A multi-stage tandem scanning method for improving multipole resolution

Abstract

The present application discloses a multi-stage series scanning method for improving the resolution of a multipole, including: allowing ions to enter a multipole mass analysis device, and setting multiple stable zones for multiple ion mass-to-charge ratios, and combining multiple stable zones in series, and adjusting the combination relationship between each stable zone and the corresponding scan line, thereby changing the way ions pass through the multipole mass analysis device, thereby improving the screening flux and resolution of the multipole mass analysis device for ions. The present application can achieve the combination of multipole stable zones and scan lines from the perspective of process control by setting different voltage parameter AC components and / or DC components in different time periods without changing the hardware structure of the multipole, thereby changing the way ions pass through the multipole, significantly improving the detection flux and resolution, and the method is simple and has broad application prospects.

Description

Technical Field

[0001] The present application relates to a method for improving the resolution of a mass spectrometer, and in particular to a multi-stage tandem scanning method for improving the resolution of a multipole, and belongs to the technical field of analysis. Background Art

[0002] Quadrupole mass analyzer, also known as quadrupole for short, is an important type of mass spectrometer, mainly used in analytical methods for measuring the mass-to-charge ratio of ions. Quadrupole belongs to dynamic mass spectrometry. Since it only uses pure electric field and does not involve magnetic field, its structure is simple. Quadrupole only requires that the incident ion energy is less than a certain upper limit, and does not require the incident ion to achieve energy focusing. It is suitable for ions with a certain energy dispersion, and its scanning speed is fast. The instrument sensitivity and resolution can be adjusted by adjusting the voltage parameters to determine the ion mass. Similar variants of quadrupole include hexapole, octopole, etc.

[0003] In a quadrupole mass spectrometer, generally speaking, the resolution from when ions are incident on the quadrupole mass analyzer to when they are emitted from the quadrupole mass analyzer is controlled by the stability region and the scan line, usually only allowing ions with a specific mass-to-charge ratio (m / z) to pass. Figure 1 As shown in the figure, the curved triangle area is the stable area α of the quadrupole, which is the area where the ions to be measured complete the curved motion and stably pass through the quadrupole; the oblique line is the scan line I of the quadrupole, which is controlled by the DC component (U) and AC component (V) of the voltage parameter and has a slope k. The length of the intersection of the scan line and the stable area is the incident ion width L, that is, the specific mass-to-charge ratio m / z value range.

[0004] Taking a single quadrupole as an example, in the prior art, its voltage parameters usually remain unchanged when ions enter and exit the quadrupole electric field, and only ions with a specific mass-to-charge ratio pass through. If the U and V applied to the quadrupole are adjusted, that is, the slope k is reduced, L can be widened. In this state, the ion screening flux will increase, but at the same time, the m / z resolution of the quadrupole will decrease. For details, please refer to Figure 2a , setting A0 indicates the current quadrupole voltage parameter, which determines the slope of the scan line. When the slope corresponding to A0 is large, the goal is to allow ions with a narrow m / z value range to pass through, so the ion flux is low and the resolution is high, which belongs to "narrow in and narrow out". When the slope of A0 is small, such as A0 = A1, please refer to Figure 2b The goal is to allow ions with a wider m / z value range to pass through, so the ion flux is high and the resolution is low, which belongs to "wide in and wide out".

[0005] Therefore, the quadrupole mass analyzer in the prior art cannot achieve high throughput and high resolution at the same time because it adopts a single stable zone setting state, that is, improving the resolution will lead to a problem of reduced throughput, but increasing the flux will inevitably reduce the resolution. How to achieve high throughput and high resolution at the same time is a problem that the industry has always been eager to solve. Summary of the invention

[0006] The main purpose of the present application is to provide a multi-stage tandem scanning method for improving the multipole resolution, which can achieve high throughput and resolution without changing the hardware conditions of the multipole mass analysis device, thereby overcoming the shortcomings of the prior art.

[0007] In order to achieve the aforementioned invention objectives, the technical solutions adopted in this application include:

[0008] Some embodiments of the present application provide a multi-stage tandem scanning method for improving the resolution of a multipole, which includes: allowing ions to enter a multipole mass analysis device (hereinafter referred to as a multipole), and setting multiple stable zones for multiple ion mass-to-charge ratios, and combining the multiple stable zones in series, and adjusting the combination relationship between each stable zone and the corresponding scanning line, thereby changing the way ions pass through the multipole mass analysis device, thereby improving the screening flux and resolution of the multipole mass analysis device for ions.

