A fully automatic liquid replacement system

Abstract

The present invention relates to the field of biological equipment, and specifically to a fully automatic liquid exchange system for adding or aspirating liquid from a cell storage container; comprising: a cap screwing device, a liquid aspirating device, a liquid adding device, and a weighing platform arranged in sequence; wherein the cap screwing device is used to unscrew or screw the cover of the cell storage container; the liquid aspirating device comprises a liquid aspirating needle, a liquid aspirating tube, a liquid aspirating peristaltic pump, and a waste liquid storage device connected in sequence to aspirate the liquid in the cell storage container; the liquid adding device comprises a liquid adding needle, a liquid adding tube, a liquid adding peristaltic pump, and a liquid adding storage mechanism connected in sequence to add culture medium to the cell storage container. The system of the present application can be used in processes requiring liquid adding and aspirating in a cell production line, effectively realizing the comprehensive automation of cell production.

Description

Technical Field

[0001] The invention relates to the field of biological equipment, and in particular to a fully automatic liquid replacement system. Background Art

[0002] Mass production of cells is a key factor in the industrial application of cells. The current cell culture mainly includes the following steps: liquid replacement, digestion, neutralization, centrifugation, discarding the supernatant, resuspending and sieving, counting, centrifugation, and resuspending and freezing... There are many liquid addition and liquid aspiration operations in the above process.

[0003] However, currently cell fluid replacement mainly relies on manual labor, with a small number of operations and long operation time, which can easily lead to inconsistency between batches, affect product quality to a certain extent, and even cause pollution.

[0004] Therefore, an automated liquid changing device is urgently needed. Although there are some liquid adding devices, it is found in the actual application process that the existing liquid adding devices have the defects of not being able to accurately and quantitatively change the liquid and not being able to meet the requirements of automation. Summary of the invention

[0005] The present invention aims to provide a fully automatic liquid replacement system, which can be used in the process of adding liquid and aspirating liquid in a cell production line, and effectively realizes the comprehensive automation of cell production.

[0006] To achieve the above-mentioned purpose, the present invention proposes the following technical solutions: a fully automatic liquid replacement system, used for adding liquid or aspirating liquid in a cell storage container; integrated with a capping device, a liquid aspirating device, a liquid adding device and a weighing platform;

[0007] The cover screwing device is used to screw open or screw close the cover of the cell storage container;

[0008] The liquid aspirating device is used to aspirate the liquid in the cell storage container;

[0009] The liquid adding device is used to add culture solution into the cell storage container;

[0010] The weighing platform is used for weighing the cell storage container;

[0011] The liquid suction device comprises a liquid suction needle, a liquid suction tube, a liquid suction peristaltic pump and a waste liquid storage device which are connected in sequence; the liquid adding device comprises a liquid adding needle, a liquid adding tube, a liquid adding peristaltic pump and a liquid adding storage mechanism which are connected in sequence; the liquid suction device also comprises a first lifting module, and the liquid suction needle is installed on the first lifting module;

[0012] The liquid adding device further comprises a second lifting module, and the liquid adding needle is mounted on the second lifting module;

[0013] The capping device comprises a capping mechanism and a clamping jaw control mechanism;

[0014] The capping mechanism comprises:

[0015] The cap screwing spindle can rotate around its own axis;

[0016] A clamping jaw group is installed on the end of the cap screwing spindle; the clamping jaw group includes a clamping jaw limiter and a plurality of clamping jaws;

[0017] The clamping jaw limiter includes a plurality of elastic collars;

[0018] The clamping jaws include a clamping portion, a mounting fulcrum connected to the cap screwing spindle, and a limiting structure, which are sequentially arranged; the limiting structure corresponds to the cap screwing spindle section, and the limiting structure has a slope structure on one side facing the cap screwing spindle, wherein the slope structure is an inclined surface structure with an inclined direction facing the cap screwing spindle; the slope structures of the clamping jaws in the clamping jaw group together form a truncated cone-like cavity;

[0019] Wherein, the elastic collar is sleeved on the other side of each clamping jaw limiting structure in the clamping jaw group;

[0020] The gripper control mechanism comprises:

[0021] The clamping jaw control shaft is coaxially designed with the cap screwing main shaft and can move in its own axial direction; at the same time, the end of the clamping jaw control shaft is provided with a control terminal;

[0022] Wherein, the control terminal is located in the quasi-conical cavity, and when the position of the control terminal relative to the quasi-conical cavity is different, the rotation angle of the mounting fulcrum of the clamp is different, and the opening and closing degree of the clamp group is also different.

[0023] As an improved technical solution of the present application, at least one annular sealing ring is provided on the liquid aspiration needle or the liquid addition needle.

[0024] As an improved technical solution of the present application, it also includes a sterilization device, which includes a sterilization pipe and a sterilization source; the sterilization source is connected to the inlet of the liquid-adding peristaltic pump; one end of the sterilization pipe is connected to the liquid-adding needle, and the other end of the sterilization pipe is connected to the liquid-adding needle.

[0025] As an improved technical solution of the present application, the sterilization source is water vapor above 121°C; at the same time, the outlet of the liquid suction peristaltic pump is connected to the external water outlet pipe through a pipeline; a one-way valve is provided on the pipeline; and a filter membrane is provided on the one-way valve.

[0026] As an improved technical solution of the present application, the sterilization source adopts alcohol with a volume concentration of 75%; the inlet of the liquid-adding peristaltic pump is provided with a pipeline switching mechanism, and the pipeline switching mechanism includes a connecting pipe; the connecting pipe is used to connect the inlet of the liquid-adding peristaltic pump to the sterilization source or the liquid storage bag.

