Ion source, mass spectrometer, and ion generation method

Abstract

This allows for more precise focusing of the post-ionization laser beam and maintains the ion source in optimal or better condition. [Solution] The ion source 100 includes a substrate 1, a first laser generator 2, a second laser generator 3, a detector 4, and a drive mechanism 5. The substrate 1 supports the sample, and the first laser generator 2 emits a first laser beam 2a onto the substrate 1, desorbing and ionizing the sample to form a particle plume. The focusing position of the second laser generator 3 is located away from the sample and the substrate 1, and is separated from the substrate 1 by a predetermined distance, ionizing the particle plume to obtain signal ions. The detector 4 detects the signal intensity of the signal ions, and the drive mechanism 5 moves the focusing position of the second laser generator 3. The endpoint of the focusing position is determined based on a comparison between the respective signal intensities detected by the detector 4 during the movement of the focusing position.

Description

Technical Field

[0001] The present invention relates to the field of ion analysis technology, and more specifically, to an ion source, a mass spectrometer, and an ion generation method.

Background Art

[0002] MALDI-2 is a method of ionizing after laser-induced MALDI (Matrix-assisted laser desorption / ionization), and the sensitivity for various analysis targets (for example, phospholipids and glycolipids, steroids, sugar chains, and pharmaceuticals) can be improved by 1 to 3 digits (Science, 2015, 10, 348(6231), 211-5). However, since all commercially available MALDI-2 ion sources operate under vacuum conditions, it is difficult to install samples, and it is not suitable for the analysis of volatile samples.

[0003] Niehaus et al. reported on a self-made MALDI-2 ion source that operates in an atmospheric pressure environment (J. Am. Soc. Mass Spectrom. 2020, 31, 11, 2287-2295), showing the possibility of MALDI-2 operation in an atmospheric pressure environment. However, MALDI-2 operation in an atmospheric pressure environment is still difficult, especially the alignment of the post-ionization laser beam is difficult.

Summary of the Invention

Problems to be Solved by the Invention

[0004] Theoretically, the post-ionization laser beam should overlap with the particle plume ablated by the ablation laser. However, in the study of this invention, the inventors found that under atmospheric pressure conditions, the particle plume size can be very small, so the focusing position of the post-ionization laser beam can only tolerate errors at the micrometer level. In the previously reported MALDI-2 ion source, the alignment of the post-ionization laser beam is achieved by precise mechanical calibration before measurement, both in vacuum and atmospheric pressure environments, and the post-ionization laser beam is mechanically fixed when the ion source is operating. Therefore, users cannot determine whether the MALDI-2 ion source is functioning optimally to achieve the highest sensitivity. Furthermore, many factors, such as substrate unevenness and interference from electric fields or airflow, can cause mechanical errors in the laser-particle plume alignment process, all of which lead to problems where the MALDI-2 cannot operate optimally.

[0005] Therefore, finding a way to focus the post-ionization laser beam more precisely and maintain the ion source in an optimal or better state is an urgent technical challenge that needs to be addressed. [Means for solving the problem]

[0006] A first aspect of the present invention provides an ion source comprising a substrate, a first laser generator, a second laser generator, a detector, and a drive mechanism. The substrate is used to support a sample. The first laser generator emits a first laser beam toward the substrate to desorb and ionize the sample to obtain a particle plume. The focus position of the second laser generator is located away from the substrate and at a predetermined distance from the substrate, and the second laser generator ionizes the particle plume to obtain signal ions. The detector detects the signal intensity of the signal ions. The drive mechanism is used to move the focus position of the second laser generator, and the endpoint of the focus position is determined based on a comparison between the respective signal intensities detected during the movement of the focus position.

[0007] Optionally, the second laser generator includes a laser oscillator and a group of optical mirrors, the group of optical mirrors being positioned in the laser path of the laser oscillator, and a drive mechanism connected to the group of optical mirrors, thereby changing the laser path of the laser oscillator by moving or rotating the group of optical mirrors.

[0008] Optionally, the ion source further includes a sensor used to receive a second laser beam emitted by a second laser generator, and the endpoint of the focusing position is determined based on the detection result of the sensor.