[0009] In one embodiment, the multi-stage tandem scanning method specifically includes: allowing ions to enter a multipole mass analysis device, and adjusting the operating parameters of the multipole mass analysis device at different times to form a plurality of stable zones, and adjusting the combination relationship between each stable zone and the corresponding scanning line.

[0010] In one embodiment, the multi-stage serial scanning method specifically includes: setting a plurality of stable areas with different start time values ​​in sequence, thereby realizing a serial combination of the plurality of stable areas.

[0011] In one embodiment, the scanning intervals of two adjacent stable zones intersect, that is, the incident intervals of the adjacent stable zones have overlapping parts.

[0012] In one embodiment, the operating parameters of the multipole mass analysis device include a DC component U and / or an AC component V of a voltage parameter.

[0013] In one embodiment, the multi-stage tandem scanning method specifically includes: adjusting U and / or V to change the slope of the scanning line corresponding to a stable area, thereby changing the length of the line segment where the scanning line intersects the stable area, that is, the incident ion width, which is also the ion passage area corresponding to the stable area.

[0014] In one embodiment, the plurality of stabilization regions have the same incident ion width.

[0015] In one embodiment, at least two of the stabilization regions have different incident ion widths.

[0016] In one embodiment, in the multipole mass analysis device, a plurality of stable regions and corresponding scan lines are combined in series to form an ion passing region, and the ion passing region only allows ions with a specified mass-to-charge ratio to pass through.

[0017] In one embodiment, the multipole mass analysis device includes one or more combinations of quadrupole, multiple quadrupole, hexapole, octopole, and ion trap mass analysis devices, but is not limited thereto. The multiple quadrupole can be a combination of double quadrupoles or more quadrupoles.

[0018] The present application mainly adjusts the setting of the multipole stable interval, by changing the multipole from one stable zone to multiple stable zones, and combining the multiple stable zones front and back, to achieve the effect of "wide in and narrow out", that is, the incident ion width is large and the exit ion width is small, to achieve the effect of high flux and high resolution. More intuitively, the principle of the present application can also be referred to Figure 3 .

[0019] In a typical implementation, several stable regions with the same incident ion width but different ion starting values ​​are combined in a front-to-back manner to achieve the effect of "wide in and narrow out". For example, see Figure 4 , where the quadrupole has two stable zones connected in series. When ions enter the single quadrupole, the stable zone of the quadrupole is set to state A, allowing a large number of ions to enter the quadrupole; later, the stable zone setting of the quadrupole is changed from state A to state B, allowing only some ions to pass through in state B. In state A, ions corresponding to a wider m / z value range enter the quadrupole. When the quadrupole is converted to state B, among these ions that have entered the quadrupole, only ions that meet both states A and B can finally pass through the quadrupole smoothly.

[0020] In this application, the incident ion width is also called the incident interval, which refers to the m / z value range of the ions formed by the scan line and the corresponding stable area entering the multipole electric field. The exit ion width is also called the exit interval, which refers to the m / z value range of the ions formed by the combined stable area and the scan line leaving the multipole electric field.

[0021] Compared with the prior art, the present invention can achieve the combination of the multipole stable region and the scanning line from the perspective of process control by setting different voltage parameters AC component, DC component or combination thereof in different time periods without changing the multipole hardware structure, thereby changing the way ions pass through the multipole to achieve high flux and high resolution. The method of the present invention is simple and easy to implement, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 It is a schematic diagram of a stable region and scanning line of a quadrupole in the prior art;

[0024] Figure 2a-2b It is a schematic diagram of the influence of scanning lines with different slopes on the ion entry and exit interval in the prior art;

[0025] Figure 3 is a schematic diagram of a multi-stage tandem scanning method for improving multipole resolution in the present application;

[0026] Figure 4 It is a schematic diagram of a stable region process control of a quadrupole in a typical implementation scheme of the present application;

[0027] Figure 5 is a schematic diagram of a quadrupole arrangement in Example 1;

[0028] Figure 6 is a schematic diagram of a quadrupole arrangement in Example 2;

[0029] Figure 7 is a schematic diagram of a hexapole arrangement in Example 3;

[0030] Figure 8 is a schematic diagram of a double quadrupole arrangement in Example 4;

[0031] Fig. 9 This is a schematic diagram of a triple quadrupole setup in Example 5. DETAILED DESCRIPTION

[0032] As mentioned above, in view of the problem that the existing quadrupole cannot achieve both high throughput and high resolution effects in a single stable zone setting, the applicant has proposed the technical solution of the present application, which mainly starts from the multipole process control level and adopts a combination of multiple stable zones and multiple scanning lines to change the way ions pass through the multipole, thereby achieving high throughput while also improving the resolution. The operation is simple and there is no need to change the original hardware structure of the multipole.

