Sample storage device and sample delivery method

By designing sample storage devices and delivery methods, the problem of pathogen leakage during sample transfer was solved, achieving fully sealed transfer and safety of samples, which is suitable for cryo-electron microscopy research in P3 laboratories.

CN121590855APending Publication Date: 2026-03-03GUANGZHOU NAT LAB
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Patent Information

Application Number
CN202511806395.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-12-03
Publication Date
2026-03-03

AI Technical Summary

Technical Problem

In the prior art, there is a low safety issue of pathogen leakage during the process of loading samples from the transfer cassette or sample carrier into the cryo-electron microscopy system, especially in operation steps such as sample loading and sample carrier insertion, which may lead to pathogen contamination of the environment and damage to the sample.

Method used

A sample storage device was designed, including a cavity, a sealing mechanism, a conveying device, and a vacuum system. The cavity is equipped with a sample storage area and an environmental buffer zone. The sealing mechanism achieves double sealing, and the device is connected to a cryo-electron microscope through a conveying channel. The vacuum system maintains a vacuum environment during the conveying process to ensure the safe transfer of samples.

Benefits of technology

It enables fully enclosed transfer of samples during the transfer process, avoiding pathogen leakage and ensuring the safety and integrity of the samples, making it suitable for high-quality cryo-electron microscopy research in P3 laboratory environments.

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Abstract

The invention discloses a sample storage device and a sample delivery method, and the device comprises a cavity which is internally provided with a first area for storing samples and a second area for environment buffering; the sealing mechanism is arranged on the cavity and is attached to the first area and the second area; the conveying device comprises a transmission assembly, and the transmission assembly is arranged in the cavity; the conveying channel is arranged on one side of the outer surface of the cavity, one end of the conveying channel is selectively communicated with the first area, and the other end is selectively communicated with a sample cavity of the cryoelectron microscope; the vacuum system is used for providing a vacuum environment for the conveying channel; the cavity is divided into the first area and the second area, the sealing mechanism is arranged to be attached to the first area and the second area respectively, and double sealing is achieved; the conveying channel is arranged between the cavity and the freezing electron microscope, the conveying device can convey the sample from the sample storage area to the freezing electron microscope through the conveying channel, it is guaranteed that the sample is not polluted in the whole conveying process, and the conveying safety is improved.
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Description

Technical Field

[0001] This application relates to the field of sample storage technology, and in particular to sample storage devices and sample delivery methods. Background Technology

[0002] With the in-depth development of virology, pathogenic microbiology, and infectious disease research, cryo-electron microscopy is playing an increasingly important role in the structural analysis of high-risk pathogens. Many important pathogens, such as SARS-CoV, Mycobacterium tuberculosis, and Bacillus anthracis, are potentially infectious. Samples of these pathogens are highly infectious, and their processing and research must be conducted in a biosafety level 3 (P3 / BSL-3) laboratory to ensure the safety of personnel and the environment.

[0003] Currently, cryo-electron microscopy research on important pathogens mainly involves installing the entire cryo-electron microscopy system in a P3-level biosafety laboratory to achieve a closed-loop biosafety process from sample preparation to imaging. However, this approach has many limitations: the construction cost of a P3 laboratory is high, 5-10 times that of a regular laboratory; maintenance or upgrades of electron microscopes in a P3 environment require strict protective procedures and professional training, resulting in high maintenance and time costs; and the negative pressure environment, special ventilation system, and strict personnel movement restrictions in a P3 laboratory may affect the stability of precision equipment and imaging quality.

[0004] To balance biosafety requirements with the aforementioned limitations, analysis reveals that cryo-electron microscopy inherently possesses biosafety characteristics. The cryo-electron microscope chamber maintains an ultra-high vacuum environment superior to 10^-5 Pa. Under such a high vacuum, no microorganisms or pathogens can survive or spread, thus eliminating the risk of environmental contamination during sample observation within the chamber. Furthermore, samples treated with liquid nitrogen are already at an extremely low temperature of -196°C, completely inhibiting pathogen activity and preventing active contamination. Therefore, the biosafety risk lies in the transfer process between sample preparation and entry into the cryo-electron microscope chamber. This process requires removing the sample from the P3 environment, transporting it via a sample transfer cassette or rod, and then loading it into the cryo-electron microscope system. In traditional procedures, samples are briefly exposed to the atmosphere during transfer, especially during sample loading and rod insertion, posing a risk of pathogen leakage into the surrounding environment and potential sample damage, resulting in lower safety. Summary of the Invention

[0005] This application aims to at least address one of the aforementioned technical problems existing in the prior art. To this end, this application provides a sample storage device and a sample delivery method, which can solve the problem of low safety due to pathogen leakage when loading samples from transfer cassettes or sample carriers into cryo-electron microscopy systems.

