Dynamic ion filtering for reducing highly abundant ions

Abstract

The present disclosure includes a computer-implemented method for filtering out at least one selected ion from an ion beam by the following steps: determining the selected ion with a selected ion mass, selected charge and/or selected mass to charge ratio; determining at least one predefinable region with predefinable ions, whose ion masses, charges and/or mass to charge ratios are greater than or smaller than the selected ion mass, the selected charge and/or the selected mass to charge ratio of the selected ion; isolating the predefinable region of the ion beam along a trajectory of the ion beam, and detecting the predefinable ions within the predefinable region. In addition, the present disclosure includes to a computer program which is configured to perform a method according to the present disclosure and to a computer program product having the computer program.

Claims

1. A computer-implemented method for increasing a sensitivity of a mass spectrometer, the method comprising: selecting an ion from an ion beam, the selected ion having a selected ion mass, selected charge, and/or selected mass-to-charge ratio for which an intensity in a mass spectrum exceeds a limit value; filtering the selected ion from the ion beam, the filtering comprising: defining a portion of the ion beam comprising other ions whose ion masses, charges and/or mass-to-charge ratios are greater or less than the selected ion mass, the selected charge and/or the selected mass-to-charge ratio of the selected ion, respectively; isolating the other ions of the defined portion of the ion beam along a trajectory of the ion beam, wherein the selected ion is stopped along the trajectory using a first ion trap; and enriching or depleting the other ions using a second ion trap; and detecting the other ions within the defined portion of the ion beam using a detector of the mass spectrometer.

2. The method of claim 1, wherein: the defined portion includes a first portion and a second portion; the first portion includes other ions whose ion masses, charges and/or mass-to-charge ratios are greater than the selected ion mass, the selected charge and/or the selected mass-to-charge ratio of the selected ion, respectively; and the second portion includes other ions whose ion masses, charges and/or mass-to-charge ratios are less than the at least one selected ion mass, the selected charge and/or the selected mass-to-charge ratio of the selected ion, respectively.

3. The method of claim 1, wherein the masses, charges, mass-to-charge ratios and/or intensities of ions of the ion beam are determined, or wherein the masses, charges, mass-to-charge ratios and/or intensities of the other ions comprising the defined portion are determined.

4. The method of claim 1, wherein at least one mass spectrum of the ion beam and/or of the defined portion is generated.

5. The method of claim 4, wherein the selected ion is selected at least based on the at least one mass spectrum and/or on an ion mass, a charge, a mass-to-charge ratio and/or an intensity, or wherein the selected ion is selected based on a list.

6. The method of claim 1, wherein substantially all ions outside the defined portion are deflected from the trajectory.

7. The method of claim 1, wherein substantially all ions outside the defined portion are stopped along the trajectory.

8. The method of claim 1, wherein an enrichment factor or depletion factor is determined.

9. The method of claim 1, wherein the other ions of the defined portion are enriched or depleted with a predefinable enrichment factor or with a predefinable depletion factor.

10. The method of claim 1, wherein, substantially, only the selected ion with the selected ion mass, charge, and/or mass-to-charge ratio is removed from the ion beam.

11. The method of claim 1, wherein the selected ion includes at least two different selected ions, each having a selected ion mass, charge, and/or mass-to-charge ratio, and wherein the at least two different selected ions are determined.

12. A non-transitory computer-readable medium for increasing a sensitivity of a mass spectrometer, comprising instructions thereon, that when executed by a computer, cause the computer to perform the method according to claim 1.

13. The method of claim 1, wherein, substantially, only the selected ion with the selected ion mass, charge, and/or mass-to-charge ratio is deflected from the ion beam.

14. A method for increasing a sensitivity of a mass spectrometer, the method comprising: selecting an ion from an ion beam, the selected ion having a selected ion mass, selected charge, and/or selected mass-to-charge ratio for which an intensity in a mass spectrum exceeds a limit value; filtering the selected ion from the ion beam, the filtering comprising: defining a portion of the ion beam comprising other ions whose ion masses, charges and/or mass-to-charge ratios are greater or less than the selected ion mass, the selected charge and/or the selected mass-to-charge ratio of the selected ion; isolating the other ions of the defined portion of the ion beam along a trajectory of the ion beam, wherein the selected ion is removed from the defined portion of the ion beam using ion optics, or wherein the selected ion is stopped along the trajectory using a first ion trap; and enriching or depleting the other ions using a second ion trap; and detecting the other ions within the defined portion of the ion beam using a detector of the mass spectrometer, wherein: the defined portion includes a first portion and a second portion; the first portion includes other ions whose ion masses, charges and/or mass-to-charge ratios are greater than the selected ion mass, the selected charge and/or the selected mass-to-charge ratio of the selected ion, respectively; and the second portion includes other ions whose ion masses, charges and/or mass-to-charge ratios are less than the at least one selected ion mass, the selected charge and/or the selected mass-to-charge ratio of the selected ion, respectively.

15. The method according to claim 14, wherein the first portion and second portion are isolated and detected successively.

