Cold shielding structure, sample bearing unit and use method of cold shielding structure
By designing the mounting section and heat sink section of the cold shielding structure, the problems of water molecule contamination and weak magnetic field in cryo-electron microscopy were solved, enabling high-resolution imaging and comprehensive observation, and making it suitable for the low-temperature environment of cryo-electron microscopy.
Patent Information
- Application Number
- CN202511173450.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-20
- Publication Date
- 2026-03-03
AI Technical Summary
In existing technologies, the grid of cryo-electron microscopes easily absorbs water molecules from the microscope tube, leading to sample contamination. The weak magnetic field strength affects the imaging resolution. Optimization of the grid movement path cannot achieve comprehensive observation. The thermally driven structure is not suitable for low-temperature environments. The carrier cannot achieve cold shielding during the microscopic imaging process.
A cold shielding structure is designed, including a mounting section and a heat sink. The heat sink is located on both sides of the mounting section to absorb water molecules. The thickness of the mounting section is smaller than that of the heat sink to reduce the pole shoe spacing. The carrier net moves unidirectionally through the slit area to achieve comprehensive observation. The cold shielding structure body moves along the length of the slit to simplify the movement.
It effectively avoids sample contamination, enhances magnetic field strength, ensures imaging resolution, simplifies movement, enables comprehensive observation, and is suitable for the low-temperature environment of cryo-electron microscopy.
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Figure CN121595607A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of electron microscopy, and in particular to a cold shielding structure, a sample carrier unit, and a method of using the cold shielding structure. Background Technology
[0002] Cryo-electron microscopy requires the protection of frozen samples, but in current electron microscopes, the sample support grid easily absorbs water molecules from the microscope tube, leading to water contamination of the frozen sample. Furthermore, the shielding structure in current cryo-electron microscopes is located in a relatively large volume between the two pole pieces, resulting in a weak magnetic field between the pole pieces and affecting imaging resolution.
[0003] The electronic lenses in the related technologies are equipped with magnetic shielding components with low temperatures. However, the large magnetic shielding components located between the upper and lower electronic lenses still result in a weak magnetic field strength between the upper and lower electronic lenses, which is not conducive to improving imaging resolution.
[0004] Secondly, related technologies alter the shape of the sample observation area in the grid to optimize the movement path of the grid during electron microscopy observation. However, the grid in this technology is used to detect nanomaterials and does not have a cold shielding structure, thus failing to address the problem of weak magnetic field strength caused by the form of the cold shielding structure.
[0005] Furthermore, the related technology has a thermal drive structure on the outside of the carrier mesh. The thermal drive structure is used to drive the carrier mesh to move. However, the thermal drive structure needs to be heated to work properly and is not suitable for the low-temperature environment of cryo-electron microscopy.
[0006] Meanwhile, in related technologies, the sample carrier net can only be adjusted in height and cannot be moved horizontally. When the field of view of the electron microscope cannot completely cover the area of the carrier net used to carry the sample, the electron microscope cannot achieve a comprehensive observation of the sample.
[0007] In addition, the related technology has a carrier that can be detachably connected to the grid, but the carrier is not suitable for microscopic imaging during sample preparation and cannot achieve cold shielding. Summary of the Invention
[0008] This application aims to address at least one of the technical problems existing in the prior art. To this end, this application proposes a cold shielding structure capable of absorbing water molecules in the electron microscope tube through a heat sink.
[0009] This application also proposes a method for using a sample carrier unit and a cold shielding structure.
[0010] According to a first aspect embodiment of the present application, the cold shielding structure includes a cold shielding structure body, the cold shielding structure body includes a mounting part and heat sinks located on opposite sides of the mounting part, the mounting part is used to mount a carrier net, the carrier net is used to carry a sample, the heat sinks are used to conduct heat to the mounting part, and when the cold shielding structure is in working state, the temperature of the cold shielding structure body is lower than the temperature of the carrier net.
[0011] The cold shielding structure according to the embodiments of this application has at least the following beneficial effects: the heat sink in the body of the cold shielding structure is located on opposite sides of the mounting part. Since the temperature of the heat sink is lower than that of the mounting part used to mount the grid, the heat sink can absorb water molecules in the electron microscope tube and prevent the sample from being contaminated by water molecules; the mounting part has a small thickness and is located between the upper and lower pole pieces of the electron microscope, which helps to reduce the distance between the upper and lower pole pieces of the electron microscope, facilitates the increase of the magnetic field strength between the upper and lower pole pieces, and ensures imaging resolution; at the same time, the thicker heat sink is located on both sides of the mounting part and does not occupy the space between the upper and lower pole pieces, further facilitating the reduction of the distance between the upper and lower pole pieces, thereby ensuring imaging resolution.
