Quadrupole mass spectrometer with quadrupole mass filter as a mass separator

Abstract

In a scan measurement in which a mass scan is repeated across a predetermined mass range, when a voltage is returned from a termination voltage of one scan to an initiation voltage for the next scan, an undershoot or other drawbacks occur to destabilize the voltage value. Therefore, an appropriate waiting time is required. Conventionally, this waiting time has been set to be constant regardless of the analysis conditions. On the other hand, in the quadrupole mass spectrometer according to the present invention, the mass difference M between the scan termination mass and the scan initiation mass is computed based on the specified mass range, and a different settling time is set in accordance with this mass difference. When the mass difference M is small and hence requires only a short voltage stabilization time, a relatively short settling time is set. This shortens the cycle period of the mass scan, which increases the temporal resolution.

Claims

1. A method for executing a quadrupole mass spectrometer which includes a quadrupole mass filter for selectively allowing an ion having a specific mass to pass through and a detector for detecting the ion which has passed through the quadrupole mass filter and which performs a scan measurement in which a cycle of scanning a mass of ions which pass through the quadrupole mass filter across a predetermined mass range is repeated, the method comprising: applying a predetermined voltage by a quadrupole driver to each of electrodes composing the quadrupole mass filter; and in performing the scan measurement by a controller, setting a scan margin at least either above or below a specified mass range by a scan margin width, which is a difference between a scan initiation mass and a mass with which the scan measurement is actually initiated or a difference between a mass with which the scan measurement is actually terminated and a scan termination mass, and controlling the quadrupole driver in such a manner as to change the voltage applied to each of the electrodes composing the quadrupole mass filter so as to scan a mass range which is wider than the specified mass range by the scan margin, and wherein the scan margin width is changed in accordance with a scan rate (mass per unit time).

2. The method according to claim 1, wherein the controller decreases the scan margin width as the scan rate decreases.

3. The method according to claim 1, wherein the controller further changes the scan margin width in accordance with the scan initiation mass.

4. The method according to claim 3, wherein the controller further changes the scan margin width in accordance with an acceleration voltage for an ion injected into the quadrupole mass filter.

5. The method according to claim 2, wherein the controller further changes the scan margin width in accordance with a scan initiation mass.

6. The method according to claim 5, wherein the controller further changes the scan margin width in accordance with an acceleration voltage for an ion injected into the quadrupole mass filter.

7. The method according to claim 1, wherein the scan margin width is calculated by k[scan rate][m/z value].sup.1/2, where k is a constant and m/z value is the scan initiation mass.

8. The method according to claim 7, wherein k is determined by an ion acceleration voltage for an ion injected into the quadrupole mass filter.

9. A method for executing a quadrupole mass spectrometer which includes a quadrupole mass filter for selectively allowing an ion having a specific mass to pass through and a detector for detecting the ion which has passed through the quadrupole mass filter and which performs a scan measurement in which a cycle of scanning a mass of ions which pass through the quadrupole mass filter across a predetermined mass range is repeated, the method comprising: applying a predetermined voltage by a quadrupole driver to each of electrodes composing the quadrupole mass filter; and performing the scan measurement by setting a scan margin at least either above or below a specified mass range by a scan margin width, which is a difference between a scan initiation mass and a mass with which the scan measurement is actually initiated, or a difference between a mass with which the scan measurement is actually terminated and a scan termination mass, and controlling the quadrupole driver in such a manner as to change the voltage applied to each of the electrodes composing the quadrupole mass filter so as to scan a mass range which is wider than the specified mass range by the scan margin, and wherein the scan margin width is changed with a scan rate (mass per unit time), the scan initiation mass, or an acceleration voltage for an ion injected into the quadrupole mass filter.