16. The method according to claim 14, wherein the first portion and second portion are isolated one after the other, collected in the second ion trap, and subsequently detected together.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The present invention will now be explained in greater detail with reference to the following figures. Identical elements in the figures are given the same reference symbols. Shown are:

(2) FIG. 1 shows a first, schematically represented, embodiment of a method according to the present disclosure, in which the ions outside the predefinable region are deflected from the trajectory;

(3) FIG. 2 shows a second, schematically represented, embodiment of a method according to the present disclosure, in which the ions outside the predefinable region are stopped along the trajectory; and

(4) FIGS. 3a-3d show schematically represented mass spectra (a) before and (b-d) after the filtering out of selected ions from the ion beam in question.

DETAILED DESCRIPTION

(5) FIG. 1 schematically illustrates a first possible embodiment of the method according to the invention. An ion beam 1 contains different ions with different ion masses m.sub.1-m.sub.3. The ions can also differ in terms of their charges z.sub.1-z.sub.3 and/or mass-to-charge ratios m.sub.1/z.sub.1-m.sub.3/z.sub.3. For the sake of simplicity, however, the following description relates only to three different ions contained in the ion beam 1 and having ion masses m.sub.1-m.sub.3. The considerations can be applied in each case mutatis mutandis with regard to the charges z.sub.1-z.sub.3 and/or mass-to-charge ratios m.sub.1/z.sub.1-m.sub.3/z.sub.3.

(6) The ion beam 1 can be generated by any ionization process known from the prior art. In reality, an ion beam 1 contains a plurality of different ions and ion fragments. The three different ions m.sub.1, m.sub.2, m.sub.3 are accordingly to be understood as examples.

(7) According to the invention, at least one ion is selected—here, the ion m.sub.1 in the ion beam 1. In addition, at least one predefinable region B.sub.1, which does not contain the selected ion m.sub.1, is determined. In the present case, the predefinable region B.sub.1 contains the ions with the ion masses m.sub.2 and m.sub.3.

(8) The predefinable region B.sub.1 is then isolated along its trajectory F by the selected ion or ions with the ion mass m.sub.1 in the ion beam 1 being deflected (2) from the trajectory F. Deflection of the ions can be effected, for example, by means of suitable ion optics.

(9) The selected ions m.sub.1 can be determined according to one of the previously described embodiments, e.g., on the basis of their intensity within a mass spectrum of the ion beam 1. The non-deflected ions m.sub.2 and m.sub.3 within the region B.sub.1 can then finally be detected by means of a detector 3. The detector 3 can also be any detector known from the prior art.

(10) In addition to individual selected ions with ion masses m.sub.1, it is likewise possible for selected ions within selected ranges for the ion masses, charges, and/or mass-to-charge ratios to be deflected as a whole from the trajectory F.

(11) FIG. 2 schematically illustrates a further embodiment of the method according to the invention. Also, in the case of FIG. 2, the ion m.sub.1 in the ion beam 1 is selected, and the predefinable region B.sub.1, which does not contain the selected ion m.sub.1, is determined. In the present case, the predefinable region B.sub.1 also contains the ions with the ion masses m.sub.2 and m.sub.3.

(12) In contrast to FIG. 1, according to FIG. 2, in order to isolate the predefinable region B.sub.1, the selected ion with ion mass m.sub.1 in the ion beam 1 is stopped (4) along the trajectory F. For this purpose, an ion trap can be used, for example, which is designed such that the selected ion with ion mass m.sub.1 in the ion beam 1 remains along the trajectory F in the ion trap 4. The non-deflected ions with the ion masses m.sub.2 and m.sub.3 within the region B.sub.1 can then finally be detected by means of the detector 3.

(13) As in the case of FIG. 1, the selected ions with ion masses m.sub.1 can be determined according to one of the previously described embodiments—for example, on the basis of their intensity within a mass spectrum of the ion beam 1. In the case of FIG. 2 as well, the detector 3 can be any detector known from the prior art.

(14) In addition to the embodiment in FIG. 1, the device 1 according to FIG. 2 comprises a further ion trap 5, which is arranged in front of the detector 3. The ions with the ion masses m.sub.2 and m.sub.3 within the predefinable region B.sub.1 are enriched or depleted in the ion trap 5 before they impinge on the detector 3.

(15) A schematic illustration of the method according to the invention is the subject matter of FIG. 3. Different mass spectra are there shown over the respective, full available range of the mass-to-charge ratios I(m/z). Furthermore, the ions selected in each case are, for the purposes of FIG. 3, selected on the basis of their mass-to-charge ratios m.sub.x/z.sub.x.

(16) In the mass spectrum shown in FIG. 3a, ions with the mass-to-charge ratio m.sub.1/z.sub.1 can be identified. In other words, for ions with the mass-to-charge ratio m.sub.1/z.sub.1, the mass spectrum has an intensity I above the sensitivity limit d.sub.L of the mass spectrometer with which the mass spectrum was created. Ions with other mass-to-charge ratios m.sub.x/z.sub.x are not identifiable due to their low concentrations within the ion beam 1.

