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. 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.

Description

INTRODUCTION

The invention relates to a method and apparatus for obtaining improved signal relative to noise without loss of the a nebulizer with having a first passageway 14, the liquid sample exiting a second orifice or exit 15 of the first passageway 15 14 under conditions which create a vapor of charged or ionized droplets or "electrospray" electrosprayed aerosol 11. The invention provides a rather different electrospray particle transport as compared with conventional electrospray processes. FIG. 1 depicts the transport of the electrospray droplets in the electrosprayed aerosol 11 from the second orifice exit 15 of the first passageway 15 14, through the distance to the entrance or opening 17 of the second passageway 17 22, and entering the second passageway 18 22 where the orientation angle θ of the center axis of the exiting electrospray electrosprayed aerosol 11 and the center axis of the second passageway 22 is between 75 degrees and 105 degrees relative to each other. The angle may be greater than 105, in principle as great as 180; best results have been obtained at settings at or near 90 degrees. (As shown in FIG. 1, the angle θ defines the location of the first passageway 14, that is, the nebulizer or other source of electrosprayed aerosol 11, relative to the second passageway 22, that is, the entry into the vacuum system. The angle θ is considered to be zero (0) degrees when the exit 15 for the electrosprayed aerosol 11 and the center axis of the first passageway 14 are pointing directly at the entrance 17 and the center axis of the second passageway 22. The angle θ is considered to be 180 degrees when the exit 15 for the electrosprayed aerosol 11 and the center axis of the first passageway 14 are pointing directly away from the entrance 17 and the center axis of the second passageway 22). The charged droplets forming the electrosprayed aersol 11 are electrostatically attracted laterally across the gap between the exit 15 of the first passageway 15 14 into the opening 17 of the second passageway 17 22. The electrostatic attraction is generated by attaching voltage sources to components of the apparatus. A first voltage source 16 V1 is connected to a housing 19 which houses the second passageway 22. The housing 19 is not necessarily an enclosure but may be in any shape that can act as a guide for the ions and can support fluid dynamics of a drying gas (see below discussion). A second voltage source 18 V2 is connected to the second passageway 22. The first passageway 14 is generally kept at ground potential.

In the course of crossing the gap and approaching the entrance 17 to the second passageway 22, especially after passing through an opening 21 in the housing 19 containing the second passageway 22, the electrospray electrosprayed aerosol is subjected to the cross flow of a gas 20--a condition that operates to remove solvent from the droplets, thereby leaving small charged droplets particles or ions. The small droplets ions are amenable to analysis by operation of an analytic instrument capable of detecting and measuring mass and charge of particles such as a mass spectrometer (not shown). The second passageway 22 exits into the mass spectrometer or equivalent instrument.

A standard electrospray MS system (HP 5989) with a pneumatic nebulizer provides the base structure. A spray box 12 of plexiglass or some other suitable material for preventing shock and containing noxious vapors replaces the standard spray chamber. Within the spray box 12, the nebulizer containing the first passageway 14 may be arranged in a variety of configurations, so long as the distance distances between the separate high voltage points is sources are sufficient to prevent discharges. Additional surfaces at high voltage may be used to shape the electrical fields experienced by the spray electrosprayed aerosol. In the embodiment depicted in FIG. 1, the system includes a drying gas 20 to aid desolvation and prevent spray droplets in the electrosprayed aerosol 11 from entering the orifice opening 17 of the second passageway 17 22 and the vacuum system (not shown). An alternate embodiment could include a heated capillary as the second passageway 22 in an internal source off-axis geometry, such that the capillary is off-axis with respect to quadropole the analyzer (such as a quadrupole) and detector components.

The positive ion configuration shown in FIG. 1 generally typically has the second voltage source 18 V2 set typically at -4.5 kV, and the first voltage source 16 V1 set at -4 kV, and the first passageway 14 generally comprising a needle set at ground potential. Gas, usually nitrogen at nominally 200 degree to 400 .[°]. degrees Centigrade and approximately 10 standard liter liters per minute, is typically used as a cross flow drying gas 20, although other gases can be used. The drying gas 20 flows across the aperture at approximately 90 degrees to the axis of the incoming charged molecules in the electrosprayed aerosol.

