U.S. patent number RE36,892 [Application Number 08/792,303] was granted by the patent office on 2000-10-03 for orthogonal ion sampling for electrospray .[.lc/ms.]. mass spectrometry.
This patent grant is currently assigned to Agilent Technologies. Invention is credited to James A. Apffel, Jr., James L. Bertsch, Paul C. Goodley, Kent D. Henry, Mark H. Werlich.
United States Patent |
RE36,892 |
Apffel, Jr. , et
al. |
October 3, 2000 |
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.
Inventors: |
Apffel, Jr.; James A. (Mountain
View, CA), Werlich; Mark H. (Santa Clara, CA), Bertsch;
James L. (Palo Alto, CA), Goodley; Paul C. (Cupertino,
CA), Henry; Kent D. (Newark, CA) |
Assignee: |
Agilent Technologies (Palo
Alto, CA)
|
Family
ID: |
23043172 |
Appl.
No.: |
08/792,303 |
Filed: |
January 31, 1997 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
Reissue of: |
273250 |
Jul 11, 1994 |
05495108 |
Feb 27, 1996 |
|
|
Current U.S.
Class: |
250/288 |
Current CPC
Class: |
G01N
30/7253 (20130101); H01J 49/04 (20130101); H01J
49/165 (20130101) |
Current International
Class: |
G01N
30/00 (20060101); G01N 30/72 (20060101); H01J
49/02 (20060101); H01J 49/04 (20060101); B01D
059/46 (); H01J 049/00 () |
Field of
Search: |
;250/288,288A,281 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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52-66488 |
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Jan 1977 |
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JP |
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59-845 |
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Jan 1984 |
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JP |
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1-146242 |
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Jun 1989 |
|
JP |
|
4-132153 |
|
May 1992 |
|
JP |
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6-060847 |
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Mar 1994 |
|
JP |
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WO 85/02490 A1 |
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Jun 1985 |
|
WO |
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WO 95/24259 A1 |
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Sep 1995 |
|
WO |
|
Other References
Apffel et al., "Gas-Nebulized Direct Liquid Introduction Interface
for Liquid Chromatography/Mass Spectrometry", Anal. Chem., 1983,
vol. 55, p. 2280-2284 No Month. .
Bruins et al., "Ion Spray Interface for Combined Liquid
Chromatography/Atmospheric Pressure Ionization Mass Spectrometry",
Anal. Chem., 1987, vol. 59, p. 2642-2646 No Month. .
Whitehouse et al., "Electrospray Interface for Liquid
Chromatographs and Mass Spectrometers", Anal. Chem., 1985, vol. 57,
No. 3, p. 675-679 No Month. .
Garcia et al., "Optimization of the Atmospheric Pressure Chemical
Ionization Liquid Chromatography Mass Spectrometry Interface",J.
Am. Soc. Mass. Spectrom.,1996, vol. 7, No. 1, p. 59-65. No Month.
.
Hagiwara et al., "Optimum Needle Materials of the Corona Discharge
Electrode for Quantitative Analysis by Liquid
Chromatography/Atmospheric Pressure Chemical Ionization-Mass
Spectrometry", J. Mass. Spectrom. Soc. Jpn., 1995, vol. 43, No. 6,
p. 365-371. No Month. .
Takada et al., "Atmospheric Pressure Chemical Ionization Interface
for Capillary Electrophoresis/Mass Spectrometry", Anal. Chem., Apr.
15, 1995, vol. 67, No. 8, p. 1474-1476. .
Doerge et al., "Multiresidue Analysis of Sulfonamides Using Liquid
Chromatography with Atmospheric Pressure Chemical Ionization Mass
Spectrometry", Rapid Communications in Mass Spectrom., Dec. 1993,
vol. 7, No. 12, p. 1126-1130. .
Willoughby et al., "Monodisperse Aerosol Generation Interface for
Combining Liquid Chromatography with Mass Spectroscopy", Anal.
Chem., 1984, vol. 56, p. 2626-2631 No Month. .
Yamashita et al., "Electrospray Ion Source. Another Variation on
the Free-Jet Theme", J. Phys. Chem., 1984, vol. 88, p. 4451-4459.
.
Kambara et al., "Ionization Charateristics of Atmospheric Pressure
Ionization by Corona Discharge", Mass Spectroscopy, Sep. 1976, vol.