[0012] According to some embodiments of this application, the thickness of the mounting portion is less than the thickness of the heat sink portion, so that the electrode shoes of the electron microscope are arranged through the space between each of the heat sink portions.
[0013] According to some embodiments of this application, the thickness of the mounting portion on which the carrier net is installed is 0.85mm-2mm.
[0014] According to some embodiments of this application, the mounting portion includes a support structure connecting each of the heat sink portions, the support structure being used to support the carrier net.
[0015] According to some embodiments of this application, the mounting part is provided with an observation window, and the area of the carrier net used to hold the sample is exposed from the observation window.
[0016] According to some embodiments of this application, the mounting part further includes a clamping structure, each of the heat sinks is connected to the clamping structure, the interval between each clamping structure defines the observation window, and the clamping structure is spaced apart from the support structure to form a slot for inserting the carrier net.
[0017] According to some embodiments of this application, the clamping structure is formed as a clamping plate, which is located on top of the carrier net.
[0018] According to some embodiments of this application, the two heat sinks are symmetrically arranged about the mounting portion.
[0019] According to some embodiments of this application, the heat sink has an inclined surface on the side connected to the mounting portion, so that the thickness of the heat sink and the mounting portion gradually transitions.
[0020] According to a second aspect embodiment of the present application, the sample carrier unit includes the above-described cold shielding structure and a carrier mesh, the carrier mesh including a support film for carrying a sample, and the support film having a slit area for observing the sample.
[0021] According to some embodiments of this application, the carrier net is detachably connected to the mounting portion.
[0022] The sample carrying unit according to the embodiments of this application has at least the following beneficial effects: the sample is carried in the slit region, and the cold shielding structure body can ensure the comprehensiveness of the observation by moving along the length direction of the slit region. There is no need for the cold shielding structure body to move in multiple directions, which simplifies the movement mode of the cold shielding structure body and avoids structural interference between the cold shielding structure body and the pole shoes in the electron microscope.
[0023] According to some embodiments of this application, the cold shielding structure body can move in one direction, and the direction of movement of the cold shielding structure body is the length direction of the slit region.
[0024] According to some embodiments of this application, the length of the slit region is 0.5mm-3mm.
[0025] According to some embodiments of this application, the width of the slit region is 1μm-10μm.
[0026] According to some embodiments of this application, the mounting portion includes a support structure, the support structure having a hollow portion, and the projection of the slit region onto the support structure is within the range of the hollow portion.
[0027] According to some embodiments of this application, the mounting portion further includes a clamping structure, each of the heat sink portions is connected to the clamping structure, there is a gap between each of the clamping structures, and the projection of the slit region on the mounting portion is within the range of the gap.
[0028] According to some embodiments of this application, the carrier mesh further includes a substrate supporting the support film, the substrate having an imaging window, and the projection of the slit region onto the substrate being within the range of the imaging window.
[0029] The method of using the shielding structure according to the third aspect embodiment of this application includes:
[0030] Lower the temperature of the cold shielding structure body so that the temperature of the cold shielding structure body is lower than the temperature of the carrier network.
[0031] The sample-carrying net is installed in the mounting section;
[0032] The cold shielding structure body drives the carrier mesh to pass through the gap between the pole shoes of the electron microscope.
[0033] The method of using the cold shielding structure according to the embodiments of this application has at least the following beneficial effects: Using the aforementioned cold shielding structure and sample carrying unit, the heat sink in the cold shielding structure body is located on opposite sides of the mounting part. Since the temperature of the heat sink is lower than the temperature of the mounting part used to mount the grid, the heat sink can absorb water molecules in the electron microscope tube, preventing the sample from being contaminated by water molecules. The mounting part has a smaller thickness and is located between the upper and lower pole shoes of the electron microscope, which helps to reduce the distance between the upper and lower pole shoes, facilitating an increase in the magnetic field strength between the upper and lower pole shoes and ensuring imaging resolution. Simultaneously, the thicker heat sink is located on both sides of the mounting part, not occupying the space between the upper and lower pole shoes, further facilitating a reduction in the distance between the upper and lower pole shoes, thereby ensuring imaging resolution. The sample is carried in the slit region, and the cold shielding structure body can ensure comprehensive observation simply by moving along the length of the slit region, without requiring the cold shielding structure body to move in multiple directions, simplifying the movement mode of the cold shielding structure body and avoiding structural interference between the cold shielding structure body and the pole shoes in the electron microscope.
