Continuous culture medium supplementing device with degerming function for perfusion type cell culture

By designing a continuous medium supplement device for perfusion cell culture, combined with online filtration and sterilization technology, the problems of cumbersome transfer process and high risk of bacterial infection in the prior art are solved, and efficient and safe medium addition is achieved.

CN223033368UActive Publication Date: 2025-06-27山东省食品药品审评查验中心
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Patent Information

Application Number
CN202420630482.8
Authority / Receiving Office
CN · China
Patent Type
Utility models(China)
Current Assignee / Owner
Filing Date
2024-03-29
Publication Date
2025-06-27
Estimated Expiration
2034-03-29

AI Technical Summary

Technical Problem

In the existing perfusion cell culture, the culture medium is manually or other means transferred to the supplement device for injection. The process is cumbersome, affects work efficiency, has high labor intensity, many steps, and has a high risk of bacterial infection, especially when the injection amount is large or the culture time is long.

Method used

A continuous medium supplement device with sterilization function for perfusion cell culture was designed. Combined with the online filtration and sterilization method, the continuous operation of the dosing system is ensured by replacing the filter element, reducing the risk of bacterial infection, and improving work efficiency.

Benefits of technology

Through the use of this device, the risk of bacterial infection caused by the medium transfer process is significantly reduced, and the work efficiency is improved. It is suitable for perfusion cell culture with large dosage or long culture time.

✦ Generated by Eureka AI based on patent content.

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Abstract

The utility model discloses a continuous culture medium supplementing device with a degerming function for perfusion type cell culture, and solves the problems that after a culture medium is degermed and filtered, the culture medium is transferred to the supplementing device in a manual or other manner and then is added, but the manner is tedious in process, affects the working efficiency and is inconvenient to operate. The device comprises an electric heating sleeve, an electric stirring machine is installed in the middle of the top end of the electric heating sleeve, a tenth electromagnetic valve is connected to the outer side of the top end of the electric heating sleeve, and a culture medium outlet is formed in the other side of the tenth electromagnetic valve. According to the device disclosed by the utility model, an on-line filtering and sterilizing mode is combined, and the continuous operation of the adding system is ensured by only replacing the filter element, so that the bacterial contamination risk caused by a culture medium transfer process is greatly reduced, and meanwhile, the working efficiency is improved.
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Description

Technical Field

[0001] The utility model belongs to the field of perfusion culture medium addition and sterilization, and particularly relates to a culture medium addition device with dual functions of continuous addition and sterilization. Background Technique

[0002] Cell perfusion culture is a process in which cells and a culture medium are added to a reactor together, and during the cell amplification process, part of the conditioned culture medium is continuously taken out, and at the same time, fresh culture medium is continuously perfused. To ensure the aseptic operation of the culture medium during perfusion culture, it is necessary to perform aseptic treatment on the culture medium before addition.

[0003] However, the existing method is to filter the culture medium for sterilization and then transfer it to the supplementary addition device by manual or other means for addition. However, such a method is not only cumbersome, affects work efficiency, but also has a large labor intensity, many steps, and a high risk of bacterial contamination during the transfer process. If the addition amount of the culture medium is small or the culture time is short, the traditional operation method can still be used. However, if the addition amount is large or the culture time is long, the traditional method will bring more risks of bacterial contamination. Content of the Utility Model

[0004] In view of the above situation, in order to overcome the defects of the prior art, the utility model provides a continuous culture medium supplementary addition device with a sterilization function for perfusion cell culture, effectively solving the problem that after the culture medium is sterilized and filtered, it is transferred to the supplementary addition device by manual or other means for addition. However, such a method is not only cumbersome, affects work efficiency, but also has a large labor intensity, many steps, and a high risk of bacterial contamination during the transfer process.