[0006] To achieve the above objectives, the technical solution adopted in this application is as follows: According to the first aspect, this application provides a sample storage device, including... The cavity has a first area inside for storing samples and a second area on its outer surface for environmental buffering. A sealing mechanism is provided on the cavity and fits against the first and second regions to seal the cavity. A conveying device, including a transmission component disposed within the cavity; A delivery channel is located on one side of the outer surface of the cavity. One end of the channel is selectively connected to the first region, and the other end is selectively connected to the sample chamber of the cryo-electron microscope. The delivery assembly is able to acquire samples and deliver them to the sample chamber of the cryo-electron microscope via the delivery channel. A vacuum system is provided to create a vacuum environment for the transport channel.

[0007] According to some embodiments of this application, the sealing mechanism includes a door body, a first sealing strip, and a second sealing strip. A third region is provided on the side surface of the door body near the cavity. The shape of the third region matches the shape of the first region. The first sealing strip is disposed in accordance with the outer edge contour of the third region. The second sealing strip is embedded in the door frame groove of the door body, and the outer edge contour of the door body is in contact with the second region.

[0008] According to some embodiments of this application, the sample storage device further includes an intelligent control system for controlling the opening and closing of the door.

[0009] According to some embodiments of this application, the door is an inflatable airtight door, and both the first sealing strip and the second sealing strip are inflatable sealing strips. The intelligent control system can deflate or inflate the first sealing strip and the second sealing strip according to the opening or closing of the door.

[0010] According to some embodiments of this application, when the transport channel is evacuated, the transport channel is isolated from the sample chamber of the cryo-electron microscope. When the vacuum level of the transport channel reaches the vacuum level of the sample chamber of the cryo-electron microscope, the transport channel is connected to the sample chamber of the cryo-electron microscope, and the sample can enter the sample chamber of the cryo-electron microscope from the transport channel.

[0011] According to some embodiments of this application, a first valve is provided on the side of the first area near the conveying channel. The first valve can connect or disconnect the first area from the conveying channel, and the intelligent control system can control the opening and closing of the first valve.

[0012] According to some embodiments of this application, one end of the delivery channel is connected to a first valve, and the other end is connected to a cryo-electron microscope via a connector.

[0013] According to some embodiments of this application, the connector is a flange, and the flange specifications are matched with the cryo-electron microscope.

[0014] According to some embodiments of this application, the flange includes a flange body and connecting bolts, the flange body mating with the cryo-electron microscope has a knife edge, and there are a plurality of connecting bolts distributed circumferentially along the surface of the flange body.

[0015] According to some embodiments of this application, a second valve is provided between the conveying channel and the connector. The second valve can connect or disconnect the connection between the conveying channel and the cryo-electron microscope. The intelligent control system can control the opening and closing of the second valve.

[0016] According to some embodiments of this application, the transmission component is a variable diameter structure, with its outermost contour fitting against the inner wall of the transmission channel to form a seal.

[0017] According to some embodiments of this application, the transmission assembly includes a sealing section, a transition section and a clamping section in sequence along the sample transport direction. The outer diameter of the sealing section is larger than that of the clamping section, thereby forming a variable diameter structure. The sealing section is fitted with the inner wall of the transport channel, and a sealing ring is provided on the outer contour of the sealing section to maintain the vacuum environment of the transport channel during the transmission process.

[0018] According to some embodiments of this application, the conveying device further includes a drive structure and a track mechanism. The drive mechanism is located on the side of the cavity away from the conveying channel, and the track mechanism is arranged parallel to the first region. The conveying component can move along the track mechanism under the drive of the drive component to realize the conveying of the sample.

[0019] According to some embodiments of this application, the conveying device further includes a drive base, which is disposed on the track mechanism. One end of the drive base is connected to the transmission component, and the other end is connected to the drive mechanism, for driving the transmission component to move.

