A laser ion source tissue sample detection device

Abstract

This invention belongs to the field of analytical testing and discloses a laser ionization source tissue sample detection device, including a laser, a light guide arm, a mounting platform, and an ionization cavity. The ionization cavity comprises an ionization chamber and an ion source, forming a hollow chamber. The mounting platform is installed within the hollow chamber of the ionization cavity and has a sample-carrying platform with a clamping device. The laser's emission port is connected to one end of the light guide arm, and the other end of the light guide arm extends above the sample-carrying platform. A lens or optical fiber is installed inside the light guide arm to achieve lossless laser transmission. Utilizing the advantages of the light guide arm and three-dimensional displacement stage, it achieves high-sensitivity, precise operation, efficient ionization, and accurate positioning, enabling the laser to be used at various distances, achieving efficient ionization and high-sensitivity mass spectrometry detection of tissue samples such as biological tissues, animal and plant tissues, and clinical sample slides.

Description

Technical Field

[0001] This invention belongs to the field of detection device technology, specifically relating to a laser ion source tissue sample detection device. Background Technology

[0002] The statements herein provide only background information in relation to this invention and do not necessarily constitute prior art.

[0003] Laser desorption / ionization (LAI) technology utilizes a laser beam of a specific wavelength to precisely irradiate the surface of a solid or semi-solid sample. After the laser energy is absorbed by the sample, it causes the surface molecules to rapidly heat up and desorb (evaporate) within an extremely short time (nanoseconds to femtoseconds), forming gaseous molecules or aerosols. These aerosols containing sample molecules are then introduced into the mass spectrometer interface using a negative pressure device for ionization and detection. While this technology offers advantages such as high spatial resolution, non-contact detection, and precise energy control, the need for electrospray ionization (ESI) after sample desorption makes the coupled system cumbersome and increases technical complexity, limiting its application in certain research fields.

[0004] Electrospray desorption / ionization (DESI) technology uses a high-speed stream of charged solvent droplets (usually an aqueous solution containing an organic solvent) to bombard the sample surface. Upon collision with sample molecules, the solvent droplets desorb the analytes from the surface, forming gaseous "secondary droplets." These secondary droplets desolvate in an electric field, releasing charged ions that enter the mass spectrometer. This enables analytical applications in pathology, pharmaceuticals, and bacteria, offering advantages such as simplicity, reliability, no sample pretreatment required, and high reproducibility. However, this technology requires the introduction of organic solvents, leading to poor stability, low ionization efficiency, and potential sample contamination during the detection process, thus affecting instrument performance. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the purpose of this invention is to provide a laser ion source tissue sample detection device.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solution:

[0007] This invention provides a laser ion source tissue sample detection device, comprising a laser, a light guide arm, a mounting platform, an ionization cavity, and a mass spectrometer, wherein...

[0008] The mounting platform is installed in the ionization chamber, and a carrying platform is provided on the mounting platform, with a clamping device provided on the carrying platform;

[0009] The laser's output port is connected to one end of the light guide arm, and the other end of the light guide arm extends above the loading platform. The light guide arm is equipped with a lens or optical fiber to achieve lossless transmission of the laser. The laser is used to inject sufficient energy into the sample tissue to directly ionize it.

[0010] The outlet of the ionization chamber is connected to the inlet of the mass spectrometer.

[0011] The beneficial effects achieved by one or more embodiments of the present invention described above are as follows:

[0012] The laser ionization source tissue sample detection device of the present invention integrates a laser ionization source and a tissue sample mounting platform to achieve mass spectrometry detection of tissue samples under efficient ionization. The laser ionization source transmits laser light to the loading platform within the ionization chamber via a light guide arm, injecting sufficient energy into the tissue sample held on the platform, allowing for direct ionization of the tissue sample. This eliminates the need for pretreatment of the tissue sample or the addition of other ionization equipment, and the process does not introduce any other solvents. It achieves efficient desorption and ionization of sample molecules, offering advantages such as simple operation, good detection stability, high ionization efficiency, and no solvent contamination. Attached Figure Description

[0013] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0014] Figure 1 This is a schematic diagram of the overall structure of the laser ion source tissue sample detection device according to an embodiment of the present invention;

[0015] Figure 2 This is a schematic diagram of the structure of the tissue sample mounting platform device according to an embodiment of the present invention;

[0016] Figure 3 This is a schematic diagram of the structure of the ionization cavity according to an embodiment of the present invention;

[0017] Figure 4 This is a schematic diagram of the structure of the three-dimensional displacement stage of the vehicle according to an embodiment of the present invention;

[0018] Figure 5 This is a schematic diagram of the structure of the three-dimensional moving platform on the top surface of the ionization cavity according to an embodiment of the present invention;

[0019] Figure 6 This is a schematic diagram of the structure of the three-dimensional displacement stage of the light guide arm according to an embodiment of the present invention;

[0020] Figure 7 This is an exploded structural diagram of the ionization cavity according to an embodiment of the present invention.