24, No. 3, p. 229-236. .
Lee et al., "Real-Time Reaction Monitoring by
Continuous-Introduction Ion-Spray Tandem Mass Spectrometry", J. Am.
Chem. Soc., 1989, vol. III, No. 13, p. 4600-4604..
|
Primary Examiner: Anderson; Bruce C.
Claims
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.
Description
INTRODUCTION
The invention relates to a method and apparatus for obtaining
improved .Iadd.signal relative to noise without loss of
.Iaddend.ion collection efficiency in electrospray .[.on.].
.Iadd.mass spectrometry, including liquid chromatography/mass
spectrometry (LC/MS.Iadd.).Iaddend..
Initial systems for electrospray LC/MS utilized flow splitters that
divided the HPLC .Iadd.(high performance liquid chromatography)
.Iaddend.column effluent in such a way that a small portion,
typically 5-50 micro liters per minute, was introduced into the
"spray chamber".Iadd., .Iaddend.while the major portion was
directed to a waste or fraction collector. Because .Iadd.these
.Iaddend.low flow rates were introduced into electrospray
.Iadd.(ES) mass spectrometry (MS) .Iaddend.systems, it became
possible to generate .[.spray.]. .Iadd.electrosprayed aerosol
.Iaddend.solely through the use of electrostatic forces. Since
ES/MS .[.is.]. .Iadd.generally provides .Iaddend.a concentration
sensitive detector, this does not result in loss of sensitivity
when compared with introduction of all the flow .Iadd.from the HPLC
column effluent .Iaddend.into the spray chamber (assuming equal
charging and sampling efficiencies). However, the use of flow
splitters has gained a bad reputation due to potential plugging
problems and poor reproducibility.
Newer electrospray systems generate a charged .[.spray.]. .Iadd.or
ionized aerosol .Iaddend.through the combination of electrostatic
forces and .[.an.]. assisted nebulization. The assisted
nebulization .Iadd.generally .Iaddend.generates an aerosol from the
HPLC .Iadd.column .Iaddend.effluent, while the electric field
induces a charge on the droplets, which ultimately results in the
generation of desolvated analyte ions via an ion evaporation
process. The assisted nebulization can be done with pneumatic,
ultrasonic, or thermal nebulization or by some other nebulization
technique.
In each of these newer assisted nebulizer systems, it has been
necessary to design the system so that the solvated droplets
present in the .Iadd.electrosprayed .Iaddend.aerosol do not enter
the vacuum system. This has been accomplished in several ways.
.Iadd.In conventional electrospray/nebulization mass spectrometry
systems, the electrosprayed aerosol exiting from the nebulizer is
sprayed directly towards the sampling orifice or other entry into
the vacuum system such as a capillary. That is, the electrosprayed
aerosol exiting from the nebulizer and the entry into the vacuum
system are located along a common central axis, with the nebulizer
effluent pointing directly at the entry into the vacuum system and
with the nebulizer being considered to be located at an angle of
zero (0) degrees relative to the common central axis..Iaddend.
.[.In one currently available system,.]. .Iadd.One previous
approach directed at improving performance adjusts the aerosol to
spray "off-axis". That is, .Iaddend.the aerosol is sprayed .[."off
axis".]. .Iadd."off-axis".Iaddend. at an angle of as much as 45
degrees with respect to the .Iadd.central .Iaddend.axis of the
sampling orifice. In addition, a counter current .[.drying.]. gas
is .[.sprayed.]. .Iadd.passed .Iaddend.around the sampling orifice
to blow the solvated droplets away from the orifice. The gas
.[.pressures.]. .Iadd.velocities .Iaddend.typically used
.[.generates.]. .Iadd.generate .Iaddend.a plume of small droplets
and optimal performance appears to be limited to a flow rate of 200
microliters per minute or lower.
In another currently available system, an aerosol is generated
pneumatically and aimed directly at the entrance of a heated
capillary tube .Iadd.providing a passageway .Iaddend.into the
vacuum system. Instead of desolvated ions entering the capillary,
large charged droplets are drawn into the capillary and the
droplets are desolvated while in transit. The evaporation process
takes place in the capillary as well. A supersonic jet of vapor
exits the capillary and the analyte ions are subsequently focused,
mass analyzed and detected. There are several disadvantages to this
system. The use of the high temperature capillary may result in
thermal degradation of thermally labile samples. In the supersonic
jet expansion, the desolvated ions and vapor may recondense.Iadd.,
.Iaddend.resulting in solvent clusters and background signals.
