Mass spectrometry device and method based on multiple modes

Abstract

The invention provides a mass spectrometry device and method based on multiple modes. The mass spectrometry device comprises an ion source, a detector and a power supply, the multi-stage transmission unit is arranged between the ion source and the detector; the transmission unit comprises an ion lens and a multi-pole rod; the input end of the control unit is connected with the power supply, the output end of the control unit is connected with the multi-pole rod and the ion lens, and the control unit is used for adjusting the voltage of the multi-pole rod and the ion lens, so that the transmission unit is selectively in an ion transmission mode, an ion filtering mode and an ion storage mode. The invention has the advantages of high sensitivity, simple structure and the like.

Description

Technical Field

[0001] The present invention relates to mass spectrometry technology, and in particular to a mass spectrometry analysis device and method based on multi-mode. Background Art

[0002] Ion trap mass spectrometry is adopted by many mass spectrometers because of its high sensitivity, convenient processing, high working pressure, and support for multi-stage tandem mass spectrometry analysis. In mass spectrometers, the ion optical transmission system plays an important role. Its main function is to efficiently transmit the ions ionized in the ion source to the mass analyzer working under high vacuum. However, in the transmission channel from ion generation to entering the mass analyzer, the ion transmission efficiency is extremely low, and the ion pass rate is less than 1%. Therefore, it is very important to optimize the ion optical transmission system.

[0003] The voltage parameters of each component of the ion transmission system will affect the transmission efficiency of the ion transmission system, and thus affect the analysis results. The voltage is generally divided into RF voltage and DC voltage. How to effectively control them to achieve the optimal output voltage according to different analysis requirements is a difficult problem.

[0004] RF voltage generally refers to the RF voltage of each ion guide including ion funnel, quadrupole, multipole and other devices. It has a greater impact on the relative abundance of ions with different mass-to-charge ratios and can better confine the ions.

[0005] DC voltage generally refers to the voltage of the ion guide and its interface (ion gate). In ion trap mass spectrometry, in order to reduce the space charge effect, an ion gate is usually required to control the number of ions entering the ion trap. Ion gates are generally divided into two categories: one is a consumption type ion gate (when the ion gate is closed, ions transmitted from the source end are continuously removed from the ion transmission channel), and the other is a blocking type ion gate (by applying a higher potential barrier, ions transmitted from the source end continue to move forward, but the ions remain in the ion transmission channel).

[0006] In an ion trap mass spectrometer that uses a depletion-type ion gate, it is easier to use the AGC (automatic gain control) method to adjust the number of ions in the ion trap, and the instrument's quantitative capability (linear response) is usually strong; however, the use of a depletion-type ion gate will result in only a portion of the ions being available for mass spectrometry analysis, which may result in a decrease in instrument sensitivity or detection limit. In contrast, in an ion trap mass spectrometer that uses a barrier-type ion gate, the number of ions in the ion trap cannot be adjusted very accurately, and the instrument's quantitative capability is usually poor. However, with a barrier-type ion gate, ion utilization can be relatively high, which will improve instrument sensitivity or detection limit and other performance.

[0007] In actual application, sometimes the instrument needs to have high sensitivity and detection ability only when detecting low-concentration samples, but the quantitative range is not so wide, and sometimes the instrument needs to be matched with a chromatogram with a larger quantitative range. In order to meet different detection needs, new challenges are posed to the voltage control system of the ion trap mass spectrometer. The traditional single ion gate control in and out to solve the defect of limited ion trap capacity is not enough to meet a variety of detection needs. In addition, the length of the ion gate opening time is also restricted by related factors. If the time is too long, it is easy to be affected by the space charge effect, and if the time is too short, the signal intensity of low-concentration samples will not be greatly improved. Summary of the invention

[0008] In order to solve the deficiencies in the above-mentioned prior art solutions, the present invention provides a mass spectrometry analysis device based on multi-mode.

