Differential ion mobility spectrometer

Abstract

To provide a DMS that has high resolution to differentiate different ion species.SOLUTION: A differential mobility spectrometer 10 comprises: a pair of electrodes 121, 122 that are provided extending in a channel through which gas flows; an ion supply unit 14 that is provided on the upstream side of the electrodes and supplies ions to be measured to between the electrodes; an ion detection unit 15 that is provided on the downstream side of the electrodes; a distributed voltage application unit 131 that applies distributed voltage to between the electrodes to satisfy t1×|V1|=t2×|V2|, the distributed voltage being the high frequency voltage at a frequency f comprising a first voltage V1 continuing for a first time t1 and a second voltage V2 continuing for a second time t2 longer than the first time, having a polarity opposite to the first voltage, and being smaller than the first voltage; a compensation voltage application unit 132 that applies, to between the electrodes, a compensation voltage that is a DC voltage having an amplitude larger than the second voltage and smaller than the first voltage; and a distributed voltage control unit 161 that controls the distributed voltage application unit to change the frequency while the ion supply unit supplies the ions to be measured.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a differential ion mobility spectrometer (DMS). [Background technology]

[0002] DMS is a technology that separates ions according to the difference in mobility between high and low electric fields by injecting analyte ions into a gas flow between parallel plate electrodes, applying a dispersion voltage (DV) to the electrodes, which is a high-frequency voltage with asymmetric amplitude and pulse width and zero time average, and utilizing the nonlinear change in ion mobility with respect to E / N (E is the electric field strength, N is the gas density). By superimposing a predetermined DC voltage called a compensation voltage (CV) on the DV to correspond to the change in ion mobility caused by the dispersion voltage DV, only the target ions can be passed and detected.

[0003] The nonlinear change in mobility due to DV can be roughly classified into the following three types based on the interaction between the analyte ion and the gas molecules (Non-Patent Document 1; see FIG. 9 of the present application). Type A: The mobility difference (mobility in a high electric field minus the mobility difference in a low electric field) increases monotonically as E / N increases. The main principle behind mobility change is that at low E / N, ions and gas molecules form clusters, resulting in low mobility, and at high E / N, the high kinetic energy of ions causes declustering (cluster elimination), resulting in increased mobility. Type C: The mobility difference monotonically decreases with increasing E / N (the mobility difference becomes negative and its absolute value increases). The mobility change due to clustering / declustering between ions and gas molecules is small, and the mobility change due to the hard sphere collision mechanism becomes dominant. As a result, the effective temperature of ions increases and the mobility decreases as E / N increases. Type B: Mobility changes by the Type A mechanism up to a certain E / N, and then by the Type C mechanism at E / Ns beyond that.

[0004] The type of mobility change that can separate analyte ions using DMS depends on the chemical and physical properties of the ion species, so it may not be possible to separate isomers with similar properties. Therefore, in conventional DMS, a method is known in which a polar solvent gas called a modifier gas is introduced into the DMS cell to promote ion-gas molecule cluster formation and increase the mobility change due to Type A, thereby improving separation ability (Non-Patent Document 2). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. WO2010 / 125357 [Non-patent literature]

[0006] [Non-Patent Document 1] BB Schneider et al., "Differential Mobility Spectrometry / Mass Spectrometry History, Theory, Design Optimization, Simulations, and Applications," Mass Spectrometry Reviews, John Wiley & Sons, Inc. (USA), Vol. 35, No. 6, pp. 687-737, 2016 (online publication May 11, 2015) [Non-patent document 2] RW Purves and 5 others, "Using Gas Modifiers to Significantly Improve Sensitivity and Selectivity in a Cylindrical FAIMS Device," Journal of the American Society for Mass Spectrometry, (USA), Volume 25, Pages 1274-1284, September 20, 2023. [Non-patent document 3] MFC Girard et al., "Effects of the LC mobile phase in vacuum differential mobility spectrometry-mass spectrometry for the selective analysis of antidepressant drugs in human plasma," Analytical and Bioanalytical Chemistry, Springer Nature, Germany, Vol. 414, pp. 7243-7252, August 17, 2022 Summary of the Invention [Problem to be solved by the invention]

[0007] As mentioned above, the resolution of DMS can be improved by introducing a modifier gas consisting of polar molecules that easily attach to ions. However, for ions that still have low binding affinity to the modifier gas molecules, the gas molecules may not attach sufficiently, resulting in poor resolution for distinguishing between different ion species.

