A cold stage for cryo-em and a control system thereof

Abstract

The application relates to the technical field of electron microscope equipment, and particularly discloses a cold stage for a cryo-EM and a control system thereof, which comprises a cryo-EM body and a sample placing mechanism. The sample placing mechanism comprises a bottom plate, a flange ring, an adjusting unit, a guide rail, a sliding block and a sample stage. The cryo-EM body is fixedly connected with the bottom plate and located above the bottom plate. The flange ring is fixedly connected with the bottom plate and located below the bottom plate. The guide rail is fixedly connected with the bottom plate and located above the bottom plate. The number of the adjusting units is two. The two adjusting units are arranged above the bottom plate. The output ends of the adjusting units penetrate through the guide rail. The sliding block is slidably connected with the guide rail and located in the guide rail. The sample stage is fixedly connected with the sliding block. The structure can move the sample stage, facilitates placing or replacing the observed substance, and makes the placed observed substance in the best state and position.

Description

Technical Field

[0001] This invention relates to the field of electron microscopy equipment technology, and in particular to a cryo-electron microscope cold stage and its control system. Background Technology

[0002] Currently, cryo-electron microscopy is a device used to enable real-time observation of biological and polymeric materials that are sensitive to electron beams. The cold source of cryo-electron microscopy is basically liquid helium or liquid nitrogen. However, after a period of observation, the liquid nitrogen or liquid helium will be depleted, and the coolant needs to be refilled, resulting in a short working time.

[0003] In existing technologies, a cold source is provided by using a cold head to achieve the cooling temperature of liquid helium or liquid nitrogen. This method is convenient to use and has a long operating time.

[0004] However, in the existing technology, because the sample stage is placed below the cryo-electron microscope body and is partially blocked by the cryo-electron microscope body, it will be obstructed when placing the observed material, making it difficult to place the observed object conveniently. Summary of the Invention

[0005] The purpose of this invention is to provide a cold stage for cryo-electron microscopy and its control system, which aims to solve the technical problem in the prior art where the sample stage is placed below the cryo-electron microscope body and is partially blocked by the cryo-electron microscope body, which hinders the placement of the observed material and makes it difficult to place the observed object conveniently.

[0006] To achieve the above objectives, the present invention provides a cryo-electron microscope (cryo-EM) stage, comprising a cryo-EM body and a loading mechanism. The loading mechanism includes a base plate, a flange ring, adjustment units, a guide rail, a slider, and a sample stage. The cryo-EM body is fixedly connected to the base plate and located above it. The flange ring is fixedly connected to the base plate and located below it. The guide rail is fixedly connected to the base plate and located above it. Two adjustment units are respectively positioned above the base plate, with the output end of each adjustment unit passing through the guide rail. The slider is slidably connected to the guide rail and located inside it. The sample stage is fixedly connected to the slider and located above it.

[0007] Each of the adjustment units includes an electric cylinder and an electromagnetic component. The electric cylinder is fixedly connected to the base plate and located above the base plate. The electromagnetic component is fixedly connected to the output end of the electric cylinder and is located at one end of the output end of the electric cylinder. The electromagnetic component passes through the guide rail.

[0008] Each electromagnetic component includes a main rod, an energized coil, and an outer cylinder. The main rod is fixedly connected to the output end of the electric cylinder and is located at one end of the output end of the electric cylinder. The main rod passes through the guide rail. The energized coil is fixedly connected to the main rod and is sleeved on the outer wall of the main rod. The outer cylinder is fixedly connected to the main rod and is sleeved on the outer wall of the main rod. The energized coil is located between the main rod and the outer cylinder.

[0009] The sample stage includes a plate, a cold-conducting plate, a connecting sleeve, and an outer ring. The plate is fixedly connected to the slider and is located above the slider. The cold-conducting plate is fixedly connected to the plate and is located above the plate. The connecting sleeve is fixedly connected to the cold-conducting plate and is located on the outer wall of the cold-conducting plate. The outer ring is fixedly connected to the cold-conducting plate and is located above the cold-conducting plate.

[0010] The sample stage also includes a cooling adhesive, which is uniformly applied to the inner wall of the connecting sleeve.

[0011] The cryo-electron microscope stage further includes a cooling mechanism, which is located above the base plate.

[0012] The cooling mechanism includes a frame, a cooling pipe, a contact plate, a shell, and insulation material. The frame is fixedly connected to the base plate and located above the base plate. The shell is fixedly connected to the frame and located above the frame. The cooling pipe is disposed inside the frame, and the space between the cooling pipe and the frame is filled with the insulation material. The contact plate is fixedly connected to the cooling pipe and located at one end of the cooling pipe.

