Freeze sample preparation machine

Abstract

The utility model provides a kind of frozen sample preparation machine.The frozen sample preparation machine is used to prepare frozen sample, comprising: rack (1);First lifting mechanism (2) is set on rack (1), including the lifting seat (3) that can be lifted relative to rack (1), lifting seat (3) is provided with mounting position;Sample preparation device (4), including sealed chamber (5) and sample preparation mechanism (6), sealed chamber (5) is located on the movement path of sample, sample preparation mechanism (6) is located in sealed chamber (5), sample preparation mechanism (6) includes sample preparation tray (7), and the sample preparation angle of sample preparation tray (7) is adjustable;Freezing container (15) is set below sample preparation device (4), and located on the movement path of sample.The frozen sample preparation machine of the utility model can flexibly sample as required, easily generate the sample ice crystal thickness satisfying demand, and has high production efficiency and high sample preparation quality.

Description

Technical Field

[0001] This utility model relates to the field of transmission electron microscopy sample preparation technology, and more specifically, to a cryogenic sample preparation machine. Background Technology

[0002] A cryogenic sample preparation machine is a device used to prepare biological, material, or industrial samples at ultra-low temperatures (typically below -150°C). It uses rapid freezing (such as liquid nitrogen cooling) to fix the sample in its original state, avoiding sample damage caused by temperature changes or chemical treatments (such as ice crystal formation and protein denaturation). Cryogenic sample preparation machines are key tools in structural biology (such as protein structure analysis) and nanomaterials research, driving the development of cryo-electron microscopy.

[0003] Cryo-electron microscopy (Cryo-EM) is a technique that uses an electron microscope to perform high-resolution three-dimensional structural analysis of rapidly frozen biological macromolecules, cells, or viruses at ultra-low temperatures (approximately -180°C). Because it preserves samples in a near-native state, it has become a revolutionary tool in the field of structural biology.

[0004] Cryogenic sample preparation is a method of processing samples at ultra-low temperatures (typically <-150°C) to preserve their original structure and chemical state to the greatest extent possible, avoiding ice crystal damage, molecular denaturation, or structural collapse caused by room temperature processing. This technique is a core pretreatment step in cryo-electron microscopy (cryo-EM), low-temperature materials analysis, and other fields. Through ultra-low temperature fixation and precise processing, cryogenic sample preparation provides samples in near-natural states for high-resolution microscopic imaging, making it a cornerstone technology in structural biology, materials science, and medical research. With advancements in cryo-electron microscopy and computational algorithms, its application boundaries will continue to expand.

[0005] In the field of cryo-electron microscopy sample preparation, the ice crystal thickness of the sample has a decisive impact on the imaging quality. Current cryo-electron microscopy sample preparation methods produce samples with relatively uniform thicknesses, making it difficult to flexibly achieve different ice crystal thickness gradients according to sample preparation requirements. This results in inconsistent sample quality, often leading to damage due to excessive thinness or obscured images due to excessive thickness. Multiple sample preparation cycles are often required, which is not only inefficient but also makes it difficult to guarantee sample quality. Utility Model Content

[0006] The main purpose of this invention is to provide a cryogenic sample preparation machine that can flexibly prepare samples as needed, easily generate sample ice crystal thickness that meets the requirements, and has high production efficiency and high sample quality.

[0007] To achieve the above objectives, according to one aspect of the present invention, a cryogenic sample preparation machine is provided for preparing frozen samples, comprising:

[0008] frame;

[0009] The first lifting mechanism is mounted on the frame and includes a lifting seat that can be raised and lowered relative to the frame, and the lifting seat is provided with a mounting position.

[0010] The sample preparation device includes a sealed chamber and a sample preparation mechanism. The sealed chamber is located on the movement path of the sample, and the sample preparation mechanism is located in the sealed chamber. The sample preparation mechanism includes a sample preparation plate, and the sample preparation angle of the sample preparation plate is adjustable.

[0011] The freezing container is positioned below the sample preparation device and along the sample's movement path. This structure allows for flexible sample preparation as needed, easily generating the required ice crystal thickness, resulting in high efficiency and high sample quality.

[0012] Furthermore, the sample preparation mechanism also includes a mounting frame and an angle adjustment structure. The angle adjustment structure is mounted on the mounting frame, and the sample preparation tray is mounted on the angle adjustment structure, with the angle adjustment structure adjusting the sample preparation angle. This structure facilitates the installation of the angle adjustment structure and the adjustment of the sample preparation angle of the sample preparation tray.

