Combined electrophoresis-electrospray interface and method

Abstract

A system and method for analyzing molecular constituents of a composition sample includes: forming a solution of the sample, separating the solution by capillary electrophoresis into an eluent of constituents longitudinally separated according to their relative electrophoretic mobilities, electrospraying the eluent to form a charged spray in which the molecular constituents have a temporal distribution; and detecting or collecting the separated constituents in accordance with the temporal distribution in the spray. A first high-voltage (e.g., 5-100 KVDC) is applied to the solution. The spray is charged by applying a second high voltage (e.g., ±2-8 KVDC) between the eluent at the capillary exit and a cathode spaced in front of the exit. A complete electrical circuit is formed by a conductor which directly contacts the eluent at the capillary exit, or by conduction through a sheath electrode discharged in an annular sheath flow about the capillary exit.

We claim: 
     
       1. A method of producing high resolution analyte separations capable of being analyzed by numerous analytical detectors, which comprises: providing a source of an analyte sample solution and a source of a sheath electrode liquid;   electrophoretically separating said analyte sample solution to form a high resolution analyte eluent;   discharging the separated analyte eluent and the sheath electrode liquid in adjoining flows;   electrospraying an electrically-charged spray containing the separated analyte eluent and the sheath electrode liquid.   
     
     
       2. A method according to claim 1 in which the sheath electrode liquid is discharged in a sheath flow surrounding the flow of separated analyte eluent. 
     
     
       3. A method according to claim 2, which includes conducting said electrophoretic separation of the sample solution in an electrically nonconductive capillary, providing a conductive means for electrically contacting the sheath electrode liquid, and coupling said conductive means in a high voltage circuit for electrophoretically separating sample solution and electrospraying the separated analyte eluent and sheath electrode liquid. 
     
     
       4. A method according to claim 1 which includes conducting said electrophoretic separation of the sample solution in a capillary, discharging the separated analyte eluent from a central exit opening in the capillary, and separately discharging the sheath electrode liquid in an annular, sheath flow about the exit of the capillary. 
     
     
       5. A method according to claim 4 which includes applying a high voltage potential to the analyte sample solution between the source of the analyte sample solution and to the sheath electrode liquid to drive said electrophoretic separation. 
     
     
       6. A method according to claim 4 which includes applying a voltage potential between the sheath electrode liquid and a detector or collector spaced in axial proximity to capillary exit opening for electrospraying the separated analyte eluent together with the sheath electrode liquid. 
     
     
       7. A method according to claim 1 including controlling one of sheath electrode liquid flow rate and composition so that the combined flows of analyte eluent and sheath electrode liquid can be electrosprayed. 
     
     
       8. A method according to claim 1 in which the sheath electrode liquid has an ionic strength under 10 -3  molar and a flow rate in a range of 1 to 50 microliters per minute. 
     
     
       9. A method according to claim 1 including independently controlling the electrophoretic separation and electrospraying steps. 
     
     
       10. A system for producing high resolution separation of analyte composition for analysis by an analytical detector, which comprises: a source of an analyte sample solution;   a source of a sheath electrode liquid;   means for electrophoretically separating said analyte sample solution to form a high resolution analyte eluent;   means for discharging the separated analyte eluent and sheath electrode liquid in adjoining flows; and   means for electrospraying said sheath electrode liquid and separated analyte eluent together without substantial distortion of the analyte separation.   
     
     
       11. The system of claim 10, which includes means for directly imparting an electrical potential to said sheath electrode liquid and thereby to the separated analyte eluent immediately prior to said electrospraying. 
     
     
       12. The system of claim 10, which includes an electrically nonconductive capillary for conducting said electrophoretic separation, and means disposed about an outlet end of said capillary for discharging the sheath electrode liquid in an annular sheath flow around the discharged analyte eluent. 
     
     
       13. The system of claim 12, which further includes means for forming an electrical contact with said sheath electrode liquid and thereby with the separated analyte eluent and a first high voltage supply coupled to said electrical contact means to form a first high voltage circuit through said analyte eluent for electrophoretically separating same. 
     
     
       14. The system of claim 12, which further includes means for forming an electrical contact with said sheath electrode liquid and thereby with the separated analyte eluent and a second voltage supply coupled to said electrical contact means to form a second voltage potential between the analyte eluent and a detector or collector in spaced proximity to said outlet end of the capillary for electrospraying the eluent. 
     