[0027] As an improved technical solution of the present application, the liquid adding and storage mechanism includes a liquid storage box and a liquid storage bag located in the liquid storage box; a through hole is provided on the liquid storage box; a liquid outlet joint is provided at the bottom of the liquid storage bag; the liquid outlet joint is connected to the liquid adding tube through the through hole.

[0028] As an improved technical solution of the present application, the liquid storage box has an inclined surface inside, and a liquid storage bag fixing portion is provided on the top of the inclined surface. Beneficial Effects

[0029] It can be seen from the above technical solutions that the technical solution of the present invention provides a fully automatic liquid replacement system, which can realize automatic liquid addition and automatic liquid aspiration of a cell storage container, and is suitable for liquid replacement operations during cell culture.

[0030] This application integrates the capping device, the liquid suction device and the liquid adding device, and realizes the precise liquid replacement of cell factories, centrifuge tubes, etc. during the cell culture process through the control of the external control system and the displacement of the robot arm. At the same time, the whole process can be set to be carried out in a closed environment, effectively avoiding environmental pollution during the cell culture process. At the same time, the automatic control system can realize quantitative liquid suction and quantitative liquid addition during the liquid replacement process, which can ensure the mass production of cells.

[0031] The present application sets up a first lifting module and a second lifting module to control the liquid aspiration needle and the liquid adding needle respectively, so that the liquid aspiration needle and the liquid adding needle have different working positions. By controlling the positions of the liquid adding needle and the liquid aspiration needle, the liquid adding needle and the liquid aspiration needle can meet different working conditions, such as: completing liquid addition, completing liquid aspiration, or sterilizing the pipeline after connecting the liquid adding needle and the liquid aspiration needle.

[0032] The present application provides an annular sealing ring on the liquid adding needle and the liquid aspiration needle, which is suitable for sterilization in various situations, such as steam sterilization, and effectively ensures the safety and airtightness of the sterilization process.

[0033] The sterilization device of the present application uses a pipeline to connect the liquid adding needle and the liquid suction needle, so that the sterilization source, liquid adding pump, liquid adding needle, sterilization tube, sterilization pipeline, liquid suction needle, liquid suction pump, etc. are connected into a sealed whole; at the same time, due to the annular sealing ring arranged on the liquid adding needle and the liquid suction needle, the sealing and safety of the sterilization process are effectively guaranteed, and sterilization can be carried out in various forms such as gas sterilization or liquid sterilization.

[0034] An inclined surface is provided in the liquid adding and storing mechanism of the present application to ensure that the liquid in the liquid storage bag can be sucked up by the liquid suction pump, while avoiding liquid residue in the liquid storage bag.

[0035] The present application provides a capping device, which has better automation characteristics than the capping mechanism in the prior art and can effectively avoid damage to the cell storage container caused by failure in the automation control process.

[0036] In summary, the liquid exchange system of the present application is mainly used to match the automated control production of cells, can meet the needs of multiple liquid changes during mass production of cells, and is applied to automated production lines for various types of cell culture.

[0037] It should be appreciated that all combinations of the foregoing concepts, as well as additional concepts described in greater detail below, may be considered to be part of the inventive subject matter of the present disclosure, provided such concepts are not mutually inconsistent.

[0038] The foregoing and other aspects, embodiments and features of the present invention can be more fully understood from the following description in conjunction with the accompanying drawings. Other additional aspects of the present invention, such as the features and / or beneficial effects of the exemplary embodiments, will be apparent from the following description or learned from the practice of the specific embodiments according to the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component shown in various figures may be represented by the same reference numeral. For clarity, not every component is labeled in every figure. Embodiments of various aspects of the present invention will now be described by way of example and with reference to the accompanying drawings, in which:

[0040] Figure 1 A schematic diagram showing the overall structure of the cap-tightening device of the present application is shown;

[0041] Figure 2 A front view of the cap-tightening device of the present application is shown;

[0042] Figure 3 A schematic diagram showing a partially exploded structure of the cap-tightening device of the present application is shown;

[0043] Figure 4 A diagram showing the principle of the control terminal of the present application for adjusting the opening and closing degree of the clamping jaw assembly;

[0044] Figure 5 Draw a general schematic diagram of the fluid replacement system of this application;

[0045] Figure 6 An integrated diagram of a set of capping device, liquid adding device and liquid suction device of the present application is shown;

[0046] Figure 7Draw a diagram of the pipeline connections during the sterilization process of this application;

[0047] Figure 8 A schematic diagram of the structure of the liquid adding and storing mechanism of the present application is shown.

[0048] In the figure: 1. Capping servo motor; 2. Gripper opening and closing motor; 3. Gripper control shaft; 4. Belt; 5. Support plate; 6. Buffer component; 7. Elastic collar; 8. Clamping protection plate; 9. Clamping part; 10. Mounting fulcrum; 11. Capping spindle; 12. Positioning device; 13. Gripper mounting sleeve; 14. Control terminal; 15. Slope structure; 16. Channel; 17. Boss; 18. Slot; 19, liquid adding peristaltic pump; 20, sterilization source; 21, liquid aspiration needle; 22, liquid adding needle; 23, liquid aspiration peristaltic pump; 24, liquid storage tank; 25, inclined plane; 26, liquid storage bag fixing part; 27, weighing platform.