The term "passageway", as used in this application herein with respect to the second passageway, means "ion guide" in any form whatever whatsoever. It is possible that the passageway be is of such short length relative to the opening diameter that it may be called an orifice. Other ion guides, including capillaries, which are or may come to be used, can operate in the invention. The configurations herein are not meant to be restrictive, and those skilled in the art will see possible configurations not specifically mentioned here but which are included in the teaching and claims of this invention.

EXAMPLES

A number of different configurations have proved been proven possible. Examples of certain tested configurations follow.

FIG. 2 shows a configuration of the invention in which a third voltage source, a plate 29 V3, is positioned beside the exit 15 of the first passageway 15 14 and distal to the side near to which the first voltage source 16 V1 and opening 17 to the second passageway cavity 17 22 are positioned. The plate 29 runs third voltage source V3 provides a positive voltage relative to the first voltage source 16 V1. Experiments show that the charged droplet electrospray electrosprayed aerosol "sees" a mean voltage between the plate 29 24 and the charged housing 19. Results suggest that the repeller effect may be captured and ion collection yield increased by careful sculpting of both the electric field and the gas flow patterns.

FIG. 3 shows a two voltage source system as in FIG. 2 with the addition of a grounded spray chamber 26 wherein V3 is at ground potential. The spray chamber 26 operates to contain the electrosprayed aerosol and route condensed vapor to waste.

FIG. 4 shows the addition of a ring-shaped electrode 28 or fourth voltage source V4 encircling the flow electrosprayed aerosol exiting from the needle or first passageway 14 at ground, with all of the elements configured as in FIG. 3. The ring-shaped electrode 28 or fourth voltage source V4 induces a charge in the droplets by virtue of the potential difference in charge between the droplets and the ring-shaped electrode 28 or fourth voltage source V4. Other potentials in the system can be used to direct the sampling of ions.

Claims

1. An apparatus for converting a liquid solute sampled sample into ionized molecules, comprising:

a first passageway having a center axis, an orifice for accepting a liquid solute sample and an exit for discharging the liquid solute sample from the first passageway in the form of an electrospray electrosprayed aerosol containing charged ionized 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 in the housing and connected to a second voltage source, the second passageway having a center axis, an orifice for receiving charged ionized molecules attracted from the electrospray electrosprayed aerosol 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 ionized molecules in the electrospray electrosprayed aerosol 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; 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.

2. The apparatus of claim 1 wherein an the 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 about 90 degrees.

3. The apparatus of claim 2 1 further comprising means for directing a stream of a drying gas in front of the orifice of the second passageway such that ionized 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 ionized 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 electrosprayed aerosol 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 capillary 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-to-charge of ionized 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 ionized 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 ionized 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 electrosprayed aerosol 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 capillary 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 electrosprayed aerosol 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 electrosprayed aerosol discharged from the first passageway is encircled by the third voltage source. 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.21. The apparatus of claim 20 wherein a voltage source is connected to a passageway.22. The apparatus of claim 20 wherein said angle is about 90

degrees.23. The apparatus of claim 20 further comprising a gas source.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.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.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.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.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.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.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.31. The apparatus of claim 20 wherein said first passageway comprises a needle.32. The apparatus of claim 20 wherein said first passageway comprises a capillary.33. The apparatus of claim 20 wherein said second passageway comprises a capillary.34. The apparatus of claim 33 wherein said capillary is heated.35. The apparatus of claim 20 wherein said second passageway comprises an orifice.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.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.38. The apparatus of claim 37 wherein said

element is a plate.39. The apparatus of claim 20 and further comprising an analytical instrument in fluid communication with an exit of said second passageway.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.41. The apparatus of claim 40 wherein said analytical instrument comprises a mass spectrometer.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.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.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.45. The apparatus of claim 44 wherein a voltage source is connected to a passageway.46. The apparatus of claim 44 wherein said angle is about 90 degrees.47. The apparatus of claim 44 further comprising a gas source.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.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.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.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.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.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.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. The apparatus of claim 44 wherein said first passageway comprises a needle.56. The apparatus of claim 44 wherein said first passageway comprises a capillary.57. The apparatus of claim 44 wherein said second passageway comprises a capillary.58. The apparatus of claim 57 wherein said capillary is heated.59. The apparatus of claim 44 wherein said second passageway comprises an orifice.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.61. The apparatus of claim 44 further comprising an analytical instrument in fluid communication with an exit of said

second passageway.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.63. The apparatus of claim 62 wherein said analytical instrument comprises a mass spectrometer.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.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.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.67. The apparatus of claim 66 wherein said element is a plate.