CN216970078U

CN216970078U - Feed supplement device

Info

Publication number: CN216970078U
Application number: CN202220688581.2U
Authority: CN
Inventors: 王兵兵; 郭进; 黄小芳; 刘巧玲; 尹江峰
Original assignee: Sanyou Biopharmaceuticals Co Ltd
Current assignee: Sanyou Biopharmaceuticals Co Ltd
Priority date: 2022-03-28
Filing date: 2022-03-28
Publication date: 2022-07-15
Anticipated expiration: 2032-03-28

Abstract

The utility model provides a material supplementing device which comprises an accommodating cavity, a sealing element, a conducting element and a pressure adjusting device, wherein a plurality of first chambers which are mutually partitioned are formed in the accommodating cavity, and each first chamber is provided with an opening on the upper surface of the accommodating cavity; the closing piece forms a second chamber at the top of the containing cavity, and the second chamber is communicated with the first chamber through each opening; a plurality of access ends of the conducting piece are respectively communicated with the first chambers; the air pressure adjusting device is hermetically connected with the second chamber, the input end of the air pressure adjusting device is arranged outside the accommodating cavity, and the output end of the air pressure adjusting device is communicated with the accommodating cavity or the sealing piece. The communicating piece is communicated with the accommodating cavity in the closing piece, so that the using process of the reactor is greatly simplified, the hardware requirement of a laboratory is reduced, and the environment protection is facilitated.

Description

Feed supplement device

Technical Field

The utility model relates to a material supplementing device.

Background

Protein drugs such as antibodies have recently been remarkably effective in the treatment of cancer, autoimmune diseases, and the like; the production of protein drugs such as antibodies requires the expression of animal cells such as CHO-S and CHO-K1 cells as hosts. With the expansion of production scale, corresponding culture processes need to be developed for corresponding host cells (cell lines) containing target genes; and the bioreactor is widely applied to the development of cell culture processes. However, in order to provide corresponding nutrients to cells continuously during the cell culture process, the bioreactor needs to be connected with various pipelines for supplementing nutrients and additives, such as a supplement A, a supplement B, sugar, an antifoaming agent and the like. Therefore, before each culture process development experiment, researchers need to connect more than 4 feeding bottles to the bioreactor through thermoplastic pipelines. Therefore, the bioreactor has the characteristics of multiple openings and multiple pipelines, and the characteristics not only increase the complexity of the experiment, but also greatly improve the workload of researchers.

The current commonly used feed preparation process comprises: the method comprises the steps of alkali soaking of a glass supplement bottle, cleaning of the bottle, pipeline assembly, air tightness inspection, sterilization, feed liquid addition and connection of the supplement bottle and a bioreactor. The operation process of feeding comprises: preparing an electronic balance, and connecting a feeding pipeline. Therefore, each feeding preparation process is very time-consuming, and the experimenter needs to start the preparation of the feeding bottle before one week; in the material supplementing process, each material supplementing bottle can only contain one material liquid, and experimenters need to frequently replace material supplementing pipelines, so that time and labor are wasted. Moreover, the access of such multiple pipes adds complexity to the overall process, leading to increased uncontrollable factors. The traditional feeding method also puts corresponding requirements on hardware facilities of a laboratory, for example, when 10 bioreactors are needed in one experiment, at least 2 pipe connecting machines are needed to operate because each bioreactor needs to be connected with more than 4 bottles, if the pipe connecting machines are limited, the pipe connecting machines can only be compensated by manpower, which does not meet the characteristics of high throughput and high automation in the future of biological science, and therefore, the current situation needs to be changed urgently.

SUMMERY OF THE UTILITY MODEL

The utility model aims to solve the technical problem that a bioreactor in the prior art is provided with multiple openings and multiple pipelines, so that the experiment complexity is increased, and a feeding device is provided.

The utility model solves the technical problems through the following technical scheme:

a feed supplement device, comprising:

the device comprises an accommodating cavity, a first cavity and a second cavity, wherein a plurality of mutually partitioned first cavities are formed in the accommodating cavity, and each first cavity is provided with an opening on the upper surface of the accommodating cavity;

a closure forming a second chamber at the top of the receiving cavity, the second chamber communicating with the first chamber through each of the openings;

the access ends of the conducting piece are respectively communicated with the first chambers;

the air pressure adjusting device is hermetically connected with the second chamber, the input end of the air pressure adjusting device is arranged outside the second chamber, and the output end of the air pressure adjusting device is communicated with the accommodating cavity or the sealing piece.

