Patent Application
20150144781
This invention relates generally to ion sources and their methods of operation. More specifically, although not exclusively, the invention relates to electrospray ion sources for use in Mass Spectrometers where the ion source inlet is connected to a chromatography column.
Ion sources for Mass Spectrometers (MS) can be adapted to receive solvents and samples that are eluted from Chromatography systems. The sources are made of particular materials, and designed in particular geometries in order to optimize the efficiency of ionisation and consequently, optimize the transmission of the ions through the ion source and into the mass analysers of the instrument. However, in the early stages of a Liquid Chromatography (LC) experiment, salts, buffers and other potential contaminants may be dissolved in the solvent eluting from the LC, which may be harmful to the efficiency of the ion source, and potentially damaging to the performance of other parts of the Mass Spectrometer if they pass through the ion source into the vacuum chamber.
Currently, this issue is generally solved by having a valve in between the LC and MS source, so that unwanted eluant from the LC system does not enter the ion source of the MS, instead the eluant passes to waste. However, the valves are costly, and stopping the flow of the eluant through the connective tubing may potentially lead to blockages in the tubing and ion source inlet system. Furthermore, an in-line valve may also cause dispersion, increasing the peak width, and so compromise the LC's ability to separate samples.
Therefore, it is a non-exclusive object of the invention to provide an improved method of control of the supply of ions, and an improved ion source for use in an LC-MS instrument and more specifically to provide an alternative method of regulating the flow of ions from the ion source into the MS vacuum assembly that overcomes or at least mitigates the problems associated with the prior art methods and systems.
According to a first aspect of the invention, a method for controlling the supply of ions from a Liquid Chromatograph (LC) through an ion source and into a Mass Spectrometer (MS) is provided. The method comprises the steps of operating the ion source in a first mode where eluant produced in the LC passes through a probe into a source volume but is prevented from entering an inlet of the MS in an ionized form, changing one or more operating parameters of the ion source and operating the ion source in a second mode where at least some ions are produced in said ion source and pass through said MS inlet into the MS.
It would be appreciated that the method may comprise changing the one or more operating parameters to switch the ion source from the first mode to the second mode and/or from the second mode to the first mode.
In a preferred embodiment, a first voltage is applied to the ion source probe in the first mode, and a second voltage is applied to the ion source probe in the second mode, wherein the second voltage may be higher than the first voltage. Preferably the first voltage is between 0 and 0.5 kV, more preferably between 0 and 0.2 kV, most preferably substantially equal to zero. Preferably, the second voltage is between 0.5 and 7 kV, more preferably between 1 and 5 kV and most preferably between 2 and 4 kV.
In one embodiment of the present invention, a first nebulizer gas flow is emitted (applied) at the exit of the probe in the first mode and a second nebulizer gas flow is emitted (applied) at the exit of the probe in the second mode, wherein the second nebuliser gas flow may be greater than the first nebuliser gas flow. Preferably the first nebulizer gas flow is between 0 and 10 L/hr, but most preferably substantially equal to zero. Preferably, the second nebulizer gas flow is between 50 and 500 L/hr, more preferably between 70 and 300 L/hr and most preferably between 100 and 200 L/hr.
In another embodiment of the invention, a first cone gas flow is directed (applied) along the sampling cone in the first mode and a second cone gas flow is directed (applied) along the sampling cone in the second mode, wherein the second cone gas flow may be less than the first cone gas flow. Preferably, the first cone gas flow is between 100 and 1200 L/hr, more preferably between 100 and 600 L/hr and most preferably between 250 and 500 L/hr. Preferably, the second cone gas flow is between 0 and 200 L/hr, but most preferably between 0 and 100 L/hr.
In one embodiment of the invention, the step of changing one or more operating parameters is performed (e.g. changing from the first mode to the second mode) when compounds of interest are present or detected in the eluant produced in said LC.
In a preferred embodiment of the invention, the ion source is operated in the first mode upon the start of a LC run and in the second mode upon elution of compounds of interest from said LC.
In the preferred embodiment, the method includes providing an ion source, for example that is adapted and arranged to perform the method.