[0013] Furthermore, the adjustment end of the angle adjustment structure is equipped with a rotation drive structure. The sample preparation disk is installed on the drive end of the rotation drive structure and rotates around its own axis under the driving action of the rotation drive structure. The above structure can adjust the water absorption area of ​​the absorbent filter paper, which can not only avoid contaminating the sample, but also ensure the water absorption capacity of the absorbent filter paper, improve the utilization efficiency of the absorbent filter paper, and ensure the sample preparation quality.

[0014] Furthermore, the mounting frame is equipped with a position adjustment structure, and an angle adjustment structure is located on top of the position adjustment structure. The position adjustment structure is used to adjust the sample preparation tray to regulate the distance between the sample preparation tray and the sample's movement path. This structure allows for greater movement space for the sample preparation tray, enabling it to accommodate various sizes of mesh supports and meet the movement requirements of different types of mesh supports, thus providing better adaptability.

[0015] Furthermore, a force feedback sensor is incorporated into the position adjustment structure. This structure enables better control of the clamping force on the sample during sample preparation, resulting in more precise force control.

[0016] Furthermore, there are two sample preparation trays, the distance between the two trays is adjustable, and / or at least one of the two trays is detachable. This structure conveniently meets the space requirements of the carrier support, providing better applicability and enabling the sample preparation trays to meet the sample preparation requirements of different sizes and specifications.

[0017] Furthermore, the sample preparation angle of the sample preparation plate can be adjusted within a range of 3° to 10°. This structure allows for adjustment of the contact angle (i.e., the sample preparation angle) between the sample preparation plate and the sample during sample preparation, thereby enabling precise control to obtain the desired ice crystal thickness gradient target, significantly improving the quality of cryo-electron microscopy sample preparation and ensuring high-resolution imaging.

[0018] Furthermore, the sealed chamber is equipped with at least two light sources of different wavelengths, which are independently controlled; or, the sealed chamber is equipped with a light source holder that can accommodate the installation of at least two different wavelength light sources. During sample preparation, this structure allows for the selection of a suitable light source as needed, effectively preventing changes or damage to the sample state, better meeting the environmental requirements for sample preparation, and ensuring the quality of the prepared sample.

[0019] Furthermore, the sample preparation device also includes a temperature control structure, a humidity control structure, a temperature sensor, and a humidity sensor. The temperature sensor detects the temperature inside the sealed chamber, and the humidity sensor detects the humidity inside the sealed chamber. The temperature control structure adjusts the temperature inside the sealed chamber based on the temperature data detected by the temperature sensor, and the humidity control structure adjusts the humidity inside the sealed chamber based on the humidity data detected by the humidity sensor. The temperature and humidity controls inside the sealed chamber are linked and controlled in a coordinated manner. This structure enables precise control of the temperature and humidity inside the sealed chamber, thereby more effectively meeting the sample preparation requirements.

[0020] Furthermore, the cryogenic sample preparation machine also includes a second lifting mechanism. The freezing container is located at the lifting end of the second lifting mechanism, and the distance between the freezing container and the sealed chamber is adjusted by the second lifting mechanism. This structure effectively controls the transfer distance and time of the sample from preparation to freezing, ensuring that the sample is rapidly immersed in the cryogenic preparation along the shortest path in the shortest time. This significantly reduces the sample's exposure time in air, thereby reducing the risk of ice crystal formation and improving the efficiency of sample preparation and freezing quality.

[0021] Furthermore, the outer periphery of the freezing container is provided with a gripping structure, which is either recessed or protruding from the outer periphery of the freezing container. This structure facilitates gripping by operators, effectively preventing personal injury accidents and sample damage.

[0022] By applying the technical solution of this utility model, the cryogenic sample preparation machine precisely controls the vertical movement of the lifting seat through a first lifting mechanism supported by the frame. Combined with the coordinated positioning of the adjustable-angle sample preparation plate and the freezing container below in the sealed chamber, the sample can be quickly immersed in the cryogenic preparation agent after being prepared by the sample preparation plate in the sealed chamber. This significantly improves the accuracy and consistency of sample preparation, thereby enhancing the resolution and reliability of cryo-electron microscopy imaging. Because the angle of the sample preparation plate is adjustable, different ice crystal thickness gradients can be achieved to meet the sample preparation needs of different samples. This avoids the problem of excessively thin ice crystals, which could lead to sample exposure and damage, and also avoids the problem of excessively thick ice crystals, which could result in poor light transmission and unclear sample visibility. The appropriate ice crystal thickness gradient facilitates the identification of the optimal sample thickness point for observation, improving the success rate, efficiency, and quality of sample preparation. Attached Figure Description

[0023] The accompanying drawings, which form part of this application, are used to provide a further understanding of the present invention. The illustrative embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an undue limitation of the present invention. In the drawings:

[0024] Figure 1 This is a side view of the cryogenic sample preparation machine according to an embodiment of the present invention;

[0025] Figure 2 This is a schematic diagram of the main structure of the cryogenic sample preparation machine according to an embodiment of the present invention;

[0026] Figure 3 This is a schematic diagram of the internal side view of the sample preparation device of the cryogenic sample preparation machine according to an embodiment of the present invention;

[0027] Figure 4 This is a schematic diagram of the internal main structure of the sample preparation device of the cryogenic sample preparation machine according to an embodiment of the present utility model;

[0028] Figure 5 This is a schematic diagram of the structure of the freezing container of a freezing sample preparation machine according to an embodiment of the present invention;

[0029] Figure 6 This is a schematic diagram of the structure of the freezing container of a freezing sample preparation machine according to another embodiment of the present invention;

[0030] Figure 7 This is a schematic diagram of the structure of the freezing container of a freezing sample preparation machine according to another embodiment of this utility model.

[0031] The above figures include the following reference numerals:

[0032] 1. Frame; 2. First lifting mechanism; 3. Lifting seat; 4. Sample preparation device; 5. Sealed chamber; 6. Sample preparation mechanism; 7. Sample preparation tray; 8. Mounting frame; 9. Angle adjustment structure; 10. Rotation drive structure; 11. Position adjustment structure; 12. Temperature adjustment structure; 13. Humidity adjustment structure; 14. Second lifting mechanism; 15. Freezing container; 16. Holding structure; 17. Transmission belt; 18. Transmission block; 19. Optical axis; 20. Base; 21. Net support bracket; 22. Operation panel; 23. Observation window; 24. Slider; 25. Pressure ring; 26. Main control board. Detailed Implementation

[0033] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0034] See also Figures 1 to 7 As shown in the embodiment of this utility model, a cryogenic sample preparation machine is used for preparing frozen samples, including: a frame 1; a first lifting mechanism 2, disposed on the frame 1, including a lifting seat 3 that can be raised and lowered relative to the frame 1, the lifting seat 3 being provided with an installation position; a sample preparation device 4, including a sealed chamber 5 and a sample preparation mechanism 6, the sealed chamber 5 being located on the sample's movement path, the sample preparation mechanism 6 being located inside the sealed chamber 5, the sample preparation mechanism 6 including a sample preparation plate 7, the sample preparation angle of the sample preparation plate 7 being adjustable; and a freezing container 15, disposed below the sample preparation device 4 and located on the sample's movement path.

[0035] The cryogenic sample preparation machine precisely controls the vertical movement of the lifting seat 3 via a first lifting mechanism 2 supported by the frame 1. Combined with the coordinated positioning of the adjustable-angle sample preparation plate 7 within the sealed chamber 5 and the cryogenic container 15 below, the sample, after being prepared by the sample preparation plate within the sealed chamber 5, can be rapidly immersed in the cryogenic formulation. This significantly improves the accuracy and consistency of sample preparation, thereby enhancing the resolution and reliability of cryo-electron microscopy imaging. Because the angle of the sample preparation plate 7 is adjustable, different ice crystal thickness gradients can be achieved to meet the preparation needs of various samples. This avoids the problem of excessively thin ice crystals, which could lead to sample exposure and damage, and also avoids the problem of excessively thick ice crystals resulting in poor light transmission and unclear sample visualization. The appropriate ice crystal thickness gradient facilitates the identification of the optimal sample thickness point for observation, improving the success rate, efficiency, and quality of sample preparation.

[0036] In this embodiment, the sample preparation angle of the sample preparation disk 7 is adjustable, meaning the angle between the sample preparation disk 7 and the straight line containing the sample's movement path is adjustable. By adjusting the sample preparation angle of the sample preparation disk 7, the contact angle between the sample preparation disk 7 and the sample can be changed, thereby facilitating the alteration of the ice crystal thickness gradient of the sample. The sample preparation angle of the sample preparation disk 7 refers to the angle between the sample preparation plane of one side of the sample preparation disk 7 and the straight line containing the sample's movement path. When there are two sample preparation disks 7, they are mirror-symmetrical, and the sample preparation angle of the sample preparation disk 7 refers to the angle between one side of the sample preparation disk 7 and the mirror surface. The definitions of the sample preparation angle of the sample preparation disk 7 in the above two cases are the same; they are simply different expressions under different conditions and do not lead to a change in the definition.

[0037] The sample preparation angle of the sample preparation plate 7 can be adjusted by a drive mechanism such as a motor, or by changing the specifications of the sample preparation plate 7. That is, the sample preparation plate 7 has multiple specifications and can be replaced, and different specifications of the sample preparation plate 7 can form different sample preparation angles.