[0049] In the figure: the arrow represents the direction of rotation. DETAILED DESCRIPTION

[0050] In order to make the purpose, technical solution and advantages of the embodiment of the present invention clearer, the technical solution of the embodiment of the present invention will be clearly and completely described below in conjunction with the drawings of the embodiment of the present invention. Obviously, the described embodiment is a part of the embodiment of the present invention, not all of the embodiments. Based on the described embodiment 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. Unless otherwise defined, the technical terms or scientific terms used herein should be the common meanings understood by people with ordinary skills in the field to which the present invention belongs.

[0051] This application mainly provides a fully automatic liquid replacement system for adding or aspirating liquid in a cell storage container to achieve full automation of the cell culture process, ensure a sterile environment during the cell culture process, and achieve mass production of cells. Figure 5 As shown, the main idea is to use an automated capping device, an automated liquid aspiration device, and an automated liquid adding device, and control the capping device to cap, control the liquid aspiration device to absorb the liquid in the cell storage container, and control the liquid adding device to add culture medium to the cell storage container through a control system (external setting), and finally use the capping device to control the capping to seal the cell storage container, thereby finally achieving liquid adding or liquid aspiration in the cell storage container.

[0052] The fully automatic liquid exchange system of the present application is particularly suitable for cell culture using a cell factory, or adding or aspirating liquid in a centrifuge bottle, and is suitable for a fully automated production line, using a robot arm to clamp a cell factory or a centrifuge bottle.

[0053] Application Example 1:

[0054] Specifically, when used in a cell factory for cell culture, the fully automatic liquid exchange system of the present application includes a capping device, a liquid adding device, a liquid suction device, and a weighing platform 27 arranged in sequence. In order to save space, the capping device, the liquid adding device, and the liquid suction device are designed side by side, and the weighing platform 27 is located below the liquid adding device and the liquid suction device.

[0055] In order to achieve real-time weighing of the cell factory:

[0056] During operation, the robotic arm clamps the cell factory, and the capping device unscrews the cap of the cell factory; the robotic arm places the cell factory on the weighing platform 27 for the first weighing; the liquid aspiration device absorbs the liquid in the cell factory, and the weighing platform 27 weighs the cell factory for the second time; the difference between the second weighing and the first weighing is determined to determine whether the aspiration is completed.

[0057] After the liquid aspiration is completed, the liquid adding device is turned on to add culture medium to the cell factory. After completion, the weighing platform 27 weighs it for the third time; the difference between the third weighing and the second weighing is determined to determine whether the liquid addition is accurate.

[0058] Application Example 2

[0059] Specifically, when used in a cell factory for cell culture, the difference from Application Example 1 is:

[0060] The robotic arm holding the cell factory is equipped with a camera system. After the cover of the cell factory is unscrewed by the cover screwing device, the robotic arm directly transfers the cell factory to the liquid aspiration device, which aspirates the liquid in the cell factory. The camera system and the image processing system are used to determine whether the liquid in the cell factory has been aspirated (at this time, the robotic arm is equipped with a camera system, and the camera system can be integrated with an image processing system, or an external image processing system can be used).

[0061] After the liquid aspiration is completed, the robot arm places the cell factory on the weighing platform 27, and the weighing platform 27 weighs it for the first time; the liquid adding device is turned on, and the culture medium is added to the cell factory. After completion, the weighing platform 27 weighs it for the second time; the difference between the second weighing and the first weighing is determined to determine whether the liquid addition is accurate.

[0062] In order to better understand the above technical solution, the above technical solution will be described in detail below in conjunction with the accompanying drawings and specific implementation methods. Example 1

[0063] A fully automatic liquid replacement system is used for adding or aspirating liquid from a cell storage container; Figure 5 and Figure 6 As shown, it includes: a capping device, a liquid suction device, a liquid adding device and a weighing platform 27 which are arranged in sequence.

[0064] The capping device is used to open or close the cover of the cell storage container; the capping device in this embodiment can be a capping device of the prior art, or a capping device specially designed in this application.

[0065] The liquid aspiration device comprises a liquid aspiration needle 21, a liquid aspiration tube, a liquid aspiration peristaltic pump 23 and a waste liquid storage device which are connected in sequence to aspirate the liquid in the cell storage container;

[0066] The liquid adding device comprises a liquid adding needle 22, a liquid adding tube, a liquid adding peristaltic pump 19 and a liquid adding storage mechanism which are connected in sequence, so as to add culture fluid into the cell storage container;

[0067] The weighing platform 27 is used to weigh the cell storage container, and its structure mainly adopts the weighing structure of the prior art. This application only applies it without making any improvements, but it does not affect the understanding of the technical solution of this application by those skilled in the art.

[0068] In order to facilitate practical application, the main bodies of the capping device, the liquid suction device and the liquid adding device are supported by brackets. The liquid adding peristaltic pump 19, the liquid adding storage mechanism, the liquid suction peristaltic pump 23 and the waste liquid storage are placed in the operating cabinet under the platform. In order to facilitate the robot arm to operate liquid adding or liquid suction, a telescopic drawer is provided on the operating cabinet, and the waste liquid storage and the liquid adding storage mechanism are placed in the telescopic drawer.

[0069] Furthermore, in order to realize automatic control, it also includes a telescopic limit switch (structure of the prior art, this application is only an application) and a mechanical stop switch (prior art, this application is only an application). The telescopic limit switch and the mechanical stop switch are both arranged on the movement path of the telescopic drawer, so that the robot arm receives the signal that the telescopic drawer is opened / closed in place.