10. A method for executing a quadrupole mass spectrometer which includes a quadrupole mass filter for selectively allowing an ion having a specific mass to pass through and a detector for detecting the ion which has passed through the quadrupole mass filter and which performs a scan measurement in which a cycle of scanning a mass of ions which pass through the quadrupole mass filter across a predetermined mass range is repeated, the method comprising: applying a predetermined voltage by a quadrupole driver to each of electrodes composing the quadrupole mass filter; and performing the scan measurement by setting a scan margin at least either above or below a specified mass range by a scan margin width, which is a difference between a scan initiation mass and a mass with which the scan measurement is actually initiated, or a difference between a mass with which the scan measurement is actually terminated and a scan termination mass, and controlling the quadrupole driver in such a manner as to change the voltage applied to each of the electrodes composing the quadrupole mass filter so as to scan a mass range which is wider than the specified mass range by the scan margin, and wherein the scan margin width is calculated by k[scan rate][m/z value].sup.1/2, where k is a constant and m/z value is the scan initiation mass.

11. The method according to claim 10, wherein k is determined by an ion acceleration voltage for an ion injected into the quadrupole mass filter.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a configuration diagram of the main portion of a quadrupole mass spectrometer of an embodiment of the present invention.

(2) FIG. 2 shows how the mass changes in a scan measurement.

(3) FIG. 3 is a diagram showing an actually measured relationship between the mass difference between the scan initiation mass and the scan termination mass, and the necessary voltage stabilization time in a scan measurement.

(4) FIG. 4 shows how the mass changes in an SIM measurement.

(5) FIG. 5 is a diagram showing an actually measured relationship among the scan rate, the scan initiation mass, and the scan margin width.

(6) FIG. 6 is a schematic configuration diagram mainly illustrating an ion optical system of a general quadrupole mass spectrometer.

(7) FIG. 7 schematically shows how the mass changes in a scan measurement.

EXPLANATION OF NUMERALS

(8) 1 . . . Ion Source 2 . . . Ion Transport Optical System 3 . . . Quadrupole Mass Filter 3a, 3b, 3c, 3d . . . Rod Electrode 4 . . . Detector 10 . . . Controller 101 . . . Settling Time Determiner 102 . . . Scan Margin Width Determiner 11 . . . Input Unit 12 . . . Voltage Control Data Memory 13 . . . Ion Selection Voltage Generator 15 . . . Radio-Frequency Voltage Generator 16 . . . Direct-Current Voltage Generator 17 . . . Radio-Frequency/Direct-Current Adder 18 . . . Bias Voltage Generator 19, 20 . . . Bias Adder 21 . . . Ion Optical System Voltage Generator

BEST MODE FOR CARRYING OUT THE INVENTION

(9) A quadrupole mass spectrometer of an embodiment of the present invention will be described with reference to the attached figures. FIG. 1 is a configuration diagram of the main portion of the quadrupole mass spectrometer according to this embodiment. The same components as in FIG. 6 which have been already described are indicated with the same numerals. In the quadrupole mass spectrometer according to this embodiment, a gaseous sample is injected into the ion source 1, and a gas chromatograph can be connected in the previous stage of the mass spectrometer. A liquid sample may also be analyzed by using an atmospheric pressure ion source (such as an electrospray ion source) as the ion source 1, and maintaining this ion source 1 at an atmosphere of approximate atmospheric pressure while placing the quadrupole mass filter 3 and the detector 4 in a high vacuum atmosphere by a multistage differential pumping system. In such a case, a liquid chromatograph can be connected in the previous stage of the mass spectrometer.

(10) In the quadrupole mass spectrometer of the present embodiment, inside the vacuum chamber (which is not shown) are provided the ion source 1, the ion transport optical system 2, the quadrupole mass filter 3, and the detector 4, as previously described. The quadrupole mass filter 3 has four rod electrodes 3a, 3b, 3c, and 3d provided in such a manner as to internally touch a cylinder having a predetermined radius centering on the ion optical axis C. In these four rod electrodes 3a, 3b, 3c, and 3d, two rod electrodes facing across the ion optical axis C, i.e. the rod electrodes 3a and 3c: as well as the rod electrodes 3b and 3d, are connected to each other. The quadrupole driver as a means for applying voltages to these four rod electrodes 3a, 3b, 3c, and 3d is composed of the ion selection voltage generator 13, the bias voltage generator 18, and the bias adders 19 and 20. The ion selection voltage generator 13 includes a direct-current (DC) voltage generator 16, a radio-frequency (RF) voltage generator 15, and a radio-frequency/direct-current (RF/DC) adder 17.