[0013] The cooling mechanism further includes an inner transmission tube, which is disposed inside the cooling tube, and one end of the inner transmission tube is rounded.

[0014] The present invention also provides a control system, including a cooling switch, a temperature control knob, and a drive switch. The cooling switch is disposed above the base plate, the temperature control knob is disposed above the base plate, and the drive switch is disposed above the base plate. The drive switch is electrically connected to each of the electromagnetic coils and the electric cylinder.

[0015] The present invention discloses a cryo-electron microscope cold stage and its control system. By placing the sample on the sample stage and activating one of the adjustment units to adjust the slider, the slider is pushed along the guide rail until it reaches one side of the guide rail. Then, another adjustment component is activated to drive the slider to one side of the guide rail, positioning the sample stage directly below the cryo-electron microscope body for observation. Simultaneously, the sample stage is connected to the cooling end. This structure allows the sample stage to be moved, facilitating the placement or replacement of the observed material, ensuring the material is in the optimal state and position. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 This is a schematic diagram of the structure of the first embodiment of the present invention.

[0018] Figure 2 This is a top view of the first embodiment of the present invention.

[0019] Figure 3 This is a front view of the first embodiment of the present invention.

[0020] Figure 4 This is the invention Figure 2 A cross-sectional view of the AA line structure.

[0021] Figure 5 This is the invention Figure 4 Enlarged view of the local structure at point B.

[0022] Figure 6 This is a front view of the second embodiment of the present invention.

[0023] Figure 7 This is the invention Figure 6 CC-line structural cross-sectional view.

[0024] Figure 8 This is a structural schematic diagram of the third embodiment of the present invention.

[0025] 101-Cryo-electron microscope body, 102-Base plate, 103-Flange ring, 104-Guide rail, 105-Slider, 106-Electric cylinder, 107-Main rod body, 108-Electrified coil, 109-Outer cylinder, 110-Plate body, 111-Cooling plate, 112-Connecting sleeve, 113-Outer ring, 114-Cooling adhesive, 201-Frame, 202-Cooling pipe, 203-Contact plate, 204-Shell, 205-Insulation material, 206-Inner tube, 301-Ring frame, 302-Cold head, 303-Ring, 304-Spring, 305-Adjusting ring, 306-Limit pin, 401-Refrigeration switch, 402-Temperature control knob, 403-Drive switch. Detailed Implementation

[0026] The first embodiment of this application is as follows:

[0027] Please see Figures 1 to 5 ,in Figure 1 This is a schematic diagram of the structure of the first embodiment. Figure 2 This is a top view of the first embodiment. Figure 3 This is a front view of the first embodiment. Figure 4 for Figure 2 AA-line structural cross-sectional view, Figure 5 for Figure 4 The enlarged view of a partial structure at point B shows that the present invention provides a cryo-electron microscope cold stage: including a cryo-electron microscope body 101 and a loading mechanism. The loading mechanism includes a base plate 102, a flange ring 103, an adjustment unit, a guide rail 104, a slider 105, and a sample stage. The adjustment unit includes an electric cylinder 106 and an electromagnetic assembly. The electromagnetic assembly includes a main rod 107, an energized coil 108, and an outer cylinder 109. The sample stage includes a plate 110, a cooling plate 111, a connecting sleeve 112, an outer ring 113, and cooling adhesive 114.

[0028] In this specific embodiment, the electromagnetic component is moved by the electric cylinder 106, and the slider 105 is moved by the cooperation of the electric cylinder 106 and the electromagnetic component, thereby moving the sample stage. The cold conduction plate 111 and the connecting sleeve 112 can conduct low temperature to freeze the observation sample.

[0029] The cryo-electron microscope body 101 is fixedly connected to the base plate 102 and located above the base plate 102. The flange ring 103 is fixedly connected to the base plate 102 and located below the base plate 102. The guide rail 104 is fixedly connected to the base plate 102 and located above the base plate 102. Two adjustment units are respectively positioned above the base plate 102, and the output end of each adjustment unit passes through the guide rail 104. The slider 105 is slidably connected to the guide rail 104 and located inside the guide rail 104. The sample stage is connected to the slider... Block 105 is fixedly connected and located above the slider 105. The observation sample is placed on the sample stage, and one of the adjustment units is activated to adjust the slider 105, pushing the slider 105 on the guide rail 104 until it is pushed to one side of the guide rail 104. Then, the other adjustment component is activated to drive the slider 105 to one side of the guide rail 104, so that the sample stage is located directly below the cryo-electron microscope body 101 for observation. At the same time, the sample stage is connected to the cooling end, wherein the flange ring 103 is used to install and fix the cryo-electron microscope cold stage.