[0070] Among them, the structure of the capping device specially designed in this application is as follows:

[0071] The capping device comprises a capping mechanism and a clamping jaw control mechanism;

[0072] The capping mechanism comprises:

[0073] The cap screwing spindle can rotate around its own axis;

[0074] A clamping jaw group is installed on the end of the cap screwing spindle; the clamping jaw group includes a clamping jaw limiter and a plurality of clamping jaws; the clamping jaw limiter includes a plurality of elastic collars; the clamping jaw includes a clamping portion, a mounting fulcrum connected to the cap screwing spindle and a limit structure arranged in sequence; the limit structure corresponds to the cap screwing spindle section, and the limit structure has a slope structure on one side facing the cap screwing spindle, and the slope structure is defined as a slope 25 structure with an inclined direction facing the cap screwing spindle; the slope structures of the clamping jaws in the clamping jaw group together constitute a truncated cone-like cavity; wherein the elastic collar is sleeved on the other side of the limit structure of each clamping jaw in the clamping jaw group;

[0075] The clamp control mechanism includes: a clamp control shaft, which is coaxially designed with the cap screwing main shaft and can move in its own axial direction; at the same time, a control terminal is provided at the end of the clamp control shaft; wherein, the control terminal is located in the quasi-conical cavity, and when the position of the control terminal relative to the quasi-conical cavity is different, the rotation angle of the mounting fulcrum of the clamp is different, and the opening and closing degree of the clamp group is also different.

[0076] In detail:

[0077] Power mechanism, such as Figure 1 As shown, the capping device includes a capping servo motor 1 and a clamping jaw opening and closing motor 2. The capping servo motor 1 is used to control the operation of the capping unit in the capping device. The clamping jaw opening and closing motor 2 is used to control the operation of the clamping jaw control unit. In practical applications, since the capping servo motor 1 and the clamping jaw opening and closing motor 2 work independently of each other, and the clamping jaw opening and closing motor 2 drives the clamping jaw control shaft 3 to move in the axial direction, the capping servo motor 1 drives the capping main shaft 11 to rotate. Therefore, in this embodiment, the capping servo motor 1 and the clamping jaw opening and closing motor 2 are arranged in parallel on the same installation platform.

[0078] Since the clamp control shaft 3 and the cap screwing main shaft 11 are coaxially designed, in order to achieve independent transmission of the two without interfering with each other, the clamp opening and closing motor 2 is coaxially installed with the clamp control shaft 3, and the cap screwing servo motor 1 is staggered with the cap screwing main shaft 11.

[0079] Furthermore, in order to improve the smoothness of the cap screwing process, the jaw opening and closing motor 2 in the present application is selected as a stepper motor, and is configured with a one-zero-one limit (a one-zero-one limit means that the stepper motor has a zero position and a limit position), giving full play to the characteristics of the stepper motor that the output torque decreases with increasing speed and drops sharply at a higher speed; it ensures that the control terminal 14 has a greater force when initially driving the slope structure 15 in the jaw assembly to move, and can also avoid violent damage to the slope structure 15 in unexpected situations.

[0080] The cap-tightening servo motor 1 described in the present application uses a servo motor to give full play to its control accuracy, so as to achieve accurate cap opening and closing.

[0081] In order to achieve precise axial movement of the jaw control shaft 3, the output shaft of the jaw opening and closing motor 2 is coaxial with the jaw control shaft 3; but if a turbine transmission is adopted, the output shaft of the jaw opening and closing motor 2 is transmitted to the jaw control shaft 3 in a turbine-worm manner (a turbine is arranged on the output shaft of the jaw opening and closing motor 2, and a worm section is arranged on the jaw control shaft 3). At this time, the output shaft of the jaw opening and closing motor 2 is not coaxial with the jaw control shaft 3.

[0082] The capping servo motor 1 is staggered with the capping spindle 11, and the capping servo motor 1 can be connected to the capping spindle 11 by belt 4 transmission, gear transmission or turbine / worm transmission (in this case, the output shaft of the servo motor is provided with a turbine, and the capping spindle 11 is provided with a worm section).

[0083] Transmission mechanism, such as Figure 2 As shown, the cap screwing spindle 11 is coaxially arranged with the clamping jaw control spindle 3, that is, the diameter of the clamping jaw control spindle 3 is smaller than the diameter of the cap screwing spindle 11, and the clamping jaw control spindle 3 is built into (penetrates) the cap screwing spindle 11. The cap screwing spindle 11 only rotates around its own axis; the clamping jaw control spindle 3 only moves linearly along its own axial direction.

[0084] In order to ensure the stability of the two in their independent movements (such as reducing the swing amplitude of the clamping jaw control shaft 3 when it is telescopically moving along its own axis; and also to increase the diversity of raw material choices when the clamping jaw control shaft 3 is produced); and also to increase the service life of the two (such as the capping deviation caused by different axes due to friction and wear after long-term use of the two). A shaft sleeve is provided between the clamping jaw control shaft 3 and the capping main shaft 11, that is, the shaft sleeve effectively ensures the coaxiality between the clamping jaw control shaft 3 and the capping main shaft 11, and ensures the relative freedom between the two.

[0085] During specific installation, one end of the cap screwing spindle 11 is installed on the support plate 5. When the clamping jaw control shaft 3 is provided with a thread (when the worm gear is driven), a matching internal thread is provided in the corresponding section on the inner side of the cap screwing spindle 11 to ensure that the clamping jaw control shaft 3 can move in the axial direction relative to the cap screwing spindle 11. When the clamping jaw control shaft 3 has no external thread, the clamping jaw control shaft 3 is directly connected to the output shaft of the clamping jaw opening and closing motor 2, and the clamping jaw control shaft 3 and the cap screwing spindle 11 are relatively limited (limited in the radial direction) by bearings. When the cap screwing spindle 11 is provided with a worm thread on the outside, a threaded through hole is provided on the support plate 5 for the cap screwing spindle 11 to rotate through; when the cap screwing spindle 11 has no external thread on the outside, the support plate 5 is provided with a through hole for the cap screwing spindle 11 to pass through, and the cap screwing spindle 11 can be installed in the through hole through a bearing.