[0009] Optionally, the sensor's detection results may include spot shape, relative spot position, and / or laser energy.

[0010] Optionally, the second laser generator includes a reflector, which refocuses the second laser beam, already focused to the first position of the particle plume, to the second position of the particle plume.

[0011] The reflecting mirror is, arbitrarily, a concave mirror.

[0012] Optionally, the position or angle of the reflector is determined based on a comparison between the respective signal intensities detected during the movement or rotation of the reflector.

[0013] The operating pressure range of the ion source is optionally 1 to 10 5 It is Pa.

[0014] Optionally, the ion source is an atmospheric pressure ion source.

[0015] Optionally, the substrate includes a standard sample area and a measurement sample area, and the ion source is configured to determine the endpoint of the focusing position of the second laser generator based on the standard sample area, and then move the substrate to detect the sample in the measurement sample area.

[0016] Optionally, the movement of the focusing position by the drive mechanism has a component in a direction parallel to the surface of the substrate.

[0017] Optionally, the movement of the focusing position by the drive mechanism further has a component in a direction perpendicular to the surface of the substrate.

[0018] Optionally, the predetermined distance is 0.01 to 5 mm.

[0019] Optionally, in a region adjacent to the substrate, the laser path of the first laser generator is along a direction inclined with respect to the surface of the substrate, and the laser path of the second laser generator is along a direction parallel to the surface of the substrate.

[0020] Optionally, further includes a control unit, the control unit is communicably connected to both the detector and the drive mechanism, and the end point of the focusing position is determined by comparison by the control unit.

[0021] A second aspect of the present invention provides a mass spectrometer including the ion source according to the first aspect of the present invention.

[0022] A third aspect of the present invention is Desorbing and ionizing a sample using a first laser beam to obtain a particle plume; Ionizing the particle plume using a second laser beam to obtain signal ions; Detecting the signal intensity of the signal ions while moving the focusing position of the second laser beam; Determining an end point of the focusing position of the second laser beam based on a comparison between the respective signal intensities corresponding to different focusing positions of the second laser beam; Positioning the focusing position of the second laser beam at the end point; Providing an ion generation method including.

Brief Description of Drawings

[0023] [Figure 1] It is a schematic configuration diagram of an ion source according to an embodiment of the present invention. [Figure 2] It is a schematic configuration diagram of a preferred ion source according to another embodiment of the present invention. [Figure 3] It is a schematic configuration diagram of the arrangement of the optical mirror group in the embodiment of FIG. 2. [Figure 4] It is a schematic system configuration diagram of a mass spectrometer according to some embodiments of the present invention. [Figure 5] It is a flowchart of an ion generation method according to some embodiments of the present invention.

Mode for Carrying Out the Invention

[0024] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. As will be understood by those skilled in the art, these embodiments merely illustrate the technical principle of the present invention and are not intended to limit the protection scope of the present invention.

[0025] The term "desorption and ionization" refers to the process of desorbing a sample from the surface of the substrate 1 and ionizing the sample. Desorption and ionization can be completed simultaneously or at different times, and the present application is not limited thereto.

[0026] FIG. 1 shows a schematic configuration diagram of an ion source 100 according to an embodiment of the present invention. As shown in FIG. 1, the ion source 100 is a MALDI-2 ion source 100. The "2" in "MALDI-2" means using a second laser beam 3a, that is, secondary ionization (or also called post-ionization) of particles / ions formed by primary desorption / ionization by the second laser generator 3. The MALDI-2 ion source 100 according to the present embodiment can be applied in an atmospheric pressure or low pressure environment. Since the environmental atmospheric pressure is high, such a pressure environment brings a compression effect to the particle plume PP (see FIG. 4), making it difficult for the particle plume PP to spread sufficiently, and thus imposing more stringent requirements on the focusing accuracy of the second laser beam 3a.

[0027] The ion source 100 according to this embodiment includes a substrate 1, a first laser generator 2, a second laser generator 3, a detector 4, a drive mechanism 5, and a control unit 6.