(17) To carry out the method according to the invention, the ions with the mass-to-charge ratio m.sub.1/z.sub.1 are selected and filtered out or removed from the ion beam 1. For this purpose, a filter window F.sub.1, containing the mass-to-charge ratio m.sub.1/z.sub.1, or a selected range containing the mass-to-charge ratio m.sub.1/z.sub.1 can, for example, be determined that contains selected ions. However, it is also possible to select only ions with a mass-to-charge ratio m.sub.1/z.sub.1.

(18) Next, a first predefinable region B.sub.1 is determined that contains ions with mass-to-charge ratios m.sub.x/z.sub.x which are smaller than the mass-to-charge ratio m.sub.1/z.sub.1. In the present case, the first predefinable region B.sub.1 comprises all ions with mass-to-charge ratios m.sub.x/z.sub.x<m.sub.1/z.sub.1. However, this is not absolutely necessary. The first predefinable region B.sub.1 can also be a portion of the ions with mass-to-charge ratios m.sub.x/z.sub.x<m.sub.1/z.sub.1. According to FIG. 3a, a second predefinable region B.sub.2 is also determined, which contains ions with mass-to-charge ratios m.sub.y/z.sub.y, where m.sub.1/z.sub.1<m.sub.y/z.sub.y.

(19) In other embodiments, only a single predefinable region B.sub.1 can also be determined. Likewise, more than two predefinable regions B.sub.1 and B.sub.2 can also be determined. All of these cases are also covered by the present invention. Each predefinable region B.sub.x contains predefinable ions with at least one predefinable mass-to-charge ratio m.sub.x/z.sub.x. However, it should be noted that the respective selected ions and predefinable regions can also be determined in other ways—for example, on the basis of ion masses, charges, and/or intensities.

(20) In the case of FIG. 3, the first and second regions B.sub.1 and B.sub.2 of the ion beam 1 are isolated from the remaining parts of the ion beam 1 for the purpose of filtering. This can be done, for example, using one of the embodiments shown in FIG. 1 or 2. The filter pattern used in FIG. 3a here comprises the filter window F.sub.1.

(21) The result of the filtering is shown in FIG. 3b. By the removal of the selected ions having a mass-to-charge ratio m.sub.1/z.sub.1, the sensitivity limit d.sub.L has been significantly reduced, so that, now, even the ions with the mass-to-charge ratios of m.sub.3/z.sub.3 and m.sub.5/z.sub.5 are detectable due to the downward shift in the dynamic sensitivity range d.sub.L. However, the intensities of the ions with mass-to-charge ratios m.sub.2/z.sub.2, m.sub.4/z.sub.4, and m.sub.6/z.sub.6—shown as dashed lines—still lie below the sensitivity limit d.sub.L.

(22) In order to be able to detect these ions as well, additional or further filtering must be carried out. For example, several selected ions can be removed from the ion beam 1 in a filtering process. Alternatively, multiple filtering operations may be performed sequentially with respect to different selected ions. This is also the case in FIGS. 3c and 3d.

(23) In order to be able to detect even less concentrated substances, such as the ions with the mass-to-charge ratios m.sub.2/z.sub.2, m.sub.4/z.sub.4, or m.sub.6/z.sub.6, according to FIG. 3c, ions with the mass-to-charge ratios m.sub.3/z.sub.3 and m.sub.5/z.sub.5 are selected, and three further predefinable regions B.sub.3-B.sub.5 determined. Furthermore, the filter windows F.sub.2 and F.sub.3 can be determined on the basis of the selected ions. The third predefinable region B.sub.3 includes, in the example shown, ions with mass-to-charge ratios to which m.sub.x/z.sub.x<m.sub.3/z.sub.3 applies. The fourth predefinable region B.sub.4 contains ions with mass-to-charge ratios to which m.sub.3/z.sub.3<m.sub.x/z.sub.x<m.sub.5/z.sub.5 applies, and the fifth predefinable region B.sub.5 contains ions with mass-to-charge ratios to which m.sub.x/z.sub.x>m.sub.5/z.sub.5 applies.

(24) After the isolation of the predefinable regions B.sub.3-B.sub.5, the ions with the mass-to-charge ratios of m.sub.2/z.sub.2, m.sub.4/z.sub.4, or m.sub.6/z.sub.6 are also clearly detectable, as illustrated in FIG. 3d.

(25) It should be noted that, for the isolation and detection of the predefinable regions B.sub.1-B.sub.5, in the case of more than one predefinable region, a wide variety of possibilities are conceivable and fall under the present invention. The predefinable regions B.sub.1-B.sub.5 can, for example, be isolated and detected successively or simultaneously. The individual regions can also be isolated one after the other and collected, but then detected together.

(26) Depending upon the application, using the method according to the invention, suitable filter patterns can be conceived which filter out selected ions with a mass-to-charge ratio m.sub.x/z.sub.x or ions of selected ranges for selected mass-to-charge ratios m.sub.x/z.sub.x-m.sub.y/z.sub.y, or which remove the corresponding ions from the ion beam 1.