[0030] Secondly, the electric cylinder 106 is fixedly connected to the base plate 102 and located above the base plate 102. The electromagnetic component is fixedly connected to the output end of the electric cylinder 106 and is located at one end of the output end of the electric cylinder 106. The electromagnetic component passes through the guide rail 104. The extension and retraction drive of the electric cylinder 106 can extend and retract the electromagnetic component. At the same time, the electromagnetic component electromagnetically attracts the slider 105, thereby achieving the purpose of moving and adjusting the slider 105.

[0031] Meanwhile, the main rod 107 is fixedly connected to the output end of the electric cylinder 106 and is located at one end of the output end of the electric cylinder 106. The main rod 107 passes through the guide rail 104. The energized coil 108 is fixedly connected to the main rod 107 and is sleeved on the outer wall of the main rod 107. The outer cylinder 109 is fixedly connected to the main rod 107 and is sleeved on the outer wall of the main rod 107. The energized coil 108 is located between the main rod 107 and the outer cylinder 109. The outer cylinder 109 protects the energized coil 108. When the slider 105 is moved, the energized coil 108 is energized, thereby giving the main rod 107 electromagnetic force, so that the main rod 107 magnetically attracts and fixes the slider 105.

[0032] In addition, the plate 110 is fixedly connected to the slider 105 and located above the slider 105; the cold-conducting plate 111 is fixedly connected to the plate 110 and located above the plate 110; the connecting sleeve 112 is fixedly connected to the cold-conducting plate 111 and located on the outer wall of the cold-conducting plate 111; the outer ring 113 is fixedly connected to the cold-conducting plate 111 and located above the cold-conducting plate 111; the connecting sleeve 112 is used to connect the cooling equipment; the plate 110 supports the cold-conducting plate 111; and the outer ring 113 presses down on the cold-conducting plate 111, thus forming a container that can hold the object to be observed; wherein the cold-conducting plate 111 and the connecting sleeve 112 are both made of copper or silver.

[0033] Furthermore, the coolant 114 is evenly applied to the inner wall of the connecting sleeve 112. The application of the coolant 114 can eliminate connection gaps and enhance the conduction of low temperature when connecting the cooling equipment.

[0034] When using the cryo-electron microscope cold stage of this embodiment, the sample is placed on the sample stage, and one of the adjustment units is activated to adjust the slider 105, pushing the slider 105 onto the guide rail 104 until it reaches one side of the guide rail 104. Then, another adjustment component is activated to drive the slider 105 to one side of the guide rail 104, so that the sample stage is directly below the cryo-electron microscope body 101 for observation. Simultaneously, the sample stage is connected to the cooling end. Within the adjustment unit, the extension and retraction drive of the electric cylinder 106 can extend and retract the electromagnetic component, which in turn electromagnetically attracts the slider 105, achieving the purpose of moving and adjusting the slider 105. In the electromagnetic assembly, the outer cylinder 109 protects the energized coil 108 and energizes the coil 108 when the slider 105 is moved, thereby giving the main rod 107 electromagnetic force, which magnetically fixes the slider 105. In the sample stage, the connecting sleeve 112 is used to connect the cooling equipment, the plate 110 supports the cooling plate 111, and the outer ring 113 presses the cooling plate 111, forming a container for loading the object to be observed. The cooling plate 111 and the connecting sleeve 112 are both made of copper or silver. The application of the cooling adhesive 114 can eliminate connection gaps when connecting the cooling equipment and enhance the conduction of low temperature.

[0035] The second embodiment of this application is as follows:

[0036] Based on the first embodiment, please refer to Figure 6 and Figure 7 ,in Figure 6This is a front view of the second embodiment. Figure 7 for Figure 6 The present invention provides a cryo-electron microscope cold stage, which includes a cooling mechanism comprising a frame 201, a cooling pipe 202, a contact plate 203, a shell 204, insulation material 205, and an inner transmission pipe 206.

[0037] In this specific embodiment, the low temperature is conducted through the contact plate 203, and the housing 204 protects the insulation material 205 and the cold conduction pipe 202. The insulation material 205 can prevent the loss of temperature.