     
       15. The system of claim 10, which includes an electrically nonconductive capillary for conducting said electrophoretic separation, said capillary including an outlet section, a conductive tube surrounding said outlet end and spaced outward therefrom to provide a passage surrounding the outlet section, and means for introducing the flow of sheath electrode liquid into the passage, the tube and capillary having axially adjacent outlets positioned to discharge a sheath flow of the sheath electrode liquid around the discharged analyte eluent. 
     
     
       16. The system of claim 15 in which the capillary outlet section protrudes from the outlet of the conductive tube. 
     
     
       17. The system of claim 15, including means for coupling a voltage potential to the conductive tube for electrically contacting said eluting analyte. 
     
     
       18. The system of claim 15, including: conductive means for making electrical contact with the conductive tube;   detector means for detecting constituents of a spray of the analyte solution;   a first voltage supply means coupled to said conductive means for applying a first high voltage potential between the source and the sheath electrode liquid at the capillary outlet to electrophoretically separate the analyte sample; and   a second voltage supply means coupled to said conductive means for applying a second voltage potential between the sheath electrode liquid at the capillary outlet and the detector means.   
     
     
       19. A system for producing high resolution separation of analyte composition for analysis by an analytical detector, which comprises: a source of an analyte sample solution;   a source of a sheath electode liquid;   means for electrophoretically separating said analyte sample solution to form a high resolution analyte eluent;   means for discharging the separated analyte eluent and sheath electrode liquid in adjoining flows;   means for electrospraying said sheath electrode liquid and separated analyte eluent together without substantial distortion of the analyte separation;   an electrically noncoductive capillary for conducting said electrophoretic separation, said capillary including an outlet section, a conductive tube surrounding said outlet end and spaced outward therefrom to provide a passage surrounding the outlet section; and   a tee having the capillary passing through opposite legs thereof and movable axially therein independently of the tube for relatively positioning the outlets of the tube and capillary;   the tube and capillary having axially adjacent outlets positioned to discharge a sheath flow of the sheath electrode liquid around the discharged analyte eluent.   
     
     
       20. The system of claim 10 including means for controlling the flow of sheath electrode liquid independently of the capillary flow. 
     