[0028] Of these, the substrate 1 is used to support the sample, and its specific material is not limited here. In a preferred embodiment, the substrate 1 may be a metal plate or a plate having a conductive layer, thereby allowing a certain electric field to be applied to the substrate 1. Alternatively, in another preferred embodiment, the substrate 1 may be a transparent plate, such as a glass plate, in which case the laser generator (first laser generator 2 and / or second laser generator 3) is placed on the side of the substrate 1 away from the sample, and the light beam emitted from the laser generator can pass through the substrate 1 and irradiate the sample.

[0029] The first laser beam 2a emitted by the first laser generator 2 and the second laser beam 3a emitted by the second laser generator 3 contain high-energy photons capable of desorbing and ionizing sample particles. The first laser generator 2 may be positioned on the same side of the substrate 1 as the sample, or on the side of the transparent substrate 1 away from the sample, as long as the emission surface of the first laser generator 2 is directed toward the substrate 1 or the emitted laser beam is guided toward the substrate 1. The first laser generator 2 can emit the first laser beam 2a onto the sample on the substrate 1, desorbing and ionizing the sample. The sample is first desorbed by the first laser beam 2a, forming ions, and these sample ions diffuse away from the substrate 1 to form a particle plume PP.

[0030] The focusing position FP (see Figure 4) of the second laser generator 3 is located away from the sample substrate 1 and separated from the substrate 1 by a predetermined distance, that is, it is pre-set to be aligned with the region where the particle plume PP exists. The "predetermined distance" can be freely selected depending on the specific situation, and generally, the predetermined distance is preferably 0.01 to 5 mm, and the ion concentration in the particle plume PP in this region is relatively high. The second laser beam 3a emitted by the second laser generator 3 can secondarily ionize the particle plume PP at the focusing position FP and obtain signal ions. After obtaining the particle plume PP by first desorption and ionization by the first laser generator 2, post-ionization of the particle plume PP can improve the ionization effect of various analytes and improve the detection sensitivity of the detector 4.

[0031] In the region adjacent to the substrate 1, the laser path of the second laser beam 3a within the range corresponding to the surface of the substrate 1 is preferably along a direction parallel to the surface of the substrate 1 and is focused at a particle plume PP located at a predetermined distance from the sample. The laser path of the first laser beam 2a emitted by the first laser generator 2 can be incident in a direction perpendicular to the surface of the substrate 1, that is, the laser path of the first laser beam 2a can intersect perpendicularly with the laser path of the second laser beam 3a. Preferably, the laser path of the first laser beam 2a is incident in a direction inclined with respect to the surface of the substrate 1 and is focused at a sample on the surface of the substrate 1.

[0032] The signal ions obtained by irradiating the particle plume PP with the second laser generator 3 enter the detector 4, and the detector 4 calculates the signal intensity of the signal ions based on the amount of signal ions detected. The detector 4 may be a mass detector or any other suitable type of sensor capable of detecting the amount of ions. In some embodiments, the ion source 100 according to this embodiment may be used as the ion source 100 of a mass spectrometer, and the signal intensity may be detected based on the mass detector of the mass spectrometer, for example, the detector of a quadrupole mass spectrometer or a time-of-flight mass spectrometer.

[0033] In the ion source 100, due to reasons such as sample load batch, instrument transport, and system errors / tolerances, the second laser beam 3a may not be able to be accurately focused onto the particle plume PP, and the focusing of the second laser beam 3a needs to be calibrated. To complete the calibration process more accurately, the ion source 100 according to this embodiment further includes a drive mechanism 5 and a control unit 6.

[0034] Of these, the drive mechanism 5 is used to move the focusing position FP of the second laser generator 3. The specific moving structure of the drive mechanism 5 is not limited here, but may be a rotating shaft structure or a moving rail type. For example, in a preferred embodiment, the entire second laser generator 3 may be fixed on the moving rail, or a part of the second laser generator 3, such as the optical mirror group, may be fixed on the moving rail. By controlling the movement of the entire or a part of the second laser generator 3, the focusing position FP of the laser beam emitted by the second laser generator 3 is adjusted. Alternatively, in another preferred embodiment, by attaching one or more lenses or mirrors in the optical mirror group of the second laser generator 3 to a rotating shaft structure, the focusing position FP of the second laser beam 3a emitted by the second laser generator 3 can be adjusted by rotating the rotating shaft structure, and all of these means are within the scope of protection of the present invention.