In the technical scheme, the conducting piece penetrates through the closing piece to be communicated with the containing cavity, and the plurality of first chambers of the containing cavity and the conducting piece are only needed to be connected with the plurality of additives into the reactor. The air pressure adjusting device can supplement the air pressure in the accommodating cavity during continuous material supplement, so that the material liquid is conveyed to the reactor continuously. Because the feed liquid can remain in switching on the piece after deriving, hold intracavity gas through the extraction of air pressure adjusting device this moment, reduce and hold intracavity atmospheric pressure, realize switching on the backward flow of remaining feed liquid in the piece, avoid the feed liquid to remain in switching on the piece. Greatly simplifying the using process of the reactor, reducing the hardware requirement of a laboratory and being more beneficial to environmental protection.

Preferably, a plurality of the incoming ends of the conducting element pass through the accommodating cavity through the corresponding openings and then pass through the closing element, the outgoing end of the conducting element is formed outside the closing element, a unified liquid guiding channel is further formed, and the liquid guiding channel is connected to the reactor.

In this technical scheme, the end that connects out of leading to the piece can be followed and held the intracavity feed liquid and derive behind the closure piece.

Preferably, the lead-through member includes a first portion and a second portion, the first portion being disposed in the accommodating chamber, the second portion being disposed in the closure member, and the first portion and the second portion being detachably connected.

In this technical scheme, after closure and holding chamber interconnect, the pipeline that switches on two parts of piece can align and compress tightly each other, realizes the intercommunication to through the first portion and the second part that switch on the piece, conveniently connect feed liquid and reactor, the realization will hold the function that the feed liquid in the chamber was derived.

Preferably, the feeding device comprises at least one water stop member, and the water stop member is arranged at the connection end of the conduction member.

Among this technical scheme, to the correspondence that needs supply liquid lead on a piece and connect other and lead on a piece and connect the exit end outside the exit end, can use the stagnant water piece to carry out this and lead on a sealing that connects the exit end, use the peristaltic pump to pump the feed liquid that does not have the pipeline that stagnant water piece blocked simultaneously. According to needs, the feed liquid in the cavity that does not have the switching-on piece pipeline of stagnant water spare can independently switch on needs. The conducting piece is fixedly arranged in the middle of the sealing piece and penetrates out of the sealing piece to be connected with the outside, and when the sealing piece is installed on the containing cavity, the conducting piece can be installed on the containing cavity together.

Preferably, the gas pressure adjusting device is a gas exchange channel and is used with a syringe, a syringe nozzle of the syringe is communicated with the second chamber through the gas exchange channel, and a push rod of the syringe is arranged outside the closed piece.

In the technical scheme, the air pressure adjusting device is simple, convenient and easy to obtain and convenient to operate by adopting the injector.

Preferably, a first air filter membrane is arranged in a gas exchange channel area where the air pressure adjusting device is connected with the second chamber.

In this technical scheme, first air filter membrane can realize the hydrophobic and separate the fungus effect.

Preferably, the plurality of outlet ends of the conducting member form a unified liquid guiding channel outside the second chamber.

In this technical scheme, lead to a plurality of incoming ends that the piece inserts each cavity and hold chamber and the outside unification of closed piece, reduce the port quantity of feed supplement device and outside switch-on, be convenient for test.

Preferably, the accommodating cavity is a bottle body, the closing piece is a cover body, and the closing piece is in threaded connection with one side of the opening of the accommodating cavity.

In the technical scheme, the cover body and the bottle body are screwed and unscrewed to realize the attachment and separation of the closing piece and the containing cavity, so that the sealing is convenient to generate air tightness and the cover is opened to supplement feed liquid.

Preferably, the closing part is provided with a baffle integrated with the conducting part in a direction towards the accommodating cavity, the baffle closes the opening, the conducting part penetrates through the baffle, the accommodating cavity is provided with a blocking piece at the opening of the first part of the conducting part, and the upper part of the access end of the conducting part is fixedly connected to the blocking piece and forms a channel.

In this technical scheme, the baffle can be fixed a position to leading to a second part, avoids this part to lead to a position change. Simultaneously the baffle can avoid holding the feed liquid in the cavity chamber and spill over, and the baffle can prevent to hold the mixing of various feed liquids when the chamber accident is emptyd. The baffle plate can position the first part of the conducting part, so that the position change of the conducting part is avoided, when the material supplementing device is closed for use, the baffle plate and the baffle plate are aligned and pressed with each other, and the channel of the conducting part is further communicated.

Preferably, the baffle plate and the blocking piece are both made of elastic pieces.

In this technical scheme, the elastic component can realize the airtight combination of bottle and lid through elastic deformation, avoids holding the intracavity liquid and spills over.

Preferably, the access end is located at the bottom of the corresponding first chamber.

In this technical scheme, the incoming end that switches on the piece can contact the bottom of first cavity for switch on the piece and can switch on more feed liquids in the first cavity.