[0020] According to the second aspect, this application provides a sample delivery method, comprising the following steps: S100: The connector is connected to the cryo-electron microscope. The sample is loaded into the first area, and the second area is sterilized. S200, the connector is connected to the cryo-electron microscope, and the transmission component acquires the sample in the first region; S300, the transport component carries the sample from the transport channel to the sample chamber of the cryo-electron microscope.

[0021] According to some embodiments of this application, step S300 further includes the following steps: S310. After the transmission component acquires the sample, the intelligent control system controls the first valve to open, and the transmission component drives the sample into the conveying channel. S320. After the transfer component moves to the vicinity of the second valve and the outermost contour of the transfer component fits into the transfer channel, the vacuum system evacuates the transfer channel. S330. Once the vacuum level of the delivery channel matches the vacuum level inside the sample chamber of the cryo-electron microscope, the intelligent control system controls the second valve to open, and the delivery assembly delivers the sample into the sample chamber of the cryo-electron microscope. S340. After delivery is completed, the transfer component returns to the delivery channel, the second valve closes, the transfer component continues to return to the first area, the first valve closes, and the transfer component delivers the sample again, thus repeating the cycle.

[0022] The beneficial effects of this application are: This application divides the interior and exterior of the cavity into a first region and a second region, respectively, separating the sample storage area and the external buffer zone. It also provides a sealing mechanism that corresponds to and fits the first and second regions, respectively, to achieve a double seal for the cavity and ensure its airtightness. A transport channel that maintains a vacuum environment is provided between the cavity and the cryo-electron microscope. The transport device can transport the sample from the sample storage area to the cryo-electron microscope through the transport channel, ensuring that the sample is not contaminated during the entire transport process and improving transport safety.

[0023] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Attached Figure Description

[0024] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which: Figure 1 This is a perspective view of the sample storage device provided in the embodiments of this application.

[0025] Figure 2 This is a schematic diagram of a sample placed in a storage device according to an embodiment of this application.

[0026] Figure 3 This is a schematic diagram of the cavity in an embodiment of this application.

[0027] Figure 4 This is a schematic diagram of the first and second sealing strips in the retracted state of the sealing mechanism in an embodiment of this application.

[0028] Figure 5This is a schematic diagram of the expansion state of the first and second sealing strips in the sealing mechanism of this application embodiment.

[0029] Figure 6 This is a schematic diagram of the conveying mechanism structure in an embodiment of this application.

[0030] Figure 7 This is a schematic diagram of the transmission component in the conveying channel according to an embodiment of this application.

[0031] Figure 8 This is a schematic diagram of the first valve and the second valve in an embodiment of this application.

[0032] Figure 9 This is a flowchart of the sample delivery method provided in the embodiments of this application.

[0033] Figure label: 100. Cavity; 110. First region; 120. Second region; 130. Third region; 140. First valve; 150. Caster wheel; 200. Sealing mechanism; 210. Door body; 220. First sealing strip; 230. Second sealing strip; 240. Handle; 300. Conveying device; 310. Drive motor; 320. Linear guide rail; 330. Transmission assembly; 331. Sealing ring; 332. Gripper; 333. Sealing section; 334. Transition section; 335. Clamping section; 340. Drive base; 350. Ball screw; 400. Conveying channel; 410. Connecting component; 411. Flange body; 412. Connecting bolt; 420. Second valve. Detailed Implementation

[0034] The embodiments of this application are described in detail below with reference to the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain this application, and should not be construed as limiting this application.

[0035] In the description of this application, it should be understood that the terms "center", "middle", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "axial", "radial", "circumferential", etc., indicating the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application.

[0036] In the description of this application, "several" means one or more, "multiple" means two or more, "greater than," "less than," and "exceeding" are understood to exclude the stated number, while "above," "below," and "within" are understood to include the stated number. The use of "first" and "second" in the description is merely for distinguishing technical features and should not be construed as indicating or implying relative importance, or implicitly indicating the number of indicated technical features, or implicitly indicating the order of the indicated technical features.

[0037] In the description of this application, unless otherwise expressly specified and limited, the terms "set up," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0038] In the description of this application, the use of terms such as "as one implementation," "an embodiment," "some examples," "some embodiments," "illustrative embodiment," "example," "specific example," "some examples," etc., indicates that the specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0039] Reference Figures 1 to 8 As shown, the following are specific embodiments of this application.