     
       21. A system according to claim 10 including means for introducing a sheath gas flow surrounding the combined analyte eluent and sheath electrode liquid flows. .Iadd.22. A method of producing high resolution analyte separations capable of being analyzed by numerous analytical detectors, which comprises: providing a source of an analyte sample solution and a source of a sheath liquid;   separating a source of an analyte sample solution in a capillary to form a flow of analyte eluent;   discharging the separated analyte eluent from a central outlet opening in the capillary and separately discharging the sheath liquid in a annular sheath flow about the outlet of the capillary in coaxially adjoining flows;   electrospraying an electrically-charged spray containing the separated analyte eluent and the sheath liquid; the capillary outlet opening protruding from an outlet of a surrounding sheath flow tube. .Iaddend. .Iadd.23. A method of producing high resolution analyte separations capable of being analyzed by numerous analytical detectors, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   separating said analyte sample solution in a capillary to form a flow of analyte eluent;   discharging the separated analyte eluent form a central outlet opening in the capillary and separately discharging the sheath liquid in an annular sheath flow about the outlet of the capillary in coaxially adjoining flows;   electrospraying an electrically-charged spray containing the separated analyte eluent and the sheath by applying a voltage potential between the combined flows of analyte eluent and sheath liquid and a detector or collector spaced in axial proximity to capillary outlet opening for electrospraying the separated analyte eluent together with the sheath liquid. .Iaddend. .Iadd.24. A method of producing high resolution analyte separations capable of being analyzed by numerous analytical detectors, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   separating said analyte sample solution to form a flow of analyte eluent;   discharging the separated analyte eluent and the sheath liquid in coaxially adjoining flows;   electrospraying an electrically-charged spray containing the separated analyte eluent and the sheath liquid, the sheath liquid having an ionic strength under 10 -3  molar and a flow rate in a range of 1 to 50 microliters per minute. .Iaddend. .Iadd.25. A method of producing high resolution analyte separations capable of being analyzed by numerous analytical detectors, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   separating said analyte sample solution to form a flow of analyte eluent by conducting said separation of the sample solution in a nonconductive capillary;   discharging the separated analyte eluent from a central outlet opening in the capillary, separately discharging the sheath liquid in an annular sheath flow about the outlet of the capillary, the separated analyte eluent and sheath liquid being discharged in coaxially and adjoining flows;   electrospraying an electrically-charged spray containing the separated analyte eluent and the sheath liquid, a voltage potential being applied between the sheath liquid and a detector or collector spaced in axial proximity to the capillary outlet opening for electrospraying the separated analyte eluent together with the sheath liquid. .Iaddend. .Iadd.26. A method of introducing an analyte solution to an analytical detector, which comprises:   providing a source of an analyte sample solution and a source of sheath liquid:   introducing the analyte sample solution to a capillary having an outlet in which the capillary outlet protrudes from an outlet of a surrounding sheath flow tube;   discharging the analyte sample solution from the capillary outlet and discharging the sheath liquid in a sheath flow coaxially surrounding the discharged analyte sample solution;   electrospraying an electrically-charged spray containing the analyte sample solution and the sheath liquid. .Iaddend. .Iadd.27. A method of introducing an analyte solution to an analytical detector, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   introducing the analyte sample solution to a capillary having an outlet;   discharging the analyte sample solution from the capillary outlet and discharging the sheath liquid ina sheath flow coaxially surrounding the discharged analyte sample solution;   electrospraying an electrically-charged spray containing the analyte sample solution and the sheath liquid by applying a voltage potential between the combined flows of analyte sample solution and sheath liquid and a detector or collector spaced in axial proximity to the capillary outlet opening for electrospraying the analyte sample solution together with the sheath liquid. .Iaddend. .Iadd.28. A method according to claim 27 including controlling one of sheath liquid flow rate and composition so that the combined flows of analyte eluent and sheath liquid can be electrosprayed. .Iaddend. .Iadd.29. A method according to claim 27 in which the electrically-charged spray is directed into a mass spectrometer. .Iaddend. .Iadd.30. A method introducing an analyte solution to an analytical detector, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   introducing the analyte sample solution to a capillary having an outlet;   discharging the analyte sample solution from the capillary outlet and discharging the sheath liquid in a sheath flow coaxially surrounding the discharged analyte sample solution;   electrospraying an electrically-charged spray containing the analyte sample solution and the sheath liquid, the sheath liquid having an ionic strength suitable for electrospraying and a flow rate in a range of 1 to 50 microliters per minute. .Iaddend. .Iadd.31. A method of introducing an analyte solution to an analytical detector, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   introducing the analyte sample solution to a nonconductive capillary having an outlet;   discharging the analyte sample solution from the capillary outlet and discharging the sheath liquid in a sheath flow coaxially surrounding the discharged analye sample solution;   electrospraying an electrically-charged spray containing the analyte sample solution and the sheath liquid, the sheath liquid being discharged in an annular sheath flow about the outlet of the capillary, and applying a voltage potential between the sheath liquid and a detector