[0034] According to some embodiments of this application, the cold shielding structure body passes along the gap between the pole pieces of the electron microscope, including:
[0035] The cold shielding structure body moves along the length of the slit area of the carrier mesh.
[0036] 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
[0037] The present application will be further illustrated below with reference to the accompanying drawings and embodiments. It should be noted that the embodiments illustrated in the following drawings are exemplary and are only used to explain the present application, and should not be construed as limiting the present application.
[0038] Figure 1 This is a schematic diagram of the cold shielding structure applied to an electron microscope according to an embodiment of this application;
[0039] Figure 2 This is a cross-sectional schematic diagram of the carrier mesh installed in the body of the cold shielding structure in the embodiment of the present application of the cold shielding structure of an electron microscope;
[0040] Figure 3 This is a cross-sectional schematic diagram of the carrier mesh disassembled from the main body of the cold shielding structure in the cold shielding structure of an electron microscope according to an embodiment of this application;
[0041] Figure 4 This is a cross-sectional schematic diagram of the carrier mesh in the cold shielding structure of an electron microscope, as described in the embodiments of this application.
[0042] Figure label:
[0043] 100; 101; 102; 1021;
[0044] Cold shielding structure body 200; heat sink 201; inclined surface 2011; support structure 202; hollow part 2021; clamping structure 203; observation window 2031. Detailed Implementation
[0045] 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.
[0046] 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.
[0047] 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.
[0048] 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.
[0049] In the description of this application, the use of terms such as "one embodiment," "some embodiments," "an example," "some instances," "some embodiments," "illustrative embodiment," "example," "specific example," and "some examples" 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. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.
[0050] like Figure 1 and Figure 2 As shown in the figure, this application provides a cold shielding structure, which includes a cold shielding structure body 200. Specifically, the cold shielding structure of this application is used in cryo-electron microscopy.
[0051] The cold shielding structure body 200 includes a mounting part and a heat sink part 201. The carrier net 100, which cooperates with the cold shielding structure 200, is used to support the sample. The cold shielding structure body 200 is connected to the carrier net 100, and the cold shielding structure body 200 is used to conduct heat to the carrier net 100.
[0052] Furthermore, the cold source is connected to the heat sink 201, thereby conducting cooling to the heat sink 201. The heat sink 201 then conducts cooling to the mounting section. Since the mounting section is used to connect to the carrier net 100, the mounting section ultimately conducts cooling to the carrier net 100, facilitating the freezing of the sample carried in the carrier net 100. It can be understood that when the cold shielding structure is in operation, the temperature of the heat sink 201 is lower than the temperature of the mounting section, and the temperature of the mounting section is lower than the temperature of the carrier net 100.
[0053] Since the vacuum inside the electron microscope is not a perfect vacuum, the grid 100 will dissipate heat, and its temperature will gradually rise even without a cold source. Therefore, when the heat sink 201 conducts heat to the grid 100, the grid still has environmental heat dissipation issues, so the temperature of the heat sink 201 needs to be kept lower than the temperature of the grid 100.
[0054] Meanwhile, the lower-temperature heat sink 201 absorbs water molecules from the electron microscope tube more easily than the mesh 100, preventing water molecules from condensing on the sample and thus preventing water contamination of the mesh 100. Furthermore, since the cold shielding structure 200 is used as a disposable consumable, once it absorbs water molecules from the electron microscope tube, there is no need to heat the cold shielding structure to dissolve contaminants, thereby improving the efficiency of cryo-electron microscopy.
[0055] In some examples, the mounting section is used to mount the carrier mesh 100, and the heat sink section 201 is used to conduct heat to the carrier mesh 100.
[0056] The mounting part for mounting the carrier net 100 is located in the middle of the cold shielding structure body 200, and the number of heat sinks 201 is set to two. The two heat sinks 201 are located on both sides of the cold shielding structure body 200, that is, the two heat sinks 201 are connected to the opposite sides of the mounting part.
[0057] Meanwhile, to ensure the heat transfer efficiency of the heat sink 201, it needs to have a certain thickness, while the mounting part, as a connecting structure of the carrier mesh 100, does not require a large thickness. Therefore, the thickness of the mounting part is less than the thickness of the heat sink 201. Furthermore, since the electron beam formed by the electron microscope's pole pieces needs to be focused on the portion of the carrier mesh 100 used to support the sample, the upper and lower pole pieces of the electron microscope are located at the top and bottom of the carrier mesh 100, respectively; that is, the upper and lower pole pieces are located at the top and bottom of the mounting part, respectively.