[0009] The objective of the present invention is achieved through the following technical solutions: A multi-mode mass spectrometry device, comprising an ion source, a detector and a power supply; the mass spectrometry device also comprises: A multi-stage transmission unit, the multi-stage transmission unit is arranged between the ion source and the detector, the transmission unit comprises an ion lens and a multipole; A control unit, wherein the input end of the control unit is connected to the power supply, and the output end of the control unit is connected to the multipole and the ion lens, and is used to adjust the voltage of the multipole and the ion lens so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode.

[0010] Another object of the present invention is to provide a mass spectrometry analysis method, which is achieved by the following technical solutions: According to the mass spectrometry analysis method of the mass spectrometry analysis device of the present invention, the mass spectrometry analysis method is: The control unit adjusts the voltages of the multipole and the ion lens in the multistage transmission unit according to the sample state and the sample concentration, so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode; The sample is ionized and the ions enter the detector through a multi-stage transmission unit.

[0011] Compared with the prior art, the present invention has the following beneficial effects: 1. Good quantitative ability; Different working modes can be realized in the same mass spectrometer, which can be applied to different scenarios and provide better quantitative and detection capabilities; 2. Simple structure; No additional equipment is required, the selected multi-pole transmission rod is low-cost, effectively reducing costs, with simple structure and easy operation; 3. High sensitivity; The control unit is used to realize the switching of various working modes, with fast switching, wide detection range and high sensitivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The disclosure of the present invention will become easier to understand with reference to the accompanying drawings. It is easy for those skilled in the art to understand that these drawings are only used to illustrate the technical solution of the present invention and are not intended to limit the scope of protection of the present invention. In the drawings: Figure 1 is a schematic structural diagram of a multi-mode mass spectrometry analysis device according to an embodiment of the present invention; Figure 2 is a timing diagram of the working mode according to an embodiment of the present invention. DETAILED DESCRIPTION

[0013] Figure 1-Figure 2 The following description describes optional specific embodiments of the present invention to teach those skilled in the art how to implement and reproduce the present invention. In order to teach the technical solution of the present invention, some conventional aspects have been simplified or omitted. Those skilled in the art will understand that variations or replacements derived from these specific embodiments will be within the scope of the present invention. Those skilled in the art will understand that the following features can be combined in various ways to form multiple variations of the present invention. Thus, the present invention is not limited to the following optional specific embodiments, but is only limited by the claims and their equivalents.

[0014] Example 1

[0015] The multi-mode mass spectrometry device according to embodiment 1 of the present invention is as follows: Figure 1 As shown, the multi-mode based mass spectrometry analysis device comprises: Ion source 1, detector 210 and power supply; A multi-stage transmission unit 2, wherein the multi-stage transmission unit 2 is arranged between the ion source 1 and the detector 210, and the transmission unit comprises an ion lens and a multipole; A control unit, wherein the input end of the control unit is connected to the power supply, and the output end of the control unit is connected to the multipole and the ion lens, and is used to adjust the voltage of the multipole and the ion lens so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode.

[0016] In order to accurately match the mode, further, the control unit works as follows: According to the sample status and sample concentration, the mode of the transmission unit is adjusted.

[0017] In order to improve the detection capability and sensitivity, further, as the sample concentration increases, the transmission unit changes from the ion storage mode or the ion filtration mode to the ion transmission mode, and the downstream transmission unit changes earlier than the upstream transmission unit; wherein, when the sample concentration is minimum, the multi-stage transmission units from upstream to downstream are in the ion transmission mode, ion filtration mode and ion storage mode respectively.

[0018] In order to accurately match the mode, further, the control unit works as follows: The radio frequency voltage of the multipole is adjusted according to the mass-to-charge ratio of the sample.

[0019] In order to improve the sensitivity, further, if the mass-to-charge ratio is less than the first threshold, the radio frequency voltage is 0.5m+50; If the mass-to-charge ratio is between the first threshold and the second threshold, the RF voltage is 0.325m+67.5; If the mass-to-charge ratio is between the second threshold and the third threshold, the RF voltage is 0.24m+110; If the mass-to-charge ratio is greater than the third threshold, the RF voltage is 350V.

