An automated method and system for cryopreservation of biobank samples

Abstract

The present invention discloses a freezing method and system for an automated biological sample library, and relates to the technical field of biological sample storage. The freezing method for an automated biological sample library can determine whether emergency freezing of biological samples is required by real-time detection of the environmental conditions in the sample library, so that normal sample test tube access can be performed through a biological sample placement module and a biological sample access module in a normal state, and in an abnormal state, the biological sample placement module can be emergency frozen through an emergency freezing module, solving the problem that it is difficult to detect the environment in the sample library in real time and to perform emergency freezing when the sample library is abnormal in the prior art.

Description

Technical Field

[0001] The present invention relates to the technical field of biological sample storage, and in particular to a freezing method and system for an automated biological sample library. Background Art

[0002] A biobank is a device that collects, processes, and stores samples of biological macromolecules, cells, tissues, and organs of healthy and diseased organisms in a standardized manner. Most biological samples need to be stored in a deep cryogenic environment, especially some biobanks used to store cells for transfusion into the human body, which need to be stored in an environment close to the temperature of liquid nitrogen. Taking a biobank that stores human embryos as an example, the embryos need to go through a complex cooling process first, and then be stored in liquid nitrogen, and they need to be protected in a deep cryogenic environment throughout the process.

[0003] The Chinese invention patent with the announcement number CN108298242B discloses a storage and access system for biological samples at minus 80 degrees and a storage and access method thereof. The storage and access system includes a storage body, multiple minus 80 degrees cold storage body units, a cold storage body unit door opening manipulator, a lifting manipulator, a shifting manipulator, a scanning freezing tube system and a freezing tube sorting system. The storage body is provided with a sample entry and exit window, and the minus 80 degrees cold storage body unit is provided with a cold storage, a cold storage body unit door and a freezing shelf. The freezing shelf is located in the cold storage, and the cold storage body unit door opening manipulator is used to open or close the cold storage body unit door. The lifting manipulator can control the sample to move along the X-axis, Y-axis and Z-axis directions and can control the freezing shelf to move along the X-axis, Y-axis and Z-axis directions. The shifting manipulator can control the sample to move along the X-axis and Y-axis directions, the scanning freezing tube system is used to scan the QR code of the sample, and the freezing tube sorting system is used to classify the sample. The storage and access system realizes the automation of biological sample storage and access, improves the working efficiency of the storage and access system, and has a low error rate.

[0004] However, it is difficult for existing technologies to detect the environment in the sample library in real time, and it is difficult to perform emergency freezing when there are abnormalities in the sample library. Summary of the invention

[0005] In view of the deficiencies of the prior art, the present invention provides a method and system for freezing an automated biological sample library, which solves the problem that the prior art is difficult to detect the environment in the sample library in real time and difficult to perform emergency freezing when abnormalities exist in the sample library.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solutions: a method for freezing an automated biological sample library, comprising a freezer provided with a test tube access window, wherein the freezer is provided with a biological sample placement module, a biological sample access module, an emergency freezing module located at the bottom of the biological sample placement module, and a sample library abnormality detection module: wherein the biological sample placement module is used to place biological sample test tubes, the biological sample placement module comprises a placement rack and a placement box, the placement box is placed inside the placement rack, and the placement box is used to place biological sample test tubes; the biological sample access module is used to store and access biological sample test tubes, and the biological sample access module is arranged above the placement rack; the sample library abnormality detection module is used to detect the operating status of the sample library in real time and determine whether the sample library has an abnormal operating status; the emergency freezing module is used to store the biological sample placement module for emergency freezing when the sample library abnormality detection module detects that the freezer has an abnormal operating status.

[0007] Furthermore, the placement rack includes a bottom plate, a support frame and a top plate, the support frame is fixedly connected to the surface of the bottom plate, and the top plate is fixedly connected to the top of the support frame; a plurality of placement cavities are arranged inside the support frame, and a limiting convex strip is arranged inside the placement cavity, and a limiting card slot is provided on the surface of the placement box, and the limiting convex strip is used to connect with the limiting card slot when storing and accessing the placement box; a partition hole plate is also fixedly connected between the top plate and the bottom plate, each hole on the partition hole plate corresponds to a placement box respectively, and an exhauster is fixedly connected to each hole on the partition hole plate; the partition hole plate is movably connected to the placement box, and the partition hole plate is spaced from the inner wall of the support frame, and a ventilation hole is provided on the top of the top plate; a placement groove is provided on the surface of the placement rack, and the above-mentioned biological sample test tube is placed inside the placement groove.

[0008] Furthermore, the emergency freezing module includes an emergency freezing box, the inner wall size of the emergency freezing box is the same as the size of the top plate and the bottom plate, the emergency storage component is arranged on the emergency freezing box, and a connecting valve for connecting to an external emergency freezing medium delivery device is installed at the bottom of the emergency freezing box; a first refrigeration port and a second refrigeration port are opened on the bottom plate; and a support component for limiting the placement rack is also arranged on the emergency freezing box.