[0008] The problem that the present invention seeks to solve is to provide a DMS that has high resolution to distinguish between different ion species. [Means for solving the problem]

[0009] The differential ion mobility analyzer according to the present invention, which has been made to solve the above problems, a pair of electrodes extending into a flow path through which a gas flows; an ion supply unit provided upstream of the pair of electrodes and configured to supply ions to be measured between the pair of electrodes; an ion detector provided downstream of the pair of electrodes; a dispersed voltage application unit that applies, between the pair of electrodes, a dispersed voltage Vd that is a high-frequency voltage with a frequency f, and that is composed of a first voltage V1 that continues for a first time t1 and a second voltage V2 that continues for a second time t2 that is longer than the first time t1 and has an opposite polarity to the first voltage V1 and a smaller magnitude than the first voltage V1, such that t1×|V1|=t2×|V2|; a compensation voltage application unit that applies a compensation voltage Vc, which is a DC voltage having a magnitude between the first voltage V1 and the second voltage V2, between the pair of electrodes; a dispersion voltage control unit that controls the dispersion voltage application unit so as to change the frequency f while the ions to be measured are being supplied from the ion supply unit; Equipped with. [Effects of the Invention]

[0010] If the frequency f is changed while the ions to be measured are being supplied from the ion supply unit, i.e., while measuring ion mobility, the length of the first time t1 and the second time t2 changes, which changes the degree of clustering / declustering between ions and gas molecules, and therefore the resolution. Therefore, it is possible to find conditions with high resolution by performing measurements while changing the frequency f. Alternatively, it is possible to perform measurements under multiple conditions with different frequencies f, and then use the measurement results obtained with high resolution. In either case, different ion species can be distinguished with higher resolution.

[0011] In the present invention, since the resolution can be increased by changing the frequency f, it is not essential to use a modifier gas made of polar molecules in the gas flowing through the flow channel. Of course, it is preferable to use a modifier gas to further increase the resolution.

[0012] Patent Document 1 describes that the lower the pressure of the gas supplied between the electrodes, the smaller the frequency of the dispersion voltage should be, but does not explain why. Furthermore, the document does not describe changing the frequency of the dispersion voltage during measurement. Because the degree of clustering / declustering between ions and gas molecules depends on the physical and chemical properties of each ion species, even if the frequency of the dispersion voltage is uniformly determined based on the gas pressure, it is not necessarily possible to perform measurements with high resolution. In contrast, the present invention makes it possible to find conditions for performing measurements with high resolution by changing the frequency of the dispersion voltage during measurement. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 1 is a schematic diagram showing an embodiment of a DMS according to the present invention. [Figure 2] 4 is a graph showing an example of a dispersion voltage applied between a first electrode and a second electrode in the DMS of the present embodiment. [Figure 3] 6 is a graph showing an example of a compensation voltage applied between a first electrode and a second electrode in the DMS of the present embodiment. [Figure 4] 4 is a flowchart showing the operation of the DMS of the present embodiment. [Figure 5] A schematic diagram showing the attachment / detachment of gas molecules to ions during the second period when the dispersion voltage (electric field) is low, and during the first period when the dispersion voltage (electric field) is high. [Figure 6] 6 is a graph showing an example of a measurement result obtained by the DMS of the present embodiment. [Figure 7] 10 is a graph showing the results of measuring the change in compensation voltage (corresponding to the change in mobility) at which the detected intensity peaks relative to E / N for several examples with different dispersion voltage frequencies. [Figure 8] 10 is a flowchart showing the operation of a DMS according to a modified example. [Figure 9] Graph showing a typical example of change in mobility with respect to E / N. DETAILED DESCRIPTION OF THE INVENTION

[0014] An embodiment of a differential ion mobility analyzer (DMS) according to the present invention will be described with reference to FIGS.

[0015] (1) Configuration of the DMS of this embodiment 1 shows a schematic configuration of a DMS 10 according to this embodiment. The DMS 10 includes a pair of electrodes 12 consisting of a first electrode 121 and a second electrode 122, a power supply 13, an ion supply unit 14, a control unit 16, an input unit 17, and a display unit 18. An ion detector 155 included in a mass spectrometer 15 functions as the ion detector of the DMS 10.