[0038] In one embodiment, the first lifting mechanism 2 further includes a drive motor and two transmission wheels, each mounted on the frame 1 and spaced vertically. The lifting seat 3 includes a transmission belt 17, a transmission block 18, and an optical shaft 19. The end of the drive motor is connected to the transmission wheel at the top of the frame 1. The transmission belt 17 is fitted onto the two transmission wheels. The transmission block 18 is fixedly connected to one side of the transmission belt 17 and moves up and down with that side of the transmission belt to achieve the lifting adjustment of the lifting seat 3. The transmission block 18 includes a main block and an extension block. The main block is fixedly connected to the transmission belt 17, and the extension block is mounted on the main block and extends outward from the main block. The top end of the optical shaft 19 is fixedly connected to the extension block. A mounting position is located on the optical shaft 19 for mounting the net support bracket 21.

[0039] In one embodiment, the first lifting mechanism 2 includes a screw drive mechanism, and the lifting seat 3 is installed on the screw of the screw drive mechanism to realize lifting adjustment. The lifting seat 3 includes a transmission block 18 and an optical shaft 19. The transmission block 18 is installed on the screw and is lifted and lowered under the driving action of the screw. The optical shaft 19 is installed on the transmission block 18 and moves up and down together with the transmission block 18.

[0040] In one embodiment, the first lifting mechanism 2 may further include a linear motor, a cylinder or a hydraulic cylinder, and the lifting seat 3 includes an optical axis 19, which is directly disposed at the lifting end of the lifting mechanism.

[0041] In one embodiment, the sample preparation mechanism 6 further includes a mounting frame 8 and an angle adjustment structure 9. The angle adjustment structure 9 is disposed on the mounting frame 8, and the sample preparation plate 7 is mounted on the angle adjustment structure 9, and the sample preparation angle is adjusted by the angle adjustment structure 9.

[0042] In this embodiment, the mounting bracket 8 provides a mounting base for the angle adjustment structure 9. The mounting bracket 8 is suspended from the top wall of the sealed chamber 5, and the angle adjustment structure 9 is installed at the bottom of the mounting bracket 8. The mounting bracket 8 is, for example, a T-shaped bracket. The top of the T-shaped bracket is fixedly connected to the top wall of the sealed chamber 5, providing a more stable mounting structure. The angle adjustment structure 9 is provided at the bottom, providing more operating space for its installation. The mounting bracket 8 and the angle adjustment structure 9 work together to facilitate the installation of the angle adjustment structure 9 and the adjustment of the sample preparation angle of the sample preparation tray 7.

[0043] The angle adjustment structure 9 includes a motor and a connecting arm. The first end of the connecting arm is connected to the bottom of the mounting frame 8, and the second end extends towards the sample preparation area. The motor is mounted on the extended end of the connecting arm, and the sample preparation disk 7 is mounted on the drive end of the motor. The sample preparation angle is adjusted by driving the motor. Using a motor as the drive structure enables stepless adjustment of the sample preparation angle of the angle adjustment structure 9, providing a wider adjustment range and greater flexibility, thus better meeting sample preparation needs.

[0044] In one embodiment, the angle adjustment structure 9 can also adopt a gear transmission structure or a ratchet structure, which can also achieve the adjustment of the sample preparation angle of the sample preparation plate 7.

[0045] In one embodiment, the adjustment end of the angle adjustment structure 9 is provided with a rotation drive structure 10, and the sample preparation disk 7 is installed on the drive end of the rotation drive structure 10 and rotates around its own axis under the driving action of the rotation drive structure 10.

[0046] In this embodiment, the rotation drive structure 10 is a motor. The rotation drive structure 10 is set at the output end of the motor of the angle adjustment structure 9 and is driven by the motor of the angle adjustment structure 9 to swing. The sample preparation disk 7 is set at the output end of the motor of the rotation drive structure 10 and rotates under the driving action of the motor of the rotation drive structure 10, so as to realize the rotation of the sample preparation disk 7 around its own axis.

[0047] The sample preparation tray 7 typically has absorbent filter paper on its surface to remove moisture from the sample, thus improving sample quality. However, existing sample preparation trays 7 have a fixed rotation angle and cannot rotate along their own axis. Therefore, the position where the absorbent filter paper absorbs moisture from the sample is always fixed. This can easily contaminate different samples, and the absorbent paper's absorption capacity weakens after use, failing to achieve effective water absorption and thus affecting sample preparation quality. By designing the sample preparation tray 7 to rotate around its own axis, after each absorption cycle, the absorbent paper can be rotated by an angle around its axis, adjusting the absorption area. This avoids sample contamination while maintaining the absorbent paper's absorption capacity, improving its utilization efficiency and ensuring sample preparation quality.