[0035] By flexibly moving the second laser generator 3, the focusing position FP of the second laser generator 3 can be adjusted to match the diffusion direction of the particle plume PP. Generally, the movement of the second laser generator 3 includes the X and Y axis directions horizontal to the substrate 1 and the Z axis direction perpendicular to the substrate 1. Movement in these multiple directions allows the second laser generator 3 to be focused to any position within the particle plume PP region.

[0036] In this embodiment, the control unit 6 is connected to the detector 4 and also to the drive mechanism 5. The control unit 6 determines the endpoint of the focusing position FP of the second laser generator 3 based on a comparison of the respective signal intensities detected by the detector 4 during the movement of the focusing position FP. Specifically, before starting the calibration process of the second laser generator 3, the position and orientation of the first laser generator 2 are first fixed, and the first laser beam 2a emitted by the first laser generator 2 is focused onto the sample on the surface of the substrate 1. Next, the calibration of the second laser generator 3 is performed. When the focusing position FP of the second laser generator 3 is at point A1, the signal intensity detected by the detector 4 is I1, and as the second laser generator 3 moves or rotates, the focusing position FP is sequentially A2, A3, A4, ..., A n Move to the point, and accordingly, the signal intensities detected by detector 4 at each of the above points will be I2, I3, I4, ..., In. Then, compare the signal intensities at each point. For example, if the detection results are I1~I n If I4 shows the maximum value, it can be determined that A4 is a reasonable focusing position FP, and the movable part of the drive mechanism 5 of the second laser generator 3 can be fixed to fix the focusing position FP of the second laser generator 3. In the subsequent measurement process, the second laser generator 3 is always fixed focused at point A4, and point A4 becomes the endpoint of the focusing position FP of the second laser generator 3 in this example.

[0037] By acquiring different signal intensities detected by the detector 4 during the movement of the focusing position FP, the most reasonable or more reasonable focusing position FP can be effectively determined, thereby improving the post-ionization effect of the second laser generator 3.

[0038] Because the second laser beam 3a is very close to the substrate (0.01 to 5 mm), there is a risk that the high-energy laser beam may accidentally irradiate the substrate 1 during movement, damaging the sample on the substrate 1. Preferably, the ion source 100 of this embodiment further includes a sensor (not shown), and the second laser beam 3a is received by the sensor after passing through the particle plume PP. The sensor can be a charge-coupled element capable of detecting the spot shape, relative spot position, and / or laser energy of the received second laser beam 3a. Under initial conditions, the relative position of the second laser beam 3a and the substrate 1 can be roughly determined based on the relative spot position, thereby reducing adjustment time. During the movement of the second laser beam 3a, it is possible to determine whether the second laser beam 3a has accidentally irradiated the substrate 1 based on the received spot shape, relative spot position, and / or laser energy, and to make corrections in a timely manner.

[0039] The ion source 100 of this embodiment can maintain relatively high detection sensitivity even in a relatively high operating pressure environment. Specifically, the operating pressure range of the ion source 100 according to this embodiment is 1 to 10 5 The pressure is Pa. In some embodiments, this ion source 100 can be used in an atmospheric pressure environment; that is, the ion source 100 according to this embodiment may be an atmospheric pressure ion source.

[0040] Figure 2 is a schematic diagram of a preferred ion source 100 according to another embodiment of the present invention. Figure 3 is a schematic diagram of the arrangement of the optical mirror group in the embodiment of Figure 2. Looking at Figures 2 and 3 together, the second laser generator 3 includes a laser oscillator 3b and an optical mirror group 3c, and the optical mirror group 3c is arranged in the laser path of the laser oscillator 3b. Because the laser oscillator 3b is large in volume and weight, a drive mechanism 5 is preferably connected to the optical mirror group 3c to facilitate movement and improve the stability of the laser optical path during movement. The drive mechanism 5 changes the laser path of the laser oscillator 3b by moving or rotating the optical mirror group 3c, thereby changing the focus position FP of the laser beam without moving the laser oscillator 3b. The optical mirror group 3c may include, but is not limited to, one or more lenses, such as convex lenses, concave lenses, or reflective mirrors, or one or more combinations thereof.

