Mass spectrometer and its optical system

Abstract

The present invention relates to a mass spectrometer and an optical system thereof. The optical system adopts a mass spectrometer ion source design based on a solid-state laser, which has the advantages of long life, short pulse time, compact size, high repetition frequency, etc. compared with an N2 laser, and is helpful to improve the resolution of the mass spectrometer and reduce the frequency of maintenance. In particular, the optical system is configured by completely fixing the solid-state laser, the entire optical path system and the housing on an optical fixed platform, and the optical path system is located in the housing, so the structure is very stable and easy to install and maintain. When in use, the laser spot size can be adjusted by adjusting the distance between the first focusing lens and the collimating lens, which is convenient to use.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometry, and in particular to a mass spectrometer and an optical system thereof. Background Art

[0002] Matrix-assisted laser desorption time-of-flight mass spectrometer (MALDI-TOFMS) is a widely used biological mass spectrometer. It mixes the sample to be analyzed with the matrix to form a co-crystal. When the laser irradiates the co-crystal, the matrix absorbs the energy of the laser and then transfers the energy to the sample, causing the sample to undergo a desorption and ionization process. The particles generated by the sample ionization are accelerated under the action of the electric field and eventually reach the time-of-flight mass spectrometer detector. Different substances arrive at the mass spectrometer detector at different times, so the molecular weight of the ions can be accurately calculated based on the arrival time of different ions. This soft ionization mass spectrometry analysis technology is particularly suitable for the detection of substances such as proteins, peptides, and nucleic acids. The linear structure of MALDI-TOFMS can avoid the fragmentation of unstable macromolecules during flight to a limited extent, so the mass range of the analysis can reach millions of Daltons.

[0003] The linear MALDI-TOFMS currently used for microbial identification still mainly uses nitrogen molecule lasers (N2 lasers) as ionization sources. The wavelength of the N2 laser is 337nm, which is particularly suitable for the ionization of MALDI-TOFMS. In addition, the N2 laser has the advantage of being inexpensive, so it has always been popular. The beam generated by the N2 laser is generally larger than 3mm, or even larger. It is generally necessary to connect to the light outlet of the N2 laser through an optical fiber for beam introduction, and then adjust the beam size through an optical lens; or use a traditional frame to install and fix it separately.

[0004] Although N2 lasers are widely used, they have many disadvantages. For example, the service life of N2 lasers is short. The service life of a typical N2 laser is only 50 million pulse emissions. Laboratories generally need to replace lasers regularly. The pulse width of N2 lasers is generally not less than 3ns, which will increase the time dispersion of ions in the initial generation, ultimately affecting the resolution. The repetition frequency of N2 lasers is low, generally only 20Hz to 60Hz, which is far from enough for high-throughput sample analysis or mass spectrometry imaging analysis. N2 lasers are generally large in size and the diameter of the laser beam they produce is also large, so optical fiber is required for beam introduction. However, optical fiber introduction will greatly reduce the beam energy, or it can be installed and fixed with a mirror frame, which will make the debugging and maintenance of the optical path complicated and cumbersome, easily affected by dust, and have weak system stability. Although the mass spectrometry system using N2 laser as the ionization source can change the energy of the laser, it is not easy to change the spot size, and a series of complex optical adjustments are required to achieve it. Summary of the invention

[0005] Based on this, it is necessary to provide a mass spectrometer and an optical system thereof to solve the many problems existing in the traditional mass spectrometer using N2 laser.

[0006] The technical solution of the present invention to solve the above technical problems is as follows.

[0007] An optical system of a mass spectrometer comprises an optical fixed platform and a solid laser, an optical path system and a housing arranged on the optical fixed platform;

[0008] The optical path system comprises a first focusing lens, a collimating lens and a second focusing lens. The laser beam emitted by the solid laser generates a divergent laser beam through the first focusing lens. The divergent laser beam becomes a collimated laser beam after passing through the collimating lens. The collimated laser beam can be incident on the sample after being focused by the second focusing lens.