[0040] In a first aspect, this application provides a sample storage device, including a cavity 100, a sealing mechanism 200, a conveying device, a conveying channel 400, and a vacuum system. The cavity 100 has a first region 110 for storing samples inside and a second region 120 for environmental buffering on its outer surface. The first region 110 is filled with liquid nitrogen and maintained at a temperature of -196°C to ensure that the sample is in an extremely low temperature state and that pathogen activity is completely inhibited.

[0041] The sealing mechanism 200 is disposed on the cavity 100 and fits against the first region 110 and the second region 120 to achieve sealing of the cavity 100.

[0042] The conveying device 300 includes a transmission component 330, which is disposed inside the cavity 100. Specifically, the transmission component 330 is disposed above the first region 110 and is used to acquire samples.

[0043] The transport channel 400 is located on one side of the outer surface of the cavity 100. One end of the channel is selectively connected to the first region 110, and the other end is selectively connected to the sample chamber of the cryo-electron microscope. The transport assembly 330 can acquire samples and deliver them to the sample chamber of the cryo-electron microscope via the transport channel 400.

[0044] Vacuum system, used to provide a vacuum environment for the transport channel 400.

[0045] In some embodiments, the sealing mechanism 200 includes a door body 210, a first sealing strip 220 and a second sealing strip 230. A third region 130 is provided on the side surface of the door body 210 near the cavity 100. The shape of the third region 130 matches the shape of the first region 110. The first sealing strip 220 is disposed in accordance with the outer edge contour of the third region 130. The second sealing strip 230 is embedded in the door frame groove of the door body 210. The outer edge contour of the door body 210 is in contact with the second region 120.

[0046] When the door 210 is closed, the third region 130 fits tightly with the first region 110 to form a first sealing region, and the outer edge of the door 210 fits with the second region 120 to form a second sealing region. The double-fitting seal ensures the airtightness of the cavity.

[0047] In some embodiments, the first sealing strip 220 and the second sealing strip 230 are non-pneumatic sealing strips, which rely on their own elastic deformation to fit into the third region 130 and the second region 120 respectively to achieve sealing.

[0048] The sample storage device also includes an intelligent control system, which controls the opening and closing of the door 210.

[0049] In some embodiments, the door 210 is an inflatable airtight door, capable of withstanding a certain pressure difference when closed to prevent gas leakage. Simultaneously, both the first sealing strip 220 and the second sealing strip 230 are inflatable sealing strips, and the intelligent control system can simultaneously deflate or inflate the first sealing strip 220 and the second sealing strip 230 according to the opening or closing of the door 210. After the door 210 is closed, gas is injected through the intelligent control system to expand it, improving the sealing performance.

[0050] In some embodiments, the door 210 is provided with a handle 240 for easy opening and closing of the door, and the bottom of the door 210 is provided with a number of casters 150 for easy movement of the sample storage device.

[0051] In some embodiments, the third region 130 is a raised structure, and the door body 210 is made of stainless steel, which has the characteristics of low temperature resistance and corrosion resistance.

[0052] The delivery device 300 includes a transfer assembly 330, which is disposed within the cavity 100 and above the first region 110, facilitating sample transfer. The transfer assembly 330 is capable of acquiring samples within the first region 110 and delivering them via the delivery channel 400 to the sample chamber of the cryo-electron microscope.

[0053] A vacuum system (not shown) is used to provide a vacuum environment for the transport channel 400. When the transport channel 400 is evacuated, the transport channel 400 is isolated from the sample chamber of the cryo-electron microscope. When the vacuum level of the transport channel 400 reaches the vacuum level of the sample chamber of the cryo-electron microscope, the transport channel 400 is connected to the sample chamber of the cryo-electron microscope, and the sample can enter the sample chamber of the cryo-electron microscope from the transport channel 400.

[0054] In some embodiments, a first valve 140 is provided on the side of the first region 110 near the transport channel 400, the first valve 140 being able to connect or disconnect the first region 110 from the transport channel 400. One end of the transport channel 400 is connected to the first valve 140, and the other end is connected to the cryo-electron microscope via a connector 410. A second valve 420 is provided between the transport channel 400 and the connector 410, the second valve 420 being able to connect or disconnect the transport channel 400 from the cryo-electron microscope.