[0009] Furthermore, the support assembly includes a support member, to which a plug-in board is fixedly connected via the output end of the electric cylinder, a support groove is provided on one side of the surface of the support member, the support groove is used for plugging with the plug-in board, and a U-shaped plate is also fixedly connected to the interior of the support member, the U-shaped plate is also used for plugging with the plug-in board.

[0010] Furthermore, a flow groove is provided on the surface of the placement box, and the flow groove at least surrounds a part of the placement groove, and a liquid inlet valve is installed on one side of the placement box; the interior of the placement cavity is also connected to a closing member, and a first liquid discharge valve and a second liquid discharge valve are respectively installed on one side of the closing member, and the second liquid discharge valve is located at the bottom of the first liquid discharge valve; a first magnet sheet is fixedly connected to the surface of the placement box, and the surface of the first magnet sheet is connected to the surface of the closing member, and a magnet block is fixedly connected to the surface of the partition hole plate, and the surface of the magnet block is connected to the surface of the closing member; a leak-proof component is arranged on the surface of the closing member corresponding to the position of each placement groove; a slide groove is provided on the surface of the closing member, and the inner side wall of the slide groove is movably connected to the surface of the limiting convex strip.

[0011] Furthermore, the leakage-proof component includes a movable part, a connecting groove is provided on the surface of the closing part, the surface of the movable part is movably connected to the inner wall of the connecting groove, a positioning column is fixedly connected to the inside of the connecting groove, the movable part is movably sleeved on the surface of the positioning column, a reset spring is fixedly connected to the surface of the movable part, and the other end of the reset spring is movably connected to the inner wall of the connecting groove; a connecting part is threadedly connected to the inner wall of the movable part; the biological sample access module can access the biological sample tube through the connecting part.

[0012] Furthermore, the biological sample access module includes an electric push rod, which is fixedly connected to the surface of the emergency cryogenic storage box, and the output end of the electric push rod is fixedly connected to a guide rail member, and the surface of the guide rail member is connected to a first electric slider, and the first electric slider is fixedly connected to the sliding frame; the surface of the sliding frame is fixedly connected to an insertion rod, and the insertion rod is movably connected to the guide rail member, and the bottom of the sliding frame is fixedly connected to a first electromagnet, and the surface of the first electromagnet is connected to the surface of the top plate; the surface of the sliding frame is fixedly connected to a connecting frame, and the connecting frame is fixedly connected to a first guide rail, and the first guide rail is connected to a test tube placement unit for taking and placing biological sample test tubes; the connecting frame is provided with a drawing and placing unit for taking and placing the placement box.

[0013] Furthermore, the test tube picking and placing unit includes a second electric slider, a second guide rail and a third electric slider, the second electric slider is connected to the first guide rail, the second guide rail is fixedly connected to the second electric slider, and the third electric slider is connected to the second guide rail; the third electric slider is fixedly connected to the moving frame, the interior of the moving frame is connected with a picking and placing push rod through a connecting bearing, the output end of the picking and placing push rod is fixedly connected to a second electromagnet, the surface of the picking and placing push rod is fixedly sleeved with a gear ring, the surface of the moving frame is connected with a gear through a driving motor, and the gear is meshed with the gear ring; a magnetic conductive column is fixedly provided at the center position of the connecting piece, and a second magnet sheet is fixedly connected to the top cover of the biological sample test tube; the surface of the moving frame is also fixedly connected to a fixed push rod, and an arc block is fixedly connected to the output end of the fixed push rod.

[0014] Furthermore, the extraction and extraction unit includes a T-shaped rail, which is fixedly connected to the surface of the connecting frame, the T-shaped rail is connected to the fourth electric slider, the fourth electric slider is fixedly connected to the movable plate, the surface of the movable plate is fixedly connected to the third electromagnet, the surface of the movable plate is also fixedly connected to two clamping plates, and the two clamping plates are located on both sides of the third electromagnet; two plug-in slots are provided on the surface of the placement box, and the plug-in slots are adapted to the size of the clamping plates.

[0015] A freezing method for an automated biological sample library, using the above-mentioned freezing system for an automated biological sample library, comprises the following steps: placing a sample tube to be stored in a biological sample placement module through a biological sample access module; when it is necessary to take it, taking it out from the biological sample placement module through the biological sample access module and transferring it to an access test tube window; a sample library abnormality detection module real-time detects the running state of the sample library and determines whether the running state of the sample library is abnormal: if there is an abnormality, emergency freezing is performed on the biological sample placement module through an emergency freezing module; if there is no abnormality, freezing the biological sample through a normal module.

[0016] The present invention has the following beneficial effects:

[0017] The cryopreservation method of the automated biological sample library can determine whether emergency cryopreservation of biological samples is required by real-time detection of the environmental conditions in the sample library, so that normal sample test tube storage and access can be achieved through the biological sample placement module and the biological sample access module in normal situations, and in abnormal situations, the biological sample placement module can be urgently cryopreserved through the emergency cryopreservation module.

