Displacement platform, mass spectrometry imaging system and control method thereof

Abstract

The present invention discloses a displacement platform, a mass spectrometry imaging system and a control method thereof for mass spectrometry imaging of a sample to be tested. The mass spectrometry imaging system comprises a cabin, a workbench, a displacement platform, a sterilization module, an electrospray ionization module, a sampling module, an injection module, a mass spectrometer and a control system. The displacement platform comprises a stage with a groove, a cooling plate with a cooling channel and a phase-stabilizing medium, the groove accommodates the sample to be tested, the cooling plate is stacked with the stage, and the phase-stabilizing medium circulates in the cooling channel. The present invention ensures that large-area scanning work can be carried out continuously and stably for a long time, improves efficiency and output and ensures the accuracy of detection by the mass spectrometry imaging system.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometry detection, and in particular to a displacement platform, a mass spectrometry imaging system and a control method thereof. Background Art

[0002] The characteristic of Mass Spectrometry Imaging (MSI) is that it can directly obtain the chemical information and spatial distribution characteristics of multiple biological functional molecules on the surface of tissue sections through a single experiment without labeling or complex sample pretreatment, and can associate specific ion images with tissue pathological characteristics. Therefore, it has great application prospects in clinical medicine, molecular biology and other fields.

[0003] In the mass spectrometry imaging method, the sample is fixed on a moving platform, the electrospray needle or other desorption ionization means is kept at a suitable distance from the sample, and the moving platform is moved continuously or in pulses to perform a two-dimensional scan of the sample.

[0004] The mass spectrometry imaging system in the prior art generally has the problem of limited two-dimensional scanning range, small number of samples to be detected, and low efficiency. When expanding the scanning range of the mass spectrometry imaging system, only the increase in the stage area in the mass spectrometry imaging system is considered, and the factors affecting the increase in scanning area, such as extended scanning time, environmental changes, and increased material consumption, are not considered. Therefore, the prior art has the following technical problems:

[0005] First, as an open ion source, the sample is in direct contact with the external atmospheric environment and is greatly affected by external factors such as temperature, humidity, and dust. Especially during long-term scanning, the substance to be tested on the surface of the sample slice is prone to oxidation and deterioration, causing deviations in the analysis results.

[0006] Secondly, high-throughput testing of biological samples can easily lead to cross-contamination or health risks between different samples to be tested, and may affect the test results, making it impossible to ensure the accuracy of the test results.

[0007] Thirdly, the solvent flow path of similar mass spectrometry systems on the market that use the in-situ ionization principle is usually used in conjunction with a syringe pump. The volume of the syringe is limited, and it must be manually replaced each time the spray solvent is consumed. This can easily cause uncertainties such as solvent contamination, pipeline blockage, and positioning offset. In-situ mass spectrometry requires scanning and positioning at the μm level. Any slight change in the scanning parameters may affect the final imaging or detection effect, making it difficult to ensure the stability and consistency of sample scanning.

[0008] In summary, due to these problems, the mass spectrometry imaging system in the prior art cannot achieve 24h unattended high-throughput scanning of samples, and the night time of the mass spectrometer is not fully utilized, resulting in waste of machine time, low detection efficiency, and low production capacity. Therefore, it is necessary to provide an improved displacement platform, a mass spectrometry imaging system and a control method thereof to effectively solve the above technical problems. Summary of the invention

[0009] In view of the technical problems of low detection efficiency, low production capacity and insufficient stability of mass spectrometry imaging systems in the prior art, it is necessary to provide a displacement platform and mass spectrometry imaging system with high detection efficiency, stable environment and high accuracy.

[0010] The displacement platform for mass spectrometry imaging of a sample to be tested provided by the present invention comprises a stage with a groove, a cooling plate with a cooling channel, and a phase-stabilizing medium. The groove accommodates the sample to be tested, the cooling plate is stacked with the stage, and the phase-stabilizing medium circulates in the cooling channel.