[0020] In order to improve the detection capability and sensitivity, further, such as Figure 2 As shown, in the ion transmission mode, the DC voltage of the ion lens 24 of the second-stage transmission unit remains unchanged during the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is 10V-20V; the DC voltage of the ion lens 26 of the third-stage transmission unit remains unchanged during the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is 0-10V; the DC voltage before the ion gate between the multi-stage transmission unit and the detector 210 remains unchanged during the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is -50V- -40V; In the ion filtering mode, the voltage of the multipole increases after the 1 / 3 stage of pre-scan, the voltage range is 2000V-3000V, and remains unchanged in the subsequent stages until the ions are cleared, the conventional voltage range is 100V-500V; In the ion storage mode, the DC voltage of the ion lens 24 of the second-stage transmission unit is increased to a high voltage before pre-scanning, with a voltage range of 400V-500V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remains unchanged in the subsequent stages until the ions are cleared; the DC voltage of the ion lens 26 of the third-stage transmission unit is increased to a high voltage after 1 / 3 of the pre-scanning stage, with a voltage range of 400V-500V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remains unchanged in the subsequent stages until the ions are cleared; the DC voltage in front of the ion gate 28 is increased to a high voltage after 2 / 3 of the pre-scanning stage, with a voltage range of 90V-100V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remains unchanged in the subsequent stages until the ions are cleared.

[0021] The mass spectrometry analysis method of the embodiment of the present invention, that is, the mass spectrometry analysis method of the mass spectrometry analysis device of this embodiment, is as follows: According to the sample state and sample concentration, the control unit adjusts the voltages of the multipole and the ion lens in the multistage transmission unit 2 so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode; The sample is ionized, and the ions pass through the multi-stage transmission unit 2 in sequence and enter the detector 210.

[0022] Example 2

[0023] An example of application of the multi-mode based mass spectrometry analysis device and method according to Example 1 of the present invention in the detection of methamphetamine in hair.

[0024] In this application example, Figure 1 As shown, the multi-stage transmission unit 2 is three-stage and is located between the ion source 1 and the detector 210. The ion source includes an atmospheric pressure inlet and an ion funnel 21, and the (ion trap) mass analyzer 29 is connected to the detector 210. The multipole 23 of the first-stage transmission unit is a single quadrupole, the multipole 25 of the second-stage transmission unit is a hyperbolic quadrupole, and the multipole 27 of the third-stage transmission unit is an octopole.

[0025] The control unit adjusts the voltage of the transmission unit (multipole and ion lens) according to the sample state and sample concentration, so that the transmission unit is selectively in the ion transmission mode, ion filtering mode and ion storage mode.

[0026] If the sample is a complex matrix, when the sample concentration is ≤10ppb, the three-stage transmission unit selects the normal transmission, ion filtration and ion storage working modes in turn; When the sample concentration is greater than 10 ppb but less than 1 ppm, the three-stage transmission unit selects the normal transmission, ion filtration and normal transmission working modes in turn; When the sample concentration is ≥1ppm, the three-level transmission unit selects the normal transmission, normal transmission and normal transmission working modes in turn; If the sample is a standard, when the sample concentration is ≤1ppb, the three-stage transmission unit selects the normal transmission, ion filtration and ion storage working modes in turn; When the sample concentration is greater than 1 ppb but less than 100 ppb, the three-stage transmission unit selects the normal transmission, ion filtration and normal transmission working modes in sequence; When the sample concentration is ≥100ppb, the three-stage transmission unit selects the normal transmission, normal transmission and normal transmission working modes in sequence.

[0027] The radio frequency voltage of the multipole is adjusted according to the mass-to-charge ratio of the sample.

[0028] If the mass-to-charge ratio is less than 100, the multipole RF voltage of the three-stage transmission unit is (0.5m+50)V; If the mass-to-charge ratio is between 100 and 500, the RF voltage is (0.325m+67.5)V; If the mass-to-charge ratio is between 500 and 1000, the RF voltage is (0.24m+110)V; If the mass-to-charge ratio is greater than 1000, the RF voltage is 350V.