The positive progress effects of the utility model are as follows:

the device can provide multiple feed liquid supplements only by one container, and changes the mode of generally needing 2 aseptic tube connectors to connect into the mode of completing the connection of 4 pipelines by only closing one supplement container. Has the characteristics of simple and convenient use and easy operation.

Drawings

FIG. 1 is a schematic structural diagram of a feeding device according to an embodiment of the present invention.

Fig. 2 is a schematic structural view of a closure member according to an embodiment of the present invention.

Fig. 3 is a schematic structural diagram of an accommodating chamber according to an embodiment of the utility model.

Fig. 4 is a top view of a receiving chamber according to an embodiment of the present invention.

Fig. 5 is a schematic structural diagram of a five-way joint according to an embodiment of the utility model.

Fig. 6 is a bottom view of a closure according to an embodiment of the present invention.

Description of the reference numerals

The containing cavity 1, the first chamber 11, the opening 12, the partition plate 13 and the baffle plate 14

Closure 2, gas exchange channel 21, second chamber 22

The conducting member 3, the inlet end 31, the outlet end 32, the thermoplastic tube 33, and the silicone hose 34

Air pressure adjusting device 4, injector interface 41

Water stop 5

A hydrophobic air filter membrane 6, a first air filter membrane 61 and a second air filter membrane 62

Drainage channel 7

Baffle 8, silica gel hose connector 8a, gas hole 8b

Five-way joint 9

Detailed Description

The present invention will be more clearly and completely described in the following description of preferred embodiments, taken in conjunction with the accompanying drawings.

As shown in figures 1 and 2, the utility model discloses a feeding device which comprises a containing cavity 1, a sealing element 2, a conducting element 3 and a gas pressure adjusting device 4. A plurality of first chambers 11 which are mutually partitioned are formed in the accommodating cavity 1, each first chamber 11 is provided with an opening 12 on the upper surface of the accommodating cavity 1, and each first chamber 11 is partitioned into 4 slots by a partition plate 13. The closure 2 forms a second chamber 22 at the top of the receiving chamber 1. The second chamber 22 communicates with the first chamber 11 through the respective air holes 8b and the respective openings 12. In this embodiment, the conducting part 3 is a solid body with 4 channels in the middle, and is a four-channel body, the access end 31 of each channel is respectively communicated with each first chamber 11, and is located at the bottom of each first chamber 11, so that the liquid located at the bottom of the corresponding first chamber 11 can enter the conducting part 3 through the access end 31, the conducting part 3 is a four-channel liquid suction pipeline, the four-channel liquid suction pipeline can suck the liquid in the corresponding slot according to specific requirements, and the multiple first chambers 11 formed in one accommodating cavity 1 and the conducting part 3 can be communicated with multiple additives into the reactor.

The lead-through member 3 comprises a first portion provided in the accommodation chamber 1 and a second portion provided in the closure member 2, the first portion and the second portion being detachably connected. After the closure member 2 and the receiving chamber 1 are connected to each other, the two parts of the duct can be aligned and pressed against each other, providing communication. By means of the first and second parts of the conducting element 3, it is convenient to connect the feed liquid to the reactor and to carry out the function of conducting the feed liquid out of the receiving chamber 1.

In this embodiment, the air pressure adjusting device 4 is hermetically connected to the second chamber 22, an input end of the air pressure adjusting device 4 is disposed outside the second chamber 22, and an output end of the air pressure adjusting device 4 is communicated with the sealing member 2. The air pressure adjusting device 4 can adjust the air pressure in the accommodating cavity 1 under the condition that the closing member 2 is tightly connected with the accommodating cavity 1. The feeding device further comprises a peristaltic pump connected to the thermoplastic tube 33 for flowing the feed liquid in each first chamber 11 of the containing cavity 1 along the corresponding conducting member 3 to the reactor. After the peristaltic pump led out the feed liquid and accommodated cavity 1, the feed liquid could be remained in conducting piece 3 after being led out, at this moment, the gas in accommodating cavity 1 is extracted through gas pressure adjusting device 4, the gas pressure in accommodating cavity 1 is reduced, and the reflux of the feed liquid remained in conducting piece 3 is realized. The process of the air pressure adjusting device for realizing the descending of the air pressure in the accommodating cavity 1 comprises the following steps: the pressure regulator 4 reduces the pressure in the second chamber 22 of the sealing member 2, indirectly and simultaneously reduces the pressure in each first chamber 11 of the accommodating chamber 1, so that the feed liquid in the conducting member 3 flows back into the first chamber 11, and the feed liquid is prevented from remaining in the conducting member 3. Greatly simplifying the using process of the reactor, reducing the hardware requirement of a laboratory and being more beneficial to environmental protection.

Of course, in other embodiments, the output end of the air pressure adjusting device 4 may be directly connected to the accommodating cavity 1.