[0005] To achieve the above object, the present utility model provides the following technical solution: A continuous medium addition device with a sterilization function for perfusion cell culture, comprising an electric heating jacket, in the middle of the top of the electric heating jacket, an electric stirrer is installed. On the outer side of the top of the electric heating jacket, a tenth solenoid valve is connected. On the other side of the tenth solenoid valve, a medium outlet is installed. On the top of the electric heating jacket, a ninth solenoid valve is fixed. On the other side of the ninth solenoid valve, a first pressure relief port is connected. In the middle of the electric heating jacket, an eighth solenoid valve is installed. On the other side of the eighth solenoid valve, a backflush drain port is fixed. At the top inside the electric heating jacket, a high-pressure nozzle is connected. At the bottom of the high-pressure nozzle, a check valve is fixed. In the middle inside the electric heating jacket, a seventh solenoid valve is installed. One end of the seventh solenoid valve is connected to a cleaning water flushing port. At the bottom inside the electric heating jacket, a filter is installed. On one side of the top of the filter, a second solenoid valve is connected. On one side of the top of the filter, a twelfth solenoid valve is installed. One end of the twelfth solenoid valve is fixed with a second pressure relief port. In the middle of the filter, a thirteenth solenoid valve is connected. One end of the thirteenth solenoid valve is connected to a reverse drain port. At the bottom end of the filter, a first solenoid valve, a fourth solenoid valve, an eleventh solenoid valve and a third solenoid valve are connected. One end of the first solenoid valve is installed with a medium inlet. One end of the fourth solenoid valve is connected to a first drain port. One end of the third solenoid valve is fixed with a filter tank cleaning water port. In the middle of the bottom end of the electric heating jacket, a steam inlet and a second drain port are installed. At the top of the steam inlet, a fifth solenoid valve is connected. At the top of the second drain port, a sixth solenoid valve is fixed. At the bottom inside the electric heating jacket, a bottom opening is provided. At the bottom of the electric stirrer, a stirring paddle is installed.

[0006] Preferably, the electric heating jacket is externally sleeved with heat-insulating rock wool.

[0007] Preferably, the stirring paddle is a metal material component.

[0008] Preferably, the top of the electric stirrer is fixed with heat dissipation fins.

[0009] Compared with the prior art, the beneficial effects of the present utility model are:

[0010] The present utility model combines the method of online filtration and sterilization, and only by replacing the filter element can the continuous operation of the dosing system be ensured, which will greatly reduce the risk of bacterial contamination caused by the medium transfer process and improve the work efficiency at the same time. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The drawings are used to provide a further understanding of the present utility model and constitute a part of the specification. They are used together with the embodiments of the present utility model to explain the present utility model and do not constitute a limitation to the present utility model. In the drawings:

[0012] Figure 1 is the overall structural schematic diagram of the present utility model;

[0013] Figure 2Schematic diagram of the installation structure of the electric mixer of the present utility model;

[0014] Figure 3 Schematic diagram of the installation structure of the filter of the present utility model;

[0015] Figure 4 Schematic diagram of the installation structure of the chemical dosing pump of the present utility model.

[0016] In the figure: 1. Electric heating jacket; 2. Electric mixer; 3. Tenth electromagnetic valve; 4. Culture medium outlet; 5. Ninth electromagnetic valve; 6. First pressure relief port; 7. Eighth electromagnetic valve; 8. Backwashing drain port; 9. High-pressure nozzle; 10. Check valve; 11. Cleaning water flushing port; 12. Second pressure relief port; 13. Reverse drain port; 14. Twelfth electromagnetic valve; 15. Thirteenth electromagnetic valve; 16. Culture medium inlet; 17. First electromagnetic valve; 18. First liquid discharge port; 19. Fourth electromagnetic valve; 20. Eleventh electromagnetic valve; 21. Third electromagnetic valve; 22. Filter tank cleaning water port; 23. Steam inlet; 24. Second liquid discharge port; 25. Sixth electromagnetic valve; 26. Fifth electromagnetic valve; 27. Second electromagnetic valve; 28. Seventh electromagnetic valve; 29. Bottom opening; 30. Filter; 31. Chemical dosing pump; 32. Stirring paddle. Specific embodiments

[0017] Next, the technical solutions in the embodiments of the present utility model will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present utility model. Obviously, the described embodiments are only a part of the embodiments of the present utility model, rather than all the embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present utility model.