[0086] The execution of the cap screwing action is decomposed into two actions: clamping and fixing the cap and rotating and opening and closing the cap. To achieve the two actions, the end of the cap screwing main shaft 11 is equipped with a clamping claw group, and the end of the clamping claw control shaft 3 is provided with a control terminal 14.

[0087] The clamping jaw group includes a plurality of clamping jaws (at least two clamping jaws), and three clamping jaws are shown in the figure of the present application (giving full play to the stability of the force of the three clamping parts 9). The clamping jaw includes a clamping part 9 arranged in sequence, a mounting fulcrum 10 connected to the cap screwing main shaft 11, and a limiting structure; the limiting structure corresponds to the section of the cap screwing main shaft 11, and the limiting structure has a slope structure 15 on the side facing the cap screwing main shaft 11. It is defined that the slope structure 15 is a slope 25 structure with an inclined direction facing the cap screwing main shaft 11; the slope structures 15 of each clamping jaw in the clamping jaw group together constitute a quasi-conical cavity; the clamping parts 9 of each clamping jaw in the clamping jaw group together form the clamping space of the cover body. An elastic collar 7 is used to be sleeved on the other side of each clamping jaw limiting structure in the clamping jaw group. When the control terminal 14 slides in the quasi-conical cavity, it overcomes the gravity of the clamping jaw group itself and overcomes the force of the elastic collar 7. During specific implementation, the elastic force of the elastic collar 7 can be adjusted according to the requirement of the clamping force to ensure the stable progress of the capping process.

[0088] In order to protect the force stability of the clamped cover body and the wide applicability, a clamping protection plate 8 is provided on the clamping portion 9 (or the entire clamping portion 9 is directly replaced by the clamping protection plate 8). The clamping protection plate 8 is an arc-shaped structure, so that when the cover body is round, the arc-shaped structure can be directly attached to the circumference of the cover body; when the cover body is square, the arc-shaped structure can form clamping points with the four corners of the square cover body to the greatest extent. More preferably, the clamping protection plate 8 can be made of silicone or elastic rubber. In order to reduce the weight of the entire device, the thickness of the clamping protection plate 8 is between 1mm and 5mm.

[0089] The control terminal 14 is located in the quasi-conical cavity, and when the position of the control terminal 14 relative to the quasi-conical cavity is different, the rotation angle of the mounting fulcrum 10 of the clamp is different, and the opening and closing degree of the clamp group is also different.

[0090] In order to fully ensure the contact surface between the control terminal 14 and the quasi-conical cavity, so as to ensure the accuracy and stability of the opening and closing degree control of the clamping part 9, the control terminal 14 adopts a quasi-conical structure matching the quasi-conical cavity; or the control terminal 14 adopts a cylindrical structure, and the diameter of the cylindrical structure is set to be between the diameter of the smallest end face and the diameter of the largest end face of the quasi-conical cavity.

[0091] Preferably, the control terminal 14 can rotate relative to the clamp control shaft 3 to avoid the accuracy problem caused by the friction and wear between the control terminal 14 and the slope structure 15 during the cap tightening process. At the same time, in order to avoid the control terminal 14 from rubbing against the slope structure 15 or causing scratches when the control terminal 14 adjusts the opening and closing degree of the clamp assembly, the edge of the control terminal 14 adopts a rounded transition.

[0092] like Figure 4 As shown, since the size of the cover is not fixed during the cover screwing process, the clamping and unclamping processes of the cover require the clamping jaw group to have different clamping jaw sizes. The adjustment of the clamping jaw size in the present application is achieved by the cooperation of the clamping jaw group and the control terminal 14. Specifically, when the control terminal 14 is located at the lowest end of the slope structure 15 (i.e., the end of the slope structure 15 adjacent to the clamping portion 9 of the clamping jaw), the clamping jaw group has the largest opening, i.e., the largest clamping size. At this time, the clamping jaw opening and closing motor 2 is started, the clamping jaw control shaft 3 rotates upward, driving the control terminal 14 to move upward along the axis of the clamping jaw control shaft 3, and the control terminal 14 slides up along the slope structure 15. Since the clamping jaw group is fixed by the cover screwing main shaft 11, the slope structure 15 of each clamping jaw will rotate around the fixed point on the cover screwing main shaft 11 to achieve the opening adjustment of the clamping jaw group, and as the control terminal 14 slides up, the larger the amplitude, the smaller the opening of the clamping jaw group.

[0093] In order to adjust the opening and closing degree of the clamping jaw group, the present application has the following features when designing the clamping jaw group:

[0094] When the slope structure 15 of the jaw group is arranged in the cap screwing spindle 11, each jaw in the jaw group has an installation fulcrum 10, and each jaw is installed on the cap screwing spindle 11 through the installation fulcrum 10; each jaw has a clamping portion 9, and the clamping portion 9 is located at the end of the cap screwing spindle 11; each jaw has a slope structure 15, and the slope structure 15 is located inside the end of the cap screwing spindle 11. At the same time, all the slope structures 15 in the jaw group constitute a quasi-conical structure; a groove 18 is provided on the outside of the slope structure 15, and an elastic collar 7 is provided on the outside of the jaw group, and the collar is fitted in the groove 18 outside each jaw on the jaw group. When the control terminal 14 moves upward along the axis of the clamp control shaft 3, the control terminal 14 overcomes the force of the elastic collar 7, causing the quasi-conical cavity of the clamp group to gradually change into a cylindrical cavity. At the same time, each clamp will rotate with the help of the mounting fulcrum 10, causing the clamping size of the clamp group to become smaller. This structure is suitable for the entire capping spindle 11 to rise to the same height as the distance it rotates out during the capping process, or to fall to the same height as the distance it rotates in during the capping process (this method is suitable for the capping spindle 11 to pass through the support plate 5 through threads and threaded holes). It is also suitable for the robot arm to clamp the cell factory to the same height as the distance it rotates out during the capping process, or to rise to the same height as the distance it rotates in during the capping process.