[0011] The present invention also provides a mass spectrometry imaging system equipped with the displacement platform, comprising a cabin, a workbench, the displacement platform, a sterilization module, an electrospray ionization module, a sampling module, an injection module, a mass spectrometer and a control system. The cabin is an openable and closable enclosed accommodation space, and the displacement platform, the electrospray ionization module, the sampling module and the injection module are all arranged on the workbench and are accommodated inside the cabin together with the workbench. The displacement platform can move relative to the workbench in its working plane, and the electrospray ionization module, the sampling module and the injection module all maintain a set distance from the displacement platform. The electrospray ionization module and the injection module are arranged relative to each other. The control system is electrically connected to the displacement platform, the sterilization module, the electrospray ionization module, the sampling module, the injection module and the mass spectrometer.

[0012] At the same time, the present invention discloses a control method of the mass spectrometry imaging system, and the specific steps are as follows:

[0013] S01. Providing a sample to be tested and a displacement platform for mass spectrometry imaging, wherein the sample to be tested is fixed on the displacement platform, and the displacement platform comprises a stage with a groove and a cooling plate with a cooling channel, wherein the cooling plate is stacked with the stage;

[0014] S02, providing a phase-stable medium, wherein the phase-stable medium circulates in the cooling channel;

[0015] S03, providing a control system, controlling the displacement platform to move to the coordinate starting point, positioning and marking the sample to be tested, and starting the test, and displaying the mass spectrometry test results.

[0016] Compared with the prior art, the displacement platform for mass spectrometry imaging of a sample to be tested, the mass spectrometry imaging system and the control method thereof provided by the present invention have the following advantages and outstanding technical effects.

[0017] First, the invention provides a displacement platform for mass spectrometry imaging of samples to be tested, which can scan up to 72 samples to be tested, with a maximum scanning range of 150mmx100mm. It can scan whole animals over a large area, greatly improving the scanning range and efficiency, and can realize automatic positioning and scanning of the mass spectrometry imaging system by utilizing the movement of the displacement platform.

[0018] Secondly, in view of the long-term automatic scanning work of open mass spectrometry imaging, the sample to be tested will be exposed to the atmospheric environment for a long time, and the sample to be tested is easily affected by factors such as temperature and dust particles. The displacement platform can achieve the stability of the test environment and the accuracy of the test results. The displacement platform adopts a structural design of cooling and maintaining an inert gas atmosphere, which can keep the properties of the sample unchanged during long-term operation.

[0019] Again, the mass spectrometry imaging system provided by the invention, based on the use of the displacement platform, is also equipped with an electrospray ionization module, a sampling module, an injection module and a sterilization module. The electrospray ionization module adopts a high-pressure liquid phase pump combination to increase the spray solution capacity, stabilize the spray speed, and provide a heating unit to heat the spray needle to improve the sensitivity of desorption detection; the sampling module provides a shooting positioning function, so that the detection results of multiple samples can be matched one by one with the samples to be tested; the injection module provides an online PI device to detect and discover more compounds; the sterilization module provides an ultraviolet lamp to provide a sterilization and disinfection environment inside the mass spectrometry imaging system to avoid cross-infection between multiple samples, mutual interference, and influence on the detection environment.

[0020] In summary, the displacement platform, mass spectrometry imaging system and control method thereof for mass spectrometry imaging of the sample to be tested provided by the present invention ensure that large-area scanning work can be carried out continuously and stably for a long time, improve efficiency and output and ensure the accuracy of detection by the mass spectrometry imaging system. In addition, the overall system structure has low installation difficulty and the control system is simple and convenient. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative work, among which:

[0022] Figure 1 A schematic diagram of the three-dimensional structure of the mass spectrometry imaging system provided by the present invention;

[0023] Figure 2 for Figure 1 The three-dimensional decomposition schematic diagram of the mass spectrometry imaging system shown;