[0029] like Figure 2 As shown, in the ion transmission mode, the DC voltage of the ion lens 24 (middle ion lens) of the second-stage transmission unit remains unchanged during the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is 10V-20V; the DC voltage of the ion lens 26 (rear ion lens) of the third-stage transmission unit remains unchanged during the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is 0-10V; the DC voltage in front of the ion gate between the multi-stage transmission unit and the detector 210 remains unchanged during the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is -50V- -40V.

[0030] In the ion filtering mode, the voltage of the multipole is increased after the pre-scan 1 / 3 stage, the voltage range is 2000V-3000V, and remains unchanged in the subsequent stages until the ions are cleared, the normal voltage range is 100V-500V.

[0031] In the ion storage mode, the DC voltage of the ion lens 24 of the second-stage transmission unit is increased to a high voltage before pre-scanning, with a voltage range of 400V-500V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remains unchanged in the subsequent stages until the ions are cleared; the DC voltage of the ion lens 26 of the third-stage transmission unit is increased to a high voltage after 1 / 3 of the pre-scanning stage, with a voltage range of 400V-500V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remains unchanged in the subsequent stages until the ions are cleared; the DC voltage in front of the ion gate 28 is increased to a high voltage after 2 / 3 of the pre-scanning stage, with a voltage range of 90V-100V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remains unchanged in the subsequent stages until the ions are cleared.

[0032] The mass spectrometry analysis method of the embodiment of the present invention, that is, the mass spectrometry analysis method of the mass spectrometry analysis device of this embodiment, is as follows: Hair is a complex matrix. The content of methamphetamine in hair is very low, less than 10ppb. The three-stage transmission unit selects normal transmission, ion filtration and ion storage working modes in turn.

[0033] like Figure 2 As shown, the DC voltage of the ion lens 24 of the second-stage transmission unit always maintains a stable voltage of 13V during the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing; the DC voltage of the ion lens 26 of the third-stage transmission unit is the same as the DC of the ion lens 24, and also always maintains a stable voltage during the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing. At this time, the DC voltage of the ion lens 26 is 5V, and the Q guide rod RF is increased to a high voltage of 140V after 1 / 3 of the pre-scanning stage, and remains unchanged in the subsequent stages until the ions are cleared; the DC voltage before the ion gate 28 is increased to a high voltage of 0V after 2 / 3 of the pre-scanning stage, and drops to a low voltage of -40V after continuing for 1 / 3 of the pre-scanning stage, and remains unchanged in the subsequent stages until the ions are cleared.

[0034] The mass-to-charge ratio of methamphetamine is 150, and the optimal radio frequency voltage obtained is 98.75V, that is, the radio frequency voltages of the ion funnel 21, the quadrupole 23, the hyperbolic quadrupole 25, and the octopole 27 fluctuate within the range of 98.75V, and the fluctuation range does not exceed 50V.

[0035] In the ion pre-scanning stage, ions generated by the atmospheric pressure inlet enter the multi-stage transmission unit 2 through the transmission capillary. The ion lenses and ion gates 28 at each stage are adjusted according to the Figure 2 Set the voltage and mode of operation.

[0036] During the ion injection and cooling stage, since the air pressure in the vacuum chamber is reduced and the vacuum degree is improved, a small amplitude RF voltage is increased and maintained, so that the ions can be injected to the maximum extent and the kinetic energy can be reduced by collision with the buffer gas in the mass analyzer 29, and the ions can be effectively captured by the mass analyzer 29; during the mass scanning stage, as the RF voltage gradually increases, the ions are ejected from the mass analyzer 29 in sequence according to the mass-to-charge ratio, and the detector 210 starts to detect the ions and generate a spectrum; during the ion clearing stage, the RF voltage is reduced to zero, the ions in the mass analyzer 29 are cleared, and preparation for the next stage of analysis is made, and the above steps are repeated during the analysis process.