[0048] In one embodiment, a mounting hole is provided in the center of the sample preparation tray 7, and a pressure ring 25 is installed in the mounting hole to press and fix the absorbent filter paper. The pressure ring 25 includes a mounting shaft and a clamping flange disposed on the outer periphery of the mounting shaft. The clamping flange is a thin sheet structure to avoid interference with the sample preparation of the sample preparation tray 7. The mounting shaft is installed in the mounting hole to realize the installation and fixation of the pressure ring 25 on the sample preparation tray 7. The mounting shaft of the pressure ring 25 and the mounting hole can be an interference fit, a snap-fit, or a screw connection, etc.

[0049] In one embodiment, the mounting bracket 8 is provided with a position adjustment structure 11, and an angle adjustment structure 9 is provided on the position adjustment structure 11. The position adjustment structure 11 is used to adjust the sample preparation plate 7 by translation, so as to adjust the distance between the sample preparation plate 7 and the movement path of the sample.

[0050] In this embodiment, the position adjustment structure 11 is used to adjust the distance between the sample preparation tray 7 and the sample holding grid support 21, such as tweezers, so that the sample preparation tray 7 has a larger range of motion, can adapt to the use of grid supports 21 of various sizes, and can meet the movement of different types of grid supports 21, thus having better adaptability.

[0051] In this embodiment, the position adjustment structure 11 translates to adjust the sample preparation plate 7, so that the movement of the sample preparation plate 7 is translational. This allows the position adjustment of the sample preparation plate 7 to be achieved without changing the sample preparation angle of the sample preparation plate 7, thereby reducing the angle adjustment of the sample preparation plate 7 and ensuring the angle adjustment accuracy of the sample preparation plate 7.

[0052] In one embodiment, the position adjustment structure 11 includes a slider 24 and a drive structure. A groove, which is T-shaped, is provided at the bottom of the mounting bracket 8. The slider 24 is a T-shaped block. The drive structure is driven to connect with the slider 24, driving the slider 24 to slide within the groove, thereby adjusting the displacement of the sample tray 7. The drive structure can be, for example, a linear motor, a telescopic cylinder (such as a pneumatic or hydraulic cylinder), or a screw drive structure. The connecting arm of the angle adjustment structure 9 is located at the bottom end of the slider 24 extending from the groove and moves together with the slider 24, driving the rotation drive structure 10 located on the angle adjustment structure 9 to move together, thereby driving the sample tray 7 located on the rotation drive structure 10 to move, thus adjusting the position of the sample tray 7.

[0053] When there are two sample preparation disks 7, there are two position adjustment structures 11, two rotation drive structures 10, and two angle adjustment structures 9, which are set in a mirror-symmetrical arrangement relative to the two sample preparation disks 7, so as to realize the synchronous adjustment of the position, sample preparation angle and rotation angle of the two sample preparation disks 7.

[0054] In one embodiment, a force feedback sensor is provided on the position adjustment structure 11. The position adjustment structure 11 adjusts the clamping force during the sample preparation process based on the clamping force detected by the force feedback sensor, thereby flexibly controlling the clamping force and clamping time. This adapts to the needs of various sample preparation scenarios and provides a more suitable clamping force, improving sample preparation quality. Since the sample preparation angle and the rotation position of the sample preparation disk 7 are generally not adjusted further after adjustment, the clamping action is mainly achieved by the position adjustment structure 11. Therefore, by controlling the clamping force and clamping time of the position adjustment structure 11, the clamping force on the sample during the sample preparation process can be well controlled, resulting in more precise force control.

[0055] In one embodiment, there are two sample preparation trays 7, and the distance between the two sample preparation trays 7 is adjustable.

[0056] In this embodiment, the two sample preparation trays 7 are mirror-symmetrical structures, and the distance between them is adjustable, which can conveniently meet the activity space requirements of the carrier support 21 and has better applicability, so that the sample preparation trays 7 can meet the sample preparation requirements of different sizes and specifications.

[0057] In one embodiment, at least one of the two sample preparation trays 7 is removable.

[0058] In this embodiment, a loading window is provided on the side wall of the sealed chamber 5, and a sealing cover is detachably provided at the loading window. The loading window can be adapted to the installation requirements of the camera. When sample observation is required, the sealing cover can be opened on the side where the loading window is located, and the sample preparation tray 7 on that side can be removed, leaving one sample preparation tray 7. Then, the camera can be installed in the loading window, so that a sealed fit is formed between the camera and the side wall of the sealed chamber 5. In this case, the sample preparation status can be detected in real time, which can more effectively ensure the sample preparation quality.