[0018] Of course, any product implementing the present invention does not necessarily need to achieve all of the advantages described above at the same time. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1It is a schematic diagram of the overall structure of the present invention;

[0020] Figure 2 This is a structural schematic diagram of the emergency freezing storage box of the present invention;

[0021] Figure 3 It is a structural schematic diagram of the plug board of the present invention;

[0022] Figure 4 This is a schematic diagram of the internal structure of the placement rack of the present invention;

[0023] Figure 5 This is a schematic diagram of the internal structure of the emergency freezing box of the present invention;

[0024] Figure 6 This is a schematic diagram of the structure of the U-shaped plate of the present invention;

[0025] Figure 7 This is a schematic diagram of the structure of the second refrigeration port of the present invention;

[0026] Figure 8 This is a schematic diagram of the structure of the separation orifice plate of the present invention;

[0027] Fig. 9 It is a structural schematic diagram of the guide rail member of the present invention;

[0028] Fig.10 It is a structural schematic diagram of the third electromagnet of the present invention;

[0029] Fig.11 It is a schematic diagram of the gear structure of the present invention;

[0030] Fig.12 It is a structural schematic diagram of the magnetic conductive column of the present invention;

[0031] Fig.13 This is a structural schematic diagram of the first liquid discharge valve of the present invention;

[0032] Fig.14 It is a structural schematic diagram of the flow tank of the present invention;

[0033] Fig.15 It is a structural schematic diagram of the closure member of the present invention;

[0034] Fig.16 For the present invention Fig.15 A magnified view of the structure at center;

[0035] Fig.17 It is a schematic diagram of the cryopreservation method of the present invention.

[0036] In the figure, 1, freezer; 2, placement rack; 201, bottom plate; 202, support rack; 203, top plate; 3, placement box; 4, biological sample test tube; 5, limit convex strip; 6, limit card slot; 7, placement slot; 8, flow slot; 9, liquid inlet valve; 10, closing member; 11, first liquid discharge valve; 12, second liquid discharge valve; 13, first magnet sheet; 14, magnet block; 15, slide; 16, movable member; 17, connecting slot; 18, positioning column; 19, partition plate; 20, exhaust fan; 21, ventilation port; 22, emergency freezing box; 23, first refrigeration port; 24, second refrigeration port; 25, reset spring; 26, connecting member; 27, electric push rod; 28, guide Rail member; 29, support member; 30, electric cylinder; 31, plug-in plate; 32, support groove; 33, U-shaped plate; 34, plug-in groove; 35, first electric slider; 36, sliding frame; 37, plug rod; 38, first electromagnet; 39, connecting frame; 40, first guide rail; 41, second electric slider; 42, second guide rail; 43, third electric slider; 44, moving frame; 45, pick-up and place push rod; 46, second electromagnet; 47, gear ring; 48, gear; 49, magnetic column; 50, second magnet sheet; 51, fixed push rod; 52, arc block; 53, T-shaped rail; 54, fourth electric slider; 55, moving plate; 56, third electromagnet; 57, clamping sheet. DETAILED DESCRIPTION

[0037] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0038] In the description of the present invention, it should be understood that the terms "opening", "upper", "lower", "thickness", "top", "middle", "length", "inside", "all around" and the like indicating orientation or positional relationship are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the components or elements referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0039] See also Figure 1-Figure 16The embodiment of the present invention provides a technical solution: a freezing system for an automated biological sample library, comprising a freezing library 1 provided with a test tube access window, wherein the interior of the freezing library 1 is provided with a biological sample placement module, a biological sample access module, an emergency freezing module located at the bottom of the biological sample placement module, and a sample library abnormality detection module: wherein the biological sample placement module is used to place a biological sample test tube 4, the biological sample placement module comprises a placement rack 2 and a placement box 3, the placement box 3 is placed inside the placement rack 2, and the placement box 3 is used to place the biological sample test tube 4; the biological sample access module is used to access the biological sample test tube 4, and the biological sample access module is arranged above the placement rack 2; the sample library abnormality detection module is used to detect the operating status of the sample library in real time and determine whether the sample library has an abnormal operating status; the emergency freezing module is used to store the biological sample placement module for emergency freezing when the sample library abnormality detection module detects that the freezing library 1 has an abnormal operating status.

[0040] Specifically, the placement rack 2 includes a bottom plate 201, a support frame 202 and a top plate 203, the support frame 202 is fixedly connected to the surface of the bottom plate 201, and the top plate 203 is fixedly connected to the top of the support frame 202; a plurality of placement cavities are arranged inside the support frame 202, and a limiting convex strip 5 is arranged inside the placement cavity, and a limiting card slot 6 is provided on the surface of the placement box 3, and the limiting convex strip 5 is used to connect with the limiting card slot 6 when accessing the placement box 3; a partition hole plate 19 is also fixedly connected between the top plate 203 and the bottom plate 201, each hole on the partition hole plate 19 corresponds to a placement box 3, and an exhauster 20 is fixedly connected to each hole on the partition hole plate 19; the partition hole plate 19 is movably connected to the placement box 3, and there is a gap between the partition hole plate 19 and the inner wall of the support frame 202, and a ventilation hole 21 is provided on the top of the top plate 203; a placement groove 7 is provided on the surface of the placement rack 2, and the above-mentioned biological sample test tube 4 is placed inside the placement groove 7.