[0024] Figure 3 for Figure 2 The structure block diagram of the mass spectrometry imaging system is shown;

[0025] Figure 4 for Figure 2 A three-dimensional exploded schematic diagram of the displacement platform shown;

[0026] Figure 5 For along Figure 4 A cross-sectional view of line VV is shown;

[0027] Figure 6 for Figure 2 The schematic diagram of the three-dimensional structure of the sterilization module shown;

[0028] Figure 7 for Figure 2 The schematic diagram of the three-dimensional structure of the electrospray ionization module shown;

[0029] Figure 8 for Figure 2 The schematic diagram of the three-dimensional structure of the sampling module shown;

[0030] Fig. 9 for Figure 2 The schematic diagram of the three-dimensional structure of the injection module shown; and

[0031] Fig.10 The figure is a flow chart of the mass spectrometry imaging system control method. DETAILED DESCRIPTION

[0032] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] Please refer to Figure 1 , Figure 2 and Figure 3 ,in Figure 1 A schematic diagram of the three-dimensional structure of the mass spectrometry imaging system provided by the present invention, Figure 2 for Figure 1 The three-dimensional decomposition diagram of the mass spectrometry imaging system is shown in FIG. Figure 3 for Figure 2The mass spectrometry imaging system 100 is used to perform mass spectrometry analysis and imaging on the sample to be tested, and the mass spectrometry imaging system 100 includes the displacement platform 10, the cabin 20, the workbench 30, the sterilization module 40, the electrospray ionization module 50, the sampling module 60, the injection module 70, the mass spectrometer 80 and the control system 90.

[0034] The cabin body 20 has an openable and closed enclosed receiving space, including a hatch cover 21 and a cabin bottom 23, which are movably connected and detachable, and there is no restriction on the transparency, color, pattern and style of the hatch cover 21. The hatch cover 21 is surrounded by a side wall and a bottom wall to form an open receiving space. The cabin bottom 23 is covered at the opening of the hatch cover 21 and cooperates with the hatch cover 21 to form the receiving space, and there is no restriction on the combination method and opening and closing method of the two.

[0035] The displacement platform 10 , the sterilization module 40 , the electrospray ionization module 50 , the sampling module 60 , and the injection module 70 are all disposed on the workbench 30 , and are accommodated in the accommodation space of the cabin 20 together with the workbench 30 .

[0036] The electrospray ionization module 50, the sampling module 60 and the injection module 70 all maintain a set distance from the displacement platform 10. The electrospray ionization module 50 and the injection module 70 are arranged opposite to each other. The control system 90 is electrically connected to the displacement platform 10, the electrospray ionization module 50, the sampling module 60, the injection module 70 and the mass spectrometer 80.

[0037] Please refer to Figure 2 and Figure 4 ,in Figure 4 for Figure 2 The displacement platform 10 is used for mass spectrometry imaging of the sample to be tested, and includes a support 11, a cooling plate 13, a phase-stabilizing medium 15 (see Figure 5 ), stage 17 and fixed module 19. The cooling plate 13 is sandwiched between the support body 11 and the stage 17. The fixed module 19 includes a screw knob 191, a spring 193 and a slider 195. The screw knob 191 passes through the slider 195 and abuts against the stage 17. The slider 195 abuts against the sample to be tested on the stage 17. By rotating the screw knob 191, the slider 195 is pushed to fix the sample to be tested on the stage 17 to avoid movement of the sample to be tested during mass spectrometry detection. The number of the screw knob 191, the spring 193 and the slider 195 is not limited by this embodiment and can be adjusted according to the scanning area of ​​the sample to be tested.

[0038] The displacement platform 10 moves relative to the workbench 30 within the working plane where it is located. The support body 11 is movably connected to the workbench 30. The control system 90 can control the support body 11 to drive the cooling plate 13, the stage 17 and the sample to be tested fixed to the stage 17 to move relative to the workbench 30 within the working plane where they are located, thereby realizing automatic positioning of the sample to be tested and cooperating with detection.