[0059] In one embodiment, the sample preparation angle of the sample preparation plate 7 can be adjusted from 3° to 10°.

[0060] By integrating an adjustable sample preparation plate 7 into the sample preparation mechanism, the adjustment range is precisely controlled between 3° and 10°. The contact angle between the sample preparation plate and the sample (i.e., the sample preparation angle) can be adjusted as needed during the sample preparation process. This allows for precise control to obtain the desired sample ice crystal thickness gradient target, significantly improving the preparation quality of cryo-electron microscopy samples and ensuring high-resolution imaging.

[0061] In one embodiment, at least two light sources of different wavelengths are provided in the sealed chamber 5, and the light sources of different wavelengths are controlled independently of each other.

[0062] In this embodiment, since the sealed chamber 5 has at least two different wavelength light sources, and the different wavelength light sources are controlled independently, the appropriate light source can be selected as needed during the sample preparation process, thereby effectively avoiding changes or damage to the sample state, better meeting the environmental requirements for sample preparation, and ensuring the sample preparation quality.

[0063] When selecting a light source, the light sources can be numbered, with each number corresponding to a wavelength. After determining the required light source, the light source can be turned on according to its number, while other light sources can be turned off, thus ensuring that the light source in the sealed chamber 5 is the required light source and meets the environmental requirements for sample preparation.

[0064] In one embodiment, a light source holder is provided in the sealed chamber 5, which is capable of accommodating the installation of at least two different wavelengths of light sources.

[0065] In this embodiment, the light source holder has good adaptability and can meet the installation requirements of light sources of different wavelengths. When it is necessary to replace the light source, the light source on the light source holder can be removed, and then the required light source can be selected and installed on the light source holder, thereby forming the required light source environment in the sealed chamber 5.

[0066] In one embodiment, the sealed chamber 5 is filled with a protective gas. The protective gas can be an inert gas or other gas that can protect the sample and prevent changes in the sample's state or damage.

[0067] In one embodiment, the sample preparation device 4 further includes a temperature regulation structure 12, a humidity regulation structure 13, a temperature sensor, and a humidity sensor. The temperature sensor is used to detect the temperature inside the sealed chamber 5, and the humidity sensor is used to detect the humidity inside the sealed chamber 5. The temperature regulation structure 12 adjusts the temperature inside the sealed chamber 5 according to the temperature data detected by the temperature sensor, and the humidity regulation structure 13 adjusts the humidity inside the sealed chamber 5 according to the humidity data detected by the humidity sensor. The temperature regulation and humidity regulation inside the sealed chamber 5 are linked and controlled.

[0068] In this embodiment, the above structure enables precise control of the temperature and humidity within the sealed chamber 5, thereby more effectively meeting the sample preparation requirements. The temperature regulation structure 12 is, for example, a semiconductor cooling chip or a refrigerant heat exchanger. The humidity regulation structure 13 is, for example, a humidifier.

[0069] In one embodiment, the temperature regulation structure 12 and the humidity regulation structure 13 can be an integrated structure, that is, the two are the same device, which can simultaneously meet the temperature and humidity regulation needs in the sealed chamber 5.

[0070] Alternatively, a single temperature and humidity sensor can be used to replace both the temperature and humidity sensors, reducing costs and saving space.

[0071] In one embodiment, the cryogenic sample preparation machine further includes a second lifting mechanism 14, with the cryogenic container 15 disposed at the lifting end of the second lifting mechanism 14, and the distance between the cryogenic container 15 and the sealed chamber 5 adjusted by the second lifting mechanism 14.

[0072] In this embodiment, the cryogenic sample preparation machine precisely adjusts the distance between the freezing container 15 and the sealed chamber 5 through the second lifting mechanism 14, effectively controlling the transfer distance and time of the sample from sample preparation to freezing. This ensures that the sample is quickly immersed in the cryogenic preparation in the shortest time and along the shortest path, greatly reducing the exposure time of the sample in the air, thereby reducing the risk of ice crystal formation and improving the efficiency of sample preparation and freezing quality.

[0073] The second lifting mechanism 14 includes a drive motor, a transmission wheel, a transmission belt, and a lifting block. The drive motor is installed at the lower part of the frame 1 and below the sample preparation device 4. Two transmission wheels are installed on the frame 1, one of which is connected to the drive motor. The transmission belt is sleeved on the transmission wheel. The lifting block is fixedly installed on the transmission belt on one side. The freezing container 15 is fixedly connected to the lifting block. The lifting and lowering of the freezing container 15 can be achieved by lifting and lowering the lifting block.