[0033] The technical solution of the present application will be described in more detail below in conjunction with several embodiments and drawings, but it should be understood that the following embodiments are only for explaining and illustrating this method, but do not limit the scope of the present application.

[0034] Embodiment 1 A two-stage tandem scanning method based on a single quadrupole comprises:

[0035] Reference Figure 5 The single quadrupole is set to have two stable regions in series. In the first stable region, the DC component U and AC component V of the voltage parameter are adjusted to reduce the scan line slope to k, and this quadrupole setting is recorded as state A; in the second stable region, similarly, the scan line slope is also reduced to k, recorded as state B; the start time value of state B is different from that of state A, but the scan intervals of states A and B overlap.

[0036] Please continue reading Figure 5 , the ions enter the single quadrupole, and the stable zone is set to state A at this time. After the ions fly for a milliseconds in state A, the stable zone setting is changed to state B. The time for the ions to pass in state B is (Xa) milliseconds, and the total time is X milliseconds. In state A, a large number of ions enter the quadrupole, and the m / z value range of these ions is relatively wide. In the case of conversion to state B, among the ions that have entered the quadrupole, only ions that meet both states A and B can finally pass through the quadrupole smoothly. For example, in state A, ions with m / z of 100.00-101.00 can enter the quadrupole, but state B only allows ions with m / z of 100.98-101.98 to pass. Although the passing width of states A and B is the same, only ions with m / z of 100.98-101.00 can pass through in the end, thus achieving high resolution. Since the width of the incident ions is large in state A, the flux of the ions entering is high, so the amount of high-resolution ions obtained after passing through states A and B is also high.

[0037] Embodiment 2 A two-stage tandem scanning method based on a single quadrupole comprises:

[0038] Reference Figure 6 The single quadrupole is arranged to have two stable regions connected in series. However, the slopes k of the two scanning lines are inconsistent. Similar to Example 1, the scanning intervals of the A and B states in this embodiment also intersect.

[0039] Please continue reading Figure 6, the ion enters the single quadrupole, and the stability zone of the quadrupole is set to state A. After the ion flies for a milliseconds in state A, the stability zone setting is changed to state B. The time for the ion to pass in state B is (Yb) milliseconds, and the total duration is Y milliseconds. In state A, a large number of ions enter the quadrupole, and the m / z value range of these ions is relatively wide. When converted to state B, among the ions that have entered the quadrupole, only ions that meet both states A and B can finally pass through the quadrupole smoothly. In state A, ions with m / z of 100.00-101.00 can enter the quadrupole, but since state B only allows ions with m / z of 100.99-101.49 to pass through. The series-connected A and B states finally allow only ions with m / z of 100.99-101.00 to pass, thereby achieving high resolution. Since the width of the incident ions in state A is large, the flux of ions entering is high, and after passing through states A and B, the amount of high-resolution ions obtained also increases.

[0040] Embodiment 3 A three-stage tandem scanning method based on a hexapole comprises:

[0041] Similar to the single quadrupole in Example 1, the hexapole in this embodiment still achieves ion transmission by controlling voltage parameters. Figure 7 For the hexapole, this embodiment sets three different voltage parameters at three different starting times, so that the hexapole changes from a single stable region to three stable regions in series, which are respectively recorded as A, B, and C states, and the slope of each scan line reaches k. The three stable regions and the scan lines are combined in series to form an ion passing region; the ion passing region formed in series ultimately only allows ions in a specific m / z value range to pass.

[0042] For example, in state A, ions with m / z of 49.90-50.05 can enter the hexapole, but in state B, only ions with m / z of 49.95-50.10 are allowed to pass through. Although the passing widths of states A and B are the same, only ions with m / z of 49.95-50.05 can pass through state B in the end. And because state C only allows ions with m / z of 50.00-50.15 to pass through, only ions with m / z of 50.00-50.05 can pass through the hexapole smoothly in the end. Since the incident ion width of state A is large, the ion flux entering is high, and after passing through states A, B, and C, the amount of high-resolution ions obtained is also high.