[0039] See also Figure 5 , for along Figure 4 The cross-sectional view of the VV line is shown. The cooling plate 13 includes a cooling channel 131, an air inlet 133 and an exhaust hole 135 which are interconnected in sequence. The cooling channel 131 is located in the cooling plate 13, and the phase-stable medium 15 circulates in the cooling channel 131. In the present embodiment, the cooling channel 131 is a meandering channel extending from the center to the edge of the cooling plate 13, and an air inlet 133 is provided at the edge near the side wall of the cooling plate 13 and a plurality of exhaust holes 135 are symmetrically arranged at the center. The phase-stable medium 15 is an inert gas that has been cooled, and the temperature of the cooling treatment is set according to the sample to be tested; of course, the cooling channel 131 is not limited to the shape of the present embodiment, and the number and position of the air inlet 133 and the exhaust hole 135 are also not limited. The phase-stable medium 15 needs to flow into the cooling channel 131 through the air inlet 133 and be discharged through the exhaust hole 135, as shown in FIG. Figure 3 As shown by the arrow in ; therefore, the structural design outside this embodiment should ensure that the cooling channel 131, the air inlet 133 and the exhaust hole 135 are interconnected, and ensure that the phase-stabilizing medium 15 can flow through the entire cooling channel 131 and contact with the cooling plate 13 to achieve a phase-stabilizing effect.

[0040] See also Figure 6 ,for Figure 2 The schematic diagram of the three-dimensional structure of the sterilization module is shown. The sterilization module 40 includes a first ultraviolet lamp 41 and a mounting seat 42. The first ultraviolet lamp 41 is arranged on the mounting seat 42. In this embodiment, the mounting seat 42 is arranged on the side of the receiving space of the cabin 20 where the hatch 21 is located. Of course, the installation position of the sterilization module 40 is not limited to this position, and can be installed at other positions in the receiving space of the cabin 20 to provide a sterilization environment for the mass spectrometry imaging system 100, thereby avoiding cross infection between multiple samples, mutual interference, and affecting the detection environment.

[0041] See also Figure 7 ,for Figure 2The electrospray ionization module 50 includes a high-pressure liquid phase pump (not shown), a spray needle 53 and a heating unit 55. The high-pressure liquid phase pump is connected to the spray needle 53 for use. The heating unit 55 is connected to the spray needle 53 to heat the inert gas delivered to the spray needle 53 and atomize the spray solution. The spray needle 53 maintains a set distance from the displacement platform 10.

[0042] See also Figure 8 ,for Figure 2 The sampling module 60 includes a bracket 61 and an optical scanning unit 63. The bracket 61 is arranged on the workbench 30. The optical scanning unit 63 is arranged on the bracket 61 and is electrically connected to the control system 90. The optical scanning unit 63 is mainly used to scan the sample to be tested. In this embodiment, the optical scanning unit 63 is a camera, but this is not limited. The optical scanning unit 63 can also use other methods that can obtain an equivalent sampling effect.

[0043] See also Fig. 9 ,for Figure 4 The three-dimensional structure diagram of the sampling module is shown; the sampling module 70 includes an ion transfer tube 71, a quartz tube 73, a second ultraviolet lamp 75, a first electrode 77 and a second electrode 79, one end of the ion transfer tube 71 is connected to the quartz tube 73, and the other end maintains a set distance with the displacement platform 10, the quartz tube 73 is sintered inside the second ultraviolet lamp 75, the second ultraviolet lamp 75 is filled with mercury vapor, and the two ends are respectively connected to the first electrode 77 and the second electrode 79.