While these clusters may be re-dissociated by collisionally induced
processes, this may interfere in identification of structural
characteristics of the analyte samples which are intentionally
subjected to collisionally induced dissociation. The large amount
of solvent vapor, ions and droplets exiting the capillary require
that the detector be arranged substantially .[.off axis.].
.Iadd.off-axis .Iaddend.with respect to the capillary to avoid
noise due to neutral droplets striking the .Iadd.mass analyzer and
.Iaddend.detector. The additional solvent entering the vacuum
.Iadd.system .Iaddend.requires larger .Iadd.capacity
.Iaddend.pumps.
In another currently available system, the .[.spray.].
.Iadd.electrosprayed aerosol .Iaddend.is generated ultrasonically.
The system is used in conjunction with a counter current drying gas
and is usually operated with the .[.spray.]. .Iadd.aerosol
.Iaddend.directed at the sampling capillary. The main disadvantages
of this system, from the practitioner's point of view, are that
optimal performance is effectively limited to less than 500
microliters per minute and .[.that.]. there are serious problems
with aqueous mobile phases. Furthermore, the apparatus is complex
and prone to mechanical and electronic failures.
In another commonly used system, a pneumatic nebulizer is used at
substantially higher inlet pressures (as compared with other
systems). This results in a highly collimated and directed
.[.droplet beam.]. .Iadd.electrosprayed aerosol.Iaddend.. This
.Iadd.aerosol .Iaddend.is aimed off-axis to the side of the orifice
.[.in.]. .Iadd.and at .Iaddend.the nozzle cap. Although this works
competitively, there is still some noise which is probably due to
stray droplets. The .Iadd.aerosol exiting the .Iaddend.nebulizer
.[.jet.]. has to be aimed carefully to minimize noise while
maintaining signal intensity.
SUMMARY OF INVENTION
.Iadd.The invention relates to an apparatus for converting a liquid
solute 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 electrosprayed
aerosol containing 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 ionized molecules attracted from the 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 ionized molecules in the
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..Iaddend.
The invention provides the capability of conducting atmospheric
pressure ionization.[.,.]. .Iadd.(.Iaddend.API.Iadd.).Iaddend.,
whether electrospray or atmospheric pressure chemical ionization
(APCI), with conventional .[.High Performance Liquid
Chromatography.]. .Iadd.high performance liquid chromatography
.Iaddend.at flow rates of greater than 1 ml/minute without flow
splitting. The invention allows desolvated ions to be separated
from comparatively large volumes of .[.vaporized.].
.Iadd.electrosprayed .Iaddend.column effluent, and then, while
keeping out as much of the solvent as possible, introducing the
desolvated ions into the vacuum system for mass detection and
analysis .[.while introducing as little of the solvent as
possible.].. The invention provides the capability of separating
desolvated ions of interest from the large volumes of vapor.[.,.].
and directing the desolvated ions from the electrospray (ES)
chamber (which .Iadd.typically .Iaddend.operates at atmospheric
pressure) to the mass spectrometer (which operates at 10.sup.-6 to
10.sup.-4 .[.Torr.]. .Iadd.torr.Iaddend.). The .Iadd.orthogonal
.Iaddend.selection .Iadd.process .Iaddend.allows the introduction
of ions without overwhelming the vacuum system and without
sacrificing the sensitivity of the system, .[.because.].
.Iadd.since .Iaddend.the maximum amount of analyte is introduced
into the vacuum system for mass analysis and detection.
Orthogonal ion sampling according to the present invention allows
more efficient enrichment of the analyte by spraying the charged
droplets .Iadd.in the electrosprayed aerosol .Iaddend.past a
sampling orifice.Iadd., .Iaddend.while directing the solvent vapor
and solvated droplets .Iadd.in the electrosprayed aerosol
.Iaddend.away .[.in a direction such.]. .Iadd.from the sampling
orifice so .Iaddend.that they do not enter the vacuum system.
