Dynamic resolution correction of quadrupole mass analyser

Abstract

A method of mass spectrometry is disclosed comprising automatically correcting the mass or mass to charge ratio resolution of a quadrupole mass filter or mass analyser one or more times during an experimental run or acquisition based upon a measurement, determination or estimation of the mass or mass to charge ratio resolution of one or more reference ions observed in a mass spectrum or mass spectral data acquired either during the same experimental run or acquisition or during a previous experimental run or acquisition.

Claims

1. A method of correcting mass or mass to charge ratio resolution drift of a quadrupole mass filter or mass analyser, said method comprising: automatically measuring a parameter during an experimental acquisition; and automatically correcting the mass or mass to charge ratio resolution of said quadrupole mass filter or mass analyser one or more times during said experimental acquisition in response to said measured parameter; wherein said parameter comprises an environmental parameter, temperature, humidity, ion current and/or space charge.

2. A method as claimed in claim 1, wherein said parameter comprises temperature and/or humidity.

3. A method as claimed in claim 1, wherein said parameter comprises a signal output from an electronic control unit.

4. A method as claimed in claim 1, wherein said step of automatically correcting the mass or mass to charge ratio resolution of said quadrupole mass filter or mass analyser comprises automatically altering a resolving DC offset voltage and/or a gain of said quadrupole mass filter or mass analyser.

5. A method as claimed in claim 1, wherein said step of automatically correcting the mass or mass to charge ratio resolution of said quadrupole mass filter or mass analyser comprises automatically altering the energy of ions passing to said quadrupole mass filter or mass analyser.

6. A method as claimed in claim 1, wherein said step of automatically correcting the mass or mass to charge ratio resolution of said quadrupole mass filter or mass analyser comprises automatically altering one or more voltages applied to a pre-filter arranged upstream of said quadrupole mass filter or mass analyser.

7. A method as claimed in claim 1, wherein said step of automatically correcting the mass or mass to charge ratio resolution of said quadrupole mass filter or mass analyser comprises automatically altering one or more voltages applied to a post-filter arranged downstream of said quadrupole mass filter or mass analyser.

8. A method as claimed in claim 1, further comprising acquiring mass spectral data during said experimental acquisition and correcting the mass position, mass accuracy or recalibrating or realigning the mass or mass to charge ratio of said mass spectral data.

9. A method as claimed in claim 8, wherein said step of correcting the mass position, mass accuracy or recalibrating or realigning the mass or mass to charge ratio of said mass spectral data is performed dynamically during said experimental acquisition and comprises automatically varying one or more voltages applied to said quadrupole mass filter or mass analyser.

10. A method as claimed in claim 8, wherein said step of correcting the mass position, mass accuracy or recalibrating or realigning the mass or mass to charge ratio of mass spectral data is performed as an automatic post-processing step.

11. A method as claimed in claim 8, further comprising acquiring further mass spectral data to confirm that the step of correcting the mass position, mass accuracy or recalibrating or realigning the mass or mass to charge ratio of mass spectral data was successful.

12. A method as claimed in claim 1, further comprising acquiring mass spectral data to confirm that the step of automatically correcting the mass or mass to charge ratio resolution of said quadrupole mass filter or mass analyser was successful.

13. A mass spectrometer comprising: a quadrupole mass filter or mass analyser; and a control system arranged and adapted: (i) to measure a parameter during an experimental acquisition; and (ii) to correct the mass or mass to charge ratio resolution of said quadrupole mass filter or mass analyser one or more times during said experimental acquisition in response to said measured parameter; wherein said parameter comprises an environmental parameter, temperature, humidity, ion current and/or space charge.

14. A mass spectrometer as claimed in claim 13, wherein said parameter comprises temperature and/or humidity.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Various embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying drawings in which:

(2) FIG. 1 illustrates three different scan lines for a quadrupole mass filter or mass analyser and the corresponding mass resolution of mass peaks when the quadrupole follows the different scan lines;

(3) FIG. 2 shows a flow chart illustrating the process of correcting the mass resolution of a quadrupole mass analyser in real time; and

(4) FIG. 3 shows a flow chart of a more complex mass resolution correction method wherein the mass or mass to charge ratio of the ions may also be recalibrated.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

(5) FIG. 1 illustrates stability diagrams for three ions (having three different mass to charge ratios) within a quadrupole rod set mass filter/analyser. The three different ions are observed as three mass peaks (Mass 1, Mass 2, Mass 3) in corresponding mass spectra.

(6) FIG. 1 also shows three different scan lines (a), (b) and (c) for the quadrupole mass filter/analyser. The scan lines (a), (b) and (c) illustrate different instrument settings for the quadrupole mass filter/analyser. FIG. 1 also shows the profile of resulting mass peaks which are obtained for each of the different scan lines (a), (b) and (c). It will be apparent that the mass resolution of the mass peaks observed in a mass spectrum is dependent upon the scan line which is followed and hence is dependent upon the instrument setting of the quadrupole mass filter/analyser.

(7) The three overlapping stability diagrams for the three different mass peaks which are shown in FIG. 1 comprise three regions which represent those areas which correspond to stable solutions to Mathieu's differential equation and hence represent solutions wherein ions have a stable trajectory through the quadrupole mass analyser. The three scan lines (a), (b) and (c) are indicated by dashed lines.