[0058] Understandably, the distance between the upper and lower pole shoes needs to be greater than the thickness of the mounting part to ensure that the cold shielding structure body 200 can move between the upper and lower pole shoes and avoid structural interference between the cold shielding structure body 200 and the pole shoes.
[0059] It is worth noting that the distance between the upper and lower pole shoes affects the magnetic field strength between them. Refer to the following reluctance formula:
[0060] R m = l / μS;
[0061] Among them, R m Let denoted as , l as , μ as , and S as , and , be the magnetic reluctance, l as , and μ as , and S as , and , be the magnetic permeability. In the upper and lower pole pieces of a cryo-electron microscope, reducing the distance between the upper and lower pole pieces is equivalent to shortening the equivalent length of the magnetic circuit. Therefore, reducing the aperture reduces the magnetic reluctance.
[0062] According to Ohm's law for magnetic circuits, when the magnetic reluctance R m When the magnetic flux decreases, the magnetic flux increases under the same magnetomotive force, which means that the magnetic field is strengthened.
[0063] It is understandable that the larger the distance between the upper and lower pole pieces of an electron microscope, the weaker the magnetic field strength between them, which is detrimental to improving the resolution of electron microscope imaging; while the smaller the distance between the upper and lower pole pieces, the stronger the magnetic field strength between them, which is beneficial to improving the resolution of electron microscope imaging.
[0064] This application places the thicker heat sink 201 on both sides of the cold shielding structure body 200, without affecting the spacing between the upper and lower pole pieces of the electron microscope. Furthermore, the thinner mounting portion is placed in the middle of the cold shielding structure body 200, which facilitates reducing the spacing between the upper and lower pole pieces of the electron microscope, thereby increasing the magnetic field strength between the upper and lower pole pieces and improving the resolution of the electron microscope imaging.
[0065] In addition, since the thickness of the heat sink 201 is greater than the thickness of the mounting part, and the mounting part is located between the two heat sinks 201, a certain space is reserved between the two heat sinks 201. This space can be used to set the electrode shoes of the electron microscope, further reducing the distance between the upper and lower electrode shoes of the electron microscope.
[0066] In some examples, the thickness of the mounting portion on which the screen 100 is mounted is 0.85mm-2mm. A smaller mounting portion thickness facilitates reducing the distance between the upper and lower pole pieces of the electron microscope. The screen 100 is detachably connected to the mounting portion to improve the flexibility of the connection between the screen 100 and the mounting portion.
[0067] like Figure 2 and Figure 3 As shown, in some examples, the mounting section includes a support structure 202, which is formed as a plate-like structure. The plate-like support structure 202 is connected between two heat sinks 201, and the support structure 202 has an upward-facing support plane, on which the carrier net 100 is placed. Therefore, the support structure 202 provides support for the carrier net 100 through the support plane, ensuring the stability of the relative position between the carrier net 100 and the cold shielding structure body 200 during observation.
[0068] Meanwhile, the thickness of the support structure 202 needs to be as small as possible while ensuring structural strength, so that the support structure 202 also has a small thickness after the carrier net 100 is placed, which makes it easier to reduce the distance between the upper and lower pole shoes of the electron microscope.
[0069] In addition, to prevent the netting 100 from wobbling in the Y-axis direction after being placed on top of the support structure 202, the dimensions of the netting 100 in the Y-axis direction are approximately the same as those of the support structure 202 in the Y-axis direction. Since the support structure 202 also has heat sinks 201 on opposite sides, when the netting 100 is placed on top of the support structure 202, the netting 100 will come into contact with the heat sinks 201 on opposite sides, and at this time, the heat sinks 201 on both sides also provide a certain positioning effect for the netting 100.
[0070] like Figure 2 and Figure 3 As shown, in some examples, the support structure 202 is provided with a hollow part 2021, which can ensure that the electron beam emitted from the upper pole piece of the electron microscope reaches the lower pole piece of the electron microscope.
[0071] In this process, the upper pole piece of the electron microscope forms an electron beam, which is first focused on the area of the grid 100 used to support the sample, thereby obtaining the characteristics of the sample. The electron beam with the sample characteristics then passes through the support structure 202 along the cutout 2021 and finally reaches the lower pole piece of the electron microscope, which facilitates the formation of an image of the sample by the lower pole piece of the electron microscope.