[0095] In order to simplify the structure, the present application also performs the following optimization, namely, providing a buffer device.

[0096] like Figure 3 As shown, the buffer device includes a clamping jaw mounting sleeve 13 installed on the cap screwing spindle 11; the clamping jaw mounting sleeve 13 can rotate coaxially with the cap screwing spindle 11, that is, the clamping jaw mounting sleeve 13 and the cap screwing spindle 11 are relatively fixed in the radial direction by connecting the sliding groove and the sliding table; and the length of the sliding groove is longer than the length of the sliding table. Another way of stating is: if a sliding groove is provided in the clamping jaw mounting sleeve 13 and a sliding table is provided on the cap screwing spindle 11, the length of the sliding groove should be longer than the length of the sliding table to ensure that the clamping jaw mounting sleeve 13 can have a certain axial movement space relative to the cap screwing spindle 11; on the contrary, if a sliding table is provided in the clamping jaw mounting sleeve 13 and a sliding table is provided on the cap screwing spindle 11, the length of the sliding groove is longer than the length of the sliding table to ensure that the clamping jaw mounting sleeve 13 can have a certain axial movement space relative to the cap screwing spindle 11.

[0097] The jaw group is mounted on the jaw mounting sleeve 13 in a manner that it can rotate around the jaw mounting sleeve 13 in a radial direction. The end of the jaw mounting sleeve 13 is provided with a channel 16 for the jaw group to rotate. Specifically, each jaw in the jaw group has a mounting fulcrum 10, and each jaw is mounted on one end of the jaw mounting sleeve 13 through the mounting fulcrum 10; preferably, the end of each jaw mounting sleeve 13 protrudes outward with a plurality of bosses 17, and a mounting bracket is formed between any two bosses 17, and the mounting fulcrum 10 is mounted on the mounting bracket by means of a pin or a screw; and during the rotation of the jaw, the rotation path of the limiting structure of the jaw passes through the channel 16.

[0098] Each clamp has a clamping portion 9, which is located outside the clamp mounting sleeve 13; each clamp has a slope structure 15, which corresponds to the main shaft 11 of the cap screwing, and all the slope structures 15 in the clamp group form a truncated cone structure; a slot 18 is provided outside the slope structure 15, and an elastic collar 7 is provided outside the clamp group, which is fitted in the slot 18 outside each clamp on the clamp group. When the control terminal 14 moves upward along the axis of the clamp control shaft 3, the control terminal 14 overcomes the force of the elastic collar 7, causing the truncated cone structure of the clamp group to gradually change to a cylindrical structure, and at the same time, each clamp will rotate with the help of the mounting fulcrum 10, causing the clamping size of the clamp group to become smaller.

[0099] In order to adjust the height change of the clamping jaw assembly during the capping process, a buffer component 6 is installed at the other end of the clamping jaw mounting sleeve 13. The buffer component 6 is arranged at the end of the clamping jaw mounting sleeve 13, and is used to compensate for the distance difference between the clamping jaw mounting sleeve 13 and the capping spindle 11 when the capping spindle 11 rotates. The buffer component 6 is a spring, one end of which is connected to the clamping jaw mounting sleeve 13 (such as using a positioning device 12, such as a boss 17 with a through hole), and the other end is fixed to a platform; it is defined that the platform is used for the installation of the capping spindle 11 and the clamping jaw control shaft 3 at the same time, that is, the aforementioned support plate 5; or the platform is an arbitrary plane arranged above the clamping jaw mounting sleeve 13.

[0100] In addition, since the technical solution of the present application can be applied to automated production lines, a method is needed to confirm whether the cell culture device delivered by the robot has a cover. The present application is designed to add a photoelectric detector, which is arranged on any plane of the clamp used to clamp the cover. In actual design, the light path between the transmitting end and the receiving end of the photoelectric detector is arranged in the middle section of the movement path of the lowest surface of the clamp group during the clamping process to ensure the accuracy of the detection.

[0101] Furthermore, in order to prevent the cover from being damaged by over-tightening during the clamping process, the present application designs the control terminal to include: an end located at the top of the clamping jaw control shaft, a control body having a quasi-conical structure or a cylindrical structure, and a spring between the end and the control body; in particular, the control body can slide along the axis of the clamping jaw control shaft. When the clamping jaw control shaft rotates out of control, in order to prevent the clamping jaw from damaging the cover, the control body will be blocked by the cavity of the quasi-conical structure, squeezing the spring, so that the control terminal has a certain buffer.