(8) It will be apparent that scan line (a) intersects the three regions representing stable trajectory so that there is only a small region above the scan line (a). Scan line (a) illustrates a mode of operation wherein the quadrupole mass filter/analyser is being operated in a narrow bandpass mode of operation. As a result, the resulting mass resolution as illustrated by the sharp peak shapes in FIG. 1(a) will be high.

(9) Scan line (b) has a lower gradient that scan line (a) and intersects the three regions so that there is a larger region above the scan line (b) compared with the situation with scan line (a). Scan line (b) illustrates a mode of operation wherein the quadrupole mass filter/analyser is being operated in a wider bandpass mode of operation compared with scan line (a). The resulting mass resolution as illustrated by the wider peak shapes in FIG. 1(b) indicates that the mass resolution is lower than that obtained when scan line (a) is followed.

(10) Scan line (c) has a lower gradient that scan line (b) and intersects the three regions so that there is a larger region above the scan line (c) compared with the situation with scan line (b). Scan line (c) illustrates a mode of operation wherein the quadrupole mass filter/analyser is being operated in a wider bandpass mode of operation compared with scan line (b). The resulting mass resolution as illustrated by the wider peak shapes in FIG. 1(c) indicates that the mass resolution is lower than that obtained when scan line (b) is followed.

(11) It will be understood that the scan lines (a), (b) and (c) shown in FIG. 1 have been exaggerated in order to illustrate aspects of the present invention.

(12) According to a preferred embodiment of the present invention lock mass, reference or calibration ions are periodically sampled and mass analysed by a quadrupole rod set mass analyser. A control system is arranged to analyse (e.g. by peak shape matching or profiling) the resolution of the mass or ion peaks observed in a mass spectrum or more generally in mass spectral data. The control system then determines the effective (instantaneous) resolution of the quadrupole mass filter or mass analyser. The control system then preferably alters one or more parameters of the quadrupole mass filter or mass analyser in order to maximise the resolution of the quadrupole mass filter or mass analyser. According to an embodiment the quadrupole mass filter or mass analyser is arranged to alter the ratio of the DC voltage to the RF voltage applied to the quadrupole mass filter/analyser. Varying the ratio of the DC voltage to the RF voltage applied to the quadrupole mass filter/analyser can have the effect of either altering the intercept of the scan lines shown in FIG. 1 and/or altering the gradient of the scan lines shown in FIG. 1. According to the preferred embodiment the intercept and/or gradient of the scan lines are altered so as to ensure that the mass or mass to charge ratio resolution of the quadrupole is set or maintained as high as possible.

(13) The preferred embodiment is therefore particularly advantageous in that the control system of a mass spectrometer preferably repeatedly monitors the resolution of a quadrupole mass filter/analyser during an experimental acquisition and preferably automatically and dynamically ensures that the resolution of the quadrupole mass filter/analyser is maintained as high as possible and is effectively prevented from drifting during an acquisition or between acquisitions.

(14) An embodiment of the present invention will now be described with reference to the flow chart shown in FIG. 2 which details the steps followed in a basic mass resolution correction method. According to the preferred embodiment lock mass data is acquired as a first step 1. The acquisition of lock mass data preferably involves sampling lockmass, reference or calibration ions using a quadrupole rod set mass analyser. The mass resolution of the lockmass, reference or calibration ions is then determined in a second step 2. For example, the profile of one or more ion or mass peaks in a mass spectrum or mass spectral data may be analysed by peak matching techniques and the resolution of the ion or mass peaks may be determined. If it is determined that the resolution of the quadrupole mass filter/analyser is sub-optimal, then a required correction is preferably calculated as a third step 3 and the correction is then preferably implemented as a fourth step 4. Implementation of the correction may involve altering the DC and/or RF voltages applied to the quadrupole rod set mass filter/analyser.

(15) A further embodiment of the present invention will now be described with reference to FIG. 3. According to the preferred embodiment if a user requests automatic mass resolution correction 5, then lock mass data is preferably acquired 6. A determination is then made 7 as to whether or not the data is within acceptable parameters. In particular, a determination is made as to whether or not the resolution of ion or mass peaks observed in a mass spectrum or mass spectral data is sufficiently high. If the data is not within acceptable parameters then a mass resolution correction is calculated and applied 8 to the quadrupole rod set mass filter/analyser. If the data is within acceptable parameters then no mass resolution correction is calculated or applied to the quadrupole rod set mass filter/analyser. After the quadrupole mass filter/analyser has been automatically corrected (if applicable) to improve the mass resolution of the quadrupole mass filter/analyser, mass position correction (or mass accuracy) may then additionally be corrected for. Mass position (or mass accuracy) correction involves realigning or recalibrating the mass or mass to charge ratio axis of a mass spectrum or mass spectral data. According to the preferred embodiment if mass position correction has been requested by a user 9, then further lock mass data is acquired 10 and a mass position (or mass accuracy) correction is preferably calculated and applied 11 to the data. Once the quadrupole mass filter/analyser has been corrected for mass resolution drift and has optionally also been corrected for mass position or mass accuracy, then further experimental mass spectral data is then preferably acquired 12.

(16) Although the present invention has been described with reference to the preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.