[0041] Specifically, the emergency freezing module includes an emergency freezing box 22, the inner wall size of the emergency freezing box 22 is the same as the size of the top plate 203 and the bottom plate 201, the emergency storage component is arranged on the emergency freezing box 22, and the bottom of the emergency freezing box 22 is installed with a connecting valve for connecting to an external emergency freezing medium delivery device; a first refrigeration port 23 and a second refrigeration port 24 are opened on the bottom plate 201; the emergency freezing box 22 is also provided with a support component for limiting the placement rack 2.

[0042] In this embodiment, in the case of emergency freezing, the first refrigeration port 23 and the second refrigeration port 24 can realize the circulation of refrigerated nitrogen to keep the temperature in the emergency freezing box 22 continuously. In addition, a circulation channel can be provided for liquid nitrogen.

[0043] Specifically, the support assembly includes a support member 29, to which a plug-in board 31 is fixedly connected via the output end of an electric cylinder 30. A support groove 32 is provided on one side of the surface of the support member 29, and the support groove 32 is used for plugging with the plug-in board 31. A U-shaped plate 33 is also fixedly connected to the interior of the support member 29, and the U-shaped plate 33 is also used for plugging with the plug-in board 31.

[0044] In this embodiment, the plug board 31 can support the placement rack 2, and can also close the vent 21 in an emergency freezing situation to prevent nitrogen leakage.

[0045] Specifically, a flow groove 8 is also provided on the surface of the placement box 3, and the flow groove 8 at least surrounds a portion of the placement groove 7, and a liquid inlet valve 9 is installed on one side of the placement box 3; a closure member 10 is also connected to the interior of the placement cavity, and a first liquid discharge valve 11 and a second liquid discharge valve 12 are respectively installed on one side of the closure member 10, and the second liquid discharge valve 12 is located at the bottom of the first liquid discharge valve 11; a first magnet sheet 13 is fixedly connected to the surface of the placement box 3, and the surface of the first magnet sheet 13 is connected to the surface of the closure member 10; a magnet block 14 is fixedly connected to the surface of the partition hole plate 19, and the surface of the magnet block 14 is connected to the surface of the closure member 10; a leak-proof component is arranged on the surface of the closure member 10 corresponding to the position of each placement groove 7; a slide groove 15 is provided on the surface of the closure member 10, and the inner side wall of the slide groove 15 is movably connected to the surface of the limiting convex strip 5.

[0046] In this embodiment, during the static process, the liquid inlet valve 9 on each placement box 3 is opened, and at the same time, the first liquid discharge valve 11 and the second liquid discharge valve 12 on the closure 10 are opened. There is a corresponding exhaust fan 20 behind each placement box 3. When the exhaust fan 20 is started, the cold air in the internal environment of the sample library can be drawn into the placement cavity through the liquid inlet valve 9, the first liquid discharge valve 11 and the second liquid discharge valve 12, so that the biological sample test tube 4 in the placement box 3 is in real time contact with the flowing cold air, and the drawn cold air will be discharged from the vent 21 on the top of the top plate 203.

[0047] Specifically, the leakage-proof component includes a movable part 16, a connecting groove 17 is provided on the surface of the closing part 10, the surface of the movable part 16 is movably connected to the inner wall of the connecting groove 17, a positioning column 18 is fixedly connected to the inside of the connecting groove 17, the movable part 16 is movably sleeved on the surface of the positioning column 18, a reset spring 25 is fixedly connected to the surface of the movable part 16, and the other end of the reset spring 25 is movably connected to the inner wall of the connecting groove 17; a connecting part 26 is threadedly connected to the inner wall of the movable part 16; the biological sample access module can access the biological sample tube 4 through the connecting part 26.

[0048] Specifically, the biological sample access module includes an electric push rod 27, which is fixedly connected to the surface of the emergency freezing box 22. The output end of the electric push rod 27 is fixedly connected to a guide rail member 28, and the surface of the guide rail member 28 is connected to a first electric slider 35, and the first electric slider 35 is fixedly connected to a sliding frame 36; the surface of the sliding frame 36 is fixedly connected to an insertion rod 37, and the insertion rod 37 is movably connected to the guide rail member 28. The bottom of the sliding frame 36 is fixedly connected to a first electromagnet 38, and the surface of the first electromagnet 38 is connected to the surface of the top plate 203; the surface of the sliding frame 36 is fixedly connected to a connecting frame 39, and the connecting frame 39 is fixedly connected to a first guide rail 40, and the first guide rail 40 is connected to a test tube placement unit for taking and placing biological sample test tubes 4; the connecting frame 39 is provided with a drawing and placing unit for taking and placing the placement box 3.

[0049] Specifically, the test tube picking and placing unit includes a second electric slider 41, a second guide rail 42 and a third electric slider 43. The second electric slider 41 is connected to the first guide rail 40, the second guide rail 42 is fixedly connected to the second electric slider 41, and the third electric slider 43 is connected to the second guide rail 42; the third electric slider 43 is fixedly connected to the moving frame 44, the interior of the moving frame 44 is connected with a picking and placing push rod 45 through a connecting bearing, the output end of the picking and placing push rod 45 is fixedly connected to a second electromagnet 46, the surface of the picking and placing push rod 45 is fixedly sleeved with a gear ring 47, the surface of the moving frame 44 is connected with a gear 48 through a driving motor, and the gear 48 is meshed with the gear ring 47; a magnetic conductive column 49 is fixedly provided through the center position of the connecting member 26, and a second magnet sheet 50 is fixedly connected to the top cover of the biological sample test tube 4; a fixed push rod 51 is also fixedly connected to the surface of the moving frame 44, and an arc block 52 is fixedly connected to the output end of the fixed push rod 51.