(11) The ion optical system voltage generator 21 applies a direct-current voltage Vdc1 to the ion transport optical system 2 in the previous stage of the quadrupole mass filter 3. The controller 10 is for controlling the operations of the ion optical system voltage generator 21, the ion selection voltage generator 13, the bias voltage generator 18, and other units. The voltage control data memory 12 is connected to the controller 10 in order to perform this operation. An input unit 11 which is operated by an operator is also connected to the controller 10. The function of the controller 10 is realized mainly by a computer including a central processing unit (CPU), a memory, and other units.

(12) In the ion selection voltage generator 13, the direct-current voltage generator 16 generates direct-current voltages U having a polarity different from each other under the control by the controller 10. The radio-frequency voltage generator 15 generates, similarly under the control of the controller 10, radio-frequency voltages V.Math.cos t having a phase difference of 180 degrees. The radio-frequency/direct-current adder 17 adds the direct-current voltages U and the radio-frequency voltages V.Math.cos t to generate two types of voltages of U+V.Math.cos t and (U+V.Math.cos t). These are ion selection voltages which determine the mass (or m/z to be exact) of the ions which pass through.

(13) In order to form, in front of the quadrupole mass filter 3, a direct-current electric field in which ions are efficiently injected into the longitudinal space of the quadrupole mass filter 3, the bias voltage generator 18 generates a common direct-current bias voltage Vdc2 to be applied to each of the rod electrodes 3a through 3d so as to achieve an appropriate voltage difference from the direct-current voltage Vdc1 applied to the ion transport optical system 2. The bias adder 19 adds the ion selection voltage U+V.Math.cos t and the direct-current bias voltage Vdc2, and applies the voltage of Vdc2+U+V.Math.cos t to the rod electrodes 3a and 3c. The bias adder 20 adds the ion selection voltage (U+V.Math.cos t) and the direct-current bias voltage Vdc2, and applies the voltage of Vdc2(U+V.Math.cos t) to the rod electrodes 3b and 3d. The values of the direct-current bias voltages Vdc1 and Vdc2 may be appropriately set based on an automated tuning performed by using a standard sample or other measures.

(14) In the quadrupole mass spectrometer of the present embodiment, a scan measurement is performed, in which a mass scan across a mass range set by a user is repeated, by changing the voltage (to be more precise, the direct-current voltage U and the amplitude V of the radio-frequency voltage) applied to each of the rod electrodes 3a through 3d of the quadrupole mass filter 3. In the scan measurement, a characterizing voltage control is performed. Hereinafter, this control operation will be described.

(15) In the scan measurement, as shown in FIG. 2(a), the applied voltage is gradually increased from the voltage corresponding to the scan initiation mass M1. On reaching the voltage corresponding to the scan termination mass M2, the applied voltage is immediately returned to the voltage corresponding to the scan initiation mass M1. This is one mass scan, i.e. one cycle. The rapid decrease in the voltage causes an undershoot and a certain amount of time is required until the voltage value stabilizes. Therefore, the operation waits until the voltage stabilizes, and then a voltage scan for the next mass scan, i.e. the next cycle, is initiated. The larger the preceding change in the voltage is, i.e. the larger the voltage difference between the scan termination voltage and the scan initiation voltage is, the larger the amount of undershoot becomes. Hence, as the mass difference M between the scan termination mass M2 and the scan initiation mass M1 becomes larger, the voltage requires a longer time stabilize (the voltage stabilization time).