[0055] In some embodiments, the intelligent control system controls the opening and closing of the first valve 140 and the second valve 420 to ensure the sealing of the entire sample storage device and the stability of sample transfer.

[0056] In some embodiments, the transfer assembly 330 has a variable diameter structure, with its outermost contour fitting against the inner wall of the transfer channel 400 to form a seal. Specifically, the transfer assembly 330 includes a sealing section 333, a transition section 334, and a clamping section 335 sequentially along the sample transfer direction. The outer diameter of the sealing section 333 is successively larger than the outer diameters of the transition section 334 and the clamping section 335, thus forming a variable diameter structure. The sealing section 333 fits against the inner wall of the transfer channel 400, and a sealing ring 331 is provided on the outer contour of the sealing section 333 to maintain a vacuum environment in the transfer channel 400 during transfer, ensuring that the sample is not contaminated during transfer.

[0057] A gripper 332 is provided on the side of the clamping section 335 away from the transition section 334 for gripping the sample. The gripper 332 includes an upper gripper and a lower gripper arranged opposite each other, which can stably grip the sample from its upper and lower surfaces. The contact surface between the gripper 332 and the sample is provided with a flexible buffer layer to ensure clamping force while avoiding mechanical damage or contamination to the sample surface.

[0058] In some embodiments, the transmission component 330 may be a robotic arm with a gripper 332. A rotary joint is provided between the robotic arm and the gripper 332. The rotary joint can drive the gripper 332 to rotate, thereby driving the gripper 332 to grip the sample downward. The material of the rotary joint is stainless steel or ceramic bearing.

[0059] In some embodiments, the conveying device 300 further includes a drive mechanism and a track mechanism. The drive mechanism is located on the side of the cavity 100 away from the conveying channel 400, and the track mechanism is arranged parallel to the first region 110, allowing the transmission component 330 to move along the track mechanism to convey the sample. The conveying device 300 also includes a drive base 340, which is mounted on the track mechanism. One end of the drive base 340 is connected to the transmission component 330, and the other end is connected to the drive mechanism, for driving the transmission component 330 to move. For moving parts such as the transmission component 330 and the track mechanism, a low-temperature lubrication technique (vacuum-grade low-temperature grease) is applied to their surfaces to ensure stable operation of each moving part under freezing conditions, such as liquid nitrogen at a temperature of -196°C.

[0060] In some embodiments, the driving mechanism is a drive motor 310, and the track mechanism is two parallel linear guide rails 320 arranged above the first region 110. The two sides of the linear guide rails 320 are fixedly connected to the cavity 100. The top and bottom of the drive base 340 are slidably connected to the linear guide rails 320, respectively. The output end of the drive motor 310 is connected to the drive base 340 through a ball screw 350. The ball screw 350 is arranged parallel to the linear guide rails 320. The drive motor 310 drives the ball screw 350 to rotate, which is converted into linear motion of the drive base 340 on the linear guide rails 320. The drive base 340 drives the transmission component 330 to move along the direction of the linear guide rails 320.

[0061] The connector 410 is a flange, and the flange specifications are compatible with the cryo-electron microscope, including but not limited to the interface specifications of equipment from brands such as ThermoFisher and JEOL. It is a metal welding flange, which includes a flange body 411 and connecting bolts 412. The mating surface between the flange body 411 and the cryo-electron microscope is a knife edge. There are several connecting bolts 412, which are distributed circumferentially along the surface of the flange body 411. The connecting bolts 412 are tightened in a cross-tightening manner to achieve a sealed connection with the cryo-electron microscope sample chamber.

[0062] The connector 410 is also equipped with a metal sealing ring at the connection point with the cryo-electron microscope. A vacuum seal is achieved by deforming the metal sealing ring through a knife-edge compression, thus ensuring a reliable airtight connection. When connecting to the cryo-electron microscope: align the flange of the cavity with the flange at the cryo-electron microscope end, place the metal sealing ring, and tighten the stainless steel bolts in a crisscross pattern, causing the knife-edge on the flange to embed into the sealing ring, achieving a vacuum-sealed connection.