[0050] The extraction and extraction unit includes a T-shaped rail 53, which is fixedly connected to the surface of the connecting frame 39, and the T-shaped rail 53 is connected to the fourth electric slider 54, and the fourth electric slider 54 is fixedly connected to the movable plate 55, and the surface of the movable plate 55 is fixedly connected to the third electromagnet 56, and the surface of the movable plate 55 is also fixedly connected to two clamping plates 57, and the two clamping plates 57 are located on both sides of the third electromagnet 56; the surface of the placement box 3 is provided with two plug-in grooves 34, and the plug-in grooves 34 are adapted to the size of the clamping plates 57.

[0051] In this embodiment, the biological sample test tube 4 can be taken and placed in normal conditions and in emergency freezing conditions through the test tube taking and placing unit and the extraction and placement unit.

[0052] Specifically, the determination of whether the sample library has an abnormal operating status includes the following steps: detecting real-time environmental data in the cryopreservation library, wherein the real-time environmental data includes the internal temperature of the sample library, the internal brightness of the sample library, the internal humidity of the sample library, the signal strength of the sample library, and the dust content per unit volume in the sample library; comparing the real-time environmental data with the reference environmental data stored in the database to obtain an environmental assessment index. If the environmental assessment index is greater than the environmental threshold stored in the database, then it is determined that the sample library has an abnormal operating status, wherein the reference environmental data includes the reference temperature of the library, the reference brightness of the sample library, the reference humidity of the sample library, and the signal strength of the sample library. The signal strength and the dust content per unit volume in the sample library are determined; if the environmental assessment index is not greater than the environmental threshold stored in the database, the freezing operation data in the placement rack 2 is detected, and the freezing operation data includes the temperature and gas flow rate in each placement cavity, and the freezing operation data is compared with the parameterized temperature and the parameterized gas flow rate in the placement cavity stored in the database to obtain the placement cavity state evaluation value. If the placement cavity state evaluation value is greater than the placement cavity evaluation threshold stored in the database, then it is determined that the sample library has an abnormal operation state; if the placement cavity state evaluation value is not greater than the placement cavity evaluation threshold stored in the database, then it is determined that the sample library does not have an abnormal operation state.

[0053] A method for freezing an automated biological sample library, using the above-mentioned freezing system for an automated biological sample library, such as Fig.17 As shown, the following steps are included: placing the sample tube to be stored in the biological sample placement module through the biological sample access module; when it is necessary to take it, taking it out from the biological sample placement module through the biological sample access module and transferring it to the access test tube window; the sample library abnormality detection module detects the operating status of the sample library in real time to determine whether the operating status of the sample library is abnormal: if there is an abnormality, the biological sample placement module is emergency frozen through the emergency freezing module; if there is no abnormality, the biological sample is frozen through the normal module.

[0054] During use, when the biological sample tube needs to be stored, the scanning device (not shown in the figure) will first scan the label on the biological sample tube 4 to obtain the set storage information. A robotic arm (not shown in the figure) is provided in the sample library. The robotic arm moves the biological sample tube 4 to the position of the corresponding placement rack 2 according to the storage information, and then stores the biological sample tube 4 through the biological sample access module.

[0055] In non-emergency situations, the biological sample access module will take out the rack 2 from the emergency freezing box 22, that is, expose the rack 2 and expose it in the sample library. The process of taking out the rack 2 from the emergency freezing box 22 is as follows:

[0056] The first electromagnet 38 at the bottom of the sliding frame 36 is energized to generate magnetic force and adsorbed on the top plate 203, which is a magnetic conductive material 203. Then the electric cylinder 30 drives the plug-in board 31 to contract, and both plug-in boards 31 are out of contact with the top plate 203. Then the electric push rod 27 extends, and drives the sliding frame 36 to move upward through the guide rail 28. Under the action of the first electromagnet 38, the entire placement rack 2 is driven to move upward. When the position of the placement rack 2 reaches the set position, the electric push rod 27 stops extending, and the electric cylinder 30 drives the plug-in board 31 to reset. The two plug-in boards 31 are respectively in contact with the U-shaped plate 33 and the support groove 32, so that the placement rack 2 is supported by the plug-in board 31.

[0057] When the placement rack 2 is supported, the first electromagnet 38 is powered off. The first electric slider 35 moves along the guide rail 28, thereby driving the sliding rack 36 to move. During the movement, the insertion rod 37 plays a guiding and limiting role. When the edge of the sliding rack 36 is separated from the edge of the top plate 203, the first electric slider 35 stops moving, and then the electric push rod 27 can freely retract up and down. According to the storage information, it is determined in which placement box 3 the biological sample test tube 4 needs to be placed. The electric push rod 27 moves downward, thereby causing the sliding rack 36 to move downward. After reaching the position of the set placement box 3, the first electric slider 35 can make the sliding rack 36 move in the direction close to the placement box 3, so that the extraction and placement unit is docked with the placement box 3.