[0009] The first focusing lens, the collimating lens and the second focusing lens are arranged in the housing, and the distance between the first focusing lens and the collimating lens is adjustable.

[0010] In one embodiment, the optical system further includes a filter, and the filter is used to adjust the energy of the laser beam.

[0011] In one embodiment, the optical system further comprises a filter adjustment mechanism, and the filter adjustment mechanism is connected to the filter to drive the filter to rotate.

[0012] In one embodiment, the housing is a modular structure, comprising a first lens housing module, a second lens housing module and a third lens housing module connected in sequence, and the first focusing lens, the collimating lens and the second focusing lens are respectively arranged in the first lens housing module, the second lens housing module and the third lens housing module;

[0013] The first lens housing module and the second lens housing module can move relative to each other to adjust the distance between the first focusing lens and the collimating lens.

[0014] In one embodiment, the optical system further includes a lens adjustment mechanism, which is connected to the first lens housing module and / or the second lens housing module for adjusting the relative position of the first lens housing module and the second lens housing module.

[0015] In one embodiment, the housing further includes a first reflective housing module, a second reflective housing module and / or a third reflective housing module, and correspondingly, the optical path system further includes a first reflector disposed in the first reflective housing module, a second reflector disposed in the second reflective housing module and / or a third reflector disposed in the third reflective housing module;

[0016] The first reflective housing module is connected between the first lens housing module and the second lens housing module, the second reflective housing module is connected between the second lens housing module and the third lens housing module, and the third reflective housing module is connected behind the third lens housing module.

[0017] In one of the embodiments, the optical system further comprises a reflection adjustment mechanism, wherein the reflection adjustment mechanism is connected to the first reflector, the second reflector and / or the third reflector for adjusting the angle of the corresponding reflector.

[0018] In one embodiment, adjacent housing modules are connected together via a threaded connection structure;

[0019] The relative movement between the first lens housing module and the second lens housing module is adjusted by a screw-type adjustment structure.

[0020] In one of the embodiments, the optical path system is also provided with an optical shaping lens for flattening the laser spot so that the Gaussian distributed laser energy is transformed into a laser beam with a flat-top uniform energy distribution and / or a photoelectric trigger module for zero-jitter triggering of the mass spectrometer's electronically controlled pulse system.

[0021] A mass spectrometer comprises the optical system described in any one of the above embodiments.

[0022] The mass spectrometer and its optical system adopt a mass spectrometry ion source design based on a solid-state laser. Compared with the N2 laser, it has the advantages of long life, short pulse time, compact size, high repetition frequency, etc., which helps to improve the resolution of the mass spectrometer and reduce the frequency of maintenance. In particular, the optical system is very stable and easy to install and maintain by completely fixing the solid-state laser, the entire optical path system and the housing on an optical fixed platform. The optical path system is located inside the housing. When in use, the laser spot size can be adjusted by adjusting the distance between the first focusing lens and the collimating lens, which is easy to use. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 A schematic diagram of the structure of an optical system of a mass spectrometer according to an embodiment of the present invention;

[0024] Figure 2 for Figure 1 A cross-sectional view of the optical system shown;

[0025] Figure 3 for Figure 1 Schematic diagram of optical path principle of the optical system shown;

[0026] Figure 4 is a curve showing the relationship between the displacement of the first focusing lens and the diameter of the focal spot;

[0027] Figure 5 is the actual light spot measurement result;

[0028] Figure 6 FIG. 4 is a schematic structural diagram of an optical system according to another embodiment. DETAILED DESCRIPTION

[0029] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. The preferred embodiments of the present invention are given in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0030] It should be noted that when an element is referred to as being "disposed on" another element, it may be directly on the other element or there may be an intermediate element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be an intermediate element at the same time.