[0072] Furthermore, the area of the carrier 100 used to support the sample is the slit area 101. In order to facilitate the electron beam to pass through the slit area 101 and the hollow part 2021 in sequence, the projection of the slit area 101 on the support structure 202 is located within the range of the hollow part 2021.
[0073] like Figure 2 and Figure 3 As shown, in some examples, the mounting section is provided with an observation window 2031, through which the area of the mesh 100 used to support the sample is exposed. When the electron microscope is in operation, the electron beam emitted from the upper pole piece first passes through the observation window 2031, thereby reaching the area of the mesh 100 used to support the sample. After passing through the cutout section 2021, the electron beam finally reaches the lower pole piece, thus completing the imaging of the sample.
[0074] The mounting section also includes a clamping structure 203, which, together with the support structure 202, restricts the carrier net 100 and prevents it from detaching from the cold shielding structure body 200.
[0075] Both heat sinks 201 are provided with clamping structures 203, that is, the number of clamping structures 203 is set to two. Both clamping structures 203 extend a certain distance towards the middle of the cold shielding structure body 200, and the two clamping structures 203 are symmetrical to each other.
[0076] Meanwhile, the two clamping structures 203 are not connected, so a certain gap is formed between the two clamping structures 203, and this gap is the observation window 2031.
[0077] Furthermore, the clamping structure 203 and the supporting structure 202 are spaced apart; specifically, the clamping structure 203 and the supporting structure 202 are distributed vertically. When the supporting structure 202 supports the net 100 at its bottom, the clamping structure 203 is located at the top of the supporting structure 202. The gap between the clamping structure 203 and the supporting structure 202 defines a slot for inserting the net 100.
[0078] In some examples, the clamping structure 203 is formed as a plate-like structure, i.e., a clamping plate, and the support structure 202 is also formed as a plate-like structure, i.e., a support plate. The clamping plates and support plates spaced apart from each other form slots for inserting the carrier net 100. Since there are two clamping plates, there are also two slots. The two sides of the carrier net 100 are respectively inserted into the two slots.
[0079] In some examples, the cold shielding structure body 200 is made of metal, which has high heat transfer efficiency, making it easy for the cold shielding structure body 200 to conduct heat to the carrier mesh 100, and also making it easy for the cold shielding structure body 200 at a lower temperature to absorb water molecules in the electron microscope tube.
[0080] In some examples, the radial dimension of the upper electrode shoe of the electron microscope gradually decreases in the direction close to the support structure 202, thus the upper electrode shoe of the electron microscope is roughly formed into a conical structure. Similarly, the radial dimension of the lower electrode shoe of the electron microscope also gradually decreases in the direction close to the support structure 202, that is, the lower electrode shoe of the electron microscope is also roughly formed into a conical structure.
[0081] To accommodate the shapes of the upper and lower electrode shoes of the electron microscope and ensure a safe distance between the heat sink 201 and the electrode shoes, the heat sink 201 has an inclined surface 2011 on the side connecting to the mounting part. This allows for a gradual transition in thickness between the heat sink 201 and the mounting part, and the inclined surface 2011 has the same inclination angle as the sidewall of the electron microscope electrode shoe. Simultaneously, by providing a gradual transition in thickness between the two, the stress between the heat sink 201 and the mounting part can be reduced, thus mitigating the risk of breakage at the junction of the heat sink 201 and the mounting part 121.
[0082] In addition, this application embodiment also provides a sample carrying unit, which includes a carrier net 100 and a cold shielding structure body 200. The area on the carrier net 100 for carrying the sample is relatively narrow. When the carrier net 100 moves unidirectionally, the operator can complete omnidirectional observation through the pole shoes of the electron microscope without designing a large aperture for observation in the pole shoes, i.e., without setting a large field of view in the cryo-electron microscope. The reduction in the aperture in the electron microscope pole shoes is beneficial to improving the magnetic field strength between the pole shoes and ensuring the imaging resolution of the cryo-electron microscope. At the same time, as Figure 1 As shown, the carrier mesh 100 and the cold shielding structure body 200 of this application only move in the X-axis direction and do not need to move in the Y-axis direction. The space in the Y-axis direction is used to arrange the heat sink 201, which plays a role in cold shielding, so as to avoid structural interference between the heat sink 201 and the pole shoes in the electron microscope. When designing the distance between the upper and lower pole shoes of the electron microscope, only the thickness of the mounting part needs to be considered, which is conducive to reducing the distance between the upper and lower pole shoes of the electron microscope. The reduction of the distance between the upper and lower pole shoes of the electron microscope is conducive to improving the magnetic field strength between the pole shoes, and further ensuring the imaging resolution of the cryo-electron microscope.