[0058] The extraction and placement unit includes two clamping pieces 57, between which a third electromagnet 56 is arranged. The two clamping pieces 57 can be inserted into the two insertion slots 34, and then the third electromagnet 56 is energized to make the two clamping pieces 57 move toward each other, so as to be in close contact with the insertion slots 34. Then the fourth electric slider 54 moves along the T-shaped rail 53, driving the moving plate 55 to move, so as to extract the placement box 3 from the placement cavity and place it on the sliding rack 36.

[0059] The robot arm transfers the biological sample test tube 4 to the bottom of the test tube placement unit, the second electromagnet 46 in the test tube placement unit is energized, and a second magnet sheet 50 is fixedly connected to the top cover of the biological sample test tube 4. The second electromagnet 46 can attract the biological sample test tube 4, and then the robot arm withdraws. The test tube placement unit is moved to the top of the designated placement slot 7 by adjusting the first guide rail 40, the second electric slider 41, the second guide rail 42 and the third electric slider 43. The placement push rod 45 is extended to place the biological sample test tube 4 inside the placement slot 7. After the placement is completed, the second electromagnet 46 is de-energized and reset.

[0060] The process of taking the biological sample tube 4 is opposite to the above process.

[0061] During the static process, the liquid inlet valve 9 on each placement box 3 is opened, and at the same time, the first liquid discharge valve 11 and the second liquid discharge valve 12 on the closure 10 are opened. There is a corresponding exhaust fan 20 behind each placement box 3. When the exhaust fan 20 is started, the cold air in the internal environment of the sample library can be drawn into the placement cavity through the liquid inlet valve 9, the first liquid discharge valve 11 and the second liquid discharge valve 12, so that the biological sample test tube 4 in the placement box 3 is in real time contact with the flowing cold air, and the drawn cold air will be discharged from the vent 21 on the top of the top plate 203.

[0062] It should be noted that the magnetic force of the first magnet sheet 13 on the placement box 3 is smaller than the magnetic force of the magnet block 14 . In addition, when the placement box 3 is extracted from the sample library, the magnetic force generated by the third electromagnet 56 being energized is greater than the magnetic force of the first magnet sheet 13 , but smaller than the magnetic force of the magnet block 14 .

[0063] The sample library anomaly detection module will perform real-time detection to detect the real-time environmental data in the cryopreservation library, where the real-time environmental data includes the internal temperature csw of the sample library, the internal brightness csd of the sample library, the internal humidity css of the sample library, the signal strength csx of the sample library, and the dust content per unit volume csc of the sample library. The real-time environmental data will be compared with the reference environmental data stored in the database to obtain the environmental assessment index hp. If the environmental assessment index is greater than the environmental threshold stored in the database, then it is judged that the environment is abnormal and emergency freezing is required. The reference environmental data includes the reference temperature ccw of the library, the reference brightness ccd of the sample library, the reference humidity ccs of the sample library, the reference signal strength ccx of the sample library, and the reference dust content per unit volume ccc of the sample library.

[0064] The calculation formula of hp is as follows:

[0065]

[0066] In addition, the abnormality detection module will also detect the freezing operation data in the placement rack 2, which includes the temperature fsw and gas flow rate qss in each placement cavity, and compare the freezing operation data with the parameter temperature fcw and parameter gas flow rate qcs in the placement cavity stored in the database to obtain the placement cavity state evaluation value. If the placement cavity state evaluation value fp is greater than the placement cavity evaluation threshold stored in the database, it is judged as an abnormality and emergency freezing is required.

[0067] fp=|fsw-fcw|+|qss-qcs|.

[0068] Emergency freezing is to place the placement rack 2 in the emergency freezing box 22, which can be achieved by the electric push rod 27. When the placement rack 2 moves downward to the inside of the emergency freezing box 22 and the top plate 203 is flush with the top of the emergency freezing box 22, the electric push rod 27 stops moving, and then the two plug boards 31 are reset to close the vent 21. The connection valve at the bottom of the emergency freezing box 22 is opened. When the placement chamber state evaluation value does not exceed the placement chamber evaluation threshold, the external emergency freezing medium delivery device inputs gaseous frozen nitrogen into the emergency freezing box 22, and the exhaust fan 20 operates. After the frozen nitrogen enters from the second refrigeration port 24, it flows out from the first refrigeration port 23 and is frozen by the frozen nitrogen. At this time, the liquid inlet valve 9, the first liquid discharge valve 11 and the second liquid discharge valve 12 are all in the open state. If the placement chamber state evaluation value exceeds the placement chamber evaluation threshold, liquid frozen nitrogen is delivered to freeze the placement box 3 in liquid nitrogen.

[0069] The method of taking the biological sample tube 4 in the case of emergency cryopreservation is as follows:

[0070] If the cryopreservation is carried out by freezing nitrogen, the liquid inlet valve 9, the first liquid discharge valve 11 and the second liquid discharge valve 12 are all closed first, and then the placement rack 2 moves upward to the outside of the emergency freezing box 22, and after being supported by the support assembly, the extraction unit takes out the placement box 3. Different from the above content, the magnetic force generated by the power supply of the third electromagnet 56 is greater than the magnetic force of the magnet block 14, and under the action of the third electromagnet 56, the placement box 3 will be taken out of the placement cavity together with the closure 10.