[0021] Among them, 1-laser; 2-light guide arm; 3-mounting platform; 4-ionization cavity; 5-mass spectrometer; 6-three-dimensional adapter plate; 7-carrier bracket; 8-carrier fixing plate; 9-object platform; 10-glass slide;

[0022] 11-Ionization chamber shell; 11-1 Mass spectrometer connector; 11-2 Intermediate component; 11-3 Three-dimensional fixture; 11-4 Connecting piece; 11-5 Fixing rod;

[0023] 12-Top surface three-dimensional fixing plate; 13-Top surface three-dimensional adapter plate;

[0024] 14-Light guide arm three-dimensional displacement stage; 14-1 Micrometer; 14-2 First locking screw; 14-3 First worktable surface; 14-4 First base; 14-5 Guide rail;

[0025] 15-Light guide arm clamp;

[0026] 16-Carrier three-dimensional displacement stage; 16-1 Handwheel; 16-2 Second locking screw; 16-3 Second worktable; 16-4 Second base; 16-5 Precision screw. Detailed Implementation

[0027] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0028] A laser ion source tissue sample detection device includes a laser, a light guide arm, a mounting platform, an ionization cavity, and a mass spectrometer, wherein...

[0029] The mounting platform is installed in the ionization chamber, and a carrying platform is provided on the mounting platform, with a clamping device provided on the carrying platform;

[0030] The laser's output port is connected to one end of the light guide arm, and the other end of the light guide arm extends above the loading platform. The light guide arm is equipped with a lens or optical fiber to achieve lossless transmission of the laser. The laser is used to inject sufficient energy into the sample tissue to directly ionize it.

[0031] The outlet of the ionization chamber is connected to the inlet of the mass spectrometer.

[0032] The laser ionization source of this invention can transmit laser light to the carrier platform through the light guide arm, injecting sufficient energy into the tissue sample held on the carrier platform, so that the tissue sample can be directly ionized. Therefore, there is no need to pre-treat the tissue sample or add other ionization equipment. Moreover, no other solvents are introduced during the process, realizing efficient desorption and ionization of sample molecules. It has the advantages of simple operation, good detection stability, high ionization efficiency, and no solvent pollution.

[0033] The light guide arm contains a lens assembly, consisting of multiple precision lenses (such as collimating lenses and focusing lenses) connected in series. Each joint has a lens pair; the front lens collimates the laser into parallel light, and the rear lens refocuses it at the output end. This design ensures that the laser maintains a stable optical path as it passes through each joint, preventing divergence.

[0034] The collimated parallel light propagates in the light guide arm channel in the form of total internal reflection; the lens surface is coated with an anti-reflection film, which significantly reduces reflection loss to achieve lossless transmission of laser light.

[0035] The platform is equipped with a clamping device to hold and secure the carriers containing tissue samples, preventing them from deviating or falling off.

[0036] In some embodiments, the mounting platform is installed on a three-dimensional displacement stage of the vehicle.

[0037] The three-dimensional displacement stage of the carrier can achieve three-dimensional movement, thereby driving the tissue sample mounting platform to move in three dimensions within the ion source structure.

[0038] In some embodiments, a mass spectrometer is also included, the sample inlet of which is connected to the hollow chamber of the ionization cavity via a pipe for mass spectrometry detection.

[0039] In some embodiments, the top of the ionization cavity is hollowed out to accommodate a light guide arm.

[0040] In some embodiments, the emitting end of the light guide arm is fixed to the top three-dimensional adapter plate by a light guide arm clamp, the top three-dimensional adapter plate is mounted on the three-dimensional displacement stage of the light guide arm, and the three-dimensional displacement stage of the light guide arm is mounted on the ionization cavity.

[0041] The three-dimensional displacement stage of the light guide arm can adjust the position of the light guide arm accordingly to suit the laser ionization treatment of tissue samples.

[0042] Preferably, the top three-dimensional adapter plate is provided with an arc-shaped hollow structure. One side of the light guide arm clamp can be rotatably mounted on the top three-dimensional adapter plate, and the other side can be detachably mounted on the arc-shaped hollow structure by bolts, so that the arc-shaped hollow structure forms a slide when the light guide arm rotates.

