Biomedical Microdevices

, Volume 1, Issue 1, pp 7–26 | Cite as

Microfabrication Technology for the Production of Capillary Array Electrophoresis Chips

  • Peter C. Simpson
  • Adam T. Woolley
  • Richard A. Mathies
Article

Abstract

Improvements in the fabrication, sample handling and electrical addressing of capillary array electrophoresis (CAE) chips have permitted the development of high density, high-throughput devices capable of analyzing 48 samples in about 20 minutes. The fabrication of high density capillary arrays on 10 cm diameter substrates required the characterization of glasses that yield high quality etches and the development of improved sacrificial etch masks. Using these improved fabrication techniques, high-quality, deep channel etches are routinely obtained. Methods for bonding large area substrates and for drilling arrays of 100 or more access holes have also been developed. For easier sample introduction, we use an array of sample wells fabricated from an elastomeric sheet. The practicality of these technologies is demonstrated through the analysis of 12 DNA samples in parallel on a microfabricated CAE chip, the development of methods for injecting multiple samples onto a single capillary without cross contamination, and the operation of a microfabricated array of 12 capillaries with 4 sample injections per capillary that can analyze 48 samples.

DNA Analysis capillary array electrophoresis confocal fluorescence detection multiplex sample injection glass micromachining capillary electrophoresis chips 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    D.J. Harrison, A. Manz, Z. Fan, H. Ludi, and H.M. Widmer, Anal. Chem. 64, 1926–1932 (1992).Google Scholar
  2. 2.
    S.C. Jacobson, R. Hergenroeder, L.B. Koutny, R.J. Warmack, and J.M. Ramsey, Anal. Chem. 66, 1107–1113 (1994).Google Scholar
  3. 3.
    D.J. Harrison, K. Fluri, K. Seiler, Z. Fan, C.S. Effenhauser, and A. Manz, Science 261, 895–897 (1993).Google Scholar
  4. 4.
    C.S. Effenhauser, A. Manz, H.M. Widmer, Anal. Chem. 65, 2637– 2642 (1993).Google Scholar
  5. 5.
    S.C. Jacobson, R. Hergenroder, A.W. Moore., and J.M. Ramsey, Anal. Chem. 66, 4127–4132 (1994).Google Scholar
  6. 6.
    S.C. Jacobson, A.W. Moore, and J.M. Ramsey, Anal. Chem. 67, 2059–2063 (1995).Google Scholar
  7. 7.
    L.B. Koutny, D. Schmalzing, T.A. Taylor, and M. Fuchs, Anal. Chem. 68, 18–22 (1996).Google Scholar
  8. 8.
    A.T. Woolley and R.A. Mathies, Proc. Natl. Acad. Sci. 91, 11348– 11352 (1994).Google Scholar
  9. 9.
    S.C. Jacobson and J.M. Ramsey, Anal. Chem. 68, 720–723 (1996).Google Scholar
  10. 10.
    C.S. Effenhauser, A. Paulus, A. Manz, and H.M. Widmer, Anal. Chem. 66, 2949–2953 (1994).Google Scholar
  11. 11.
    A.T. Woolley and R.A. Mathies, Anal. Chem. 67, 3676–3680 (1995).Google Scholar
  12. 12.
    M.A. Northrup, M.T. Ching, R.M. White, and R.T. Watson, Digest of Technical Papers: Transducers 1993 (IEEE, New York, NY, 1993), pp. 924–926.Google Scholar
  13. 13.
    M.A. Burns, C.H. Mastrangelo, T.S. Sammarco, F.P. Man, J.R. Webster, B.N. Johnson, B. Foerster, D. Jones, Y. Fields, A.R. Kaiser, and D.T. Burke, Proc. Natl. Acad. Sci. U.S.A. 93, 5556– 5561 (1996).Google Scholar
  14. 14.
    A.T. Woolley, D. Hadley, P. Landre, A.J. deMello, R.A. Mathies, and M.A. Northrup, Anal. Chem. 68, 4081–4086 (1996).Google Scholar
  15. 15.
    Z. Liang, N. Chiem, G. Ocvirk, T. Tang, K. Fluri, and D.J. Harrison, Anal. Chem. 68, 1040–1046 (1996).Google Scholar
  16. 16.
    R.A. Mathies and X.C. Huang, Nature 359, 167–169 (1992).Google Scholar
  17. 17.
    A.T. Woolley, G.F. Sensabaugh, and R.A. Mathies, Anal. Chem. 69, 2181–2186 (1997).Google Scholar
  18. 18.
    K. Fluri, G. Fitzpatrick, N. Chiem, and D.J. Harrison, Anal. Chem. 68, 4285–4290 (1996).Google Scholar
  19. 19.
    Z.H. Fan and D.J. Harrison, Anal. Chem. 66, 177–184 (1994).Google Scholar
  20. 20.
    P.C. Simpson, Capillary Electrophoresis Chip Fabrication and Improvements in DNA Sequencing Resolution, M. Eng. Degree Project, Cornell University, 1996.Google Scholar
  21. 21.
    G.R. Cokelet, R. Soave, G. Pugh, and L. Rathbun, Microvascular Research 46, 394–400 (1993).Google Scholar
  22. 22.
    I. Kheterpal, J.R. Scherer, S.M. Clark, A. Radhakrishnan, J. Ju, C.L. Ginther, G.F. Sensabaugh, and R.A. Mathies, Electrophoresis 17, 1852–1859 (1996).Google Scholar
  23. 23.
    O. Trepte and A. Liljeborg, Opt. Eng. 33, 3774–3780 (1994).Google Scholar
  24. 24.
    We evaluated CCD detection of the CAE chips using a line focused laser beam.We found that rather high laser power (~ 300 mW) was necessary to optimally excite fluorescence in the channels and that background fluorescence from the CAE chip reduced the signal-tonoise ratio. The DNA detection sensitivity with the CCD was therefore about 10 x worse than with the confocal detection system, primarily because of the higher background glass fluorescence due to poorer spatial filtering with the CCD system. The scanning confocal system was therefore preferred because of its better detection limits and lower laser power requirements.Google Scholar
  25. 25.
    R.L. Brumley, Jr. and L.M. Smith, Nucleic Acids Res. 19, 4121– 4126 (1991).Google Scholar
  26. 26.
    S. Hjerten, J. Chromatogr. 347, 191–198 (1985).Google Scholar
  27. 27.
    Y. Xia, E. Kim, X.-M. Zhao, J.A. Rogers, M. Prentiss, and G.M. Whitesides, Science 273, 347–349 (1996).Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Peter C. Simpson
    • 1
  • Adam T. Woolley
    • 1
  • Richard A. Mathies
    • 1
  1. 1.Mathies Research Group, Department of Chemistry, M.C. 1460University of CaliforniaBerkeley

Personalised recommendations