Method for controlling sample introduction in microcolumn separation ...

OTHER PUBLICATIONS

Burggraf, N., et al., "Synchronized Cyclic Capillary Electrophoresis: A Novel Concept for High-Performance Separations Using Low Voltages", Analytical Methods and Instruments, 1(1): 55-59 (1993).

Effenhauser, Carlo S., "Effects of Electrokinetic Sample Injection on the Composition of Small Volume Samples in Capillary Electrophoresis", Analytical Methods and Instrumentation 1: (3) 172-176 (1993).

Effenhauser, C.S., et al., "Glass Chips for High-Speed Capillary Electrophoresis Separations with Submicrometer Plate Heights", American Chemical Society 65: 2637-2642 (1993).

Harrison, D.J., et al., "Miniaturized Chemical Analysis Systems and their Fabrication: An Alternative to Chemical Sensors", The Electrochemical Society, Inc., Chemical Sensors II, 93-7: 546-552 (1993).

Harrison, D.J., et al., "Rapid separation of fluorescein derivatives using a micromachined capillary electrophoresis system", Analytica Chimica Acta, 283: 361-366 (1993). Koutny, L.B., et al., "Microscale Chemical Instrumentation: Capillary Separations on a Chip", Thirty-Third ORN/DOE Conference On Analytical Chemistry in Energy Technology (1992).

Manz, A., et al., "Design of an Open-tubular Column Liquid Chromatograph Using Silicon Chip Technology", Sensors and Actuators, Bl: 249-255 (1990).

Manz, A., et al., "Planar Chips Technology for Miniaturization of Separation Systems: A Developing Perspective in Chemical Monitoring", Advances in Chromatography, 33: 2-66 (1993).

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Primary Examiner—-James H. Reamer

(74) Attorney, Agent, or Firm—Perkins Coie LLP; Peter J.

Dehlinger; Larry W. Thrower

In a method for controlling sample introduction in microcolumn separation techniques, more particularly in capillary electrophoresis (CE), where a sample is injected as a sample plug into a sampling device which comprises at least a channel for the electrolyte buffer and a supply and drain channel for the sample. The supply and drain channels discharge into the electrolyte channel at respective supply and drain ports. The distance between the supply port and the drain port geometrically defines a sample volume. The injection of the sample plug into the electrolyte channel is accomplished electrokinetically by applying an electric field across the supply and drain channels for a time at least long enough that the sample component having the lowest electrophoretic mobility is contained within the geometrically defined volume. The supply and drain channels each are inclined to the electrolyte channel. Means are provided for electrokinetically injecting the sample into the sample volume. The resistance to flow of the source and drain channels with respect to the electrolyte buffer is at least about 5% lower than the respective resistance to flow of the electrolyte channel.

3 Claims, 2 Drawing Sheets

OTHER PUBLICATIONS

Pentoney, S.L., et al., "On-Line Connector for Microcolumns: Application to the On-Column o —Phthaldialdehyde Derivatization of Amino Acids Separated by Capillary Zone Electrophoresis", Anal. Chem., 60: 2625-2629 (1988). Seiler, K., et al., "Planar Glass Chips for Capillary Electrophoresis: Repetitive Sample Injection, Quantitation, and Separation Efficiency", Anal. Chem., 65: 1481-1488(1993). Stegehuis, D.S., et al., "Analyte focusing in capillary electrophoresis using on-line isotachophoresis", Journal of Chromatography, 591: 341-349 (1992). Demi, M., et al., "Electric sample splitter for capillary zone electrophoresis" Journal of Chromatography 320:159-165 (1985).

Harrison, D.J., et al., "Capillary Electrophoresis and Sample Injection Systems Integrated on a Planar Glass Chip" Analytical Chem 64:(17):1927-1932 (1992).

Harrison, D.J., and Glavina, P.G., "Toward miniaturized electrophoresis and chemical analysis systems on silicon: an alternative to chemical senors" Sensors and Actuators BIO: 107-116 (1993).

Harrison, D.J., et al., "Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip" Science 261:895-897 (1993).

Manz, A., et al., "Miniaturized Total Chemical Analysis Systems: a Novel Concept for Chemical Sensing" Sensors and Actuators Bl:244-248 (1990).

Verheggen, P.E.M., et al., "Simple sampling device for capillary isotachophoresis and capillary zone electrophoresis" Journal of Chromatography 452:615-622 (1988).

* cited by examiner