US20090283674A1

US20090283674A1 - Efficient Atmospheric Pressure Interface for Mass Spectrometers and Method

Info

Publication number: US20090283674A1
Application number: US11/833,209
Authority: US
Inventors: Reinhold Pesch
Original assignee: Thermo Fisher Scientific Bremen GmbH
Current assignee: Thermo Fisher Scientific Bremen GmbH
Priority date: 2006-11-07
Filing date: 2007-08-02
Publication date: 2009-11-19
Also published as: US8148679B2; WO2008055667A3; JP2010508643A; JP2010508535A; JP2012114096A; US8148680B2; CA2668829C; US8642949B2; DE112007002661T5; DE112007002686B4; CA2668763C; US20100038533A1; DE112007002661B4; GB2456284A; US20100038532A1; WO2008055667A2; CA2668763A1; CA2668762A1; WO2008061628A2; GB0909032D0

Abstract

An interface for atmospheric pressure ionization sources has an ion transfer tube with a plurality of passageways through a sidewall such that background gas can be pumped away before it reaches an exit end of the ion transfer tube. A flow of the background gas out the exit end is reduced, and a proportion of laminar flow in the ion transfer tube may be increased. Pressure in the ion transfer tube is also reduced and desolvation is increased. In one embodiment, an enclosure surrounds an inner tube of the ion transfer tube within a first vacuum chamber such that the enclosure provides a reduced pressure region within the first vacuum chamber. Overall, transport efficiency is increased.

Description

This application claims priority to a provisional U.S. patent application Ser. No. 60/857,737 by Alexander A. Makarov et al., entitled “ION TRANSFER TUBE WITH SPATIALLY ALTERNATING DC FIELDS”, filed Nov. 7, 2006, the disclosure of which is hereby incorporated herein by reference.

FIELD OF THE INVENTION

This application is directed to ion inlet sections of mass spectrometers, ion transfer tube assemblies, ion transfer tubes, and methods of transporting ions from an atmospheric pressure ion source into a vacuum chamber of a mass spectrometer.

BACKGROUND OF THE INVENTION

Various approaches have been undertaken to increase desolvation and otherwise increase the number of ions introduced into the ion optics of a mass spectrometer from an atmospheric pressure ion source. One typical practice is to heat a capillary tube to increase desolvation of sample liquid droplets and to reduce the size of the droplets from electrospray ionization or chemical ionization sources, for example. U.S. Pat. No. 5,245,186 to Chait et al. teaches heating the capillary tube with a wire. U.S. Pat. No. 4,935,624 to Henion et al. teaches controlled heating of a capillary tube. Others have utilized a counter-flow of heated gas to increase desolvation prior to entry of the spray into the capillary tube.
U.S. Pat. No. 4,977,320 to Chowdhury et al. and others have relied upon the strong flow of gas that accompanies the sample spray through the capillary tube from an atmospheric pressure region into the vacuum region to help focus the droplets toward a center of the capillary tube. U.S. Pat. No. 5,157,260 to Mylchreest et al. teaches use of tube lenses at an exit end of the capillary tube for focusing ions. Others have utilized electrodes at various locations to focus and/or urge ions toward an orifice of a skimmer or other ion optical element to cause ions to enter lower pressure regions of mass spectrometers.
Various techniques for alignment and positioning of the sample spray, capillary tube, and skimmer have been implemented to maximize the number of ions from the source that are actually received into the ion optics of mass spectrometers.
Nevertheless, a majority of the ions generated in the ion source do not survive during transport from the source to the ion optics. Rather, the majority of the ions miss an entrance of the capillary tube, miss an entrance into the ion optics through a narrow orifice, and/or impinge on walls of a capillary tube or nearby plates, and are lost. Thus, there is a need to increase the number of ions from an ambient pressure ion source that are successfully transported through the capillary tube, reach the ion optics, and are transported into the mass spectrometer for analysis.