[0016] Here, the mass spectrometer 15 used in this embodiment will be described. This mass spectrometer 15 has an ionization chamber 1510 at approximately atmospheric pressure, a low vacuum chamber 1511 communicating with the ionization chamber 1510 via a desolvation tube 1521, a medium vacuum chamber 1512 communicating with the low vacuum chamber 1511 via a skimmer 1522, and a high vacuum chamber 1513 communicating with the medium vacuum chamber 1512 via an orifice 1523. Note that a sampling cone may be used instead of the desolvation tube 1521. The three vacuum chambers are differentially evacuated by a vacuum pump 156 so that the pressure decreases (the degree of vacuum increases) from the low vacuum chamber 1511 to the high vacuum chamber 1513. When differential evacuation is performed in this manner, a flow (flow path) of gas (atmosphere) drawn from the ionization chamber 1510 is formed in the low vacuum chamber 1511 between the desolvation tube 1521 and the skimmer 1522. The first electrode 121 and the second electrode 122 of the DMS 10 are arranged so as to sandwich the gas flow therebetween, in other words, so as to sandwich the line connecting the desolvation tube 1521 and the skimmer 1522 therebetween.

[0017] An ion guide 153 is disposed within the intermediate vacuum chamber 1512, which transports ions that have passed through the electrode 12 of the DMS 10 to the high vacuum chamber 1513. Within the high vacuum chamber 1513, in order from the position closest to the intermediate vacuum chamber 1512, are disposed a front quadrupole mass filter 1541, a collision cell 1540, a rear quadrupole mass filter 1543, and an ion detector 155, and within the collision cell 1540 is disposed an intermediate quadrupole mass filter 1542. An electron multiplier, for example, can be used as the ion detector 155. The components disposed within the intermediate vacuum chamber 1512 and the high vacuum chamber 1513 are similar to those in conventional mass spectrometers, and therefore detailed description thereof will be omitted.

[0018] As described above, in this embodiment, a flow of air (gas flow path) drawn from the ionization chamber 1510 is formed between the first electrode 121 and the second electrode 122, and therefore air can be used as an ion transport gas in the DMS 10. Furthermore, a gas composed of polar molecules may be mixed with the air. Furthermore, a flow path for introducing and transporting the gas molecules may be provided separately from the gas flow path, and the gas may be introduced into the DMS 10. By these methods, the polar gas molecules introduced and the ions undergo clustering and declustering, thereby further improving resolution. Examples of gases composed of polar molecules that can be used include 2-propanol, methanol, and acetonitrile.

[0019] The power supply 13 is made up of a dispersed power supply (dispersed voltage application unit) 131 and a compensation power supply (compensation voltage application unit) 132. The dispersed power supply 131 and the compensation power supply 132 are power supplies that apply a dispersed voltage Vd and a compensation voltage Vc, which will be described below, between the first electrode 121 and the second electrode 122. That is, the dispersed power supply 131 and the compensation power supply 132 apply a voltage in which the dispersed voltage Vd and the compensation voltage Vc are superimposed between the first electrode 121 and the second electrode 122.

[0020] As shown in FIG. 2, the dispersion voltage Vd is a high-frequency voltage with a period T=(t1+t2) and a frequency f=1 / T. The high-frequency voltage Vd is composed of a first voltage V1 that lasts for a first time t1 and a second voltage V2 that lasts for a second time t2, which is longer than the first time t1, and has the opposite polarity to the first voltage V1 and a smaller magnitude than the first voltage V1. The frequency f can be set, for example, within a range of 1 kHz to 100 MHz. In this embodiment, the high-frequency voltage is a square wave. However, a high-frequency voltage having a waveform other than a square wave, such as a clipped wave or a sine wave, may also be used. In this embodiment, the electrode 12 is disposed in a low-vacuum chamber 1511. Since clustering / declustering is more likely to occur as the pressure between the first electrode 121 and the second electrode 122 decreases, it is preferable to change the frequency f to a lower value (so that the first time t1 and the second time t2 become longer). For example, when the pressure between first electrode 121 and second electrode 122 is approximately atmospheric pressure, the frequency is preferably set in the range of 0.01 MHz to 100 MHz, and more preferably in the range of 0.1 MHz to 1 MHz. On the other hand, when the pressure between first electrode 121 and second electrode 122 is close to vacuum, the frequency f is preferably set in the range of 1 kHz to 1 MHz, and more preferably in the range of 0.01 MHz to 0.1 MHz.