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0032] Please combine Figure 1 , Figure 2 and Figure 3 An embodiment of the present invention provides an optical system 10 of a mass spectrometer, which includes an optical fixed platform 100, a solid laser 200, an optical path system 300 and a housing 400. The solid laser 200, the optical path system 300 and the housing 400 are arranged on the optical fixed platform 100.

[0033] The solid laser 200 is fixed on the optical fixed platform 100. In this embodiment, the wavelength of the laser emitted by the solid laser 200 is 343nm. Compared with the traditional N2 laser, the solid laser 200 has the advantages of long service life, small laser pulse width, high repetition frequency, small size, etc., which can significantly improve the resolution of the matrix-assisted laser desorption time-of-flight mass spectrometer, reduce the frequency of maintenance, and is conducive to the miniaturization design of the instrument.

[0034] The optical path system 300 includes a first focusing lens 310, a collimating lens 320, and a second focusing lens 330. The laser beam emitted by the solid laser 200 generates a divergent laser beam through the first focusing lens 310, and the divergent laser beam becomes a collimated laser beam after passing through the collimating lens 320. The collimated laser beam can be incident on the sample after being focused by the second focusing lens 330. The first focusing lens 310, the collimating lens 320, and the second focusing lens 330 are arranged in the housing 400, and the distance between the first focusing lens 310 and the collimating lens 320 is adjustable.

[0035] Figure 3 The figure shows a schematic diagram of the principle of the entire optical path system 300. The distance between the solid laser 200 and the first focusing lens 310 (F1 in the figure, whose focal length is f1) is L1. The laser pulse generated by the solid laser 200 generates a divergent light beam through the first focusing lens 310. A collimating lens 320 (F2 in the figure, whose focal length is f2) is provided at a certain distance L2 behind the light beam to collimate the divergent laser beam. A second focusing lens 330 (F3 in the figure, whose focal length is f3) is provided at a certain distance L3 of the collimated light beam to focus the collimated light beam again. According to the focal length parameters of the selected lens, the desired spot size can be obtained at a certain distance L4. By adjusting the distance between the first focusing lens 310 and the collimating lens 320, the laser spot size can be continuously adjustable at a fixed position.

[0036] Figure 4 The graph is a relationship curve between ω1 (diameter of the laser spot at a fixed position) and the displacement of the first focusing lens 310 at different ω0 (diameter of the spot emitted by the solid laser 200) simulated by the software under the parameters shown in Table 1.

[0037] Table 1

[0038]

[0039] In a specific example, the optical path system 300 further includes a filter (not shown). The filter may be, but is not limited to, a neutral density filter, etc., for adjusting the energy of the laser beam. More specifically, the filter may be disposed after the second focusing lens 330 to adjust the energy of the laser beam focused by the second focusing lens 330.

[0040] Furthermore, the optical system 10 also includes a filter adjustment mechanism. The filter adjustment mechanism is connected to the filter to drive the filter to rotate. The filter adjustment mechanism can be a mechanism such as a steering gear, and its rotation can drive the filter to rotate, thereby achieving continuous adjustment of the laser capacity.

[0041] In order to reduce the volume of the entire optical system 10 as much as possible, the present invention creatively optimizes the structure of the optical system 10. In a specific example, the housing 400 adopts a modular structure design, including a first lens housing module 410, a second lens housing module 420 and a third lens housing module 430 connected in sequence. The first focusing lens 310, the collimating lens 320 and the second focusing lens 330 are respectively arranged in the first lens housing module 410, the second lens housing module 420 and the third lens housing module 430.