[0083] like Figure 3 and Figure 4 As shown, in some examples, the carrier mesh 100 is used to support the sample. The carrier mesh 100 includes a support film and a substrate 102. The support film supports the sample, while the substrate 102 supports the bottom of the support film to enhance the structural strength of the carrier mesh 100.
[0084] Furthermore, the support membrane has several pore structures, and the distribution of the pore structures can be set according to actual needs. When the sample liquid reaches the support membrane, the sample liquid will be carried in the pore structures.
[0085] like Figure 3 and Figure 4As shown, in some examples, the support membrane is provided with a slit region 101, and a pore structure is provided in the slit region 101, so that the slit region 101 is used to hold the sample liquid.
[0086] Furthermore, the substrate 102 is provided with an imaging window 1021. The substrate 102 has a hollow structure, and the hollow region of the substrate 102 defines the imaging window 1021. The electron beam formed by the upper pole piece of the electron microscope can pass through the imaging window 1021 to reach the lower pole piece of the electron microscope, which facilitates the formation of an image of the sample by the lower pole piece of the electron microscope.
[0087] Simultaneously, when the support film is attached to the top of the substrate 102, the edge of the support film is attached to the upper surface of the substrate 102, while the middle part of the support film covers the hollow area of the substrate 102. The electron beam formed by the upper pole piece of the electron microscope first reaches the support film and acquires the characteristics of the sample on the support film. The electron beam carrying the sample characteristics then propagates to the lower pole piece, thus initially completing the imaging process of the sample.
[0088] It is understandable that when the support film is attached to the top of the substrate 102, the slit region 101 on the support film is located within the hollow region of the substrate 102, that is, the projection of the slit region 101 onto the substrate 102 is located within the imaging window 1021. The electron beam is first focused on the sample within the slit region 101, and then the sample feature information within the slit region 101 is transmitted to the lower pole piece.
[0089] Furthermore, the supporting effect of substrate 102 cannot extend to the support film portion within the hollow area of substrate 102. To ensure the structural strength of the support film portion within the hollow area of substrate 102, corresponding support beams can be provided on the surface of the support film. Specifically, the structural form of the support beams can be set according to actual needs.
[0090] It is understandable that the slit region 101 of the supporting membrane can be enclosed by a supporting beam or by other solid structures used to support the supporting membrane.
[0091] In some examples, the aperture of the channel used to form the electron beam in the electron microscope pole piece determines the size of the spot formed by the electron beam on the support film. It can be understood that the larger the aperture size of the channel, the larger the spot size formed, that is, the larger the field of view of the cryo-electron microscope; the smaller the aperture size of the channel, the smaller the spot size formed, that is, the smaller the field of view of the cryo-electron microscope.
[0092] Meanwhile, the aperture of the channel is also related to the magnetic field strength between the upper and lower pole shoes of the electron microscope, as shown in the following magnetoresistance formula:
[0093] R m = l / μS;
[0094] Among them, R mLet be the magnetic reluctance, l be the magnetic path length, μ be the permeability, and S be the cross-sectional area of the magnetic path. In the upper and lower pole pieces of a cryo-electron microscope, reducing the aperture is equivalent to shortening the equivalent length of the magnetic path. Therefore, reducing the aperture reduces the magnetic reluctance, as shown in the following Ohm's law formula for magnetic paths:
[0095] Φ=F m / R m ;
[0096] Where Φ is the magnetic flux, F m For magnetomotive force, when the magnetic reluctance R m When the magnetomotive force F decreases, at the same magnetomotive force F m As the magnetic flux Φ increases, refer to the following formula:
[0097] B = μH;
[0098] Φ = BS;
[0099] Where B is the magnetic flux density, and an increase in magnetic flux Φ means an increase in the magnetic field.
[0100] It is understandable that the larger the aperture of the channel, the weaker the magnetic field strength between the upper and lower pole pieces of the electron microscope, which is not conducive to improving the resolution of electron microscope imaging; while the smaller the aperture of the channel, the stronger the magnetic field strength between the upper and lower pole pieces of the electron microscope, which can improve the resolution of electron microscope imaging.