[0071] After that, the tube taking and placing unit moves to the set position, and the fixed push rod 51 drives the arc block 52 to move downward, so that the arc block 52 squeezes the leak-proof component, so that the movable part 16 in the leak-proof component squeezes the reset spring 25, so that the bottom of the movable part 16 contacts the placement box 3, and the other space between the placement box 3 and the closure 10 is isolated from the outside world. Then, the second electromagnet 46 is connected to the magnetic column 49 on the connecting part 26, and the second electromagnet 46 is energized. The gear 48 rotates under the action of the driving motor, thereby rotating the taking and placing push rod 45 through the gear ring 47, and the taking and placing push rod 45 contracts at the same time, separating the connecting part 26 from the movable part 16, and the biological sample tube 4 can also be taken out by magnetic force.

[0072] If the cryopreservation is liquid nitrogen, the difference from the above is that before the placement rack 2 moves upward to the outside of the emergency cryopreservation box 22, the connection valve at the bottom of the emergency cryopreservation box 22 is opened, the vent 21 on the top plate 203 is opened, and the liquid nitrogen is recovered. However, the liquid inlet valve 9 and the first liquid discharge valve 11 are opened, and the second liquid discharge valve 12 is closed, so liquid nitrogen will remain in the flow tank 8. After that, the liquid inlet valve 9, the first liquid discharge valve 11 and the second liquid discharge valve 12 are all closed, and the placement rack 2 moves upward to the outside of the emergency cryopreservation box 22, and the above steps are repeated to remove the biological sample tube 4.

[0073] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0074] The preferred embodiments of the present invention disclosed above are only used to help explain the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to only specific implementation methods. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. An automated biological sample library cryopreservation system, comprising a cryostat (1) provided with a test tube access window, characterized in that: The freezer (1) is provided with a biological sample placement module, a biological sample storage and access module, an emergency freezing module located at the bottom of the biological sample placement module, and a sample library abnormality detection module: The biological sample placement module is used to place a biological sample test tube (4), and the biological sample placement module comprises a placement rack (2) and a placement box (3), wherein the placement box (3) is placed inside the placement rack (2), and the placement box (3) is used to place the biological sample test tube (4); The biological sample access module is used for accessing biological sample test tubes (4), and the biological sample access module is arranged above the placement rack (2); The sample library abnormality detection module is used to detect the running status of the sample library in real time and determine whether the sample library has an abnormal running status; The emergency freezing module is used to store the biological sample placement module for emergency freezing when the sample library abnormality detection module detects that the freezing library (1) has an abnormal operating state.

2. The automated biological sample library cryopreservation system according to claim 1, characterized in that: The placement rack (2) comprises a bottom plate (201), a support frame (202) and a top plate (203); the support frame (202) is fixedly connected to the surface of the bottom plate (201), and the top plate (203) is fixedly connected to the top of the support frame (202); A plurality of placement cavities are arranged inside the support frame (202), and a limiting convex strip (5) is arranged inside the placement cavity. A limiting card slot (6) is provided on the surface of the placement box (3), and the limiting convex strip (5) is used to connect with the limiting card slot (6) when storing or accessing the placement box (3); A partition hole plate (19) is also fixedly connected between the top plate (203) and the bottom plate (201), each hole on the partition hole plate (19) corresponds to a placement box (3), and an exhauster (20) is fixedly connected to each hole on the partition hole plate (19); The partition hole plate (19) is movably connected to the placement box (3), the partition hole plate (19) is spaced from the inner wall of the support frame (202), and a ventilating hole (21) is provided on the top of the top plate (203); A placement groove (7) is provided on the surface of the placement rack (2), and the biological sample test tube (4) is placed inside the placement groove (7).

3. The automated biological sample library cryopreservation system according to claim 2, characterized in that: The emergency freezing module comprises an emergency freezing box (22), the inner wall size of the emergency freezing box (22) is the same as the size of the top plate (203) and the bottom plate (201), the emergency storage assembly is arranged on the emergency freezing box (22), and a connecting valve for connecting to an external emergency freezing medium conveying device is installed at the bottom of the emergency freezing box (22); The bottom plate (201) is provided with a first refrigeration opening (23) and a second refrigeration opening (24); The emergency freezing storage box (22) is also provided with a support assembly for limiting the placement rack (2).

4. The automated biological sample library cryopreservation system according to claim 3, characterized in that: The support assembly comprises a support member (29), a plug-in board (31) is fixedly connected to the support member (29) via the output end of an electric cylinder (30), a support groove (32) is provided on one side of the surface of the support member (29), the support groove (32) is used for plugging with the plug-in board (31), and a U-shaped plate (33) is fixedly connected inside the support member (29), and the U-shaped plate (33) is also used for plugging with the plug-in board (31).