Claims

1. A multi-mode mass spectrometry device, comprising an ion source, a detector and a power supply; characterized in that: The mass spectrometry device also includes: A multi-stage transmission unit, the multi-stage transmission unit is arranged between the ion source and the detector, the transmission unit comprises an ion lens and a multipole; A control unit, wherein the input end of the control unit is connected to the power supply, and the output end of the control unit is connected to the multipole and the ion lens, and is used to adjust the voltage of the multipole and the ion lens so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode.

2. The multi-mode mass spectrometry analysis device according to claim 1, characterized in that: The working mode of the control unit is: According to the sample status and sample concentration, the mode of the transmission unit is adjusted.

3. The multi-mode mass spectrometry analysis device according to claim 2, characterized in that: As the sample concentration increases, the transmission unit changes from the ion storage mode or the ion filtration mode to the ion transmission mode, and the downstream transmission unit changes earlier than the upstream transmission unit.

4. The multi-mode mass spectrometry analysis device according to claim 3, characterized in that: When the sample concentration is minimum, the multi-stage transmission unit from upstream to downstream is in ion transmission mode, ion filtration mode and ion storage mode in sequence.

5. The multi-mode mass spectrometry analysis device according to claim 2, characterized in that: The working mode of the control unit is: The radio frequency voltage of the multipole is adjusted according to the mass-to-charge ratio of the sample.

6. The multi-mode mass spectrometry analysis device according to claim 5, characterized in that: If the mass-to-charge ratio is less than the first threshold, the RF voltage is 0.5m+50; If the mass-to-charge ratio is between the first threshold and the second threshold, the RF voltage is 0.325m+67.5; If the mass-to-charge ratio is between the second threshold and the third threshold, the RF voltage is 0.24m+110; If the mass-to-charge ratio is greater than the third threshold, the RF voltage is 350V.

7. The multi-mode mass spectrometry analysis device according to claim 1, characterized in that: In the ion transmission mode, the DC voltage of the ion lens of the second-stage transmission unit remains unchanged in the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is 10V-20V; the DC voltage of the ion lens of the third-stage transmission unit remains unchanged in the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is 0-10V; the DC voltage in front of the ion gate between the multi-stage transmission unit and the detector remains unchanged in the four stages of pre-scanning, ion injection cooling, mass analysis, and ion clearing, and the voltage range is -50V- -40V; In the ion filtering mode, the voltage of the multipole increases after the 1 / 3 stage of pre-scan, the voltage range is 2000V-3000V, and remains unchanged in the subsequent stages until the ions are cleared, the conventional voltage range is 100V-500V; In the ion storage mode, the DC voltage of the ion lens of the second-stage transmission unit is increased to a high voltage before pre-scanning, with a voltage range of 400V-500V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remaining unchanged in subsequent stages until the ions are cleared; the DC voltage of the ion lens of the third-stage transmission unit is increased to a high voltage after 1 / 3 of the pre-scanning stage, with a voltage range of 400V-500V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remaining unchanged in subsequent stages until the ions are cleared; the DC voltage in front of the ion gate is increased to a high voltage after 2 / 3 of the pre-scanning stage, with a voltage range of 90V-100V, and lasts for 1 / 3 of the pre-scanning stage before reducing the voltage and remaining unchanged in subsequent stages until the ions are cleared.

8. The multi-mode mass spectrometry analysis device according to claim 1, characterized in that: The multipole of the first-stage transmission unit is a single quadrupole, the multipole of the second-stage transmission unit is a hyperbolic quadrupole, and the multipole of the third-stage transmission unit is an octopole.

9. The mass spectrometry analysis method according to any one of claims 1 to 8, wherein the mass spectrometry analysis method comprises: The control unit adjusts the voltages of the multipole and the ion lens in the multistage transmission unit according to the sample state and the sample concentration, so that the transmission unit is selectively in the ion transmission mode, the ion filtering mode and the ion storage mode; The sample is ionized and the ions enter the detector through a multi-stage transmission unit.

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