[0041] In some embodiments, as shown in Figure 3, the optical mirror group 3c of the second laser generator 3 may include a first reflector 31c and a first convex lens 32c. The first reflector 31c is used to guide the second laser beam 3a emitted by the second laser generator 3 in a direction parallel to the substrate 1, and the first convex lens 32c can focus the laser beam. The laser oscillator 3b emits a laser beam toward the first reflector 31c, and both the first reflector 31c and the first convex lens 32c are connected to a drive mechanism 5. The drive mechanism 5 can move the distance between the emitted laser beam and the substrate 1 by moving the first reflector 31c in a direction perpendicular to the plane of the substrate 1, and can move the focus position FP of the laser beam by moving the first convex lens 32c. By combining the movement of the first reflector 31c and the movement of the first convex lens 32c, the focus position FP of the second laser beam 3a can be adjusted in multiple directions. In this embodiment, the first reflector 31c is represented by a single reflector, but in other embodiments, a group of reflectors may be used instead of a single reflector to easily guide the laser beam emitted by the second laser generator 3 in a direction parallel to the substrate 1.

[0042] Furthermore, the optical mirror group 3c may also include a second reflecting mirror 33c, which refocuses the laser beam, already focused to the first position of the particle plume PP, to the second position of the particle plume PP. Figures 2 and 3 also show examples where the reflecting mirror is a concave mirror. The first and second positions may be two independent sub-regions within the region where the particle plume PP exists, or two partially intersecting sub-regions, or two overlapping sub-regions.

[0043] Based on the configuration of the optical mirror group 3c described above, preferably, when the drive mechanism 5 moves the optical mirror group 3c, the control unit 6 analyzes and determines the position or angle of the second reflector 33c based on a comparison of the respective signal intensities detected by the detector 4 during the movement or rotation of the second reflector 33c. Specifically, the drive mechanism 5 first rotates the focus of the second reflector 33c to a position away from the particle plume PP, and then moves or rotates the first reflector 31c and the first convex lens 32c, selecting a first position with a higher signal intensity based on a comparison of the different signal intensities detected by the detector 4 during the movement or rotation of the first reflector 31c and the first convex lens 32c, and then fixes the position and orientation of the first reflector 31c and the first convex lens 32c. Subsequently, the drive mechanism 5 moves or rotates only the second reflector 33c, and based on a comparison of the respective signal intensities detected by the detector 4 during the movement or rotation of the second reflector 33c, selects the second position with the higher signal intensity and fixes the position and orientation of the second reflector 33c. This means ensures not only that the focusing position FP of the primary focusing is accurate, but also that the focusing position of the secondary focusing by the second reflector 33c is accurate, thereby more effectively improving the attachment and detachment efficiency of the second laser beam 3a emitted by the second laser generator 3.

[0044] Continuing to refer to Figures 2 and 3, in this embodiment, the substrate 1 includes a standard sample area 1a and a measurement sample area 1b. A standard sample capable of generating signal ions is placed in the standard sample area 1a, and when the first laser beam 2a is irradiated onto the standard sample area 1a, a highly consistent particle plume can be generated stably for a long period of time as the substrate 1 moves, thereby ensuring sufficient time to adjust the focus position of the second laser. On the other hand, the sample to be measured is placed in the measurement sample area 1b, and the ion source 100 in this embodiment is configured to detect the sample in the measurement sample area 1b by first determining the endpoint of the focus position FP of the second laser generator 3 using the standard sample area 1a and then moving the substrate 1. By providing a standard sample area 1a and a measurement sample area 1b on the substrate 1, the optimal relative position of the laser beams emitted by the first laser generator 2 and the second laser generator 3 can be obtained by measuring a standard sample in the standard sample area 1a. Subsequently, instead of moving the first laser generator 2 or the second laser generator 3, the substrate 1 can be moved to detect the sample in the measurement sample area 1b while keeping the relative positions of the first laser generator 2 and the second laser generator 3 fixed. Using a standard sample simplifies the calibration process and improves the accuracy and reproducibility of the calibration.