[0044] See also Figure 2 , Figure 3 and Fig.10 ,in, Fig.10 The control method of the mass spectrometry imaging system is as follows:

[0045] Step S01, providing the sample to be tested and the displacement platform 10, wherein the sample to be tested is fixed on the displacement platform 10, and the displacement platform 10 comprises a stage 17 with a groove and a cooling plate 13 with a cooling channel, wherein the cooling plate 13 is stacked with the stage 17;

[0046] Step S02, providing a phase-stable medium 15, releasing the phase-stable medium 15 through the control system 90, and the phase-stable medium 15 circulates in the cooling channel 131;

[0047] Step S03, providing the control system 90, and controlling the displacement platform 10 to move within the working plane of the workbench 30 by the control system 90 until the displacement platform 10 returns to the coordinate starting point;

[0048] Step S04, providing the sampling module 60, opening the sampling module 60 through the control system 90, photographing the sample to be tested in the displacement platform 10, determining the sampling coordinates and numbering and saving;

[0049] Step S05, providing an electrospray ionization module 50, setting the spray speed and heating power of the electrospray ionization module 50 through the control system 90, and the electrospray ionization module 50 sprays high-speed charged droplets to bombard the surface of the sample to be tested in the displacement platform 10 to form desorbed ions;

[0050] Step S06, providing a sample injection module 70, utilizing negative pressure to absorb and transmit the desorbed ions, and energizing the sample injection module 70 through the control system 90 to excite the mercury vapor in the sample injection module 70, emitting ultraviolet light to irradiate the desorbed ions, and stimulating ionization;

[0051] Step S07 , providing a mass spectrometer 80 , receiving and detecting mass spectrometer ions, and reading and displaying the detection result of the mass spectrometer 80 through the control system 90 .

[0052] Step S08, providing the position information corresponding to the number of the sample to be tested saved by the control system 90, the control system 90 controls the displacement platform 10 to move to the detection position corresponding to the next number of the sample to be tested, and repeating steps S05-S08 until all the samples to be tested in the displacement platform 10 are tested.

[0053] Compared with the prior art, in the displacement platform, mass spectrometry imaging system and control method thereof provided by the present invention, by adding the cooling plate 13 and the phase-stabilizing medium 15, the cooling plate 13 and the stage 17 are stacked, and the phase-stabilizing medium 15 circulates in the cooling channel 131, so that up to 72 samples to be tested can be scanned, and the maximum scanning range is 150mmx100mm. A large area of ​​the whole animal can be scanned, which greatly improves the scanning range and scanning efficiency, and can realize horizontal plane movement to cooperate to complete the automatic positioning scanning of the mass spectrometry imaging system.

[0054] Secondly, in view of the long-term automatic scanning work of the open mass spectrometry imaging, the sample to be tested will be exposed to the atmospheric environment for a long time, and the sample to be tested is easily affected by factors such as temperature and dust particles. The displacement platform 10 can be used to achieve the stability of the test environment and the accuracy of the test results. The displacement platform 10 adopts a structural design of cooling and maintaining an inert gas atmosphere, which can keep the properties of the sample to be tested unchanged during long-term operation.

[0055] Again, the mass spectrometry imaging system 100 provided by the invention, based on the use of the displacement platform 10, is also equipped with the electrospray ionization module 50, the sampling module 60, the injection module 70 and the sterilization module 40. The electrospray ionization module 50 is combined with the high-pressure liquid phase pump to increase the spray solution capacity and stabilize the spray speed, and provides a heating unit 55 to heat the spray needle 53, thereby improving the sensitivity of desorption detection; the sampling module 60 provides a shooting positioning function, so that the detection results of multiple samples can be matched one by one with the samples to be tested; the injection module 70 provides an online PI device to detect and discover more compounds; the sterilization module 40 provides the first ultraviolet lamp 41 to provide a sterilization and disinfection environment inside the mass spectrometry imaging system 100 to avoid cross-infection and mutual interference between multiple samples, which affects the detection environment.