or collector spaced in axial proximity to capillary outlet opening for electrospraying the separated analyte eluent together with the sheath liquid. .Iaddend. .Iadd.32. A method according to claim 31 including controlling the flow of sheath liquid independently of the analyte sample solution flow. .Iaddend. .Iadd.33. A method according to claim 31 including introducing a sheath gas flow surrounding the combined analyte sample solution and sheath liquid flows. .Iaddend. .Iadd.34. A method of introducing the analyte solution to an analytical detector, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   introducing the analyte sample solution to a capillary having an outlet;   discharging the analyte sample solution from the capillary outlet and discharging the sheath liquid in a sheath flow coaxially surrounding the discharged analyte sample solution;   electrospraying an electrically-charged spray containing the analyte sample solution and the sheath liquid, the sheath flow being discharged from a conductive sheath flow tube surrounding the capillary and the electrospray voltage potential being applied to the sheath flow tube. .Iaddend. .Iadd.35. A method of introducing an analyte solution to an analytical detector, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   introducing the analyte sample solution to a capillary having an outlet;   discharging the analyte sample solution from the capillary outlet and discharging the sheath liquid in a sheath flow coaxially surrounding the discharged analyte sample solution;   electrospraying an electrically-charged spray containing the analyte sample solution and the sheath liquid, said electrospraying being carried out at near atmospheric pressure. .Iaddend. .Iadd.36. A method according to claim 35 including controlling the flow of sheath liquid independently of the analyte eluent flow. .Iaddend. .Iadd.37. A method according to claim 35 including introducing a sheath gas flow surrounding the combined analyte eluent and sheath liquid flows. .Iaddend. .Iadd.38. A method of introducing an analyte solution to an analytical detector, which comprises:   providing a source of an analyte sample solution and a source of a sheath liquid;   introducing the analyte sample solution to a capillary having an outlet and   discharging the analyte sample solution from the capillary having an outlet and discharging the analyte sample solution from the capillary outlet and discharging the sheath liquid in a sheath flow coaxially surrounding the discharged analyte sample solution;   electrospraying an electrically-charged spray containing the analyte sample solution and the sheath liquid, the electrospraying being carried out at near atmospheric pressure and the electrically-charged spray being directed into a differentially-pumped input of a mass spectrometer. .Iaddend. .Iadd.39. A method according to claim 38 including controlling one of sheath liquid flow rate and composition so that the combined flows of analyte sample solution and sheath liquid can be electrosprayed. .Iaddend. .Iadd.40. A system for introducing an analyte solution to an analytical detector for analysis, which comprises:   a source of an analyte sample solution;   a source of a sheath liquid;   a capillary for conducting the analyte sample solution to a capillary outlet;   a sheath flow tube for conducting the sheath liquid to a sheath flow outlet;   means for discharging the analyte sample solution and sheath liquid in coaxially adjoining flows;   means for electrospraying a combined flow of said sheath liquid and analyte sample solution discharged from the capillary and sheath flow outlets; and   means for directly imparting an electrical potential to said sheath liquid and thereby to the discharged analyte sample solution immediately prior to said electrospraying. .Iaddend. .Iadd.41. The system of claim 40, in which the sheath flow outlet is disposed about an outlet end portion of said capillary for discharging the sheath electrode liquid in an annular sheath flow around the discharged analyte sample solution. .Iaddend. .Iadd.42. The system of claim 40, in which the sheath flow tube surrounds the capillary and is spaced outward therefrom to provide a passage surrounding the capillary, the tube and capillary having coaxially adjacent outlets positioned to discharge a sheath flow of the sheath electrode liquid around the discharged analyte eluent. .Iaddend. .Iadd.43. The system of claim 40 including means for controlling the flow of sheath electrode liquid independently of the capillary flow. .Iaddend. .Iadd.44. A system according to claim 40 including means for introducing a sheath gas flow surrounding the combined analyte sample solution and sheath electrode liquid flows. .Iaddend. .Iadd.45. A system according to claim 40 including a third tube coaxially surrounding the sheath flow tube and capillary. .Iaddend. .Iadd.46. A system according to claim 40 in which the electrospraying is carried out at near atmospheric pressure, the analytical detector is a mass spectrometer and the mass spectrometer includes a differentially-pumped input chamber into which the electrically-charged spray is directed. .Iaddend. .Iadd.47. A system according to claim 46 in which the mass spectrometer includes means for sampling and focusing ions from the electrically-charged spray into an analysis chamber. .Iaddend. .Iadd.48. A system for introducing an analyte solution to an analytical detector for analysis, which comprises:   a source of an analyte sample solution;   a source of a sheath liquid;   an electrically nonconductive capillary for conducting the analyte sample solution to a capillary outlet;   a sheath flow tube for conducting the sheath liquid to a sheath flow outlet, the sheath flow outlet being disposed about an outlet end portion of said capillary for discharging the sheath electrode liquid in an annular sheath flow around the discharged analyte sample solution;   means for discharging the analyte sample solution and sheath liquid in coaxially adjoining flows;   means for electrospraying a combined flow of said sheath liquid and analyte sample solution discharged from the capillary and sheath flow outlets;   means for forming an electrical contact with said sheath liquid and thereby with the analyte sample solution; and   a first high voltage supply coupled to said electrical contact means to form a first high voltage circuit through said analyte