[0063] Secondly, by Figure 9 As shown, this application provides a sample delivery method, including the following steps: S100 and connector 410 are connected to the cryo-electron microscope. The sample is loaded into the first region 110, and the second region 120 is disinfected and sterilized. Specifically, the second region 120 is subjected to standardized disinfection and sterilization treatment, including multiple disinfection procedures such as ultraviolet irradiation and chemical disinfectant treatment, to ensure that there are no pathogens remaining in the second region 120.

[0064] S200, the transmission component 330 acquires the sample within the first region 110.

[0065] S300 and the transfer component 330 drive the sample from the transport channel 400 to the sample chamber of the cryo-electron microscope.

[0066] Step S300 also includes the following steps: After the S310 and the transmission component 330 acquire the sample, the intelligent control system controls the first valve 140 to open, and the transmission component 330 drives the sample into the conveying channel 400. S320. After the transfer component 330 moves to the vicinity of the second valve 420 and the outermost contour of the transfer component 330 fits into the conveying channel 400, the vacuum system evacuates the conveying channel 400. S330. Once the vacuum level of the delivery channel 400 matches the vacuum level inside the sample chamber of the cryo-electron microscope, the intelligent control system controls the second valve 420 to open, and the delivery assembly 330 delivers the sample into the sample chamber of the cryo-electron microscope. S340. After delivery is completed, the transfer component 330 returns to the delivery channel 400, the second valve 420 closes, the transfer component 330 continues to return to the first area 110, the first valve 140 closes, and the transfer component 330 delivers the sample again, and so on in a cycle.

[0067] In some embodiments, the sample storage device and sample delivery method of this application are suitable for a P3 laboratory environment.

[0068] This application divides the interior and exterior of the cavity into a first region and a second region, respectively, separating the sample storage area and the external buffer zone. A sealing mechanism is also provided, corresponding to and fitting into the first and second regions respectively, achieving a double seal for the cavity and ensuring its airtightness. A transport channel maintaining a vacuum environment is provided between the cavity and the cryo-electron microscope. The transport device can transport the sample from the sample storage area to the cryo-electron microscope through the transport channel. The transport mechanism has a variable diameter structure, with its outermost side tightly fitting against the inner wall of the transport channel and equipped with a sealing ring. This effectively prevents external gas from entering the vacuum environment along the transport mechanism, ensuring that the sample is not contaminated during the entire transport process, improving transport safety, and realizing a completely sealed transfer of the sample from the P3 environment to the cryo-electron microscope, while maintaining the sample's frozen state and integrity. This provides a safe and reliable technical guarantee for high-quality cryo-electron microscopy research of P3-level pathogens.

[0069] Although embodiments of this application have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of this application, the scope of which is defined by the claims and their equivalents.

Claims

1. A sample storage device, characterized in that, Compatible with cryo-electron microscopy, including The cavity (100) has a first region (110) for storing samples inside and a second region (120) for environmental buffering on its outer surface. A sealing mechanism (200) is provided on the cavity (100) and fits against the first region (110) and the second region (120) to achieve a seal on the cavity (100); The conveying device (300) includes a transmission assembly (330) disposed within the cavity (100); The delivery channel (400) is located on one side of the outer surface of the cavity (100), one end of which is selectively connected to the first region (110), and the other end is selectively connected to the sample chamber of the cryo-electron microscope. The transmission assembly (330) can acquire samples and deliver them to the sample chamber of the cryo-electron microscope via the delivery channel (400). A vacuum system is provided to provide a vacuum environment for the transport channel (400).

2. The sample storage device according to claim 1, characterized in that, The sealing mechanism (200) includes a door body (210), a first sealing strip (220), and a second sealing strip (230). A third region (130) is provided on the side surface of the door body (210) near the cavity (100). The shape of the third region (130) matches the shape of the first region (110). The first sealing strip (220) is set to fit the outer edge contour of the third region (130). The second sealing strip (230) is embedded in the door frame groove of the door body (210). The outer edge contour of the door body (210) fits the second region (120).

3. A sample storage device according to claim 2, characterized in that, The sample storage device also includes an intelligent control system, which is used to control the opening and closing of the door (210).

4. A sample storage device according to claim 3, characterized in that, The door (210) is an inflatable airtight door, and the first sealing strip (220) and the second sealing strip (230) are both inflatable sealing strips. The intelligent control system can deflate or inflate the first sealing strip (220) and the second sealing strip (230) according to the opening or closing of the door (210).