5. The automated biological sample library cryopreservation system according to claim 3, characterized in that: The surface of the placement box (3) is also provided with a flow groove (8), and the flow groove (8) at least surrounds a portion of the placement groove (7). A liquid inlet valve (9) is installed on one side of the placement box (3); The interior of the placement cavity is also connected to a closing piece (10), and a first liquid discharge valve (11) and a second liquid discharge valve (12) are respectively installed on one side of the closing piece (10), and the second liquid discharge valve (12) is located at the bottom of the first liquid discharge valve (11); A first magnet sheet (13) is fixedly connected to the surface of the placement box (3), and the surface of the first magnet sheet (13) is connected to the surface of the closing member (10); a magnet block (14) is fixedly connected to the surface of the partition hole plate (19), and the surface of the magnet block (14) is connected to the surface of the closing member (10); The surface of the closure member (10) is provided with leak-proof components at positions corresponding to the placement grooves (7); A sliding groove (15) is provided on the surface of the closure member (10), and the inner side wall of the sliding groove (15) is movably connected to the surface of the limiting convex strip (5).

6. The automated biological sample library cryopreservation system according to claim 5, characterized in that: The anti-leakage component comprises a movable part (16), a connection groove (17) is provided on the surface of the closing part (10), the surface of the movable part (16) is movably connected to the inner side wall of the connection groove (17), a positioning column (18) is fixedly connected inside the connection groove (17), the movable part (16) is movably sleeved on the surface of the positioning column (18), a return spring (25) is fixedly connected to the surface of the movable part (16), and the other end of the return spring (25) is movably connected to the inner side wall of the connection groove (17); The inner side wall of the movable part (16) is threadedly connected with a connecting part (26); The biological sample access module can access the biological sample test tube (4) via a connecting piece (26).

7. The automated biological sample library cryopreservation system according to claim 6, characterized in that: The biological sample access module comprises an electric push rod (27), the electric push rod (27) is fixedly connected to the surface of the emergency freezing box (22), the output end of the electric push rod (27) is fixedly connected to a guide rail (28), the surface of the guide rail (28) is connected to a first electric slider (35), and the first electric slider (35) is fixedly connected to a sliding frame (36); The surface of the sliding frame (36) is fixedly connected with an insertion rod (37), the insertion rod (37) is movably connected to the guide rail (28), the bottom of the sliding frame (36) is fixedly connected with a first electromagnet (38), the surface of the first electromagnet (38) is connected to the surface of the top plate (203); the surface of the sliding frame (36) is fixedly connected with a connecting frame (39), the connecting frame (39) is fixedly connected with a first guide rail (40), and the first guide rail (40) is connected with a test tube placement unit for placing and taking biological sample test tubes (4); The connecting frame (39) is provided with a drawing and placing unit for taking and placing the placement box (3).

8. The automated biological sample library cryopreservation system according to claim 7, characterized in that: The test tube taking and placing unit comprises a second electric slider (41), a second guide rail (42) and a third electric slider (43), wherein the second electric slider (41) is connected to the first guide rail (40), the second guide rail (42) is fixedly connected to the second electric slider (41), and the third electric slider (43) is connected to the second guide rail (42); The third electric slider (43) is fixedly connected to the moving frame (44); the interior of the moving frame (44) is connected to a pick-up and placement push rod (45) via a connecting bearing; the output end of the pick-up and placement push rod (45) is fixedly connected to a second electromagnet (46); a gear ring (47) is fixedly sleeved on the surface of the pick-up and placement push rod (45); the surface of the moving frame (44) is connected to a gear (48) via a driving motor; the gear (48) is meshed with the gear ring (47); A magnetic conductive column (49) is fixedly provided at the center of the connecting member (26) and penetrates through the connecting member; a second magnet sheet (50) is fixedly connected to the top cover of the biological sample test tube (4); A fixed push rod (51) is also fixedly connected to the surface of the movable frame (44), and an arc block (52) is fixedly connected to the output end of the fixed push rod (51).

9. The automated biological sample library cryopreservation system according to claim 7, characterized in that: The extraction and extraction unit comprises a T-shaped rail (53), the T-shaped rail (53) is fixedly connected to the surface of the connecting frame (39), the T-shaped rail (53) is connected to a fourth electric slider (54), the fourth electric slider (54) is fixedly connected to a movable plate (55), a third electromagnet (56) is fixedly connected to the surface of the movable plate (55), and two clamping plates (57) are also fixedly connected to the surface of the movable plate (55), and the two clamping plates (57) are located on both sides of the third electromagnet (56); Two insertion grooves (34) are provided on the surface of the placement box (3), and the sizes of the insertion grooves (34) and the clamping pieces (57) are adapted to each other.

10. A cryopreservation method for an automated biological sample library, applied to an automated biological sample library cryopreservation system according to any one of claims 1 to 9, characterized in that: The following steps are involved: The sample tube to be stored is placed in the biological sample placement module through the biological sample access module; When it is necessary to take it out, it is taken out from the biological sample placement module through the biological sample access module and transferred to the access test tube window; The sample library anomaly detection module detects the running status of the sample library in real time and determines whether the running status of the sample library is abnormal: If there is an abnormality, the biological sample placement module is subjected to emergency freezing through the emergency freezing module; If there is no abnormality, the biological sample is frozen through the normal module.

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