[0101] The slit region 101 of the support membrane in this application is relatively narrow, allowing the electron beam to form a small spot on the slit region 101, thus enabling comprehensive observation of the sample at its current position on the X-axis without requiring a large field of view. Therefore, the aperture of the electron beam channel in the electron microscope pole pieces is small enough to meet practical observation needs. Simultaneously, the small aperture of the electron beam channel in the electron microscope pole pieces also ensures a high magnetic field strength between the upper and lower pole pieces, thereby guaranteeing the resolution of the electron microscope imaging.
[0102] In some examples, because the slit region 101 is narrow and matches the aperture of the electron beam channel of the electron microscope pole piece, the cold shielding structure body 200 can move in one direction to ensure that the spot formed by the electron beam can complete the sweeping process within the slit region 101 without affecting the comprehensiveness of the observation.
[0103] It is understandable that the size of the electron beam spot corresponds to the width of the slit region 101. When the spot is focused at a certain position in the X-axis direction of the slit region, it ensures that the sample at that position can be fully observed. The moving direction of the cold shielding structure body 200 is the length direction of the slit region 101, i.e., the X-axis direction. When the entire cold shielding structure moves along the X-axis direction, the focusing position of the spot in the slit region 101 changes, thereby ensuring that the sample at the focusing position can be fully observed.
[0104] After the cold shielding structure 200 moves in one direction to drive the light spot to fully scan the slit region 101, all samples within the current slit region 101 are observed. When further observation is needed at a certain position in the X-axis direction of the slit region 101, the cold shielding structure 200 can also move in the opposite direction along the X-axis to the corresponding position.
[0105] Understandably, during the observation process, as the cold shielding structure 200 moves, samples from different regions on the carrier 100 arrive at the light spot position in sequence for image capture. Then, the captured images are analyzed in combination to ensure the comprehensiveness of the observation.
[0106] In some examples, the length of the slit region 101 is 0.5mm-3mm, that is, the size of the slit region 101 in the X-axis direction is 0.5mm-3mm, and the width of the slit region 101 is 1μm-10μm, that is, the size of the slit region 101 in the Y-axis direction is 1μm-10μm.
[0107] Based on the above-mentioned cold shielding structure applied to electron microscopes, various embodiments of the usage method of this application are presented below.
[0108] The method of using this cold shielding structure can be applied to the aforementioned cold shielding structure and the aforementioned sample carrier unit. The method of using this cold shielding structure includes, but is not limited to, the following steps:
[0109] Step S110: Reduce the temperature of the cold shielding structure body 200 so that the temperature of the cold shielding structure body 200 is lower than the temperature of the carrier mesh 100;
[0110] Step S120: Install the sample-carrying net 100 onto the mounting part;
[0111] Step S130: The cold shielding structure body 200 drives the carrier net 100 to pass through the gap between the pole shoes of the electron microscope.
[0112] In some examples, the cold source contacts the heat sink 201 in the cold shielding structure body 200, thereby conducting heat to the heat sink 201. When the heat sink 201 cools down, it conducts heat to the mounting portion in the cold shielding structure body 200. The mounting portion contacts the carrier mesh 100 and conducts heat to it, thereby lowering the temperature of the carrier mesh 100. This facilitates the freezing of the sample carried on the carrier mesh 100.
[0113] As can be seen from the above cooling process, the temperature of the heat sink 201 is lower than the temperature of the mounting part, and the temperature of the mounting part is lower than the temperature of the carrier mesh 100. Because the temperature of the heat sink 201 is lower, the heat sink 201 can absorb water molecules in the electron microscope tube and prevent water molecules from condensing on the sample.
[0114] Furthermore, the two sides of the carrier mesh 100 are inserted into the corresponding slots on both sides of the mounting part, so that the cold shielding structure body 200 and the carrier mesh 100 form a large contact area, which facilitates the cold shielding structure body 200 to conduct heat to the carrier mesh 100.
[0115] After the carrier mesh 100 is installed, the cold shielding structure 200 moves, causing the carrier mesh 100 to move along with it, allowing it to pass through the gap between the upper and lower pole pieces of the electron microscope. During the movement of the cold shielding structure 200 and the carrier mesh 100, the upper pole piece of the electron microscope emits an electron beam, which is focused on the sample on the carrier mesh 100. The lower pole piece then receives the electron beam carrying sample information. As the cold shielding structure 200 and the carrier mesh 100 move, the electron beam focuses on the sample at different locations on the carrier mesh 100, thus enabling comprehensive observation of the sample.
[0116] Additionally, in step S130: the cold shielding structure body 200 drives the carrier mesh 100 to pass through the gap between the pole pieces of the electron microscope, including but not limited to the following steps:
[0117] Step S131: The cold shielding structure body 200 moves along the length direction of the slit region 101 of the carrier mesh 100.