[0021] In this embodiment, as shown in Fig. 3, the compensation voltage Vc is a voltage that changes stepwise within a range from the first voltage V1 to the second voltage V2 at intervals of a third time t3, which is sufficiently longer than the period T of the dispersion voltage Vd. Each step of the compensation voltage Vc can be regarded as a DC voltage in comparison with the high-frequency voltage of the dispersion voltage Vd. Note that the range over which the compensation voltage Vc is changed is not limited to the example shown here, and may be any voltage between the first voltage V1 and the second voltage V2.

[0022] In this embodiment, the polarity of the voltage (dispersion voltage Vd and compensation voltage Vc) directed from the second electrode 122 to the first electrode 121 is defined as positive, the first voltage V1 is positive, and the second voltage V2 is negative. The first time t1 and the first voltage V1, as well as the second time t2 and the second voltage V2, are set so as to satisfy t1×|V1|=t2×|V2|.

[0023] The ion supply unit 14 supplies ions to be measured, and includes the above-mentioned ionization chamber 1510, an ionization unit 141 that ionizes the sample in the ionization chamber 1510, and the above-mentioned desolvation tube 1521. In this embodiment, electrospray ionization (ESI) is used to ionize the sample, but instead, chemical ionization (CI), atmospheric pressure ionization (API), matrix-assisted laser desorption ionization (MALDI), or the like may be used to ionize the sample in the ionization unit 141.

[0024] The DMS 10 of this embodiment may include a liquid chromatograph (LC) 19 upstream of the ionization unit 141. In this case, the components of the sample are separated in time by a column (not shown) of the LC 19, and the ions ionized by the ionization unit 141 for each component are analyzed by the DMS 10. When the DMS 10 is used under low pressure (high vacuum), the components of the mobile phase used in the LC 19 may flow between the first electrode 121 and the second electrode 122 as a gas, and the molecules constituting the mobile phase may function as part of the ion transport gas (see Non-Patent Document 3). In many cases, the mobile phase is composed of polar molecules, which contribute to improving the resolution of the DMS 10. When polar molecules of the mobile phase are used as part of the ion transport gas in this way, it is preferable to provide a sampling cone instead of the desolvation tube 1521, as described above.

[0025] The control unit 16 has the following functional blocks: a dispersion voltage control unit 161, a compensation voltage control unit (ion scanning unit) 162, and an ion detection unit (mass spectrometer) control unit 163. The control unit 16 is embodied by hardware such as a CPU and memory, and software that operates the hardware. Among the functional blocks of the control unit 16, the dispersion voltage control unit 161 controls the dispersion power supply 131 to change the frequency f of the dispersion voltage Vd while ions to be measured are supplied from the ion supply unit 14. The compensation voltage control unit 162 controls the compensation power supply 132 to change the compensation voltage Vc stepwise within a predetermined range (from the first voltage V1 to the second voltage V2 in the example of FIG. 3) while the dispersion voltage Vd is fixed at a certain frequency f (the frequency f is not changed). The ion detection unit (mass spectrometer) control unit 163 controls the mass spectrometer 15, including the ion detector 155.

[0026] The input unit 17 is a device through which the operator inputs information necessary for measurement. A keyboard, mouse, touch panel, etc. can be used for the input unit 17. The display unit 18 is a display that displays the measurement results, an input screen when inputting information into the input unit 17, etc.

[0027] (2) Operation of the DMS of this embodiment The operation of the DMS 10 of this embodiment will be described with reference to the flowchart of FIG.

[0028] When the operator performs a predetermined start operation using the input unit 17, first, the dispersion voltage control unit 161 sets the frequency f to a predetermined initial value, and also sets the compensation voltage control unit 162 to a predetermined initial value (step 1). These initial values ​​may be predetermined values, but they may also be set to values ​​input by the operator by operating the input unit 17 after an input screen is displayed on the display unit 18.

[0029] At the same time, a flow of ion transport gas consisting of atmospheric air is formed between the first electrode 121 and the second electrode 122 in the low vacuum chamber 1511 by differentially evacuating the vacuum chamber of the mass spectrometer 15 using a vacuum pump (step 2). At this time, a modifier gas is mixed into the ion transport gas as necessary. Note that either step 1 or step 2 may be performed first, or both may be performed simultaneously in parallel.