The noise level in .[.an.]. .Iadd.a mass spectrometry
.Iaddend.apparatus configured according to the present invention is
reduced by as much as five fold over current systems, resulting in
increased signal relative to noise.Iadd., and .Iaddend.hence.[.,.].
.Iadd.acheiving .Iaddend.greater sensitivity. Performance is
simplified and the system .Iadd.is .Iaddend.more robust because
optimization of .[.needle.]. .Iadd.the .Iaddend.position .Iadd.of
the first passageway.Iaddend., gas flow and voltages show less
sensitivity to small changes. The simplified performance and
reduced need for optimization also result in a system less
dependent .[.of.]. .Iadd.on .Iaddend.flow rate and mobile phase
conditions. The reduced need for optimization extends to changing
mobile phase flow rates and proportions. This means that the
.Iadd.mass spectrometry .Iaddend.system can be run under a variety
of conditions without adjustment.
Another benefit of the invention taught herein is simplified waste
removal owing to the fact that the .[.spray.]. .Iadd.electrosprayed
aerosol .Iaddend.can be aimed directly at a waste line and be
easily removed from the system. Furthermore, the present invention
provides the option of eliminating high voltage elements with no
loss of sensitivity.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a representation of an apparatus according to the present
invention.
FIG. 2 is a representation of an alternate embodiment of an
apparatus according to the present invention.
FIG. 3 is a representation of an alternate embodiment of an
apparatus according to the present invention.
FIG. 4 is a representation of an alternate embodiment of an
apparatus
according to the present invention.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 depicts an apparatus 10 configured according to the current
invention. As in conventional sample introduction, a liquid sample
is conducted through .[.the.]. .Iadd.a .Iaddend.nebulizer
.[.with.]. .Iadd.having .Iaddend.a first passageway 14, .Iadd.the
liquid sample .Iaddend.exiting a second orifice or exit .Iadd.15
.Iaddend.of the first passageway .[.15.]. .Iadd.14 .Iaddend.under
conditions which create a vapor of charged .Iadd.or ionized
.Iaddend.droplets or .[."electrospray".]. .Iadd.electrosprayed
aerosol .Iaddend.11. The invention provides a rather different
electrospray particle transport as compared with conventional
electrospray .Iadd.processes.Iaddend.. FIG. 1 depicts the transport
of the .[.electrospray.]. droplets .Iadd.in the electrosprayed
aerosol 11 .Iaddend.from the second orifice exit .Iadd.15
.Iaddend.of the first passageway .[.15.]. .Iadd.14.Iaddend.,
through the distance to the entrance .Iadd.or opening 17
.Iaddend.of the second passageway .[.17.]. .Iadd.22.Iaddend., and
entering the second passageway .[.18.]. .Iadd.22 .Iaddend.where the
orientation angle .theta. of the .Iadd.center .Iaddend.axis of the
exiting .[.electrospray.]. .Iadd.electrosprayed aerosol .Iaddend.11
and .Iadd.the center axis of .Iaddend.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.
.Iadd.(As shown in FIG. 1, the angle .theta. 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 .theta. 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 .theta. 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). .Iaddend.The charged
droplets .Iadd.forming the electrosprayed aersol 11 .Iaddend.are
electrostatically attracted laterally across the gap between the
exit .Iadd.15 .Iaddend.of the first passageway .[.15.]. .Iadd.14
.Iaddend.into the opening .Iadd.17 .Iaddend.of the second
passageway .[.17.]. .Iadd.22.Iaddend.. The electrostatic attraction
is generated by attaching voltage sources to components of the
apparatus. A first voltage source .[.16.]. .Iadd.V1 .Iaddend.is
connected to a housing 19 which houses the second passageway 22.
The housing .Iadd.19 .Iaddend.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.]. .Iadd.V2 .Iaddend.is connected to
the second passageway 22. The first passageway 14 is generally kept
at ground .Iadd.potential.Iaddend..
In the course of crossing the gap and approaching the entrance
.Iadd.17 .Iaddend.to the second passageway 22, especially after
passing through an opening 21 in the housing 19 containing the
second passageway 22, the .[.electrospray.]. .Iadd.electrosprayed
aerosol .Iaddend.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.]. .Iadd.particles
or ions.Iaddend.. The .[.small droplets.]. .Iadd.ions .Iaddend.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 .Iadd.22
.Iaddend.exits into the mass spectrometer or equivalent
instrument.