SUMMARY

In a simple form, an interface for a mass spectrometer in accordance with embodiments of the present invention includes an ion transfer tube having an inlet end opening to a high pressure chamber and an outlet end opening to a low pressure chamber. The high and low pressure chambers may be provided by any regions that have respective higher and lower pressures relative to each other. For example, the high pressure chamber may be an ion source chamber and the low pressure chamber may be a first vacuum chamber. The ion transfer tube has at least one sidewall surrounding an interior region and extending along a central axis between the inlet end and the outlet end. The ion transfer tube has a plurality of passageways formed in the sidewall. The passageways permit the flow of gas from the interior region to a reduced-pressure region exterior to the sidewall.
In another simple form, embodiments of the present invention include an ion transfer tube for receiving and transporting ions from a source in a high pressure region to ion optics in a reduced pressure region of a mass spectrometer. The ion transfer tube includes an inlet end, an outlet end, and at least one sidewall surrounding an interior region and extending along a central axis between the inlet end and the outlet end. The ion transfer tube may also include an integral vacuum chamber tube at least partially surrounding and connected to the ion transfer tube. The integral vacuum chamber tube isolates a volume immediately surrounding at least a portion of the ion transfer tube at a reduced pressure relative to the interior region. The sidewall has a structure that provides at least one passageway formed in the sidewall. The at least one passageway permits a flow of gas from the interior region to the volume exterior to the sidewall. The structure and passageway are inside the integral vacuum chamber tube. The structure of the sidewall may include a plurality of passageways.
In still another simple form, embodiments of the present invention include a method of transporting ions from an ion source region to a first vacuum chamber. The method includes admitting from the ion source region, a mixture of ions and gas to an inlet end of an ion transfer tube. The method also includes removing a portion of the gas through a plurality of passageways located intermediate the inlet end and an outlet end of the ion transfer tube. The method further includes causing the ions and the remaining gas to exit the ion transfer tube through the outlet end into the first vacuum chamber. The method may also include sensing a reduction in latent heat in the ion transfer tube due to at least one of removal of the portion of the background gas and an associated evaporation, and increasing an amount of heat applied to the ion transfer tube through a heater under software or firmware control.
The embodiments of the present invention have the advantage of reduced flow of gas through an exit end of the ion transfer tube. Several associated advantages have also been postulated. For example, the reduced flow through the exit end of the ion transfer tube decreases the energy with which the ion bearing gas expands as it leaves the ion transfer tube. Thus, the ions have a greater chance of traveling on a straight line through an aperture of a skimmer immediately downstream. Also, reduction of the flow in at least a portion of the ion transfer tube may have the effect of increasing the amount of laminar flow in that portion of the ion transfer tube. Laminar flow is more stable so that the ions can remain focused and travel in a straight line for passage through the relatively small aperture of a skimmer. With gas being pumped out through a sidewall of the ion transfer tube, the pressure inside the ion transfer tube is reduced. Reduced pressure can cause increased desolvation. Furthermore, latent heat is removed when the gas is pumped out through the sidewall. Hence, more heat may be transferred through the ion transfer tube and into the sample remaining in the interior region resulting in increased desolvation and increased numbers of ions actually reaching the ion optics.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of an example mass spectrometer with which the embodiments of the present invention may be incorporated.

FIG. 2 is a diagrammatic view of an inlet assembly in accordance with an embodiment of the present invention.

FIG. 3 is a diagrammatic view of an inlet assembly in accordance with another embodiment of the present invention.

FIG. 4 is a diagrammatic partial perspective view of an ion transfer tube in accordance with the embodiment of FIG. 3.

Like reference numerals refer to corresponding parts throughout the several views of the drawings.