[0030] After waiting until the flow rate of the ion transport gas stabilizes (usually for a predetermined time), the dispersion voltage control unit 161 and the compensation voltage control unit 162 respectively apply the dispersion voltage Vd and the compensation voltage Vc having the initial values ​​set in step 1 between the first electrode 121 and the second electrode 122 (step 3). As a result, a voltage in which the dispersion voltage Vd and the compensation voltage Vc are superimposed is applied between the first electrode 121 and the second electrode 122.

[0031] In this state, the ion supply unit 14 ionizes the sample in the ionization unit 141 and introduces the generated ions from the desolvation tube 1521 between the first electrode 121 and the second electrode 122 (step 4). In the space between the first electrode 121 and the second electrode 122, the ions move toward the skimmer 1522 with the flow of the ion transport gas, while also moving in a direction perpendicular to the direction of the ion transport gas flow due to forces from the dispersion electric field and compensation electric field generated between the electrodes by the dispersion voltage Vd and compensation voltage Vc, respectively. As a result, the ions move while tracing a zigzag trajectory.

[0032] During this movement, as shown in Figure 5, the ions 31 repeatedly undergo clustering, in which gas molecules 32 in the ion transport gas attach to the surface to form clusters 30, and declustering, in which the gas molecules 32 attached to the surface detach. During the second time period when the dispersion voltage Vd is smaller (Vd = V2), the mass and collision cross-section of the clusters 30 increase, while the strength of the dispersion electric field generated by the dispersion voltage Vd is small, so the kinetic energy the ions gain from the dispersion electric field also decreases. As a result, the ions do not have enough energy to exceed the binding energy between the ions and the gas, so clustering is likely to occur when they collide with (approach) the gas. As a result of this tendency for clustering to occur, the mass and collision cross-section of the clusters increase, and the apparent mobility of the ions decreases during the second time period. In contrast, during the first time period when the dispersion voltage Vd is larger (Vd = V1), the strength of the dispersion electric field is greater, so the ions gain enough energy to exceed the binding energy between the ions and the gas. As a result, the clustered gas molecules are declustered, and the mass and collision cross section become smaller, resulting in a smaller mobility.

[0033] As described above, due to the occurrence of clustering / declustering, the ion migration caused by the dispersion voltage Vd in Type A tends to move closer to the electrode in the first time than in the second time (due to the higher mobility). Furthermore, because the susceptibility of clustering / declustering differs depending on the physical and chemical properties of each ion species, the aforementioned migration distance caused by the dispersion voltage Vd in Type A differs for each ion species, enabling the separation of each ion species. On the other hand, although details are omitted, the ion migration caused by the dispersion voltage Vd in Type C, in contrast to Type A, tends to move closer to the electrode in the second time than in the first time (due to the higher mobility), but this does not depend on the chemical properties of each ion species. As a result of the above effects, the ion migration caused by the dispersion voltage Vd in the direction perpendicular to the flow direction of the ion transport gas occurs due to the superposition of the effects of Type A and Type C. However, for ions that are prone to clustering / declustering (i.e., those with physical and chemical properties that are prone to clustering / declustering), Type A migration is dominant, while for ions that are not prone to clustering / declustering, Type C migration is dominant.

[0034] Only ions of ion species where the movement of ions due to the dispersion voltage Vd and the movement of ions due to the compensation voltage Vc are in equilibrium reach the ion / gas outlet 113, and other ion species collide with the first electrode 121 or the second electrode 122 and do not reach the ion / gas outlet 113. The ions that reach the ion / gas outlet 113 are detected by the mass spectrometer 15, and the mass-to-charge ratio m / z of the ions is determined (step 5).

[0035] Furthermore, as the magnitude of the compensation voltage Vc is changed, the ion species detected by the mass spectrometer 15 also changes in equilibrium with the movement of ions due to the dispersion voltage Vd. Therefore, if the compensation voltage Vc has not reached the predetermined final value (No in step 5), the compensation voltage control unit 162 changes the value of the compensation voltage Vc (step 7) and performs the ion detection operation by the mass spectrometer 15 in step 5 again. This operation is performed until the compensation voltage Vc reaches the predetermined final value (Yes in step 5), and then the measurement result is displayed on the display unit 18 (step 8).