[0074] In one embodiment, the second lifting mechanism 14 may also include a lifting mechanism, such as a telescopic cylinder, or a linear motor, so that the lifting mechanism or linear motor can be used to adjust the lifting of the freezing container 15.

[0075] In one embodiment, a gripping structure 16 is provided on the outer periphery of the freezing container 15, the gripping structure 16 being recessed or protruding from the outer periphery of the freezing container 15.

[0076] By providing a grip structure 16 around the periphery of the freezing container 15, it is easy for operators to grip the container, effectively preventing personal safety accidents and sample damage.

[0077] In one embodiment, the grip structure 16 is a recessed handle provided on the outer peripheral wall of the freezing container 15. The recessed handle is recessed inward from the outer peripheral wall of the freezing container 15, allowing the operator's fingers to penetrate into the recess and grip the freezing container 15.

[0078] In one embodiment, the grip structure 16 is a handle disposed on the outer peripheral wall of the freezing container 15.

[0079] In one embodiment, multiple grooves are spaced apart on the outer periphery of the freezing container 15, and protrusions are formed between adjacent grooves. These protrusions form a grip structure 16, facilitating gripping by the operator. The multiple grooves cut along the outer periphery of the freezing container 15, resulting in a smaller width for each protrusion, thus reducing the difficulty of gripping.

[0080] In one embodiment, the cryogenic sample preparation machine further includes a mesh support 21, such as tweezers, for gripping the sample mesh and then preparing the sample.

[0081] The grid holder 21 is used to fix the electron microscope grid, ensuring its precise positioning. The grid holder 21 uses a low-temperature resistant metal support to prevent deformation due to thermal expansion and contraction, ensuring stable and reliable sample clamping. The grid holder 21 is made of, for example, titanium alloy.

[0082] In one embodiment, a through hole is provided on the bottom wall of the sealed chamber 5, and a shutter is provided at the through hole. The shutter speed is less than 80ms, thereby achieving a rapid freezing response and ensuring the sample preparation quality.

[0083] The through hole corresponds to the grid support 21 and allows the grid support 21 to carry the electron microscope grid quickly and unobstructedly, so as to quickly enter the freezing container 15 and realize the freezing and sample preparation.

[0084] In one embodiment, the cryogenic sample preparation machine also includes an operation screen 22, located on top of the frame 1. Operators can control various parameters and movements of the cryogenic sample preparation machine from the operation screen. The operation screen can be a touchscreen for simpler and more convenient operation.

[0085] In one embodiment, the cryogenic sample preparation machine also includes a main control board 26, which is electrically connected to the operation screen 22, and the operation screen 22 can be used to operate the main control board 26.

[0086] In one embodiment, an observation window 23 is provided on the front side of the sealed chamber. The observation window 23 has a transparent structure, which facilitates the observation of the sample preparation process inside the sealed chamber 5.

[0087] In one embodiment, a base 20 is provided at the bottom of the rack 1, and the freezing container 15 is supported on the base 20.

[0088] The working process of the cryogenic sample preparation machine is as follows:

[0089] First, operate the first lifting mechanism 2 to drive the optical axis 19 downward to the bottom, and wait for the tweezers to be installed.

[0090] After the tweezers are installed, the optical axis 19 is controlled to move upward to the sample application position in the sealed chamber 5. The shutter is closed, and the sealed chamber 5 is controlled to form a sealed space. Then, the temperature and humidity environment in the sealed chamber 5 is adjusted. The temperature error is controlled within ±0.5℃ and the humidity error is controlled within ±2%RH through the feedback loop, so that a constant temperature and humidity environment is formed in the sealed chamber 5.

[0091] The freezing container 15 containing the cryogenic preparation (liquid nitrogen and cryogenic liquid ethane or liquid propane) is placed on a platform driven by the second lifting mechanism 14. The second lifting mechanism 14 drives the freezing container 15 to rise to the bottom of the sealed chamber 5, so that the area of ​​the freezing container 15 containing cryogenic liquid ethane or liquid propane is aligned with the shutter position, and the sample is waited to enter the freezing container 15.

[0092] Then, the optical axis 19 is controlled to rise to the sample preparation position. The sample preparation angle of the sample preparation plate 7 is adjusted according to the sample specifications. Then, the position adjustment structure 11 is controlled to adjust the position of the sample preparation plate, so that the sample preparation plate 7 moves towards the sample position. During this process, the force applied to the sample by the position adjustment structure 11 is adjusted according to the force feedback sensor on the position adjustment structure 11, driving the sample preparation plate 7 to clamp once. Sample preparation is carried out simultaneously while the sample is being absorbed by the absorbent filter paper.