[0043] The angle of the light guide arm clamp is adjustable to adjust the incident angle of the laser, so as to input the laser at a better incident angle and achieve ionization of the sample.

[0044] When it is necessary to adjust the angle of the light guide arm clamp, loosen the nut on the bolt and rotate the light guide arm clamp along the arc-shaped hollow structure. When the rotation angle is appropriate, screw the nut inward to fix the position of the light guide arm clamp. At this time, the laser incident angle of the light guide arm is adjusted.

[0045] More preferably, the top three-dimensional adapter plate is L-shaped, including a first plate and a second plate that are connected to each other, with the light guide arm fixture mounted on the first plate and the second plate mounted on the three-dimensional displacement stage of the light guide arm.

[0046] The top three-dimensional adapter plate is designed in an L-shape to facilitate the adjustment of the angle of the light guide arm fixture and other related operations.

[0047] In some embodiments, the mounting platform includes a three-dimensional adapter plate, a carrier bracket, a carrier fixing plate, and a loading platform. The three-dimensional adapter plate is mounted on the side wall of the ionization cavity, the carrier bracket is mounted on the three-dimensional adapter plate, the carrier fixing plate is mounted on the carrier bracket, and the loading platform is horizontally mounted on the carrier fixing plate.

[0048] Preferably, the loading platform is provided with a hollow area, which is used to place a support tool for holding the tissue sample to be tested. A first clamping device and a second clamping device are respectively provided on the loading platform on both sides of the hollow area.

[0049] The carrier tool holding the tissue sample to be tested is placed in the hollowed-out area. This prevents the laser from affecting the carrier platform when the sample is subjected to laser treatment. Clamping devices are installed on the carrier platform on both sides of the hollowed-out area to clamp and fix the carrier tool on both sides, ensuring its secure fixation.

[0050] The three-dimensional displacement stage of the light guide arm and the three-dimensional displacement stage of the carrier enable the tissue sample mounting platform and the light guide arm to move within a three-dimensional space. By utilizing the advantages of the light guide arm and the three-dimensional displacement stage, high-sensitivity and fine operation, efficient ionization and precise positioning are achieved. This allows the laser to be used without being limited by the operating distance, enabling efficient ionization and high-sensitivity mass spectrometry detection of tissue samples such as biological tissues, animal and plant tissues, and clinical sample slides.

[0051] More preferably, the handle ends of the first clamping device and the second clamping device are connected by a strip connector.

[0052] When clamping and fixing tissue samples, operators typically hold the slide in one hand and open the clamping device with the other, but it is impossible to open both clamping devices simultaneously. If a strip connector is used to connect the handles of the two clamping devices, pressing the strip connector will press down the handles of both devices, simultaneously opening them and facilitating the placement of the slide.

[0053] The present invention will be further described below with reference to the embodiments and accompanying drawings.

[0054] like Figure 1As shown, a laser ion source tissue sample detection device includes a laser 1, a light guide arm 2, a mounting platform 3, an ionization cavity 4, and a mass spectrometer 5, wherein...

[0055] The ionization cavity 4 is enclosed by a hollow chamber.

[0056] The mounting platform 3 is installed in the hollow chamber of the ionization cavity 4. The mounting platform 3 is equipped with a loading platform 9, and the loading platform 9 is equipped with a clamping device.

[0057] The laser 1 has its output port connected to one end of the light guide arm 2, and the other end of the light guide arm 2 extends above the loading platform 9. The light guide arm 2 contains a lens assembly, consisting of multiple precision lenses (such as collimating lenses and focusing lenses) connected in series. A lens pair is installed at each joint; the front lens collimates the laser into parallel light, and the rear lens refocuses it at the output end. This design ensures that the laser maintains a stable optical path as it passes through each joint, preventing divergence.

[0058] like Figure 2 As shown, the mounting platform 3 includes a three-dimensional adapter plate 6, a carrier bracket 7, a carrier fixing plate 8, and a cargo platform 9. The three-dimensional adapter plate 6 is installed on the side wall of the ionization cavity, the carrier bracket 7 is installed on the three-dimensional adapter plate 6, the carrier fixing plate 8 is installed on the carrier bracket 7, and the cargo platform 9 is horizontally installed on the carrier fixing plate 8.