5. A sample storage device according to claim 1, characterized in that, When the transport channel (400) is evacuated, the transport channel (400) is isolated from the sample chamber of the cryo-electron microscope. When the vacuum degree of the transport channel (400) reaches the vacuum degree of the sample chamber of the cryo-electron microscope, the transport channel (400) is connected to the sample chamber of the cryo-electron microscope, and the sample can enter the sample chamber of the cryo-electron microscope from the transport channel (400).

6. A sample storage device according to claim 3, characterized in that, The first region (110) is provided with a first valve (140) on the side near the conveying channel (400). The first valve (140) can connect or disconnect the first region (110) from the conveying channel (400). The intelligent control system can control the opening and closing of the first valve (140).

7. A sample storage device according to claim 6, characterized in that, One end of the delivery channel (400) is connected to the first valve (140), and the other end is connected to the cryo-electron microscope via a connector (410).

8. A sample storage device according to claim 7, characterized in that, The connector (410) is a flange, and the flange specifications are matched to those of a cryo-electron microscope.

9. A sample storage device according to claim 8, characterized in that, The flange includes a flange body (411) and connecting bolts (412). The flange body (411) has a knife edge as the mating surface with the cryo-electron microscope. There are several connecting bolts (412) and they are distributed circumferentially along the surface of the flange body (411).

10. A sample storage device according to claim 7, characterized in that, A second valve (420) is provided between the conveying channel (400) and the connector (410). The second valve (420) can connect or disconnect the connection between the conveying channel (400) and the cryo-electron microscope. The intelligent control system can control the opening and closing of the second valve (420).

11. A sample storage device according to claim 1, characterized in that, The transmission component (330) has a variable diameter structure, and its outermost contour fits against the inner wall of the transmission channel (400) to form a seal.

12. A sample storage device according to claim 11, characterized in that, The transmission assembly (330) includes a sealing section (333), a transition section (334), and a clamping section (335) in sequence along the sample transport direction. The outer diameter of the sealing section (333) is larger than the outer diameter of the transition section (334) and the clamping section (335) in sequence, thereby forming a variable diameter structure. The sealing section (333) is in contact with the inner wall of the transport channel (400). A sealing ring (331) is provided on the outer contour of the sealing section (333) to maintain the vacuum environment of the transport channel (400) during the transport process.

13. A sample storage device according to claim 1, characterized in that, The conveying device (300) further includes a driving mechanism and a track mechanism. The driving mechanism is located on the side of the cavity (100) away from the conveying channel (400). The track mechanism is arranged parallel to the first region (110). The transmission component (330) can move along the track mechanism under the drive of the driving component to realize the conveying of the sample.

14. A sample storage device according to claim 13, characterized in that, The conveying device (300) also includes a drive base (340), which is mounted on the track mechanism. One end of the drive base (340) is connected to the transmission component (330), and the other end is connected to the drive mechanism to drive the transmission component (330) to move.

15. A sample delivery method, characterized in that, Includes the following steps: S100, the connector (410) is connected to the cryo-electron microscope, the sample is loaded into the first region (110), and the second region (120) is disinfected and sterilized. S200, the transmission component (330) acquires the sample within the first region (110); S300, the transfer component (330) carries the sample from the delivery channel (400) into the sample chamber of the cryo-electron microscope.

16. A sample delivery method according to claim 15, characterized in that, The S300 process also includes the following steps: S310 After the transfer component (330) acquires the sample, the intelligent control system controls the first valve (140) to open, and the transfer component (330) drives the sample into the conveying channel (400); S320, the component to be transferred (330) is moved to the vicinity of the second valve (420), and after the outermost contour of the transfer component (330) fits into the conveying channel (400), the vacuum system evacuates the conveying channel (400); S330. After the vacuum level of the delivery channel (400) is consistent with the vacuum level in the sample chamber of the cryo-electron microscope, the intelligent control system controls the second valve (420) to open, and the delivery component (330) delivers the sample into the sample chamber of the cryo-electron microscope. S340 After delivery is completed, the transfer component (330) returns to the delivery channel (400), the second valve (420) closes, the transfer component (330) continues to return to the first area (110), the first valve (140) closes, and the transfer component (330) delivers the sample again, and so on.