DETAILED DESCRIPTION OF EMBODIMENTS

As has been discussed, conventional inlet sections having atmospheric pressure ionization sources suffer from a loss of a majority of the ions produced in the sources prior to the ions entering ion optics for transport into filtering and analyzing sections of mass spectrometers. It is believed that high gas flow at an exit end of the ion transfer tube is a contributing factor to this loss of high numbers of ions. The neutral gas undergoes an energetic expansion as it leaves the ion transfer tube. The flow in this expansion region and for a distance upstream in the ion transfer tube is typically turbulent in conventional inlet sections. Thus, the ions born by the gas are focused only to a limited degree in the ion inlet sections of the past. Rather, many of the ions are energetically moved throughout a volume of the flowing gas. It is postulated that because of this energetic and turbulent flow and the resultant mixing effect on the ions, the ions are not focused to a desirable degree and it is difficult to separate the ions from the neutral gas under these flow conditions. Thus, it is difficult to separate out a majority of the ions and move them downstream while the neutral gas is pumped away. Rather, many of the ions are carried away with the neutral gas and are lost. On the other hand, the hypothesis associated with embodiments of the present invention is that to the extent that the flow can be caused to be laminar along a greater portion of an ion transfer tube, the ions can be kept focused to a greater degree. One way to provide the desired laminar flow is to remove the neutral gas through a sidewall of the ion transfer tube so that the flow in an axial direction and flow out the exit end of the ion transfer tube is reduced. Also, by pumping the neutral gas out of the sidewalls to a moderate degree, the boundary layer of the gas flowing axially inside the ion transfer tube becomes thin, the velocity distribution becomes fuller, and the flow becomes more stable.
One way to increase the throughput of ions or transport efficiency in atmospheric pressure ionization interfaces is to increase the conductance by one or more of increasing an inner diameter of the ion transfer tube and decreasing a length of the ion transfer tube. As is known generally, with wider and shorter ion transfer tubes, it will be possible to transport more ions into the ion optics downstream. However, the capacity of available pumping systems limits how large the diameter and how great the overall conductance can be. Hence, in accordance with embodiments of the present invention, the inner diameter of the ion transfer tube can be made relatively large and at the same time flow out of the exit end of the ion transfer tube can be reduced to improve the flow characteristic for keeping ions focused toward a center of the gas stream. In this way, the neutral gas can be more readily separated from the ions, and the ions can be more consistently directed through the orifice of a skimmer into the ion optics and analyzer sections downstream. The result is improved transport efficiency and increased instrument sensitivity.
Even if it is found in some or all cases, that turbulent flow results in increased ion transport efficiency, it is to be understood that decreased pressure in a downstream end of the ion transfer tube and increased desolvation due to the decreased pressure may be advantages accompanying the embodiments of the present invention under both laminar and turbulent flow conditions. Furthermore, even with turbulent flow conditions, the removal of at least some of the neutral gas through the sidewall of the ion transfer tube may function to effectively separate the ions from the neutral gas. Even in turbulent flow, the droplets and ions with their larger masses will most likely be distributed more centrally during axial flow through the ion transfer tube. Thus, it is expected that removal of the neutral gas through the sidewalls will effectively separate the neutral gas from the ions with relatively few ion losses under both laminar and turbulent flow conditions. Still further, the removal of latent heat by pumping the neutral gas through the sidewalls enables additional heating for increased desolvation under both laminar and turbulent flow conditions.
Accordingly, FIG. 1 shows an example mass spectrometer 12 having an ion source 15 in a source chamber 16 and an interface 18 between the high pressure source chamber 16 and a lower pressure first vacuum chamber 19. The ion source 15 may be, without limitation, an electrospray ionization source, a chemical ionization source, another liquid sample based atmospheric pressure ionization source, or any other source. The interface 18 may include an ion transfer tube portion 21 and an ion guide portion 24 with separate or shared pumping stages. Ions from the source 15 are introduced into the transfer tube portion 21 and move along an ion path generally on a central axis 25 through one or more additional sections to a detector 27. The sections may include one or more of each of ion guides, filters, collision cells, and analyzers, as indicated by q0, Q1, q2, and Q3. The devices in each of these sections may be operated by an electronic controller 30 under software and/or firmware control to perform the needed functions for analysis of sample ions in the mass spectrometer 12.
In the more detailed diagrammatic view of FIG. 2, a skimmer lens 33 separates the ion transfer tube portion 21 from the ion guide portion 24 of the interface 18. As shown, an ion transfer tube 36 may be supported near its entrance end 39 on a chamber wall 42 between the source chamber 16 and the first vacuum chamber 19. While FIG. 2 shows the ion transfer tube 36 with an inlet or entrance end opening in direct communication with the ion source 15, it is to be understood that one or more reduced pressure chambers may be placed intermediate the ion source 15 and the ion transfer tube 36. The one or more reduced pressure chambers may or may not have one or more additional ion transfer tubes therein.
As shown in FIG. 2, sidewall 45 of the ion transfer tube extends axially from the entrance end 39 to an exit end 48 and is surrounded by a heater 51. The heater 51 may be placed in direct contact or otherwise in any kind of thermal contact with the ion transfer tube 36. The skimmer lens 33 may have an aperture positioned proximate to the outlet or exit end 48 of the ion transfer tube 36. A tube lens or other focusing lens 52 may be disposed between the exit end 48 of the ion transfer tube 36 and the skimmer lens 33. An ion guide 54 may be located in a second vacuum chamber 57 downstream from the first vacuum chamber 19. It is to be understood that “vacuum chamber” as used herein may include any reduced pressure chamber or region that has a pressure that is lower than atmospheric pressure. High pressure and low pressure as used herein denote relative pressures in respective regions and are not to be limited to pressures relative to atmospheric or any other threshold pressure. Each of the first and second vacuum chambers 19, 57 may be pumped by the same or separate vacuum pumps as indicated by arrows 58, 59.