[0059] The platform 9 has a hollowed-out area for holding a support tool containing the tissue sample to be tested. Clamping devices are installed on both sides of the platform 9. A glass slide 10 containing the sample is placed on the platform 9, and the clamping devices hold both sides of the slide 10, ensuring the sample is positioned within the hollowed-out area. Applying laser light to the sample within the hollowed-out area prevents the laser from affecting the platform. A first clamping device and a second clamping device are respectively installed on the platform on both sides of the hollowed-out area to clamp and fix both sides of the support tool, ensuring its secure fixation.

[0060] The handles of the first and second clamping devices are connected by a strip connector. When clamping and fixing tissue samples, the operator usually holds the slide with one hand and opens the clamping device with the other, but it is impossible to open both clamping devices simultaneously. If the handles of the two clamping devices are connected by a strip connector, the handles of both clamping devices can be pressed down by pressing the strip connector, thus opening both clamping devices at the same time, making it easier to place the slide.

[0061] The strip connector can be a strip plate structure or a column structure. Anti-slip textures can also be set on the surface of the strip connector for anti-slip purposes.

[0062] like Figure 3 and Figure 5 As shown, the three-dimensional moving platform structure on the top surface of the ionization cavity includes a top three-dimensional fixing plate 12, a top three-dimensional adapter plate 13, a light guide arm three-dimensional displacement stage 14, and a light guide arm clamp 15. The top three-dimensional fixing plate 12 is a flat plate design used to support the light guide arm three-dimensional displacement stage 14 and fix it to the ionization cavity housing 11. The top three-dimensional adapter plate 13 adopts an L-shaped bracket design, serving as a transition structure. One side is connected to the light guide arm three-dimensional displacement stage 14, and the other side is used to fix the light guide arm clamp, allowing the light guide arm to move freely under the action of the light guide arm three-dimensional displacement stage 14. The light guide arm clamp 15 adopts a clamp design, which can achieve a good fixing effect on the light guide arm.

[0063] The top three-dimensional adapter plate 13 is provided with an arc-shaped hollow structure. One side of the light guide arm clamp 15 can be rotatably mounted on the top three-dimensional adapter plate 13, such as by hinge; the other side can be detachably mounted on the arc-shaped hollow structure by bolts, so that the arc-shaped hollow structure forms a slide when the light guide arm rotates.

[0064] The angle of the light guide arm clamp 15 is adjustable to adjust the incident angle of the laser, so as to input the laser at a better incident angle and achieve ionization of the sample.

[0065] When adjusting the angle of the light guide arm clamp 15, loosen the nut on the bolt and rotate the light guide arm clamp along the arc-shaped hollow structure. When the rotation angle is appropriate, screw the nut inward to re-fix the position of the light guide arm clamp. At this point, the laser incident angle of the light guide arm has been adjusted. As the light guide arm clamp rotates, the bolt slides within the arc-shaped hollow structure, further restricting the rotation of the light guide arm clamp. This allows for relatively stable angle adjustment of the light guide arm clamp and prevents the light guide arm from falling due to excessive rotation.

[0066] like Figure 6 As shown, the structure of the light guide arm's three-dimensional displacement stage 14 is an XYZ axis combined displacement platform, including a micrometer 14-1, a first locking screw 14-2, a first worktable surface 14-3, a first base 14-4, and a guide rail 14-5. The entire structure is made of blackened aluminum alloy, driven by a micrometer head, and manually adjustable with a micrometer, achieving an accuracy of 0.01mm. The motion structure uses cross roller linear guides to transmit displacement, enabling high-precision and smooth movement.

[0067] like Figure 7As shown, the ionization chamber housing 11 mainly consists of three parts: a mass spectrometer connector 11-1, an intermediate component 11-2, and a three-dimensional fixing component 11-3. These components are connected by connecting pieces 11-4 and fixed together by screw adapters and hand-tightened screws to form a whole, ensuring sufficient internal space for laser ionization of tissue samples. The ionization chamber 4 is fixedly connected to the mass spectrometer inlet via a fixing rod 11-5 for tissue sample detection.

[0068] like Figure 4 As shown, the three-dimensional displacement stage 16 is installed below the ionization chamber 4 and extends into the interior of the ionization chamber 4, with its end connected to the mounting platform 3. The three-dimensional displacement stage 16 can move in three dimensions, thereby driving the mounting platform 3 to move in three dimensions within the ionization chamber 4, so as to better ionize the tissue sample.