(16) FIG. 3 is a graph of the result of an actual measurement of the relationship between the mass difference M and the voltage stabilization time. This result shows that, for example, a voltage stabilization time of 0.5 [msec] is sufficient for a mass difference M of 200 [u], while a voltage stabilization time of 5 [msec] is required for a mass difference M of 2000 [u]. In conventional quadrupole mass spectrometers, independently of the mass difference M, a constant settling time has been set to achieve the largest voltage stabilization time. Thus, for a settling time of 5 [msec] for example, a time period of 4.5 [msec] is wasted in the case where the mass difference M is 200 [u]. The shaded triangular area in FIG. 3 corresponds to the wasted time period in conventional apparatuses. The wasted time used herein is the time when the process is waiting without initiating the next mass scan even though the voltage is already stable.

(17) In the quadrupole mass spectrometer of the present embodiment, in order to decrease the aforementioned wasted time as much as possible, the length of the waiting time until the next mass scan is initiated (i.e. the settling time) is changed in accordance with the mass difference M. For that purpose, the settling time determiner 101 included in the controller 10 holds a set of information prepared for deriving an appropriate settling time from the mass difference M. This information includes, for example, a computational expression, table, or the like, which represents the line showing the relationship between the voltage stabilization time and the mass difference M as illustrated in FIG. 3.

(18) In performing a scan measurement, the user beforehand sets the analysis conditions including the mass range, the scan rate, and other parameters through the input unit 11. Then, the settling time determiner 101 in the controller 10 computes the mass difference M from the specified mass range and obtains the settling the corresponding to the mass difference M by using the aforementioned information for deriving the settling time. Thereby, a longer settling time is set for a larger mass difference M. When repeating the mass scan across the specified mass range, the controller 10 sets the waiting time after one mass scan is terminated and before the next mass scan is initiated, to the settling time that has been determined by the settling time determiner 101. Consequently, as illustrated in FIG. 2(b), the settling time t2 becomes short for a small mass difference M, which practically shortens the cycle of the mass scan. Although no mass analysis data are obtained during the settling time, the shortened settling times increase the temporal resolution.

(19) In addition, in the quadrupole mass spectrometer of the present embodiment, not only the settling time, but also the scan margin width Ms in a mass scan is changed in accordance with the analysis conditions. The scan margin width Ms is, as shown in FIG. 2(c), the mass difference between the specified scan initiation mass Ms and the mass with which the mass scan is actually initiated. Ideally, this scan margin width Ms should be zero; however, in reality, a certain amount of scan margin width Ms is required so as to eliminate the influence of unnecessary ions remaining inside the quadrupole mass filter 3 before a mass scan is initiated. In this case, although the mass scan is initiated from the mass of MsMs, the data obtained until the mass becomes Ms are discarded for the lack of reliability. Hence, the data for equal to or more than the mass of Ms are actually reflected in the mass spectrum. A scan margin is set not only for the range equal to or less than the scan initiation mass Ms, but also for the range equal to or more than the scan termination mass Me.

(20) FIG. 5 is a graph showing the result of an actual measurement of the relationship among the scan rate, the scan initiation mass, and the scan margin width Ms. In this measurement, with different scan rates being set, the change of the signal intensities was observed while the scan initiation mass and the scan margin width were each changed to examine the scan margins width with which a reliable signal intensity could be obtained. This shows that at a slow scan rate such as 1000 [Da/sec], the scan margin width Ms can be considerably decreased. Meanwhile, at a fast scan rate such as 15000 [Da/sec], it is necessary to set a large scan margin width Ms. This is because, the faster the scan rate is, the shorter the corresponding time becomes even with the same margin width Ms. In addition, if the scan initiation mass is large, the scan margin width Ms is required to be increased. This is because, the larger the mass of an ion is, the longer it takes for the ion to pass through the quadrupole mass filter 3. As an example, in the case where the scan rate is 15000 [Da/sec] and the scan initiation mass is 1048 [u], a scan margin width Ms of 3 [u] is required. That is, even though the lower end mass of the mass spectrum is m/z 1048, it is practically necessary to initiate the mass scan from m/z 1045.