Alternatively, an interface 62 in accordance with another embodiment of the invention may include a third vacuum chamber 65 formed integrally as a unit with an ion transfer tube 68, as shown in FIG. 3. Walls create an enclosure that forms the third vacuum chamber 65 and at least partially surrounds an inner tube 71 that may be structurally analogous to the ion transfer tube 36 described with regard to the embodiment of FIG. 2 above. As indicated by arrow 75, a separate pump or a pump in common with pump(s) of one or more of the first and second vacuum chambers 19, 57 may be operably connected with the third vacuum chamber 65 in order to pump gas from within an interior region 74 inside the ion transfer tube 68 out through a sidewall 77 of the ion transfer tube 68. As with the embodiment of FIG. 2, the sidewall 77 of the ion transfer tube 68 extends axially from an entrance end 78 to an exit end 79. Also, the sidewall 77 is surrounded by a heater 51. The heater 51 may be placed in direct contact or otherwise in any kind of thermal contact with the ion transfer tube, as described with regard to the embodiment of FIG. 2.
FIG. 4 is a diagrammatic partial perspective view of the ion transfer tube 68 of FIG. 3. As shown, the inner tube 71 and the interior region 74 may be substantially the same as the ion transfer tube 36 and an interior region thereof, in accordance with the embodiment of FIG. 2. The sidewall 77 has one or more passageways 80 for fluid communication between the interior region 74 and an exterior region within the enclosure created by an enclosure sidewall 83 and enclosure end walls 86, 87, which walls form the third vacuum chamber 65. As shown by arrows 90, neutral gas is pumped from within the interior region 74 and out through the passageways 80 of the sidewall 77 into the third vacuum chamber 65 where it is pumped away. The third vacuum chamber 65 encompasses a reduced-pressure region that is located within the enclosure and extends around the sidewall 77. As may be appreciated by referring back to FIG. 3, the enclosure is disposed within the first vacuum chamber 19 and communicates with a pump 91 that may be separate or in common with other pumps in the system.
Like the embodiment of FIGS. 3 and 4, the ion transfer tube 36 of the embodiment of FIG. 2 may have similar structure in which the sidewall 45 has passageways 80, and the neutral gas is pumped away by a pump in fluid communication with the first vacuum chamber 19. As shown in FIG. 4, a sensor 93 may be connected to the ion transfer tube 68 and to the controller 30 for sending a signal indicating a temperature of the sidewall 77 or some part of the ion transfer tube 68 back to the controller 30. It is to be understood that a plurality of sensors may be placed at different positions to obtain a temperature profile. Thus, the sensor(s) 93 may thus be connected to the ion transfer tube 68 for detecting a reduction in heat as gas is pumped through the plurality of passageways 80 in the sidewall 77 of the ion transfer tube 68. The sensor(s) 93 may also be connected to the ion transfer tube 36 and controller 51 in the embodiment of FIG. 2 for heat reduction detection and control.
With further reference to the embodiment of FIGS. 3 and 4, the third vacuum chamber 65 may be utilized to introduce a flow of gas through the sidewall 71 and into an interior region 74 of the ion transfer tube 68 instead of removing the background gas, as described above. This may be achieved by adjusting the pressure in the third chamber 65 to be between atmospheric pressure and the pressure in the interior region 74. By introducing a flow of gas through passageways 80 into the interior region 74, more turbulent flow conditions may be created in which sample droplets are disrupted. The more turbulent flow conditions may thus cause the sample droplets to be broken up into smaller droplets. This disruption of the droplets is an external force disruption, as opposed to a coulomb explosion type disruption which also breaks up the droplets.
In an application of both external force and coulomb explosion disruption, both removal and addition of gas may be applied in one ion transfer tube. For example, the chamber 65 could be divided into plural regions with respective removal and addition of gas in a series of the plural regions. Thus, an alternating series of external force and coulomb explosion disruptions can be implemented to break up the droplets of the sample.
The sidewall 45 of the ion transfer tube 36 and the sidewall 77 that forms at least a part of the inner tube 71 in the embodiments of FIGS. 1-4 may be formed from a material that includes one or more of a metal frit, a metal sponge, a permeable ceramic, and a permeable polymer. The passageways 80 may be defined by the pores or interstitial spaces in the material. The pores or interstices in the material of the sidewalls may be small and may form a generally continuous permeable element without discrete apertures. Alternatively, the passageways may take the form of discrete apertures or perforations formed in the sidewalls 45, 77 of ion transfer tubes 36, 68. The passageways may be configured by through openings that have one or more of round, rectilinear, elongate, uniform, and non-uniform configurations.
Embodiments of the present invention include a method of transporting ions from a source region into a vacuum region, a method of separating and removing a background gas from a mixture of the background gas and sample ions, and a method of desolvating a sample in an interface. One or more of the methods may include heating the ion transfer tube to promote evaporation of residual liquid solvent admitted into the ion transfer tube. The methods may include the step of removing at least a portion of the gas by providing a reduced-pressure region exterior to an inner tube of the ion transfer tube. The methods may also include sensing a reduction in latent heat in the ion transfer tube due to at least one of removal of the portion of the background gas and an associated evaporation. A subsequent step to sensing may be the step of increasing an amount of heat applied to the ion transfer tube through a heater under software or firmware control.
The methods may include reducing a pressure in at least a portion of the ion transfer tube interior region such that desolvation is increased. The methods may include reducing the energy of a free jet expansion of the gas leaving the outlet or exit end of the ion transfer tube. The methods may also include reducing a velocity of a second downstream portion of the background gas that moves axially out an outlet or exit end of the ion transfer tube relative to a velocity of a first upstream portion of the background gas entering the ion transfer tube. The method may also include increasing a proportion of laminar flow along a length of the ion transfer tube.
The embodiments and examples set forth herein were presented in order to best explain the present invention and its practical application and to thereby enable those of ordinary skill in the art to make and use the invention. However, those of ordinary skill in the art will recognize that the foregoing description and examples have been presented for the purposes of illustration and example only. The description as set forth is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the teachings above without departing from the spirit and scope of the forthcoming claims.