[0102] The overall operation process of the technical solution of this application is as follows:

[0103] The jaw opening and closing motor 2 is started under the control of the program, the jaw control shaft 3 slides upward along its own axis, and the control terminal 14 rises accordingly. The control terminal 14 will gradually push open the small end of the truncated cone-like cavity, and through the action of the mounting fulcrum 10, the opening of the clamping part 9 of the jaw group increases until the opening of the clamping protection plate 8 reaches the required opening. In this process, the elastic collar 7 applies an external force to the limit structure to prevent the jaw from freely rotating around the mounting fulcrum 10 when the control terminal 14 pushes open the small end of the truncated cone-like cavity; at the same time, the elastic collar 7 also provides clamping force for the clamping part 9.

[0104] The clamping protection plate 8 clamps the cover, and at the same time, the clamping jaw opening and closing motor 2 is started under the control program (external setting) to adjust the clamping force of the clamping protection plate 8 on the cover.

[0105] The jaw opening and closing motor 2 stops running.

[0106] The cover screwing servo motor 1 is turned on and rotates under the control of an external program to realize the opening or closing of the cover.

[0107] In order to better cooperate to achieve more accurate and reliable screwing of the cap, aspiration and addition of liquid. The aspiration device also includes a first lifting module, and the aspiration needle 21 is installed on the first lifting module. The first lifting module has a first position and a second position, wherein the first position (working position) can ensure that the aspiration needle 21 can absorb all the liquid in the cell storage container, and the second position (non-working position) can ensure that the aspiration needle 21 can be higher than the position where the cell storage container moves, so as to avoid affecting the screwing of the cap or the addition of liquid to the cell storage container.

[0108] The first lifting module can be any lifting module of the prior art, or can be the structure of the present application, that is, including a first lifting motor and a first bracket. The pipette needle 21 is mounted on the first bracket and can move up and down relative to the first bracket under the drive of the first lifting motor.

[0109] The liquid adding device further comprises a second lifting module, and the liquid adding needle 22 is mounted on the second lifting module. Like the first lifting module, the second lifting module also has a first position (working position) and a second position (non-working position). Example 2

[0110] Different from Example 1, the present application is also provided with a sterilization device. Figure 7 As shown, the sterilization device includes a sterilization pipe and a sterilization source 20; the sterilization source 20 is connected to the inlet of the liquid-adding peristaltic pump 19; one end of the sterilization pipe is connected to the liquid-adding needle 22, and the other end of the sterilization pipe is connected to the liquid-imbibing needle 21.

[0111] In order to simplify the overall structure and facilitate the realization of automated operation, the sterilization pipe is supported by a rotating bracket, and the first limit position of the rotation of the rotating bracket can control the sterilization pipe and the liquid adding needle 22, or the sterilization pipe and the liquid aspiration needle 21 to be in a parallel position; the second limit position of the rotation of the rotating bracket can ensure that one end of the sterilization pipe is connected to the liquid adding needle 22, and the other end of the sterilization pipe is connected to the liquid aspiration needle 21. In order to ensure that the sterilization channel is completely closed during sterilization, at least one annular sealing ring is provided on the liquid aspiration needle 21 or the liquid adding needle 22.

[0112] Due to the special requirements of cell culture on the environment, the sterilization source 20 of the present application uses water vapor above 121°C or alcohol with a volume concentration of 75%. When using water vapor sterilization, it is only necessary to rotate the bracket to adjust to the second extreme position to ensure that one end of the sterilization pipeline is connected to the liquid adding needle 22, and the other end of the sterilization pipeline is connected to the liquid aspiration needle 21, so that the entire pipeline is in a connected state (or, directly use a robot arm to connect the sterilization pipeline to the liquid adding needle 22 and the liquid aspiration needle 21, so that the entire pipeline is in a connected state); at the same time, the liquid storage mechanism connected to the liquid adding pump is replaced with a water vapor source, and the outlet of the liquid aspiration peristaltic pump 23 is connected to the external water outlet pipe through a pipeline. In order to avoid reverse contamination of the external water outlet pipe, a one-way valve is provided on the pipeline; a filter membrane is provided on the one-way valve. In addition, when the sterilization source 20 uses water vapor above 121°C, the sterilization time is not less than 20 minutes to ensure complete sterilization.

[0113] When using alcohol with a volume concentration of 75%, a pipeline switching mechanism is provided at the inlet of the liquid-adding peristaltic pump 19. The pipeline switching mechanism includes a connecting pipe; the connecting pipe is used to connect the inlet of the liquid-adding peristaltic pump 19 to the sterilization source 20 or the liquid storage bag (using the pipeline switching mechanism of the prior art, the pipeline switching can also be achieved by clamping the connecting pipe by a mechanical arm). During the sterilization process, the bracket is first rotated to adjust to the second extreme position (or, the sterilization pipeline is directly connected to the liquid-adding needle 22 and the liquid-absorption needle 21 by a mechanical arm), ensuring that one end of the sterilization pipeline is connected to the liquid-adding needle 22, and the other end of the sterilization pipeline is connected to the liquid-absorption needle 21; the outlet of the liquid-absorption peristaltic pump 23 is connected to the waste liquid storage. Then the inlet of the liquid-adding pump is connected to the alcohol with a volume concentration of 75% through the pipeline switching mechanism. After the set time, the inlet of the liquid-adding pump is connected to the DPBS buffer (or culture solution) for flushing for the set time through the pipeline switching mechanism, and finally the overall disinfection and sterilization of the pipeline is completed.

[0114] The liquid adding device and the liquid suction device can be sterilized separately by using alcohol with a volume concentration of 75%. If the liquid adding device is sterilized, the inlet of the liquid adding peristaltic pump is connected to the sterilization source, and the liquid adding needle is connected to the waste liquid storage. Similarly, if the liquid suction device is sterilized, the liquid suction needle is connected to the sterilization source, and the outlet of the liquid suction peristaltic pump is connected to the waste liquid storage.