[0018] Such as Figure 1 , Figure 2 , Figure 3 and Figure 4As shown in the figure, an embodiment of the utility model provides a continuous medium supplementation device with a sterilization function for perfusion cell culture, including an electric heating jacket 1. In the middle of the top of the electric heating jacket 1, an electric mixer 2 is installed. On the outer side of the top of the electric heating jacket 1, a tenth electromagnetic valve 3 is connected. On the other side of the tenth electromagnetic valve 3, a medium outlet 4 is installed. On the top of the electric heating jacket 1, a ninth electromagnetic valve 5 is fixed. On the other side of the ninth electromagnetic valve 5, a pressure relief port 6 is connected. In the middle of the electric heating jacket 1, an eighth electromagnetic valve 7 is installed. On the other side of the eighth electromagnetic valve 7, a backwash drain port 8 is fixed. At the top inside the electric heating jacket 1, a high-pressure nozzle 9 is connected. At the bottom of the high-pressure nozzle 9, a check valve 10 is fixed. In the middle inside the electric heating jacket 1, a seventh electromagnetic valve 28 is installed. One end of the seventh electromagnetic valve 28 is connected to a cleaning water flushing port 11. At the bottom inside the electric heating jacket 1, a filter 30 is installed. On one side of the top of the filter 30, a second electromagnetic valve 27 is connected. On one side of the top of the filter 30, a twelfth electromagnetic valve 14 is installed. One end of the twelfth electromagnetic valve 14 is fixed with a pressure relief port 12. In the middle of the filter 30, a thirteenth electromagnetic valve 15 is connected. One end of the thirteenth electromagnetic valve 15 is connected to a reverse drain port 13. At the bottom end of the filter 30, a first electromagnetic valve 17, a fourth electromagnetic valve 19, an eleventh electromagnetic valve 20 and a third electromagnetic valve 21 are connected. At one end of the first electromagnetic valve 17, a medium inlet 16 is installed. At one end of the fourth electromagnetic valve 19, a first drain port 18 is connected. At one end of the third electromagnetic valve 21, a filter tank cleaning water port 22 is fixed. In the middle of the bottom end of the electric heating jacket 1, a steam inlet 23 and a second drain port 24 are installed. At the top of the steam inlet 23, a fifth electromagnetic valve 26 is connected. At the top of the second drain port 24, a sixth electromagnetic valve 25 is fixed. At the bottom inside the electric heating jacket 1, a bottom opening 29 is provided. At the bottom of the electric mixer 2, a stirring paddle 32 is installed.

[0019] Specifically, a heat-insulating rock wool is sleeved outside the electric heating jacket 1.

[0020] Specifically, the stirring paddle 32 is a metal material component.

[0021] Specifically, heat dissipation fins are fixed on the top of the electric mixer 2.