[0093] After sample preparation is completed, the shutter is opened and the optical axis 19 is controlled to insert the tweezers into the freezing container 15 through the shutter at maximum speed for freezing.

[0094] Then, the first lifting mechanism 2 and the second lifting mechanism 14 are controlled to descend synchronously, so that the sample on the tweezers and the freezing container are lowered to the bottom at the same time, making it convenient for the operator to take out the prepared sample for subsequent operations.

[0095] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0096] It should be noted that the terms "first," "second," etc., used in the specification, claims, and accompanying drawings of this application are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of this application described herein can be implemented in sequences other than those illustrated or described herein.

[0097] The above description is merely a preferred embodiment of this utility model and is not intended to limit the utility model. Various modifications and variations can be made to this utility model by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this utility model should be included within the protection scope of this utility model.

Claims

1. A cryogenic sample preparation machine for preparing frozen samples, characterized in that, include: Rack (1); The first lifting mechanism (2) is mounted on the frame (1) and includes a lifting seat (3) that can be lifted relative to the frame (1), and the lifting seat (3) is provided with an installation position; The sample preparation device (4) includes a sealed chamber (5) and a sample preparation mechanism (6). The sealed chamber (5) is located on the movement path of the sample, and the sample preparation mechanism (6) is located inside the sealed chamber (5). The sample preparation mechanism (6) includes a sample preparation plate (7), and the sample preparation angle of the sample preparation plate (7) is adjustable. A freezing container (15) is disposed below the sample preparation device (4) and located on the movement path of the sample.

2. The cryogenic sample preparation machine according to claim 1, characterized in that, The sample preparation mechanism (6) also includes a mounting frame (8) and an angle adjustment structure (9). The angle adjustment structure (9) is disposed on the mounting frame (8), and the sample preparation plate (7) is mounted on the angle adjustment structure (9), and the sample preparation angle is adjusted by the angle adjustment structure (9).

3. The cryogenic sample preparation machine according to claim 2, characterized in that, The angle adjustment structure (9) is provided with a rotation drive structure (10) at its adjustment end. The sample preparation disk (7) is installed at the drive end of the rotation drive structure (10) and rotates around its own axis under the driving action of the rotation drive structure (10).

4. The cryogenic sample preparation machine according to claim 2 or 3, characterized in that, The mounting bracket (8) is provided with a position adjustment structure (11), and the angle adjustment structure (9) is provided on the position adjustment structure (11). The position adjustment structure (11) is used to adjust the sample preparation plate (7) by translation, so as to adjust the distance between the sample preparation plate (7) and the movement path of the sample.

5. The cryogenic sample preparation machine according to claim 4, characterized in that, A force feedback sensor is provided on the position adjustment structure (11).

6. The cryogenic sample preparation machine according to claim 1, characterized in that, There are two sample preparation trays (7), the spacing between the two sample preparation trays (7) is adjustable, and / or at least one of the two sample preparation trays (7) is detachable.

7. The cryogenic sample preparation machine according to claim 1, characterized in that, The sample preparation angle of the sample preparation plate (7) can be adjusted from 3° to 10°.

8. The cryogenic sample preparation machine according to claim 1, characterized in that, The sealed chamber (5) is provided with at least two light sources of different wavelengths, and the light sources of different wavelengths are controlled independently; or, the sealed chamber (5) is provided with a light source holder, which can be adapted to the installation of at least two light sources of different wavelengths.

9. The cryogenic sample preparation machine according to claim 1, characterized in that, The sample preparation device (4) further includes a temperature regulation structure (12), a humidity regulation structure (13), a temperature sensor, and a humidity sensor. The temperature sensor is used to detect the temperature inside the sealed chamber (5), and the humidity sensor is used to detect the humidity inside the sealed chamber (5). The temperature regulation structure (12) adjusts the temperature inside the sealed chamber (5) according to the temperature data detected by the temperature sensor, and the humidity regulation structure (13) adjusts the humidity inside the sealed chamber (5) according to the humidity data detected by the humidity sensor. The temperature regulation and humidity regulation inside the sealed chamber (5) are linked and controlled.

10. The cryogenic sample preparation machine according to claim 1, characterized in that, The cryogenic sample preparation machine also includes a second lifting mechanism (14), the cryogenic container (15) is disposed at the lifting end of the second lifting mechanism (14), and the distance between the cryogenic container (15) and the sealed chamber (5) is adjusted by the second lifting mechanism (14).

11. The cryogenic sample preparation machine according to claim 1, characterized in that, The outer periphery of the freezing container (15) is provided with a gripping structure (16), which is recessed or protruding from the outer periphery of the freezing container (15).

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