In a further aspect of the invention an ion source for use between a Liquid Chromatograph (LC) and a Mass Spectrometer (MS) is provided, preferably configured for use in performing the above method. The ion source comprises a sample inlet for receiving eluant from a LC, a probe in fluidic communication with the sample inlet, an ion outlet in communication with or corresponding to an inlet of a MS and a source volume between the sample inlet and the ion outlet, wherein the ion source is operable, in use, between a first mode in which eluant received from the LC passes through the probe into the source volume but is substantially prevented from entering an inlet of the MS in an ionized form and a second mode in which ions are produced in the ion source and pass through the ion outlet and into the MS.
In one embodiment of the invention the ion source is an electrospray ion source.
In a further embodiment of the invention, the ion source is an impaction spraying ion source.
In this embodiment, preferably, in the second mode of operation, a voltage may be applied to an impact surface, preferably the impact surface of a pin. In a less preferred embodiment, no voltage may be applied to the surface, and ionisation may still occur, however ionisation may be less efficient.
In this embodiment, preferably, in the first mode of operation there is no nebuliser gas flow around the ion source probe.
In this embodiment, preferably, in the first mode of operation, the eluant may miss the surface, and pass to the base of the ion source, to be collected in a drain.
In a less preferred aspect of this embodiment, the LC eluant may drop onto the surface. In this instance, very little, or no ionisation will occur.
In this embodiment, preferably, the voltage applied to the surface may be switched off.
In this embodiment, preferably, in first mode of operation, the desolvation gas flow, arranged to flow from a heater positioned around the ion source probe to allow desolvation of the droplets, may be switched off.
In this embodiment, in the first mode of operation, the cone gas flow directed along the sampling cone, into the ionization volume, is preferably increased in strength to ensure that substantially none of the LC eluant not of interest to the user can pass through the sample cone into the instrument in the first mode.
In a preferred embodiment the ion source further comprises a drain for removing LC eluant, which has not been ionized and passed through the ion inlet, from the source volume.
In a further aspect, a Mass Spectrometer comprising an ion source as described is provided.
In a further aspect, a Liquid Chromatograph in combination with a Mass Spectrometer and an ion source is provided.
In one aspect, a control system operable or programmed to execute a method as described herein is provided.
One aspect of the invention provides a computer program element comprising computer readable program code means for causing a processor to execute a procedure to implement the method described herein.
In a further aspect, a computer program element is provided comprising computer readable program code means for causing a processor to execute a method as described herein.
A further aspect provides a computer readable medium embodying the computer program element described herein.
One aspect provides a computer readable medium having a program stored thereon, where the program is to make a computer execute a procedure to implement the method as described herein.
Embodiments of the invention will now be described by way of example only with reference to the accompanying drawings in which:
Turning to
The desolvation gas flow, arranged to flow from a heater 60 positioned around the ion source probe 52 to allow desolvation of the droplets, optionally could be switched off.
In the most preferred embodiment, in the first mode, the cone gas flow directed along the sampling cone 56, into the ionization volume 54 would be increased in strength to ensure that none of the LC eluant not of interest to the user can pass through the sample cone into the instrument.
A desolvation gas flow is arranged to flow from a heater 60 which is positioned around the ion source probe 52 and the gas flow is heated by the heater 60 to aid desolvation of the droplets of solvent within the spray. A cone gas flow is directed along the sampling cone 56, into the ionization volume 54 which aids desolvation and reduces surface contamination of the sampling cone 56.
The desolvation gas flow, arranged to flow from a heater 60 positioned around the ion source probe 52 to allow desolvation of the droplets optionally could be switched off.
In the most preferred embodiment, the cone gas flow directed along the sampling cone 56, into the ionization volume 54 would be increased in strength to ensure that none of the LC eluant not of interest to the user can pass through the sample cone 56 into the instrument in the first mode.
After a time, the elution of solvent with salts, buffers and other potential contaminants from the LC column may have stopped (or at least reduced to below an acceptable threshold). At a time when the solvent may contain sample of interest, the ion source 50 is preferably configured to operate in the second mode, as described with relation to
A desolvation gas flow is arranged to flow from a heater 60 which is positioned around the ion source probe 52 and the gas flow is heated by the heater 60 to aid desolvation of the droplets of solvent within the spray. A cone gas flow is directed along the sampling cone 56, into the ionization volume 54 which aids desolvation and reduces surface contamination of the sampling cone 56.
In some embodiments of the invention, the voltage applied to the ion source probe 52 is set to zero in the first mode. This would prevent ionization of the sample.