(21) FIG. 5 shows a result obtained under the condition that the ion acceleration voltage is constant, i.e. the voltage difference is constant between the direct-current bias voltage Vdc2 which is applied to the quadrupole mass filter 3 and the direct-current bias voltage Vdc1 which is applied to the ion transport optical system 2. Further, experiments demonstrate that the necessary scan margin width Ms also depends on the ion acceleration voltage. That is, the scan margin width Ms can be obtained by the following formula:
Ms=k[scan rate][m/z value].sup.1/2
where k is a constant determined by the ion acceleration voltage. The larger the acceleration voltage is, the smaller the constant k becomes. Although the constant k is also dependent on the length of the rod electrodes 3a through 3d of the quadrupole mass filter 3, this length is not important because it is not an analysis condition set by a user.

(22) In conventional quadrupole mass spectrometers, similar to the aforementioned settling time, the scan margin width Ms is also set to be a fixed value selected in the light of the worst case condition. Therefore, in the case where the scan rate is slow, where the scan initiation mass is small, or in other cases, the scan margin width is too large, and some of this time period for scanning this mass range falls under the aforementioned wasted time. On the other hand, in the quadrupole mass spectrometer of the present embodiment, the scan margin width Ms is changed in accordance with the scan rate, the scan initiation mass, and the ion acceleration voltage. For this purpose, the scan margin width determiner 102 included in the controller 10 holds a set of information prepared for deriving an appropriate scan margin width Ms from the scan rate, the scan initiation mass, and the ion acceleration voltage. This information includes, for example, a computational expression, table, or the like, which represents the line showing the relationship among the scan rate, the scan initiation mass, and the scan margin width as illustrated in FIG. 5. In addition, different computational expressions and tables are prepared for each bias direct-current voltage which determines the ion acceleration voltage.

(23) In performing a scan measurement, when the user sets the analysis conditions including the mass range, the scan rate, and other parameters, then, by using the information for deriving the aforementioned scan margin width, the scan margin width determiner 102 in the controller 10 obtains a scan margin width Ms that corresponds to the specified scan rate, the specified scan initiation mass, and the acceleration voltage which is determined by the bias direct-current voltages Vdc1 and Vdc2. The bias direct-current voltages Vdc1 and Vdc2 do not depend on the analysis conditions set by the user but are normally determined as a result of a tuning automatically performed so as to maximize the ion intensity.

(24) Consequently, for a higher scan rate and for a larger scan initiation mass, a longer scan margin width is set. In repeating the mass scan across the specified mass range, e.g. from M3 to M4, the controller 10 determines the actual mass scan range to be M3Ms through M4+Ms, based on the scan margin width Ms determined by the scan margin width determiner 102. In the case where the scan rate is low (slow) or in the case where the scan initiation mass is small, the scan margin width becomes relatively small. Therefore, the cycle period of the mass scan practically becomes short. Although no valid mass analysis data are obtained during the period of this scan margin width, the shortened scan margin widths increase the temporal solution.

(25) The aforementioned description was for the case of performing a scan measurement. However, it is a matter of course that changing the length of the settling time in accordance with the mass difference M is effective as previously described also in the case of repeatedly performing an SIM measurement in which mass analyses for previously specified plural masses are sequentially performed as shown in FIG. 4 or in the case of repeatedly performing an MRM measurement in an MS/MS analysis.

(26) In the aforementioned embodiment, it is assumed that a scan is performed from lower to higher masses. Although this is a general operation, a scan can be reversely performed from higher to lower masses. Also in this case, the aforementioned technique can be used without change.

(27) It should be noted that the embodiment described thus far is merely an example of the present invention, and it is evident that any modification, addition, or adjustment made within the spirit of the present invention is also included in the scope of the claims of the present application.