.
Figure 2: Effectiveness of DNA separations carried out using conventional polymers versus nanospheres with pressurization methods.
Figure 3: Visualization of single DNA molecules.


  1. 1

    Wehr, T., Zhu, M. & Mao, D.T. in Capillary Electrophoresis of Nucleic Acid, vol. I (eds. Mitchelson, K.R. & Cheng, J.) 167–187 (Humana Press, Totowa, NJ, 2001).

    Google Scholar 

  2. 2

    Viovy, J.L. & Dukc, T. DNA electrophoresis in polymer solutions: ogston sieving, reptation and constraint release. Electrophoresis 14, 322–329 (1993).

    CAS  Article  Google Scholar 

  3. 3

    Slater, G.W., Desruisseaux, C. & Hubert, S.J. in Capillary Electrophoresis of Nucleic Acid, vol. I (eds. Mitchelson, K.R. & Cheng, J.) 27–34 (Humana Press, Totowa, NJ, 2001).

    Google Scholar 

  4. 4

    Madabhushi, R.S. Separation of 4-color DNA sequencing extension products in noncovalently coated capillaries using low viscosity polymer solutions. Electrophoresis 19, 224–230 (1998).

    CAS  Article  Google Scholar 

  5. 5

    Lie, Y. & Rill, R.L. in Capillary Electrophoresis of Nucleic Acid, vol. I (eds. Mitchelson, K.R. & Cheng, J.) 203–213 (Humana Press, Totowa, NJ, 2001).

    Google Scholar 

  6. 6

    Buchholz, B.A. et al. Microchannel DNA sequencing matrics with a thermally controlled “Viscosity switch.” Anal. Chem. 73, 157–164 (2001).

    CAS  Article  Google Scholar 

  7. 7

    Barron, A.E., Blanch, H.W. & Soane, D.S. A transient entanglement coupling mechanism for DNA separation by capillary electrophoresis in ultradilute polymer solution. Electrophoresis 15, 597–615 (1994).

    CAS  Article  Google Scholar 

  8. 8

    Hubert, S.J., Slater, G.W. & Viovy, J.-L. Theory of capillary electrophoretic separation of DNA using ultradilute polymer solution. Macromolecules 29, 1006–1009 (1996).

    CAS  Article  Google Scholar 

  9. 9

    Heller, C. et al. Free-solution electrophoresis of DNA. J. Chromatography A 806, 113–121 (1998).

    CAS  Article  Google Scholar 

  10. 10

    Ren, H. et al. Separation DNA sequencing fragments without a sieving matrix. Electrophoresis 20, 2501–2509 (1999).

    CAS  Article  Google Scholar 

  11. 11

    Volkmuth, W.D. & Austin, R.H. DNA electrophoresis in microlithography arrays. Nature 358, 600–602 (1992).

    CAS  Article  Google Scholar 

  12. 12

    Chou, C.-F. et al. Sorting by diffusion: an asymmetric obstacle course for continuous molecular separation. Proc. Natl. Acad. Sci. USA 23, 13762–13765 (1999).

    Article  Google Scholar 

  13. 13

    Han, J. & Craighead, H.G. Separation of long DNA molecules in a microfabricated entropic trap array. Science 288, 1026–1029 (2000).

    CAS  Article  Google Scholar 

  14. 14

    Hung, L.R. et al. A DNA prism for high-speed continuous fractionation of large DNA molecules. Nat. Biotechnol. 20, 1048–1051 (2002).

    Article  Google Scholar 

  15. 15

    Doyle, P.S., Bibette, J., Bancaud, A. & Viovy, J.-L. Self-assembled magnetic matrices for DNA separation chips. Science 295, 2237 (2002).

    CAS  Article  Google Scholar 

  16. 16

    Iijima, M., Nagasaki, Y., Okada, T., Kato, M. & Kataoka, K. Core-polymerized reactive micelles from heterotelechelic amphiphilic block copolymers. Macromolecules 32, 1140–1146 (1999).

    CAS  Article  Google Scholar 

  17. 17

    de Gennes, P.G. Reptation of a polymer chain in the presence of fixed obstacles. J. Chem. Phys. 55, 572–579 (1971).

    Article  Google Scholar 

  18. 18

    Schwartz, D.C. & Koval, M. Conformational dynamics of individual DNA molecules during gel electrophoresis. Nature 338, 520–522 (1989).

    CAS  Article  Google Scholar 

  19. 19

    Smith, S.B., Aldridge, P.K. & Callis, J.B. Observation of individual DNA molecules undergoing gel electrophoresis. Science 243, 203–206 (1989).

    CAS  Article  Google Scholar 

  20. 20

    Shi, X., Richard, R.W. & Morris, M.D. DNA conformational dynamics in polymer solutions above and below the entanglement limit. Anal. Chem. 67, 1132–1138 (1995).

    CAS  Article  Google Scholar 

  21. 21

    Yoshikawa, K. Controlling the higher-order structure of giant DNA molecules. Adv. Drug Del. Rev. 52, 235–244 (2001).

    CAS  Article  Google Scholar 

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This work was partially supported by a grant funding Core Research for Evolutionary Science and Technology from the Japan Science and Technology Agency, a grant from the New Energy and Industrial Technology Development Organization of the Ministry of Economy, Trade and Industry, Japan, a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Technology, Japan, and the 21st Century COE Program, Human Nutritional Science on Stress Control, Tokushima, Japan. We thank Chie Kuwahara, Ryosuka Kodaka and Fumiko Aboshi of the Tokyo University of Science and Eduardo Jule of the University of Tokyo for preparing the nanospheres. The authors would like to thank Tomoaki Hino, Ken Hirano, Fung Xu, Mohammad Jabasini, Hideya Nagata, Yasuko Tanaka and Emi Endo of the University of Tokushima for technical and secretarial assistance.

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Correspondence to Mari Tabuchi.

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Tabuchi, M., Ueda, M., Kaji, N. et al. Nanospheres for DNA separation chips. Nat Biotechnol 22, 337–340 (2004).

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