[0045] Figure 4 is a schematic diagram of the system configuration of a mass spectrometer according to several embodiments of the present invention. Referring to Figure 4, the mass spectrometer according to this embodiment may include an ion source 100, a vacuum interface 200, an ion guide device 300, and a mass detector 400 according to any of the embodiments described above. The ion source 100 is an atmospheric pressure ion source, and the sample is desorbed in an atmospheric pressure environment, then introduced into a vacuum environment via the vacuum interface 200, and further guided through the ion guide device 300 to the mass detector 400. The mass detector 400 may be, for example, a time-of-flight mass detector 400 or a quadrupole type mass detector 400, but is not limited thereto. The mass detector 400 may be the same as the detector 4 in the embodiments described above, or it may be a different, independent mass detector 400, and is not limited thereto.

[0046] This embodiment provides an ion generation method, which is applicable to the ion source 100 and mass spectrometer with the above configuration.

[0047] Figure 5 is a flowchart of an ion generation method according to an embodiment of the present invention, and as shown in Figure 5, the ion generation method according to this embodiment is Step S1 involves using the first laser beam 2a to desorb and ionize the sample to obtain a particle plume PP, Step S2 involves using the second laser beam 3a to ionize the particle plume PP and obtain a signal ion, Step S3 involves detecting the signal intensity of the signal ion while moving the focus position of the second laser beam 3a. Step S4 determines the endpoint of the focus position of the second laser beam 3a based on a comparison of the respective signal intensities corresponding to different focus positions, The process includes step S5, which involves positioning the focus of the second laser beam 3a at its endpoint.

[0048] Specifically, the ion generation method according to this embodiment will be described based on the ion source 100 shown in Figure 1.

[0049] In step S1, the sample is placed on the substrate 1, and the first laser generator 2 emits a first laser beam 2a onto the sample on the substrate 1, causing the sample to desorb and ionize. The generated sample ions diffuse away from the substrate 1 to create a particle plume PP.

[0050] In step S2, the second laser generator 3 emits a second laser beam 3a onto the sample on the substrate 1. The second laser beam 3a is focused onto the particle plume PP, further ionizing the particles in the particle plume PP and generating more signal ions.

[0051] In step S3, the drive mechanism 5 controls the focusing position of the second laser generator 3 to move within the vicinity and region of the particle plume PP. This movement includes movement perpendicular to the substrate 1 and movement parallel to the substrate 1; in other words, the movement of the focusing position by the drive mechanism 5 includes both a component parallel to the surface of the substrate 1 and a component perpendicular to the surface of the substrate 1. Three-dimensional movement allows for the determination of the focusing position of the second laser generator 3 that maximizes the post-ionization effect. During the movement of the focusing position of the second laser generator 3 in step S3, the detector 4 remains operational at all times, detecting and recording the signal intensity in real time.

[0052] In step S4, the controller acquires the signal intensity of the signal ions detected by the detector 4 when the second laser generator 3 is focused to different positions, and determines the endpoint of the focus position of the second laser beam 3a based on a comparison of the signal intensities.

[0053] In step S5, the movable parts of the second laser generator 3 are positioned to change its position / orientation from movable to immovable (fixed). For example, the position / orientation of the second laser generator 3 is locked by a locking mechanism, fixing the focal position of the second laser beam 3a emitted by the second laser generator 3 to the endpoint determined in step S4. This ensures that the second laser generator 3 remains focused at this endpoint throughout the subsequent analysis process.

[0054] Those skilled in the art will understand that all or some of the steps of the above embodiments may be completed by hardware, or by a program that directs the relevant hardware to complete them. The program may be stored in a computer-readable storage medium such as read-only memory, disk, or optical disk.