[0022] Example 1 consists of Figure 1 、 Figure 2 、 Figure 3 and Figure 4Given that before the initial operation, first ensure that all solenoid valves are in the closed state, and load the processed filter device into Chamber ①. Open the sixth solenoid valve 25 to empty the remaining liquid in the storage bin. After emptying, close the sixth solenoid valve 25, the fifth solenoid valve 26, and the eleventh solenoid valve 20, and start high-temperature steam disinfection. The safety valves on the first pressure relief port 6 and the second pressure relief port 12 can ensure the safety inside the bin. After 30 - 45 minutes, close the fifth solenoid valve 26 and the eleventh solenoid valve 20 for online disinfection. After completion, let it stand and cool naturally, and prepare to start filtration. Open the first solenoid valve 17, the second solenoid valve 27, the tenth solenoid valve 3, the electric mixer 2, and the chemical dosing pump 31 respectively to make the equipment operate normally. Also, turn on the electric heating jacket 1 to keep the temperature of the culture medium constant. According to the task requirements, after waiting for a period of operation, the filter needs to be replaced and enter the next step. Before the operation of Chamber ②, online disinfection of Chamber ② is required. Open the eleventh solenoid valve 20 in Chamber ② for online disinfection. After completion, let it stand and cool naturally. Open the first solenoid valve 17 and the second solenoid valve 27 in Chamber ②, and close the first solenoid valve 17 and the second solenoid valve 27 in Chamber ①. The equipment runs continuously. Open the fourth solenoid valve 19 in Chamber ① to empty the culture medium liquid in the filter group, and then take out the filter group. Open the third solenoid valve 21 and the thirteenth solenoid valve 15 to wash the filter chamber. After washing, close the third solenoid valve 21 and the thirteenth solenoid valve 15, then open the fourth solenoid valve 19 to empty the water in the chamber, and then close the fourth solenoid valve 19 to prepare for the next use. The whole replacement process is Chamber ① → Chamber ② → Chamber ③ → Chamber ①. When the last operating chamber is Chamber ①, after adding the medicine, close the chemical dosing pump 31, the first solenoid valve 17, the second solenoid valve 27, the tenth solenoid valve 3, and the electric heating jacket 1. Open the fourth solenoid valve 19 and the sixth solenoid valve 25 to discharge the residual liquid in the chamber. After emptying the culture medium liquid in the filter group chamber and the storage bin, then take out the filter components in the filter chamber, and then start the backwashing process for the filter chamber and the storage bin respectively. For the filter chamber washing process, open the third solenoid valve 21 and the solenoid valve 13 to wash the filter chamber. After washing, close the third solenoid valve 21 and the thirteenth solenoid valve 15, then open the fourth solenoid valve 19 to empty the water in the chamber, and then close the fourth solenoid valve 19 to prepare for the next use. For the storage bin washing process, open the seventh solenoid valve 28 and the eighth solenoid valve 7. After the washing clean water passes through the high-pressure nozzle, discharge the washing water through the eighth solenoid valve 7. After washing, close the seventh solenoid valve 28 and the solenoid valve 8, then open the sixth solenoid valve 25 to empty the water in the chamber, and then close the sixth solenoid valve 25 to prepare for the next use.

[0023] Working principle: When using a continuous medium supplementation device with sterilization function for perfusion cell culture, before initial operation, first ensure that all solenoid valves are in the closed state, and install the processed filter device into the No. ① chamber. Open the sixth solenoid valve 25 to empty the remaining liquid in the storage chamber. After emptying, close the sixth solenoid valve 25, the fifth solenoid valve 26, and the eleventh solenoid valve 20, and start high-temperature steam sterilization. The safety valves on the pressure relief port 1 and the pressure relief port 2 can ensure the safety inside the chamber. After 30 - 45 minutes, close the fifth solenoid valve 26 and the eleventh solenoid valve 20 for online sterilization. After completion, let it stand and cool naturally, and prepare to start filtration. Open the first solenoid valve 17, the second solenoid valve 27, the tenth solenoid valve 3, the electric mixer 2, and the medicine adding pump 31 respectively to make the equipment run normally. And open the electric heating jacket 1 to keep the temperature of the medium constant. According to the task requirements, after waiting for a period of operation, the filter needs to be replaced and enter the next link. Before the No. ② chamber runs, online sterilization of the No. ② chamber is required. Open the eleventh solenoid valve 20 in the No. ② chamber for online sterilization. After completion, let it stand and cool naturally. Open the first solenoid valve 17 and the second solenoid valve 27 in the No. ② chamber, and close the first solenoid valve 17 and the second solenoid valve 27 in the No. ① chamber, and the equipment runs continuously. Open the fourth solenoid valve 19 in the No. ① chamber to empty the medium liquid in the filter group, and then take out the filter group. Open the third solenoid valve 21 and the thirteenth solenoid valve 15 to rinse the filter chamber. After rinsing, close the third solenoid valve 21 and the thirteenth solenoid valve 15, then open the fourth solenoid valve 19 to empty the water in the chamber, and then close the fourth solenoid valve 19, and prepare for the next use. The whole replacement process is: No. ① chamber → No. ② chamber → No. ③ chamber → No. ① chamber. When the last operating chamber is the No. ① chamber, after adding medicine, close the medicine adding pump 31, the first solenoid valve 17, the second solenoid valve 27, the tenth solenoid valve 3, and the electric heating jacket 1. Open the fourth solenoid valve 19 and the sixth solenoid valve 25 to discharge the residual liquid in the chamber. After emptying the medium liquid in the filter group chamber and the storage chamber, then take out the filter component in the filter chamber, and then start the backwashing process of the filter chamber and the storage chamber respectively. For the filter chamber washing process, open the third solenoid valve 21 and the solenoid valve 13 to rinse the filter chamber. After rinsing, close the third solenoid valve 21 and the thirteenth solenoid valve 15, then open the fourth solenoid valve 19 to empty the water in the chamber, and then close the fourth solenoid valve 19, and prepare for the next use. For the storage chamber washing process, open the seventh solenoid valve 28 and the eighth solenoid valve 7. After the cleaning water for rinsing passes through the high-pressure nozzle, discharge the rinsing water through the eighth solenoid valve 7. After rinsing, close the seventh solenoid valve 28 and the solenoid valve 8, then open the sixth solenoid valve 25 to empty the water in the chamber, and then close the sixth solenoid valve 25, and prepare for the next use.