[0036] 6 shows an example of a graph showing the measurement results displayed on the display unit 18. In this graph, the horizontal axis represents the compensation voltage Vc, and the vertical axis represents the detection intensity. A peak appears on the graph at the compensation voltage Vc at which ions pass through the gas flow path 110 and are detected by the mass spectrometer 15. In this embodiment, the m / z value obtained by the mass spectrometer 15 for each detected ion is superimposed on the display, but the display of this value may be omitted.

[0037] The operator looks at the graph displayed on the display unit 18 and determines whether the measurement has been performed with the required resolution. If the operator determines that the required resolution has not been obtained, the operator performs a predetermined operation using the input unit 17 to input a command to instruct re-measurement. When re-measurement is instructed (Yes in step 9), the distributed voltage control unit 161 executes control over the dispersed power source 131 to change the frequency f, and the compensation voltage control unit 162 executes control over the compensation power source 132 to return the compensation voltage Vc to its initial value (step 10). Then, the process returns to step 5 and the operations up to step 9 are executed again.

[0038] On the other hand, if the operator determines that the measurement has been performed with the required resolution, the operator inputs a command indicating that remeasurement is not necessary by performing a predetermined operation using the input unit 17. In this case (No in step 9), the series of measurement operations ends.

[0039] According to the DMS 10 of this embodiment, even if the required resolution is not achieved, conditions for higher resolution can be found by repeatedly changing the frequency of the dispersion voltage and performing measurements again, thereby enabling different ion species to be distinguished with high resolution.

[0040] Next, we present the results of measuring the change in ion mobility with changes in frequency f. In this measurement, the ions measured were glucosyl cholesterol molecules with a monovalent ammonium ion attached (m / z: 566.4). The ratio of the first time t1 to the second time t2 was 3:1, and the ratio of the magnitude of the first voltage V1 to the second voltage V2 was 1:3. Under these conditions, we measured the relationship between E / N and the value of the compensation voltage Vc at which the detection intensity peaked for three cases where the frequency f of the dispersion voltage Vd was 100 kHz, 200 kHz, and 400 kHz. Here, changes in the value of the compensation voltage Vc correspond to changes in mobility.

[0041] The measurement results are shown in FIG. 7. Note that the positive and negative signs of the vertical axis in FIG. 7 are opposite to the positive and negative signs of the vertical axis (mobility difference) in FIG. 9. This is because when the vertical axis value in FIG. 9 (i.e., the value obtained by dividing the mobility difference in a low electric field from the mobility in a high electric field) is positive, it means that the mobility is greater when a high dispersive electric field is applied (i.e., the first time) than when a low dispersive electric field is applied (i.e., the second time), and ions move toward the second electrode 122 due to the dispersive electric field. In contrast, in FIG. 7, a negative compensation voltage Vc is applied to compensate for the movement due to this dispersive electric field, so the vertical axis value is negative (similarly, a positive compensation voltage Vc is applied when the vertical axis value in FIG. 9 is negative). That is, in FIG. 7, a negative vertical axis value means that the mobility due to Type A is dominant, and a positive vertical axis value means that the mobility due to Type C is dominant. 7, it can be seen that by decreasing the frequency f of the dispersion voltage Vd from 400 kHz toward 100 kHz (the first time t1 and the second time t2 become longer), the mobility changes so that the mobility due to Type A becomes dominant. In this way, the contribution of Type A to the mobility changes depending on the frequency f of the dispersion voltage Vd, and the resolution of ion detection also changes.

[0042] (3) Modifications The present invention is not limited to the above-described embodiment, and various modifications are possible.

[0043] For example, in the above embodiment, the ion detector 155 of the mass spectrometer 15 having a specific configuration is used as the ion detector, but an ion detector of a mass spectrometer having a different configuration from the above may also be used. Furthermore, if it is not necessary to determine the m / z of ions, the cost of the device can be reduced by using an ion detector such as an electron multiplier as the ion detection unit alone, without providing the mass spectrometer 15.

[0044] In the above embodiment, the pressure in the gas flow path between the first electrode 121 and the second electrode 122 is reduced by placing the DMS 10 in the low vacuum chamber 1511 of the mass spectrometer 15, but the pressure in the gas flow path may be atmospheric pressure.