Claims

1. An interface for a mass spectrometer, comprising:

an ion transfer tube having an inlet end opening to an atmospheric pressure chamber, an outlet end opening to a low pressure chamber, and at least one sidewall surrounding an interior region through which is directed a flow of gas and ions, the sidewall extending along a central axis between the inlet end and the outlet end; at least a portion of the sidewall being fabricated from a porous material to permit the flow of gas from the interior region through the sidewall to a reduced-pressure region exterior to the sidewall.

2. The interface of claim 1, wherein the atmospheric pressure chamber comprises an ion source chamber, and the low pressure chamber comprises a first vacuum chamber.

3. The interface of claim 2, wherein the ion source chamber is configured as an electrospray ionization source.

4. The interface of claim 2, wherein the ion source chamber is configured as a chemical ionization source.

5. The interface of claim 2, wherein the reduced-pressure region is located within an enclosure extending around the sidewall, the enclosure being disposed within the first vacuum chamber and communicating with a pump.

6. The interface of claim 1, further comprising a heater in thermal contact with the ion transfer tube.

7. The interface of claim 1, wherein the porous material is at least one of a a permeable ceramic, or a permeable polymer.

8. The interface of claim 1, wherein the porous material is a porous metal.

9. The interface of claim 1, further comprising a skimmer lens having an aperture positioned proximate to the outlet end.

10-17. (canceled)