[0038] The frame 201 is fixedly connected to the base plate 102 and located above the base plate 102. The housing 204 is fixedly connected to the frame 201 and located above the frame 201. The cold-conducting pipe 202 is disposed inside the frame 201, and the space between the cold-conducting pipe 202 and the frame 201 is filled with the insulation material 205. The contact plate 203 is fixedly connected to the cold-conducting pipe 202 and located at one end of the cold-conducting pipe 202. The frame 201 supports the housing 204, and the housing 204 wraps the insulation material 205 and the cold-conducting pipe 202. The insulation material 205 can prevent the cold-conducting pipe 202 from reducing temperature loss when conducting low temperature. The contact plate 203 is used to contact the output end of the refrigeration equipment to achieve the purpose of cold conduction.

[0039] Secondly, the inner transfer tube 206 is disposed inside the cooling tube 202, and one end of the inner transfer tube 206 is rounded. The inner transfer tube 206 is made of copper or silver, which makes the cooling efficiency higher. At the same time, the rounded corner setting can better facilitate the insertion of the connecting sleeve 112.

[0040] When using a cryo-electron microscope cold stage according to this embodiment, the frame 201 supports the housing 204, and the housing 204 wraps the insulation material 205 and the cold conduction pipe 202. The insulation material 205 can prevent the cold conduction pipe 202 from reducing temperature loss when conducting low temperature. The contact plate 203 is used to contact the output end of the refrigeration equipment to achieve the purpose of conducting cold. The inner transmission pipe 206 is made of copper or silver, which makes the cold conduction efficiency higher. At the same time, the rounded corners can better facilitate the insertion of the connecting sleeve 112.

[0041] The third embodiment of this application is as follows:

[0042] Based on the second embodiment, please refer to Figure 8 ,in Figure 8The present invention provides a cryo-electron microscope cold stage as shown in the third embodiment: it further includes a cooling mechanism, which includes a ring frame 301, a cold head 302, a collar 303, a spring 304, an adjusting ring 305, and a limiting pin 306.

[0043] In this specific embodiment, the cold head 302 generates low temperature and conducts it through the contact plate 203. The cold head 302 is positioned above the contact plate 203 via the ring frame 301. The height of the collar 303 is adjusted by the adjusting ring 305, thereby adjusting the height of the cold head 302.

[0044] The ring frame 301 is fixedly connected to the housing 204 and sleeved on the outer wall of the housing 204. There are multiple collars 303, each fixedly connected to a cold head 302 and located on the outer wall of the cold head 302. Each collar 303 is sleeved on the outer wall of the ring frame 301. There are multiple springs 304, each sleeved on the outer wall of the ring frame 301 and located below the corresponding collar 303. There are multiple adjusting rings 305. The adjusting rings 305 are threadedly connected to the ring frame 301 and respectively sleeved on the outer wall of the ring frame 301. The cold head 302 generates low temperature and conducts it through the contact plate 203. The cold head 302 is set above the contact plate 203 through the ring frame 301. At the same time, the height of the sleeve ring 303 is adjusted by the adjusting rings 305, thereby adjusting the height of the cold head 302. Meanwhile, the spring 304 can make the adjusting rings 305 hold more tightly through its elasticity, so that the adjusting rings 305 are not easy to loosen.

[0045] Secondly, there are multiple limiting pins 306, each of which is threadedly connected to the ring frame 301 and located above the ring frame 301. The limiting pins 306 can prevent the adjusting ring 305 from disengaging, thus providing effective protection.

[0046] When using a cryo-electron microscope cold stage according to this embodiment, the cold head 302 generates low temperature and conducts it through the contact plate 203. The cold head 302 is disposed above the contact plate 203 by the ring frame 301. At the same time, the height of the collar 303 is adjusted by the adjusting ring 305, thereby adjusting the height of the cold head 302. Meanwhile, the spring 304 can make the adjusting ring 305 more tightly held by the elastic force, so that the adjusting ring 305 is not easy to loosen. The limiting pin 306 can prevent the adjusting ring 305 from falling off, providing an effective protection function.

[0047] The present invention also provides a control system, including a cooling switch 401, a temperature control knob 402, and a drive switch 403. The cooling switch 401 is disposed above the base plate 102, the temperature control knob 402 is disposed above the base plate 102, and the drive switch 403 is disposed above the base plate 102. The drive switch 403 is electrically connected to each of the electromagnetic coils and the electric cylinder 106.

[0048] The cooling switch 401 controls the cold head 302, turning it on and off. Simultaneously, the temperature control knob 402 ensures the cold head 302 maintains the required stability. The drive switch 403 controls the two electric cylinders 106 and the electromagnetic assembly. Pressing the drive switch 403 for the first time drives the slider 105 once, placing it below the cryo-electron microscope body 101. Pressing the drive switch 403 a second time drives the slider 105 again, placing it outside the cryo-electron microscope body 101. Each drive follows a preset path, thus enabling the drive switch 403 to drive the adjustment unit.