A standard electrospray .Iadd.MS .Iaddend.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 .Iadd.containing the first
passageway .Iaddend.14 may be arranged in a variety of
configurations.Iadd., .Iaddend.so long as the .[.distance.].
.Iadd.distances .Iaddend.between the separate high voltage
.[.points is.]. .Iadd.sources are .Iaddend.sufficient to prevent
discharges. Additional surfaces at high voltage may be used to
shape the electrical fields experienced by the .[.spray.].
.Iadd.electrosprayed aerosol.Iaddend.. In the embodiment depicted
in FIG. 1, the system includes a .[.drying.]. gas 20 to aid
desolvation and prevent .[.spray.]. droplets .Iadd.in the
electrosprayed aerosol .Iaddend.11 from entering the .[.orifice.].
.Iadd.opening 17 .Iaddend.of the second passageway .[.17.].
.Iadd.22 .Iaddend.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.].
.Iadd.the analyzer (such as a quadrupole) .Iaddend.and detector
components.
The .Iadd.positive ion .Iaddend.configuration shown in FIG. 1
.[.generally.]. .Iadd.typically .Iaddend.has the second voltage
source .[.18.]. .Iadd.V2 .Iaddend.set .[.typically.]. at -4.5 kV,
.[.and.]. the first voltage source .[.16.]. .Iadd.V1 set
.Iaddend.at -4 kV, and the first passageway 14 generally comprising
a needle .Iadd.set .Iaddend.at ground .Iadd.potential.Iaddend..
Gas, usually nitrogen at nominally 200 degree to 400 .[.degree.].
.Iadd.degrees .Iaddend.Centigrade and approximately 10 standard
.[.liter.]. .Iadd.liters .Iaddend.per minute, is typically used as
a cross flow .[.drying.]. gas .Iadd.20.Iaddend., 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 .Iadd.in the electrosprayed
aerosol.Iaddend..
The term "passageway", as used .[.in this application.].
.Iadd.herein with respect to the second passageway.Iaddend., means
"ion guide" in any form .[.whatever.]. .Iadd.whatsoever.Iaddend..
It is possible that the passageway .[.be.]. .Iadd.is .Iaddend.of
such short length relative to .Iadd.the .Iaddend.opening diameter
that it may be called an orifice. Other ion guides, including
capillaries, which are or may come to be used.Iadd., .Iaddend.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.]. .Iadd.been
proven .Iaddend.possible. Examples of certain tested configurations
follow.
FIG. 2 shows a configuration of the invention in which a third
voltage source, .[.a plate 29.]. .Iadd.V3, .Iaddend.is positioned
beside the exit .Iadd.15 .Iaddend.of the first passageway .[.15.].
.Iadd.14 .Iaddend.and distal to the side near to which the first
voltage source .[.16.]. .Iadd.V1 .Iaddend.and opening .Iadd.17
.Iaddend.to the second passageway .[.cavity 17.]. .Iadd.22
.Iaddend.are positioned. The .[.plate 29 runs.]. .Iadd.third
voltage source V3 provides .Iaddend.a positive voltage relative to
the first voltage source .[.16.]. .Iadd.V1.Iaddend.. Experiments
show .Iadd.that .Iaddend.the .[.charged droplet electrospray.].
.Iadd.electrosprayed aerosol .Iaddend."sees" a mean voltage between
the plate .[.29.]. .Iadd.24 .Iaddend.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.]. .Iadd.wherein V3 is at
ground potential.Iaddend.. The spray chamber 26 operates to contain
the .Iadd.electrosprayed .Iaddend.aerosol and route condensed vapor
to waste.
FIG. 4 shows the addition of a ring-shaped electrode .[.28.].
.Iadd.or fourth voltage source V4 .Iaddend.encircling the
.[.flow.]. .Iadd.electrosprayed aerosol .Iaddend.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.].
.Iadd.or fourth voltage source V4 .Iaddend.induces a charge in the
droplets by virtue of the potential difference in charge between
the droplets and the ring-shaped electrode .[.28.]. .Iadd.or fourth
voltage source V4.Iaddend.. Other potentials in the system can be
used to direct the sampling of ions.
* * * * *