[0069] The three-dimensional displacement stage 16 of the carrier is a dovetail groove displacement slide, including a handwheel 16-1, a second locking screw 16-2, a second worktable surface 16-3, a second base 16-4, and a precision screw 16-5. The entire structure is made of blackened aluminum alloy. It is manually adjustable in the x, y, and z axes using the precision screw, and the motion structure uses cross roller linear guides to transmit displacement.

[0070] Laser 1 is used as the desorption and ionization source for tissue samples. High-energy laser light is transmitted to the tissue sample through optical guide arm 2. The tissue sample is placed on a glass slide, which is fixed on a mounting platform 3. Optical guide arm 2 and mounting platform 3 are fixed on ionization cavity 4 and move within a certain spatial range with the help of a three-dimensional moving platform. After being ionized by the laser, the tissue sample enters the mass spectrometer 5 with the help of negative pressure, realizing high-sensitivity mass spectrometry detection.

[0071] Laser 1 uses a nanosecond solid-state laser as its pump source, with continuously adjustable pulse width and single-pulse energy. The laser energy is not limited to a specific wavelength band and includes an indicator light for precise sample detection. The light guide arm 2 incorporates a reflective lens to continuously and losslessly transmit the laser output from laser 1, and a focusing lens at the exit point ensures the output spot size reaches the micrometer level. The sample carrier platform 9 can hold sample carriers, including but not limited to glass slides 10.

[0072] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A laser ion source tissue sample detection device, characterized in that: It includes a laser, a light guide arm, a mounting platform, an ionization cavity, and a mass spectrometer, among which, The mounting platform is installed in the ionization chamber, and a carrying platform is provided on the mounting platform, with a clamping device provided on the carrying platform; The laser's output port is connected to one end of the light guide arm, and the other end of the light guide arm extends above the platform. Lenses or optical fibers are installed inside the light guide arm to achieve lossless laser transmission. The laser is used to inject sufficient energy into the sample tissue, causing it to ionize directly. A lens assembly is installed inside the light guide arm, consisting of multiple precision lenses connected in series. Lens pairs are installed at each joint; the front lens collimates the laser into parallel light, and the rear lens refocuses it at the output end. The collimated parallel light propagates within the light guide arm channel via total internal reflection. An anti-reflection coating is deposited on the lens surface. The outlet of the ionization chamber is connected to the inlet of the mass spectrometer; the top of the ionization chamber is hollowed out to accommodate the light guide arm.

2. The laser ion source tissue sample detection device according to claim 1, characterized in that: The mounting platform is installed on the vehicle's three-dimensional displacement stage.

3. The laser ion source tissue sample detection device according to claim 1, characterized in that: It also includes a mass spectrometer, whose inlet is connected to the hollow chamber of the ionization cavity via a pipe for mass spectrometry detection.

4. The laser ion source tissue sample detection device according to claim 1, characterized in that: The emitting end of the light guide arm is fixed to the top three-dimensional adapter plate by the light guide arm clamp. The top three-dimensional adapter plate is mounted on the three-dimensional displacement stage of the light guide arm, and the three-dimensional displacement stage of the light guide arm is mounted on the ionization cavity.

5. The laser ion source tissue sample detection device according to claim 4, characterized in that: The top three-dimensional adapter plate has an arc-shaped hollow structure. One side of the light guide arm clamp can be rotatably mounted on the top three-dimensional adapter plate, and the other side can be detachably mounted on the arc-shaped hollow structure by bolts, so that the arc-shaped hollow structure forms a slide when the light guide arm rotates.

6. The laser ion source tissue sample detection device according to claim 5, characterized in that: The top three-dimensional adapter plate is L-shaped and includes a first plate and a second plate that are connected to each other. The light guide arm fixture is mounted on the first plate, and the second plate is mounted on the three-dimensional displacement stage of the light guide arm.

7. The laser ion source tissue sample detection device according to claim 4, characterized in that: The mounting platform includes a three-dimensional adapter plate, a carrier bracket, a carrier fixing plate, and a cargo platform. The three-dimensional adapter plate is installed on the side wall of the ionization cavity, the carrier bracket is installed on the three-dimensional adapter plate, the carrier fixing plate is installed on the carrier bracket, and the cargo platform is horizontally installed on the carrier fixing plate.

8. The laser ion source tissue sample detection device according to claim 4, characterized in that: The loading platform is provided with a hollow area, which is used to place a support tool for holding the tissue sample to be tested. A first clamping device and a second clamping device are respectively provided on the loading platform on both sides of the hollow area.

9. The laser ion source tissue sample detection device according to claim 8, characterized in that: The handles of the first clamping device and the second clamping device are connected by a strip connector.

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