[0056] In summary, the displacement platform, mass spectrometry imaging system and control method thereof for mass spectrometry imaging of the sample to be tested provided by the present invention ensure that large-area scanning work can be carried out continuously and stably for a long time, improve efficiency and output and ensure the accuracy of detection by the mass spectrometry imaging system 100. In addition, the overall system structure has low installation difficulty and the control system is simple and convenient.

[0057] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A mass spectrometry imaging system, comprising: A cabin having a receiving space; A workbench, housed in the cabin; A displacement platform is arranged on the workbench and moves relative to the workbench in the work plane where it is located; the displacement platform comprises: a stage with a groove, the groove accommodates the sample to be tested, a cooling plate with a cooling channel, which is stacked with the stage; and a phase-stable medium circulates in the cooling channel; the cooling plate comprises an air inlet, a cooling channel and an exhaust hole which are mutually interpenetrating in sequence, the air inlet is arranged on the side wall of the cooling plate, and the cooling channel runs through the cooling plate; the phase-stable medium is an inert gas; the phase-stable medium flows into the cooling channel through the air inlet and is discharged through the exhaust hole; the displacement platform is provided with a structure for cooling and maintaining an inert gas atmosphere, so as to keep the properties of the sample to be tested unchanged during the operation of the preset time; An electrospray ionization module is arranged on the workbench; A sampling module is arranged on the workbench; A sample injection module is arranged on the workbench and is arranged opposite to the electrospray ionization module; A mass spectrometer connected to the injection module; and A control system, electrically connected to the displacement platform, the electrospray ionization module, the sampling module, the injection module and the mass spectrometer; The displacement platform, the electrospray ionization module, the sampling module and the injection module are all accommodated in the cabin.

2. The mass spectrometry imaging system according to claim 1, characterized in that: It also includes a sterilization module, which is arranged in the receiving space. The sterilization module includes a first ultraviolet lamp and a mounting fixture. The first ultraviolet lamp is arranged on the mounting fixture.

3. The mass spectrometry imaging system according to claim 1, characterized in that: The electrospray ionization module includes a spray needle, a high-pressure liquid phase pump and a heating unit. The high-pressure liquid phase pump is connected to the spray needle for use, the heating unit is connected to the spray needle, and the spray needle maintains a set distance from the displacement platform.

4. The mass spectrometry imaging system according to claim 1, characterized in that: The sampling module includes a bracket and an optical scanning unit. The bracket is arranged on the workbench. The optical scanning unit is arranged on the bracket and is electrically connected to the control system.

5. The mass spectrometry imaging system according to claim 2, characterized in that: The injection module includes an ion transfer tube, a quartz tube, a second ultraviolet lamp, a first electrode and a second electrode. One end of the ion transfer tube is connected to the quartz tube, and the other end maintains a set distance with the displacement platform. The quartz tube is sintered inside the second ultraviolet lamp. The second ultraviolet lamp is filled with mercury vapor, and both ends are connected to the first electrode and the second electrode respectively.

6. The mass spectrometry imaging system according to claim 5, characterized in that: The control system controls the movement of the displacement platform in the horizontal plane and the circulation of the phase-stabilizing medium, controls the spray flow rate and heating temperature of the electrospray ionization module, controls the sampling module to shoot samples, controls the switch of the second ultraviolet lamp, and reads and displays the detection results of the mass spectrometer.

7. A control method for a mass spectrometry imaging system, used in the mass spectrometry imaging system according to any one of claims 1 to 6, characterized in that: The steps include: A sample to be tested, a workbench and a displacement platform for mass spectrometry imaging are provided, wherein the sample to be tested is fixed on the displacement platform, and the displacement platform comprises a stage with a groove and a cooling plate with a cooling channel, wherein the cooling plate is stacked with the stage; Providing a phase-stable medium, wherein the phase-stable medium circulates in the cooling channel; A control system is provided to control the displacement platform to move to the coordinate starting point, to start the detection after positioning and marking the sample to be tested, and to display the mass spectrometry detection result.

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