sample solution for electrophoretically separating same. .Iaddend. .Iadd.49. A system for introducing an analyte solution to an analyte solution to an analytical detector for analysis, which comprises:   a source of an analyte sample solution;   a source of a sheath liquid;   a capillary for conducting the analyte sample solution to a capillary outlet;   a sheath flow tube for conducting the sheath liquid to a sheath flow outlet, the sheath flow outlet being disposed about an outlet end portion of said capillary for discharging the sheath electrode liquid in an annular sheath flow around the discharged analyte sample solution;   means for discharging the analyte sample solution and sheath liquid in coaxially adjoining flows;   means for electrospraying a combined flow of said sheath liquid and analyte sample solution discharged from the capillary and sheath flow outlets;   means for forming an electrical contact with said sheath liquid and analyte sample solution; a second voltage supply coupled to form a second voltage potential between the combined flow of said sheath liquid and analyte sample solution; and   a detector or collector in spaced proximity to said outlet of the capillary for electrospraying the eluent. .Iadd.50. A system for introducing an analyte solution to an analytical detector for analysis, which comprises:   a source of an analyte sample solution;   a source of a sheath liquid;   a capillary for conducting the analyte sample solution to a capillary outlet section;   a sheath flow tube for conducting the sheath liquid to a sheath flow outlet, the sheath flow tube surrounding the capillary and spaced outward thereform to provide a passage surrounding the capillary, the tube and capillary having coaxially adjacent outlets positioned to discharge a sheath flow of the sheath electrode liquid around the discharged analyte eluent, the capillary outlet section protruding from the outlet of the sheath flow tube;   means for discharging the analyte sample solution and liquid in coaxially adjoining flows; and   means for electrospraying a combined flow of said sheath liquid and analyte sample solution discharged from the capillary .Iaddend. .Iadd.51. A system for introducing an analyte solution to an analytical detector for analysis, which comprises:   a source of an analyte sample solution;   a source of a sheath liquid;   a capillary for conducting the analyte sample solution to a capillary outlet section;   a sheath flow tube for conducting the sheath liquid to a sheath flow outlet, the sheath flow tube surrounding the capillary and spaced outward therefrom to provide a passage surrounding the capillary, the tube and capillary having coaxially adjacent outlets positioned to discharge a sheath flow of the sheath electrode liquid around the discharged analyte eluent;   means for discharging the analyte sample solution and sheath liquid in coaxially adjoining flows; and   means for electrospraying a combined flow of said sheath liquid and analyte sample solution discharged from the capillary and sheath flow outlets including means for coupling a voltage potential to one of the capillary and the sheath flow tube for electrospraying the combined flow of said sheath liquid and analyte sample solution. .Iaddend. .Iadd.52. A system for introducing an analyte solution to an analytical detector for analysis, which comprises:   a source of an analyte sample solution;   a source of a sheath liquid;   a capillary for conducting the analyte sample solution to a capillary outlet;   a sheath flow tube for conducting the sheath liquid to a sheath flow outlet;   means for discharging the analyte sample solution and sheath liquid in coaxially adjoining flows;   means for electrospraying a combined flow of said sheath liquid and analyte sample solution discharged from the capillary and sheath flow outlets;   the capillary including an outlet section, the sheath flow tube surrounding said outlet section and being spaced outward therefrom to provide a passage surrounding the outlet section; and   a tee having the capillary passing through opposite legs thereof and movable axially therein independently of the sheath flow tube for relatively positioning the outlets of the tube and capillary;   the tube and capillary having coaxially adjacent outlets positioned to discharge a sheath flow of the sheath electrode liquid around the discharged analyte sample solution. .Iaddend. .Iadd.53. A system for introducing an analyte solution to an analytical detector for analysis, which comprises:   a source of an analyte sample solution;   a source of a sheath liquid;   a capillary for conducting the analyte sample solution to a capillary outlet;   a sheath flow tube for conducting the sheath liquid to a sheath flow outlet;   means for discharging the analyte sample solution and sheath liquid in coaxially adjoining flows;   means for electrospraying a combined flow of said sheath liquid and analyte sample solution discharged from the capillary and sheath flow outlets; and   a third tube coaxially surrounding the sheath flow tube and capillary the third tube including a plurality of tubes extending along the sheath flow tube and having outlets spaced from the capillary and sheath flow outlets for conducting a sheath a gas to the interior of the third tube such that a first portion of the sheath gas is discharged forwardly along the coaxially adjoining flows and a second portion of the sheath gas is discharged rearwardly along the tubes. .Iaddend. .Iadd.54. A system for introducing an analyte solution to an analytical detector for analysis, which comprises:   a source of an analyte sample solution;   a source of a sheath liquid;   a capillary for conducting the analyte sample solution to a capillary outlet;   a sheath flow tube for conducting the sheath liquid to a sheath flow outlet;   means for discharging the analyte sample solution and sheath liquid in coaxially adjoining flows;   means for electrospraying a combined flow of said sheath liquid and analyte sample solution discharged from the capillary and sheath flow outlets; and   the electrospraying being carried out at near atmospheric pressure, the analytical detector being a mass spectrometer and the mass spectrometer including a differentially-pumped input chamber into which the electrically-charged spray is directed, the mass spectrometer including means for desolvating the electrically-charged spray. .Iaddend.