Orthogonal ion sampling for electrospray .[.LC/MS.]. mass spectrometry

Abstract

.[.The invention teaches the uses of a plurality of electric fields and of orthogonal spray configurations of vaporized analyte which combine so as to operate to enhance the efficiency of analyte detection and mass analysis with a mass spectrometer by reducing vapor in the vacuum system and concomitant noise. Several embodiments of the invention are described for purposes of illustration..]. .Iadd.The invention relates to a method and apparatus for improving signal relative to noise without loss of ion collection efficiency in electrospray mass spectrometry, including liquid chromatography/mass spectrometry..Iaddend.

What is claimed is: 
     
       1. An apparatus for converting a .Iadd.liquid .Iaddend.solute .[.sampled.]. .Iadd.sample .Iaddend.into ionized molecules, comprising: a first passageway having a center axis, an orifice for accepting a .Iadd.liquid .Iaddend.solute sample and an exit for discharging the .Iadd.liquid solute .Iaddend.sample from the .Iadd.first .Iaddend.passageway in the form of an .[.electrospray.]. .Iadd.electrosprayed aerosol .Iaddend.containing .[.charged.]. .Iadd.ionized .Iaddend.molecules;   an electrically conductive housing connected to a first voltage source and having an opening arranged adjacent to the first passageway exit; and   a second passageway arranged within the housing adjacent to the opening .Iadd.in the housing .Iaddend.and connected to a second voltage source, the second passageway having a center axis, an orifice for receiving .[.charged.]. .Iadd.ionized .Iaddend.molecules attracted from the .[.electrospray.]. .Iadd.electrosprayed aerosol .Iaddend.and an exit, wherein the center axis of the second passageway is arranged in transverse relation to the center axis of the first passageway such that .[.charged.]. .Iadd.ionized .Iaddend.molecules in the .[.electrospray.]. .Iadd.electrosprayed aerosol .Iaddend.move laterally through the opening in the housing and thereafter pass into the second passageway under the influence of electrostatic attraction forces generated by the first and second voltage sources.Iadd.; wherein an angle formed between the center axis of the first passageway and the center axis of the second passageway is between about 75 degrees and 105 degrees.Iaddend..   
     
     
       2. The apparatus of claim 1 wherein .[.an.]. .Iadd.the .Iaddend.angle formed between the center axis of the first passageway and the center axis of the second passageway is .[.greater than 75 degrees and less than or equal to 180.]. .Iadd.about 90 .Iaddend.degrees. 
     
     
       3. The apparatus of claim .[.2.]. .Iadd.1 .Iaddend.further comprising means for directing a stream of a drying gas in front of the orifice of the second passageway such that .Iadd.ionized .Iaddend.molecules passing though the opening in the housing encounter the stream of drying gas before entering the second passageway. 
     
     
       4. The apparatus of claim 3 wherein the first and second voltage sources provide a voltage difference, whereby the difference urges the .[.charged.]. .Iadd.ionized .Iaddend.molecules through the opening in the housing, across the stream of drying gas, and into the second passageway orifice. 
     
     
       5. The apparatus of claim 4 further comprising a third voltage source arranged adjacent to the exit of the first passageway, wherein the .[.electrospray.]. .Iadd.electrosprayed aerosol .Iaddend.discharged from the first passageway is interposed between the third voltage source and the housing. 
     
     
       6. The apparatus of claim 3 wherein the first passageway comprises a needle and the second passageway comprises a capillary. 
     
     
       7. The apparatus of claim 6 wherein the .[.second passageway.]. .Iadd.capillary .Iaddend.is heated. 
     
     
       8. The apparatus of claim 3 wherein the second passageway comprises an orifice. 
     
     
       9. The apparatus of claim 1 further comprising an analytical apparatus in fluid communication with the second passageway exit, wherein the housing is interposed between the first passageway and the analytical apparatus. 
     
     
       10. The apparatus of claim 9 wherein the analytical apparatus is capable of detecting and measuring the mass .[.and.]..Iadd.-to-.Iaddend.charge of .Iadd.ionized .Iaddend.molecules which have been communicated from the second passageway exit into the analytical apparatus. 
     
     
       11. The apparatus of claim 10 wherein the analytical apparatus comprises a mass spectrometer. 
     
     
       12. The apparatus of claim 11 further comprising means for directing a stream of a drying gas in front of the second passageway orifice such that .Iadd.ionized .Iaddend.molecules passing through the opening in the housing encounter the stream of drying gas before entering the second passageway. 
     
     
       13. The apparatus of claim 12 wherein the first and second voltage sources provide a voltage difference, whereby the difference urges the .[.charged.]. .Iadd.ionized .Iaddend.molecules through the opening in the housing, across the stream of drying gas, and into the second passageway orifice. 
     
     
       14. The apparatus of claim 13 further comprising a third voltage source arranged adjacent to the exit of the first passageway, wherein the .[.electrospray.]. .Iadd.electrosprayed aerosol .Iaddend.discharged from the first passageway is interposed.[.,.]. between the third voltage source and the housing. 
     