[0045] In the above embodiment, when the compensation voltage Vc reaches its final value when the frequency f of the dispersion voltage Vd is a certain value (YES in step 6), the measurement result is displayed on the display unit (step 8), and if the operator determines that remeasurement is necessary (YES in step 9), the frequency f is changed (step 10) and remeasurement is performed. However, instead, the following processing as shown in FIG. 8 may be performed.

[0046] In this process, multiple frequencies f of the dispersion voltage Vd at which measurements are performed are determined in advance. When the compensation voltage Vc reaches its final value when the frequency f is a certain value (YES in step 6), it is determined whether the frequency f of the dispersion voltage Vd has reached its final value (step 11). If the determination is NO, the frequency f is set to a new value and the compensation voltage Vc is set to its initial value (step 12), and the operations of steps 5, 6, and 11 are performed again. If the determination in step 11 is YES, the measurement results for each frequency f are displayed on the display unit 18 (step 13), thereby completing the series of measurement operations. Note that after step 13, the operator may select the measurement result that he or she deems optimal based on the multiple measurement results displayed.

[0047] In this modified example, measurements are performed at multiple predetermined frequencies f without the operator's decision, which prevents the operator from missing an appropriate frequency f.

[0048] In the above embodiment, the compensation voltage Vc is changed by the compensation voltage control unit (ion scanning unit) 162, while the voltage value V1 at the first time and the voltage value V2 at the second time of the dispersion voltage Vd are not changed, but these voltage values ​​V1 and / or V2 (i.e., dispersion voltage Vd) may be changed together with or instead of the compensation voltage Vc. On the other hand, when detecting only one specific type of ion (checking the presence or absence of that ion), the value of the compensation voltage Vc may be fixed, and the compensation voltage control unit (ion scanning unit) 162 may be omitted.

[0049] [Aspect] It will be apparent to those skilled in the art that the above-described exemplary embodiments are examples of the following aspects.

[0050] (Item 1) A differential ion mobility analyzer according to one aspect of the present invention comprises: a pair of electrodes extending into a flow path through which a gas flows; an ion supply unit provided upstream of the pair of electrodes and configured to supply ions to be measured between the pair of electrodes; an ion detector provided downstream of the pair of electrodes; a dispersed voltage application unit that applies, between the pair of electrodes, a dispersed voltage Vd that is a high-frequency voltage with a frequency f, and that is composed of a first voltage V1 that continues for a first time t1 and a second voltage V2 that continues for a second time t2 that is longer than the first time t1 and has an opposite polarity to the first voltage V1 and a smaller magnitude than the first voltage V1, such that t1×|V1|=t2×|V2|; a compensation voltage application unit that applies a compensation voltage Vc, which is a DC voltage having a magnitude between the first voltage V1 and the second voltage V2, between the pair of electrodes; a dispersion voltage control unit that controls the dispersion voltage application unit so as to change the frequency f while the ions to be measured are being supplied from the ion supply unit; Equipped with.

[0051] According to the differential ion mobility analyzer of the first aspect, when the frequency f is changed while ions to be measured are being supplied from the ion supply unit, i.e., while measuring ion mobility, the lengths of the first time t1 and the second time t2 change, which changes the degree of clustering / declustering between ions and gas molecules, and therefore the resolution. Therefore, it is possible to find conditions with high resolution by performing measurements while changing the frequency f. Alternatively, it is possible to perform measurements under multiple conditions with different frequencies f, and then use the measurement results obtained with high resolution. In either case, different ion species can be distinguished with higher resolution.

[0052] (Item 2) A differential ion mobility analyzer according to item 2 is the apparatus according to item 1, wherein the ion detection unit is an ion detector included in a mass spectrometer.

[0053] According to the differential ion mobility analyzer of the second aspect, by using an ion detector included in a mass spectrometer as the ion detection unit, the mass-to-charge ratio of the detected ions can be determined by the mass spectrometer.

[0054] (Item 3) A differential ion mobility analyzer according to item 3 is the apparatus according to item 1 or 2, wherein a liquid chromatograph is connected to the ion supply unit.

[0055] The differential ion mobility analyzer according to the third aspect of the present invention can analyze the ions contained in each component separated by a liquid chromatograph. Furthermore, the molecules contained in the mobile phase used in the liquid chromatograph can be used as part of the gas flowing through the flow path. In this case, particularly when the mobile phase contains polar molecules, the polar molecules tend to attach to ions due to their polarity, which affects the likelihood of clustering for each ion species, thereby contributing to further improvement of resolution.