[0049] The above description discloses only one preferred embodiment of the present invention, and should not be construed as limiting the scope of the present invention. Those skilled in the art will understand that all or part of the processes of the above embodiments can be implemented, and equivalent changes made in accordance with the claims of the present invention are still within the scope of the invention.

Claims

1. A cryo-electron microscope cold stage, comprising a cryo-electron microscope body, characterized in that, It also includes a storage mechanism; The loading mechanism includes a base plate, a flange ring, an adjustment unit, a guide rail, a slider, and a sample stage. The cryo-electron microscope body is fixedly connected to the base plate and located above the base plate. The flange ring is fixedly connected to the base plate and located below the base plate. The guide rail is fixedly connected to the base plate and located above the base plate. There are two adjustment units, each located above the base plate, with the output end of each adjustment unit passing through the guide rail. The slider is slidably connected to the guide rail and located inside the guide rail. The sample stage is fixedly connected to the slider and located above the slider. The cryo-electron microscope cold stage further includes a cooling mechanism, which is disposed above the base plate. The cooling mechanism includes a frame and a housing. The frame is fixedly connected to the base plate and is located above the base plate. The housing is fixedly connected to the frame and is located above the frame. It also includes a refrigeration mechanism, which comprises a ring frame, a cold head, collars, springs, adjusting rings, and limiting pins. The ring frame is fixedly connected to the housing and is fitted onto the outer wall of the housing. There are multiple collars, each fixedly connected to the cold head and located on the outer wall of the cold head, and each collar is fitted onto the outer wall of the ring frame. There are multiple springs, each fitted onto the outer wall of the ring frame and located below the corresponding collar. There are multiple adjusting rings, each threadedly connected to the ring frame and fitted onto the outer wall of the ring frame. There are multiple limiting pins, each threadedly connected to the ring frame and located above the ring frame.

2. The cryo-electron microscope cold stage as described in claim 1, characterized in that, Each of the adjustment units includes an electric cylinder and an electromagnetic component. The electric cylinder is fixedly connected to the base plate and located above the base plate. The electromagnetic component is fixedly connected to the output end of the electric cylinder and is located at one end of the output end of the electric cylinder. The electromagnetic component passes through the guide rail.

3. The cryo-electron microscope cold stage as described in claim 2, characterized in that, Each of the electromagnetic components includes a main rod, an energized coil, and an outer cylinder. The main rod is fixedly connected to the output end of the electric cylinder and is located at one end of the output end of the electric cylinder. The main rod passes through the guide rail. The energized coil is fixedly connected to the main rod and is sleeved on the outer wall of the main rod. The outer cylinder is fixedly connected to the main rod and is sleeved on the outer wall of the main rod. The energized coil is located between the main rod and the outer cylinder.

4. The cryo-electron microscope cold stage as described in claim 3, characterized in that, The sample stage includes a plate, a cold-conducting plate, a connecting sleeve, and an outer ring. The plate is fixedly connected to the slider and is located above the slider. The cold-conducting plate is fixedly connected to the plate and is located above the plate. The connecting sleeve is fixedly connected to the cold-conducting plate and is located on the outer wall of the cold-conducting plate. The outer ring is fixedly connected to the cold-conducting plate and is located above the cold-conducting plate.

5. A cryo-electron microscope cold stage as described in claim 4, characterized in that, The sample stage also includes a cooling adhesive, which is uniformly applied to the inner surface of the connecting sleeve.

6. The cryo-electron microscope cold stage as described in claim 5, characterized in that, The cooling mechanism also includes a cooling pipe, a contact plate, and insulation material. The cooling pipe is disposed inside the frame, and the insulation material is filled between the cooling pipe and the frame. The contact plate is fixedly connected to the cooling pipe and is located at one end of the cooling pipe.

7. A cryo-electron microscope cold stage as described in claim 6, characterized in that, The cooling mechanism also includes an inner transmission tube, which is disposed inside the cooling tube, and one end of the inner transmission tube is rounded.

8. A control system for controlling a cryo-electron microscope cold stage as described in claim 7, characterized in that, It includes a cooling switch, a temperature control knob, and a drive switch. The cooling switch is located above the base plate, the temperature control knob is located above the base plate, and the drive switch is located above the base plate. The drive switch is electrically connected to each of the electromagnetic components and the electric cylinder.

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