[0024] Although embodiments of the present utility model have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principle and spirit of the present utility model. The scope of the present utility model is defined by the appended claims and their equivalents.

Claims

1. A continuous medium replenishing device with sterilization function for perfusion cell culture, comprising an electric heating jacket (1), characterized in that: The electric heating jacket (1) is provided with an electric stirrer (2) at the middle of the top end, a tenth solenoid valve (3) is connected to the outer side of the top end of the electric heating jacket (1), a culture medium outlet (4) is installed on the other side of the tenth solenoid valve (3), a ninth solenoid valve (5) is fixed at the top of the electric heating jacket (1), a pressure relief port (6) is connected to the other side of the ninth solenoid valve (5), an eighth solenoid valve (7) is installed at the middle of the electric heating jacket (1), a backwash outlet (8) is fixed to the other side of the eighth solenoid valve (7), a high-pressure nozzle (9) is connected to the top of the inner side of the electric heating jacket (1), a check valve (10) is fixed to the bottom of the high-pressure nozzle (9), a seventh solenoid valve (28) is installed at the middle of the inner side of the electric heating jacket (1), one end of the seventh solenoid valve (28) is connected to a cleaning water flushing port (11), a filter (30) is installed at the bottom of the inner side of the electric heating jacket (1), a second solenoid valve (27) is connected to one side of the top of the filter (30), a twelfth solenoid valve (14) is installed on one side of the top of the filter (30), and a seventh solenoid valve (28) is installed at the middle of the inner side of the electric heating jacket (1), a cleaning water flushing port (11) is connected to one end of the seventh solenoid valve (28), and a filter (30) is installed at the bottom of the inner side of the electric heating jacket (1), a second solenoid valve (27) is connected to one side of the top of the filter (30), a twelfth solenoid valve (14) is installed on one side of the top of the filter (30), and a seventh solenoid valve (28) is installed at the middle of the inner side of the electric heating jacket (1). A second pressure relief port (12) is fixed at one end of the twelfth solenoid valve (14); a thirteenth solenoid valve (15) is connected to the middle of the filter (30); one end of the thirteenth solenoid valve (15) is connected to the reverse drain port (13); a first solenoid valve (17), a fourth solenoid valve (19), an eleventh solenoid valve (20) and a third solenoid valve (21) are connected to the bottom of the filter (30); a culture medium inlet (16) is installed at one end of the first solenoid valve (17); a first liquid discharge port (18) is connected to one end of the fourth solenoid valve (19); a filter tank cleaning water port (22) is fixed at one end of the third solenoid valve (21); a steam inlet (23) and a second liquid discharge port (24) are installed at the middle of the bottom of the electric heating jacket (1); a fifth solenoid valve (26) is connected to the top of the steam inlet (23); a sixth solenoid valve (25) is fixed to the top of the second liquid discharge port (24); a bottom opening (29) is provided at the bottom of the inner side of the electric heating jacket (1); and a stirring paddle (32) is installed at the bottom of the electric stirrer (2).

2. A continuous medium replenishing device with sterilization function for perfusion cell culture according to claim 1, characterized in that: The electric heating sleeve (1) is externally sleeved with thermal insulation rock wool.

3. A continuous medium replenishing device with sterilization function for perfusion cell culture according to claim 1, characterized in that: The stirring paddle (32) is a metal component.

4. The continuous medium replenishing device with sterilization function for perfusion cell culture according to claim 1, characterized in that: A heat sink is fixed on the top of the electric mixer (2).