[0056] (Item 4) The differential ion mobility analyzer according to item 4 is the device according to any one of items 1 to 3, further comprising an ion scanning unit that detects ions with the ion detection unit while varying either or both of the compensation voltage Vc and the dispersion voltage Vd within a predetermined range.

[0057] According to the differential ion mobility analyzer of paragraph 4, multiple types of ions can be detected with a time difference by detecting ions with the ion detection unit while changing the compensation voltage Vc and / or the dispersion voltage Vd within a predetermined range. Note that when detecting only one specific type of ion (confirming the presence or absence of that ion), the value of the compensation voltage Vc may be fixed and the ion scanning unit may be omitted.

[0058] (Item 5) A differential ion mobility analyzer according to item 5 is the apparatus according to any one of items 1 to 4, wherein the gas contains polar molecules.

[0059] According to the differential ion mobility analyzer according to the fifth aspect, the resolution can be further improved by using a gas having polar molecules.

[0060] (Item 6) A differential ion mobility analyzer according to item 6 is the device according to any one of items 1 to 5, further comprising a pressure reducing means for reducing the pressure inside the flow channel.

[0061] When DMS analysis is performed under reduced pressure, the number density of gas molecules attached to ions is reduced, making it difficult for Type A mobility changes to occur, which tends to reduce resolution. The differential ion mobility analyzer according to paragraph 6 makes it easier for Type A mobility changes to occur even under reduced pressure, where resolution tends to decrease, thereby improving resolution. [Explanation of symbols]

[0062] 10...Differential ion mobility spectrometer (DMS) 12...Electrode 121...1st electrode 122…Second electrode 13...Power supply 131…Distributed power supply 132…Compensation power supply 14...Ion supply unit 141...Ionization section 15...Mass spectrometer 1510...Ionization chamber 1511…Low vacuum chamber 1512…Medium vacuum chamber 1513…High vacuum chamber 1521...Desolvation tube 1522...Skimmer 1523...pore 153...Ion Guide 1540...Collision cell 1541...Pre-quadrupole mass filter 1542...Middle quadrupole mass filter 1543...Post-quadrupole mass filter 155...Ion detector 156...Vacuum pump 16...Control unit 161...Distributed voltage control unit 162...Compensation voltage control unit (ion scanning unit) 163...Control unit 17...Input section 18...Display section 19...Liquid chromatograph (LC) 30...cluster 31...Aeon 32...Gas molecules

Claims

1. a pair of electrodes extending into a flow path through which a gas flows; an ion supply unit provided upstream of the pair of electrodes and configured to supply ions to be measured between the pair of electrodes; an ion detector provided downstream of the pair of electrodes; a dispersed voltage application unit that applies, between the pair of electrodes, a dispersed voltage Vd that is a high-frequency voltage with a frequency f, the dispersed voltage Vd being made up of a first voltage V1 that lasts for a first time t1 and a second voltage V2 that lasts for a second time t2 that is longer than the first time t1 and has an opposite polarity to the first voltage V1 and a smaller magnitude than the first voltage V1, such that t1×|V1|=t2×|V2|; a compensation voltage application unit that applies a compensation voltage Vc, which is a DC voltage having a magnitude between the first voltage V1 and the second voltage V2, between the pair of electrodes; a dispersion voltage control unit that controls the dispersion voltage application unit so as to change the frequency f while the ions to be measured are being supplied from the ion supply unit; A differential ion mobility analyzer comprising:

2. The differential ion mobility analyzer according to claim 1 , wherein the ion detection unit is an ion detector included in a mass spectrometer.

3. The differential ion mobility analyzer according to claim 1 or 2, wherein a liquid chromatograph is connected to the ion supply unit.

4. 3. The differential ion mobility analyzer according to claim 1, further comprising an ion scanning unit that detects ions with the ion detection unit while varying one or both of the compensation voltage Vc and the dispersion voltage Vd within a predetermined range.

5. The differential ion mobility analyzer according to claim 1 or 2, wherein the gas contains polar molecules.

6. The differential ion mobility analyzer according to claim 1 or 2, further comprising a pressure reducing means for reducing the pressure inside the flow channel.

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