[0115] like Figure 8 As shown, in order to ensure that the liquid in the liquid storage mechanism connected to the liquid adding pump can be used up, the liquid adding storage mechanism includes a liquid storage tank 24 and a liquid storage bag located in the liquid storage tank 24; the liquid storage tank 24 is provided with a through hole; the bottom of the liquid storage bag is provided with a liquid outlet joint; the liquid outlet joint is connected to the liquid adding pipe after passing through the through hole; the liquid storage tank has an inclined surface 25, and the top of the inclined surface 25 is provided with a liquid storage bag fixing portion 26. When in use, the top of the liquid storage bag is fixed to the liquid storage bag fixing portion 26, the liquid storage bag is supported by the inclined surface, and the bottom of the liquid storage bag is suspended. In order to reduce costs, the inclined surface adopts a grid structure, that is, an inclined surface structure formed by a plurality of transverse rods and a plurality of longitudinal rods interlaced. Example 3

[0116] What is different from Example 1 and Example 2 is that in the present application, the capping device, the liquid adding device and the liquid aspiration device work independently in a non-sterile state, so in actual application, two or more groups can be used as needed to achieve simultaneous capping, liquid adding and liquid aspiration of multiple cell storage containers.

[0117] It mainly realizes the automation of liquid addition and liquid aspiration processes of cell storage containers and the convenient assembly of cap screwing actions.

[0118] Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention. A person with ordinary knowledge in the technical field to which the present invention belongs may make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention shall be determined by the definition of the claims.

Claims

1. A fully automatic liquid replacement system for adding or aspirating liquid from a cell storage container; characterized in that: It is integrated with a capping device, a liquid suction device, a liquid adding device and a weighing platform; The cover screwing device is used to screw open or screw close the cover of the cell storage container; The liquid suction device is used to suck out the liquid in the cell storage container; The liquid adding device is used to add culture solution into the cell storage container; The weighing platform is used for weighing the cell storage container; The liquid suction device comprises a liquid suction needle, a liquid suction tube, a liquid suction peristaltic pump and a waste liquid storage device which are connected in sequence; the liquid adding device comprises a liquid adding needle, a liquid adding tube, a liquid adding peristaltic pump and a liquid adding storage mechanism which are connected in sequence; the liquid suction device also comprises a first lifting module, and the liquid suction needle is installed on the first lifting module; The liquid adding device further comprises a second lifting module, and the liquid adding needle is mounted on the second lifting module; The capping device comprises a capping mechanism and a clamping jaw control mechanism; The capping mechanism comprises: The cap screwing spindle can rotate around its own axis; A clamping jaw group is installed on the end of the cap screwing spindle; the clamping jaw group includes a clamping jaw limiter and a plurality of clamping jaws; The clamping jaw limiter includes a plurality of elastic collars; The clamping jaws include a clamping portion, a mounting fulcrum connected to the cap screwing spindle, and a limiting structure, which are sequentially arranged; the limiting structure corresponds to the cap screwing spindle section, and the limiting structure has a slope structure on one side facing the cap screwing spindle, wherein the slope structure is an inclined surface structure with an inclined direction facing the cap screwing spindle; the slope structures of the clamping jaws in the clamping jaw group together form a truncated cone-like cavity; Wherein, the elastic collar is sleeved on the other side of each clamping jaw limiting structure in the clamping jaw group; The gripper control mechanism comprises: The clamping jaw control shaft is coaxially designed with the cap screwing main shaft and can move in its own axial direction; at the same time, the end of the clamping jaw control shaft is provided with a control terminal; Wherein, the control terminal is located in the quasi-conical cavity, and when the position of the control terminal relative to the quasi-conical cavity is different, the rotation angle of the mounting fulcrum of the clamp is different, and the opening and closing degree of the clamp group is also different.

2. A fully automatic liquid replacement system according to claim 1, characterized in that: At least one annular sealing ring is disposed on the liquid aspiration needle or the liquid addition needle.

3. A fully automatic liquid replacement system according to claim 1, characterized in that: It also includes a sterilization device, which includes a sterilization pipeline and a sterilization source; the sterilization source is connected to the inlet of the liquid-adding peristaltic pump; one end of the sterilization pipeline is connected to the liquid-adding needle, and the other end of the sterilization pipeline is connected to the liquid-absorption needle.

4. A fully automatic liquid replacement system according to claim 3, characterized in that: The sterilization source is water vapor above 121° C.; at the same time, the outlet of the liquid suction peristaltic pump is connected to the external water outlet pipe through a pipeline; a one-way valve is arranged on the pipeline; and a filter membrane is arranged on the one-way valve.

5. A fully automatic liquid replacement system according to claim 3, characterized in that: The sterilization source uses alcohol with a volume concentration of 75%; the inlet of the liquid-adding peristaltic pump is provided with a pipeline switching mechanism, and the pipeline switching mechanism includes a connecting pipe; the connecting pipe is used to connect the inlet of the liquid-adding peristaltic pump to the sterilization source or the liquid storage bag.

6. A fully automatic liquid replacement system according to claim 1, characterized in that: The liquid adding and storing mechanism comprises a liquid storage box and a liquid storage bag located in the liquid storage box; a through hole is provided on the liquid storage box; a liquid outlet joint is provided at the bottom of the liquid storage bag; the liquid outlet joint is connected to the liquid adding pipe through the through hole.

7. A fully automatic liquid replacement system according to claim 6, characterized in that: The liquid storage box is provided with an inclined surface, and a liquid storage bag fixing portion is provided on the top of the inclined surface.

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