[0042] The first lens housing module 410 and the second lens housing module 420 can move relative to each other to adjust the distance between the first focusing lens 310 and the collimating lens 320. For example, the position of the first focusing lens 310 can be fixed, and the position of the collimating lens 320 can be adjusted; or the position of the first focusing lens 310 can be adjusted, and the position of the collimating lens 320 can be fixed; or the first focusing lens 310 and the collimating lens 320 can be designed to be positionally adjustable. Preferably, the optical system 10 further includes a lens adjustment mechanism. The lens adjustment mechanism is connected to the first lens housing module 410 and / or the second lens housing module 420 to adjust the relative position of the first lens housing module 410 and the second lens housing module 420. The lens adjustment mechanism can be a miniature stepping motor, etc., which can be automatically controlled, has high adjustment accuracy, and is easy to operate.

[0043] The housing 400 adopts a modular structural design, which greatly reduces the difficulty of installation and debugging, and facilitates the adjustment of the distance between the first focusing lens 310 and the collimating lens 320. For example, the first lens housing module 410 and the second lens housing module 420 can be threadedly connected, and the first lens housing module 410 and / or the second lens housing module 420 can be driven to rotate through the lens adjustment mechanism to perform position fine-tuning, thereby achieving continuous adjustment of the final spot size.

[0044] Further, as in Figure 1 and Figure 2In the specific example shown, the housing 400 further includes a first reflective housing module 440, a second reflective housing module 450 and a third reflective housing module 460. Accordingly, the optical path system 300 further includes a first reflector 340 disposed in the first reflective housing module 440, a second reflector 350 disposed in the second reflective housing module 450 and a third reflector 360 disposed in the third reflective housing module 460. The first reflective housing module 440 is connected between the first lens housing module 410 and the second lens housing module 420, the second reflective housing module 450 is connected between the second lens housing module 420 and the third lens housing module 430, and the third reflective housing module 460 is connected behind the third lens housing module 430. By providing the first reflector 340, the second reflector 350 and the third reflector 360, the incident angle of the laser beam can be adjusted, and it is beneficial to achieve the optimized design of the length and volume of the entire optical path system 10.

[0045] Furthermore, in the specific example shown in the figure, the first reflective housing module 440, the second reflective housing module 450 and the third reflective housing module 460 are fixed on the optical fixed platform 100 by screws. Both ends of the first reflector module 440, the second reflective housing module 450 and the third reflective housing module 460 have an outer cylinder with internal threads, and the first lens housing module 410, the second lens housing module 420 and the third lens housing module 430 are cylindrical structures with external threads, which are respectively threadedly connected with the first reflective housing module 440, the second reflective housing module 450 and the third reflective housing module 460 as inner cylinders, that is, the adjacent housing modules are connected together by a threaded connection structure, and the relative movement between the first lens housing module 410 and the second lens housing module 420 is adjusted by a spiral adjustment structure. The housing modules of the housing 400 are connected and fixed in a sleeve-type installation manner, and installation and debugging are very convenient.

[0046] In a specific example, the optical system 10 further includes a reflection adjustment mechanism, which is connected to the first reflector 340, the second reflector 350 and / or the third reflector 360 to adjust the angle of the corresponding reflector, and can easily adjust the laser emission direction and the focus position.

[0047] The modular shell 400 can place different shell modules at different positions according to needs, which is flexible and changeable. In addition, it can also be used to flatten the laser spot as needed, so that the Gaussian distributed laser energy can be transformed into a flat-top laser beam with uniform energy distribution, and / or a photoelectric trigger module for zero-jitter triggering of the mass spectrometer's electronically controlled pulse system, etc.

[0048] The shell 400 may also not contain the first reflective shell module 440, the second reflective shell module 450 and the third reflective shell module 460, or may contain one or two of the first reflective shell module 440, the second reflective shell module 450 and the third reflective shell module 460, and the orientation of the reflectors in the first reflective shell module 440, the second reflective shell module 450 and the third reflective shell module 460 may also be set as needed. Figure 6 The optical system 20 shown does not contain the second reflective housing module, and the third reflector in the third emitting housing module 21 is arranged downward, so that the laser light emitted by the solid laser 22 is finally guided out in a direction perpendicular to the optical fixing platform 23. In addition, Figure 6 The optical system 20 shown further includes a photoelectric trigger module 24 and a filter 25 .