     
       15. The apparatus of claim 12 wherein the first passageway comprises a needle and the second passageway comprises a capillary. 
     
     
       16. The apparatus of claim 15 wherein the .[.second passageway.]. .Iadd.capillary .Iaddend.is heated. 
     
     
       17. The apparatus of claim 12 wherein the second passageway comprises an orifice. 
     
     
       18. The apparatus of claim 4 further comprising a third voltage source arranged adjacent to the exit of the first passageway, wherein the third voltage source has an annular configuration and is positioned.[.,.]. such that the .[.electrospray.]. .Iadd.electrosprayed aerosol .Iaddend.discharged from the first passageway is encircled by the third voltage source. 
     
     
       19. The apparatus of claim 13 further comprising a third voltage source arranged adjacent to the exit of the first passageway, wherein the third voltage source has an annular configuration and is positioned such that the .[.electrospray.]. .Iadd.electrosprayed aerosol .Iaddend.discharged from the first passageway is encircled by the third voltage source. .Iadd.20. An apparatus for converting a liquid solute sample into charged molecules, comprising: a first passageway having an exit for discharging an aerosol containing charged molecules, wherein said aerosol containing charged molecules has a center axis;   a second passageway for receiving said charged molecules from said first passageway, said second passageway having an entrance having a center axis, and arranged a distance from said exit of said first passageway, wherein an angle formed between said center axis of said aerosol containing charged molecules exiting said first passageway and said center axis of said entrance of said second passageway is about 75 degrees to about 105 degrees; and   a housing adjacent to said second passageway wherein a voltage source is connected to said housing..Iaddend..Iadd.21. The apparatus of claim 20 wherein a voltage source is connected to a passageway..Iaddend..Iadd.22. The apparatus of claim 20 wherein said angle is about 90   
     
     
        degrees..Iaddend..Iadd.23.  The apparatus of claim 20 further comprising a gas source..Iaddend..Iadd.24. The apparatus of claim 20 wherein said second passageway for receiving said charged molecules from said first passageway is arranged so that said aerosol exiting from said first passageway substantially passes by said entrance of said second passageway..Iaddend..Iadd.25. The apparatus of claim 20 wherein said second passageway is arranged so that said charged molecules entering said entrance of said second passageway are substantially separated from said liquid solute of said sample..Iaddend..Iadd.26. The apparatus of claim 20 wherein said second passageway is arranged so that portions of said sample entering said entrance of said second passageway are substantially enriched in said charged molecules relative to said liquid solute of said sample..Iaddend..Iadd.27. The apparatus of claim 20 wherein said housing adjacent to said second passageway provides for directing a stream of a gas in front of said entrance of said second passageway and toward said 
     
     
        aerosol..Iaddend..Iadd.28.  The apparatus of claim 20 wherein a voltage source is connected to said first passageway, and said second passageway is at about ground potential..Iaddend..Iadd.29. The apparatus of claim 20 wherein a voltage source is connected to said second passageway, and said first passageway is at about ground potential..Iaddend..Iadd.30. The apparatus of claim 20 further comprising a second voltage source connected to an electrically conductive element for establishing a second electric field for creating an electrostatic force that influences said charged molecules in said aerosol to move in the direction of said entrance of said second passageway..Iaddend..Iadd.31. The apparatus of claim 20 wherein said first passageway comprises a needle..Iaddend..Iadd.32. The apparatus of claim 20 wherein said first passageway comprises a capillary..Iaddend..Iadd.33. The apparatus of claim 20 wherein said second passageway comprises a capillary..Iaddend..Iadd.34. The apparatus of claim 33 wherein said capillary is heated..Iaddend..Iadd.35. The apparatus of claim 20 wherein said second passageway comprises an orifice..Iaddend..Iadd.36. The apparatus of claim 20 further comprising an annular electrically conductive element encircling a portion of said first passageway and a second voltage source connected thereto for creating an electrostatic force that influences said charged molecules in said aerosol to move in the direction of said entrance of said second passageway..Iaddend..Iadd.37. An apparatus for converting a liquid solute sample into charged molecules, comprising: a first passageway having an exit for discharging an aerosol containing charged molecules, wherein said aerosol containing charged molecules has a center axis;   a second passageway for receiving said charged molecules from said first passageway, said second passageway having an entrance having a center axis, and arranged a distance from said exit of said first passageway, wherein an angle formed between said center axis of said aerosol containing charged molecules exiting said first passageway and said center axis of said entrance of said second passageway is about 75 degrees to about 105 degrees; and   an electrically conductive element connected to a voltage source, wherein said element is arranged adjacent to said exit of said first passageway, wherein said aerosol exiting said first passageway is interposed between said element and said entrance of said second passageway..Iaddend..Iadd.38. The apparatus of claim 37 wherein said   
     