In some embodiments of the invention the nebuliser gas flow is set to zero in the first mode, which would prevent a spray from forming from the ion source probe 52 as sample flows through the ion source probe 52.
In some embodiments of the invention, the cone gas flow may be increased in the first mode relative to the second mode to prevent sample emitted from the ion source probe 52 to be allowed through the sample cone 56 and into the Mass Spectrometer.
Additionally, or alternatively, any combination of the above features, and/or embodiments of the invention may be used to prevent sample from ionizing and entering the vacuum chamber of the Mass Spectrometer.
In a most preferred embodiment, in the first mode, the voltage applied to the ion source probe 52 is set to zero and, the nebuliser gas flow is set to zero, which would prevent a spray from forming from the ion source probe 52 as sample flows from the ion source probe 52. Furthermore, in the first mode the cone gas flow may be increased to prevent sample emitted from the ion source probe 52 to be allowed through the sample cone 56 and into the Mass Spectrometer.
Table 1 gives most preferred, and possible ranges of values for the capillary voltage, the nebulizer gas flow rate, and cone gas flow rate in both the first and the second modes according to the invention.
It would be apparent to a person skilled in the art that the source apparatus could be switched between the first mode and the second mode automatically by the control apparatus of the LCMS system at pre-determined times within the LCMS run. In a less preferred embodiment, a user could control the switching between modes.
In an alternative embodiment of the invention, a further detector may be used to identify and automatically detect the point at which samples of interest start to elute from the LCMS instrument in order to guarantee that no useful LC eluant from the Liquid Chromatography system is lost. This may take the form of, for example, a UV, or IR spectrometer.
In a further embodiment the ion source 50 may be switched from the second, ionization enabled mode to said first, non-ionizing, mode at known retention times when any unwanted ions may be known, or anticipated, to be eluting from the sample.
In the second mode of operation, no voltage may be applied to the surface 73, and ionisation may still occur, however ionisation may be less efficient.
In the first mode of operation, where no ions are formed, there is no nebuliser gas flow around the ion source probe 72. The LC eluant will not spray from the ion source probe 72.
In one embodiment, the LC eluant may drop onto the surface 73 (as might occur with the arrangement shown in
In another, preferred, embodiment, in the first mode of operation, the eluant may miss the surface 73, and pass to the base of the ion source, to be collected in a drain 75.
In one embodiment in this first mode of operation, the voltage upon the surface 73 may be switched off.
In a further embodiment of this first mode of operation, the desolvation gas flow, arranged to flow from a heater 80 positioned around the ion source probe 72 to allow desolvation of the droplets could be switched off.
In a further embodiment of this first mode of operation, the cone gas flow directed along the sampling cone 76, into the ionization volume 74 would be increased in strength to ensure that none of the LC eluant not of interest to the user can pass through the sample cone into the instrument in the first mode.
A method of analysis of a sample is also envisaged, where a sample is injected into a Liquid Chromatography system. Initially, the ion source 50 (or 70) will be set in a first mode, such that no ions are formed, and LC eluant is not passed through the sample cone 56, and into the Mass Spectrometer's analysis system. This prevents salts, impurities and other contaminants from entering the Mass Spectrometer's vacuum systems, so that they do not impair the results of the instrument due to contaminating the sample cone 56 (or 76), or the internal workings of the Mass Spectrometer's ion optical devices. In one embodiment, a solvent delay time is set by the user, this period should be long enough to allow the LC eluant that may contaminate the sample to pass through the LC and MS systems, but short enough so that the first eluted samples have not passed through the instrument.
Once the solvent delay time has expired, the ion source 50 (or 70) is switched to the second, ionization enabled mode where the voltage within the ion source 50 (or 70), the nebuliser gas flow and the cone gas flow can be set to provide ionization, so that ions will enter the Mass Spectrometer through the sample cone 56 (or 76) for analysis.
In a preferred embodiment in the second mode, the voltage on the ion source probe 52, the nebuliser gas flow and the cone gas flow optimized to allow as high ionization efficiency as possible.
It will be appreciated by those skilled in the art that any number of combinations of the aforementioned features and/or those shown in the appended drawings provide clear advantages over the prior art and are therefore within the scope of the invention described herein.
Any ranges quoted herein are inclusive.
| Number | Date | Country | Kind |
|---|---|---|---|
| 1211048.2 | Jun 2012 | GB | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/GB2013/051575 | 6/17/2013 | WO | 00 |