[0049] The present invention also provides a mass spectrometer, which includes the optical system of any of the above specific examples.

[0050] Figure 5 To adopt Figure 1 and Figure 2 The optical system 10 shown in the figure performs actual spot measurement on the focusing point, and the results show that the optical system 10 can achieve a minimum focusing effect of 16*14μm.

[0051] The mass spectrometer and its optical system 10 adopt a mass spectrometry ion source design based on a solid-state laser, which has the advantages of long life, short pulse time, compact size, high repetition frequency, etc. compared with the N2 laser, which helps to improve the resolution of the mass spectrometer and reduce the frequency of maintenance. In particular, the optical system 10 completely fixes the solid-state laser 200, the entire optical path system 300 and the housing 400 on the optical fixed platform 100, and the optical path system 300 is located in the housing 400. The structure is very stable and easy to install and maintain. When in use, the laser spot size can be adjusted by adjusting the distance between the first focusing lens 310 and the collimating lens 320, and the filter can be adjusted to finally adjust the intensity of the emitted laser, so as to achieve continuous adjustment of the laser energy, and the operation is simple.

[0052] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0053] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. An optical system of a mass spectrometer, characterized in that: It comprises an optical fixed platform and a solid laser, an optical path system and a housing arranged on the optical fixed platform; The optical path system comprises a first focusing lens, a collimating lens and a second focusing lens. The laser beam emitted by the solid laser generates a divergent laser beam through the first focusing lens. The divergent laser beam becomes a collimated laser beam after passing through the collimating lens. The collimated laser beam can be incident on the sample after being focused by the second focusing lens. The first focusing lens, the collimating lens and the second focusing lens are arranged in the housing, and the distance between the first focusing lens and the collimating lens is adjustable; The housing is a modular structure, comprising a first lens housing module, a second lens housing module and a third lens housing module connected in sequence, wherein the first focusing lens, the collimating lens and the second focusing lens are respectively arranged in the first lens housing module, the second lens housing module and the third lens housing module; The first lens housing module and the second lens housing module can move relative to each other to adjust the distance between the first focusing lens and the collimating lens; The housing further comprises a first reflective housing module, a second reflective housing module and / or a third reflective housing module, and correspondingly, the optical path system further comprises a first reflector disposed in the first reflective housing module, a second reflector disposed in the second reflective housing module and / or a third reflector disposed in the third reflective housing module; The first reflective housing module is connected between the first lens housing module and the second lens housing module, the second reflective housing module is connected between the second lens housing module and the third lens housing module, and the third reflective housing module is connected behind the third lens housing module; Also included is a reflection adjustment mechanism, the reflection adjustment mechanism is connected to the first reflector, the second reflector and / or the third reflector to adjust the angle of the corresponding reflector; It also includes a lens adjustment mechanism, which is connected to the first lens housing module and / or the second lens housing module to adjust the relative position of the first lens housing module and the second lens housing module.

2. The optical system according to claim 1, wherein: The optical path system also includes a filter, which is used to adjust the energy of the laser beam.

3. The optical system according to claim 2, characterized in that It also includes a filter adjustment mechanism, which is connected to the filter to drive the filter to rotate.

4. The optical system according to claim 1, wherein: Adjacent housing modules are connected together via a threaded connection structure; The relative movement between the first lens housing module and the second lens housing module is adjusted by a screw-type adjustment structure.

5. The optical system according to any one of claims 1 to 3, characterized in that: The optical path system is also provided with an optical shaping lens for flattening the laser spot so that the Gaussian distributed laser energy becomes a laser beam with a flat-top energy uniform distribution and / or a photoelectric trigger module for zero-jitter triggering of the mass spectrometer's electronically controlled pulse system.

6. A mass spectrometer, characterized in that The optical system comprises the optical system as claimed in any one of claims 1 to 5.

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