     
        element is a plate..Iaddend..Iadd.39.  The apparatus of claim 20 and further comprising an analytical instrument in fluid communication with an exit of said second passageway..Iaddend..Iadd.40. The apparatus of claim 39 wherein said analytical instrument is capable of detecting and measuring the mass-to-charge ratio of said charged molecules..Iaddend..Iadd.41. The apparatus of claim 40 wherein said analytical instrument comprises a mass spectrometer..Iaddend..Iadd.42. The apparatus of claim 20 wherein a voltage source is connected to said first passageway, and wherein said voltage sources are at different potentials..Iaddend..Iadd.43. The apparatus of claim 20 wherein a voltage source is connected to said second passageway, and wherein said voltage sources are at different potentials..Iaddend..Iadd.44. An apparatus for converting a liquid solute sample into charged molecules, comprising: a first passageway having an exit for discharging an aerosol containing charged molecules, wherein said exit of said first passageway has a center axis;   a second passageway for receiving said charged molecules attracted from said first passageway, said second passageway having an entrance having a center axis, and arranged a distance from said exit of said first passageway, wherein an angle formed between said center axis of said exit of said first passageway and said center axis of said entrance of said second passageway is about 75 degrees to about 105 degrees; and   a housing adjacent to said second passageway wherein a voltage source is connected to said housing..Iaddend..Iadd.45. The apparatus of claim 44 wherein a voltage source is connected to a passageway..Iaddend..Iadd.46. The apparatus of claim 44 wherein said angle is about 90 degrees..Iaddend..Iadd.47. The apparatus of claim 44 further comprising a gas source..Iaddend..Iadd.48. The apparatus of claim 44 wherein said second passageway for receiving said charged molecules from said first passageway is arranged so that said aerosol exiting from said first passageway substantially passes by said entrance of said second passageway..Iaddend..Iadd.49. The apparatus of claim 44 wherein said second passageway is arranged so that said charged molecules entering said entrance of said second passageway are substantially separated from said   
     
     
        liquid solute of said sample..Iaddend..Iadd.50.  The apparatus of claim 44 wherein said second passageway is arranged so that portions of said sample entering said entrance of said second passageway are substantially enriched in said charged molecules relative to said liquid solute of said sample..Iaddend..Iadd.51. The apparatus of claim 44 further comprising a housing wherein said housing adjacent to said second passageway provides for directing a stream of a gas in front of said entrance of said second passageway and toward said aerosol..Iaddend..Iadd.52. The apparatus of claim 44 wherein a voltage source is connected to said first passageway and said second passageway is at about ground potential..Iaddend..Iadd.53. The apparatus of claim 44 wherein a voltage source is connected to said second passageway and said first passageway is at about ground potential..Iaddend..Iadd.54. The apparatus of claim 44 further comprising a second voltage source connected to an electrically conductive element for establishing a second electric field for creating an electrostatic force that influences said charged molecules in said aerosol to move in the direction of said entrance of said second 
     
     
        passageway..Iaddend..Iadd.     The apparatus of claim 44 wherein said first passageway comprises a needle..Iaddend..Iadd.56. The apparatus of claim 44 wherein said first passageway comprises a capillary..Iaddend..Iadd.57. The apparatus of claim 44 wherein said second passageway comprises a capillary..Iaddend..Iadd.58. The apparatus of claim 57 wherein said capillary is heated..Iaddend..Iadd.59. The apparatus of claim 44 wherein said second passageway comprises an orifice..Iaddend..Iadd.60. The apparatus of claim 44 further comprising an annular electrically conductive element encircling a portion of said first passageway and a second voltage source connected thereto for creating an electrostatic force that influences said charged molecules in said aerosol to move in the direction of said entrance of said second passageway..Iaddend..Iadd.61. The apparatus of claim 44 further comprising an analytical instrument in fluid communication with an exit of said 
     
     
        second passageway..Iaddend..Iadd.62.  The apparatus of claim 61 wherein said analytical instrument is capable of detecting and measuring the mass-to-charge ratio of said charged molecules..Iaddend..Iadd.63. The apparatus of claim 62 wherein said analytical instrument comprises a mass spectrometer..Iaddend..Iadd.64. The apparatus of claim 44 wherein a voltage source is connected to said first passageway, and wherein said voltage sources are at different potentials..Iaddend..Iadd.65. The apparatus of claim 44 wherein a voltage source is connected to said second passageway, and wherein said voltage sources are at different 
     
     
        potentials..Iaddend..Iadd.66.  An apparatus for converting a liquid solute sample into charged molecules, comprising: a first passageway having an exit for discharging an aerosol containing charged molecules, wherein said exit of said first passageway has a center axis;   a second passageway for receiving said charged molecules attracted from said first passageway, said second passageway having an entrance having a center axis, and arranged a distance from said exit of said first passageway, wherein an angle formed between said center axis of said exit of said first passageway and said center axis of said entrance of said second passageway is about 75 degrees to about 105 degrees; and   an electrically conductive element connected to a voltage source, wherein said element is arranged adjacent to said exit of said first passageway, wherein said aerosol exiting said first passageway is interposed between said element and said entrance of said second passageway..Iaddend..Iadd.67. The apparatus of claim 66 wherein said element is a plate..Iaddend.