[0118] In some examples, because the width of the slit region 101 is small, the spot formed by the electron beam can ensure a comprehensive observation of the sample at its current position on the X-axis. This eliminates the need for the cold shielding structure 200 to move along the width of the slit region 101; instead, it can ensure comprehensive observation by moving the cold shielding structure 200 along the length of the slit region 101. The length of the slit region 101 is the X-axis direction.
[0119] The embodiments of this application have been described in detail above with reference to the accompanying drawings. However, this application is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of this application. Furthermore, unless otherwise specified, the embodiments and features described in the embodiments of this application can be combined with each other.
Claims
1. A cold shielding structure, characterized in that, include: The cold shielding structure body (200) includes a mounting part and heat sinks (201) located on opposite sides of the mounting part. The mounting part is used to mount a carrier net (100), which is used to carry a sample. The heat sinks (201) are used to conduct heat to the mounting part. When the cold shielding structure is in working condition, the temperature of the cold shielding structure body (200) is lower than the temperature of the carrier net (100).
2. The cold shielding structure according to claim 1, characterized in that, The thickness of the mounting portion is less than the thickness of the heat sink portion (201) so that the electrode shoes of the electron microscope are arranged through the space between each of the heat sink portions (201).
3. The cold shielding structure according to claim 1, characterized in that, The thickness of the mounting part on which the carrier net (100) is installed is 0.85mm-2mm.
4. The cold shielding structure according to claim 1, characterized in that, The mounting section includes a support structure (202) connecting each of the heat sinks (201), the support structure (202) being used to support the carrier net (100).
5. The cold shielding structure according to claim 4, characterized in that, The mounting section is provided with an observation window (2031), and the area of the carrier net (100) used to hold the sample is exposed from the observation window (2031).
6. The cold shielding structure according to claim 5, characterized in that, The mounting part further includes a clamping structure (203), each of the heat sinks (201) is connected to the clamping structure (203), the interval between the clamping structures (203) defines the observation window (1211), the clamping structure (203) and the support structure (202) are spaced apart to form a slot for inserting the carrier net (100).
7. The cold shielding structure according to claim 6, characterized in that, The clamping structure (203) is formed as a clamping plate, which is located on top of the carrier net (100).
8. The cold shielding structure according to claim 2, characterized in that, The two heat sinks (201) are symmetrically arranged about the mounting portion.
9. The cold shielding structure according to claim 2 or 8, characterized in that, The heat sink (201) has an inclined surface on the side connected to the mounting part so that the thickness of the heat sink (201) and the mounting part gradually transitions.
10. A sample carrier unit, characterized in that, include: The cold shielding structure as described in any one of claims 1 to 9; The carrier (100) includes a support membrane for carrying a sample and has a slit region (101) for observing the sample.
11. The sample carrier unit according to claim 10, characterized in that, The carrier net (100) is detachably connected to the mounting part.
12. The sample carrier unit according to claim 11, characterized in that, The cold shielding structure body (200) can move in one direction, and the direction of movement of the cold shielding structure body (200) is the length direction of the slit region (101).
13. The sample carrier unit according to claim 12, characterized in that, The length of the slit region (101) is 0.5mm-3mm.
14. The sample carrier unit according to claim 13, characterized in that, The width of the slit region (101) is 1μm-10μm.
15. The sample carrier unit according to claim 11, characterized in that, The mounting part includes a support structure (202), the support structure (202) is provided with a hollow part (2021), and the projection of the slit area (101) of the support structure (202) is located within the range of the hollow part (2021).
16. The sample carrier unit according to claim 11, characterized in that, The carrier mesh (100) also includes a substrate (102) supporting the support film. The substrate (102) is provided with an imaging window (1021). The projection of the slit region (101) onto the substrate (102) is located within the range of the imaging window (1021).
17. A method of using a cold shielding structure, characterized in that, include: Lower the temperature of the cold shielding structure body (200) so that the temperature of the cold shielding structure body (200) is lower than the temperature of the carrier mesh (100); The sample carrier net (100) is installed in the mounting part; The cold shielding structure body (200) drives the carrier net (100) to pass through the gap between the pole shoes of the electron microscope.
18. The method of using the cold shielding structure according to claim 17, characterized in that, The cold shielding structure body (200) passes through the gap between the pole pieces of the electron microscope, and includes: The cold shielding structure body (200) moves along the length of the slit region (101) of the carrier mesh (100).
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