[0043] The m / z value interval that can be detected by the method of this embodiment is 0.05, that is, the resolution is 0.05amu. The m / z value interval that can be detected by the hexapole based on a single stable region is 0.15, that is, the resolution is 0.15amu. It can be seen that the method of this embodiment improves the resolution by three times.

[0044] Embodiment 4 A three-stage tandem scanning method based on double quadrupoles comprises:

[0045] See also Figure 8 , similar to the single quadrupole of Example 1, in this embodiment, without changing the hardware setting of the double quadrupole, the stable area and the scan line in the first quadrupole are set to state A, and the stable area and the scan line in the second quadrupole are set to state B. Under the A state setting, a large number of ions enter the first quadrupole Q1, and the part of the ions that meet the setting A passes through Q1 smoothly. When these ions enter the second quadrupole Q2, the ions can pass through the quadrupole Q2 smoothly only when the setting B state is met. Therefore, the effect is achieved that ions can pass through the double quadrupole only when they meet the settings A and B states at the same time. Thus, the condition of wide entry and strict exit is achieved. In the settings of A and B states, the scan line slope k can be the same or different.

[0046] Embodiment 5 A three-stage tandem scanning method based on a triple quadrupole comprises:

[0047] See also Fig. 9 Without changing the existing triple quadrupole hardware structure, while maintaining the settings of quadrupoles Q1 and Q3 unchanged, the setting of quadrupole Q2 is changed to a sequential setting similar to that of Example 1. Ions need to simultaneously meet both the A and B states in quadrupole Q2 to pass smoothly, thereby achieving the effect of high-resolution mass spectrometry.

[0048] Although the present application has been described with reference to illustrative embodiments, it will be appreciated by those skilled in the art that various other changes, omissions, and / or additions may be made and that elements of the described embodiments may be substituted with substantial equivalents without departing from the spirit and scope of the present application. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the present application without departing from the scope of the present application. Therefore, it is not intended herein to limit the present application to the disclosed specific embodiments for carrying out the present application, but rather it is intended that the present application will include all embodiments within the scope of the appended claims.

Claims

1. A multi-stage tandem scanning method for improving multipole resolution, characterized in that: include: Ions are allowed to enter a multipole mass analyzer, and the working parameters of the multipole mass analyzer are adjusted at different times, so that a plurality of stable regions are formed for a plurality of ion mass-to-charge ratios, and the plurality of stable regions are combined in series, and the combination relationship between each stable region and the corresponding scanning line is adjusted, so as to change the way the ions pass through the multipole mass analyzer, thereby improving the screening flux and resolution of the multipole mass analyzer for ions.

2. The multi-stage tandem scanning method for improving multipole resolution according to claim 1, characterized in that: Specifically include: Multiple stable zones with different start time values ​​are set in sequence, thereby realizing a series combination of multiple stable zones.

3. The multi-stage tandem scanning method for improving multipole resolution according to any one of claims 1 to 2, characterized in that: There are overlapping parts in the incident intervals of adjacent stable zones.

4. The multi-stage tandem scanning method for improving multipole resolution according to claim 1, characterized in that: The operating parameters of the multipole mass analysis device include a DC component U and / or an AC component V of a voltage parameter.

5. The multi-stage tandem scanning method for improving multipole resolution according to claim 4, characterized in that: Specifically include: By adjusting U and / or V, the slope of the scan line corresponding to a stable region is changed, thereby changing the length of the intersection line segment of the scan line and the stable region, that is, the incident ion width.

6. The multi-stage tandem scanning method for improving multipole resolution according to claim 5, characterized in that: The plurality of stabilization regions have the same incident ion width.

7. The multi-stage tandem scanning method for improving multipole resolution according to claim 5, characterized in that: At least two of the stabilization regions have different incident ion widths.

8. The multi-stage tandem scanning method for improving multipole resolution according to claim 1, characterized in that: In the multipole mass analysis device, a plurality of stable regions and corresponding scanning lines are combined in series to form an ion passing region, and the ion passing region only allows ions with a specified mass-to-charge ratio to pass through.

9. The multi-stage tandem scanning method for improving multipole resolution according to claim 1, characterized in that: The multipole mass analysis device includes one or more combinations of quadrupole, multi-quadrupole, hexapole, octopole, and ion trap mass analysis devices.

Images