[0055] The technical means of the present invention have been described above in conjunction with the drawings, and it will be readily apparent to those skilled in the art that the scope of protection of the present invention is not limited to these specific embodiments. Equivalent modifications or substitutions can be made to the relevant technical features without departing from the principles of the present invention, and all such modified or substituted technical solutions will be included within the scope of protection of the present invention. [Explanation of symbols]

[0056] 100 Ion source, 1 substrate, 1a standard sample area, 1b measurement sample area, 2 first laser generator, 2a first laser beam, 3 second laser generator, 3a second laser beam, 3b laser oscillator, 3c optical mirror group, 31c first reflector, 32c first convex lens, 33c second reflector, 4 detector, 5 drive mechanism, 6 control unit, 200 vacuum interface, 300 ion guide device, 400 mass detector, PP particle plume, FP focus position.

Claims

1. A substrate used to support the sample, A first laser generator that emits a first laser beam toward the substrate to desorb and ionize the sample to obtain a particle plume, A second laser generator whose focusing position is located on the side of the sample away from the substrate and is separated from the substrate by a predetermined distance, the second laser generator ionizes the particle plume to obtain signal ions, A detector for detecting the signal intensity of the signal ion, A drive mechanism used to move the focusing position of the second laser generator, Equipped with, An ion source characterized in that the endpoint of the focusing position is determined based on a comparison between different signal intensities detected by the detector during the movement of the focusing position.

2. The ion source according to claim 1, characterized in that the second laser generator includes a laser oscillator and a group of optical mirrors, the group of optical mirrors is arranged in the laser path of the laser oscillator, the drive mechanism is connected to the group of optical mirrors, and the drive mechanism changes the laser path of the laser oscillator by moving or rotating the group of optical mirrors.

3. The ion source according to claim 1, further comprising a sensor, wherein the sensor receives a second laser beam emitted by the second laser generator, and the endpoint of the focusing position is determined based on the detection result of the sensor.

4. The ion source according to claim 3, characterized in that the detection result of the sensor includes spot shape, relative spot position and / or laser energy.

5. The ion source according to claim 1, wherein the second laser generator includes a reflector, and the reflector refocuses the second laser beam, which has already been focused to a first position of the particle plume, to a second position of the particle plume.

6. The ion source according to claim 5, characterized in that the reflecting mirror is a concave mirror.

7. The ion source according to claim 5, characterized in that the position or angle of the reflector is determined based on a comparison between different signal intensities detected by the detector during the movement or rotation of the reflector.

8. The operating pressure range of the ion source is 1 to 10 ５ The ion source according to claim 1, characterized in that it is Pa.

9. The ion source according to claim 8, characterized in that the ion source is an atmospheric pressure ion source.

10. The ion source according to claim 1, characterized in that the substrate includes a standard sample area and a measurement sample area, and the ion source is configured to move the substrate to detect a sample in the measurement sample area after determining the endpoint of the focusing position of the second laser generator by the standard sample area.

11. The ion source according to claim 1, characterized in that the movement of the focusing position by the drive mechanism has a component in a direction parallel to the surface of the substrate.

12. The ion source according to claim 11, characterized in that the movement of the focusing position by the drive mechanism further has a component in a direction perpendicular to the surface of the substrate.

13. The ion source according to claim 1, characterized in that the predetermined distance is 0.01 to 5 mm.

14. The ion source according to claim 1, characterized in that, in a region adjacent to the substrate, the laser path of the first laser generator is aligned in a direction inclined with respect to the surface of the substrate, and the laser path of the second laser generator is aligned in a direction parallel to the surface of the substrate.

15. The ion source according to claim 1, further comprising a control unit, wherein the control unit is communicably connected to both the detector and the drive mechanism, and the endpoint of the focusing position is determined by comparison by the control unit.

16. A mass spectrometer characterized by having an ion source according to any one of claims 1 to 15.

17. The first step involves using a laser beam to desorb and ionize the sample to obtain a particle plume, The steps include using a second laser beam to ionize the particle plume and obtain signal ions, The steps include detecting the signal intensity of the signal ion while moving the focusing position of the second laser beam, The steps include determining the endpoint of the focal position of the second laser beam based on a comparison of the respective signal intensities corresponding to different focal positions of the second laser beam, The steps include positioning the focal point of the second laser beam at the endpoint, A method for generating ions, characterized by including the following:

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