As shown in fig. 1 and 2 and fig. 6, the receiving chamber 1 is a bottle body, the closing member 2 is a lid body, and the closing member 2 is screwed on one side of an opening 12 provided in the receiving chamber 1. In this embodiment, the cover body is a built-in four-pipe, double-layer permeable type, which can isolate external bacteria. The cover body is of a double-layer hollow structure, and can also supplement air pressure in the bottle body and exchange outside air. The cover body completes the closing of the material supplementing device in a screwing mode. In other embodiments, the cover may be connected to the bottle body by means of a latch, a bolt and a nut. The bottle body is connected to the cap body in a screwing manner by means of a thread on the opening 12 of the bottle mouth and further connects the two parts of the conducting element 3. The cover body is matched with the air pressure adjusting device 4, so that the exchange use of the air in the material supplementing device and the external air is realized.

As shown in fig. 1, 2 and 6, in this embodiment, the cover body is a hollow sandwich structure, the middle is a conducting member 3 with 4 channels, the outer layer is a cover body, and the lower part is a baffle 8 which closes the cover body and is matched with the accommodating cavity 1. The lead-through member comprises a first part and a second part, the first part is arranged in the accommodating cavity, the second part is arranged in the closing member, and the first part and the second part are detachably connected. As shown in fig. 1 and 3, the inlet end 31 of the conducting member 3 passes through the accommodating cavity 1 through the opening 12 and then passes through the closing member 2 to form an outlet end 32 of the conducting member. The conducting piece 3 penetrates out of the sealing piece 2 to be communicated with the outside, the conducting piece 3 is located in the center of the sealing piece 2, and when the sealing piece 2 is installed on the accommodating cavity 1, the conducting piece 3 can be installed on the accommodating cavity 1 together. In the present embodiment, the sealing material 2 is a lid body, and the sealing material 2 is provided with a port through which the communication material 3 communicates. The inlet ends 31 of the conducting pieces 3 are provided with a plurality of inlet ends 31, a plurality of outlet ends 32 of the conducting pieces are formed outside the sealing piece 2 by the plurality of inlet ends 31, and the outlet ends 32 of the conducting pieces further form a unified liquid guide channel 7 by the five-way joint 9. The plurality of access ends 31 of the conducting piece 3 located in each first chamber 11 are finally integrated outside the accommodating cavity 1, so that the number of ports for connecting the feeding device and the outside is reduced, and the experiment is convenient. Access end 31 extends along a direction that first chamber 11 is far away from opening 12, and access end 31 is close to the chamber bottom of first chamber 11, so that conducting member 3 can conduct more feed liquid in first chamber 11. The outlet end 32 is connected to the external bioreactor through a thermoplastic pipe 33.

In the present embodiment, a four-channel-in-one thermoplastic pipeline system is adopted for the bottle outer part of the lead-through 3, and a part of the silicone hose 34 inside the accommodating cavity is connected with the closing part 2 through a silicone hose port 8a protruding from the closing part 2. The output end of the five-way joint 9 is communicated with a thermoplastic pipe 33, and the thermoplastic pipe 33 conducts the first chamber 11 and the bioreactor through the five-way joint 9. In this embodiment, the specifications of the inner diameters of the thermoplastic tube 33, the five-way joint 9, the silicone tube 34, the tube provided in the cap, and the tube provided in the bottle are not specified.

The air pressure adjusting device 4 can be externally connected with a syringe, and the syringe interface 41 is communicated with the second chamber 22. The air pressure adjusting device 4 is connected with an injector, so that the operation is convenient. The gas exchange channel region where the syringe and the second chamber 22 are connected is provided with a first air filter 61. The first air filter film 61 can realize the hydrophobic and bacteria-isolating effects, and simultaneously avoid the liquid in the accommodating cavity 1 from overflowing. In the embodiment, the closing element 2 is provided with a gas exchange channel 21, and the syringe interface 41 completes the backflow of the liquid in the conducting element 3 through the pumping of the inserted syringe.

As shown in fig. 1 and fig. 2, the feeding device further comprises a water stop member 5, and the water stop member 5 is arranged at the connection end 32 of the conduction member 3. The water stop piece 5 can seal the connection outlet 32 of the conduction piece 3, and meanwhile, a peristaltic pump is used for pumping the corresponding feed liquid of the pipeline which is not clamped by the water stop piece 5. According to the needs, the pipeline of the conduction piece 3 without the water stop piece 5 can independently conduct the required feed liquid in the cavity. In the embodiment, the water stop 5 is a water stopper.

As shown in fig. 1 and 6, a baffle 8 is arranged between the closing element 2 and the accommodating cavity 1, the lower surface of the baffle 8 is arranged towards the opening 12 and covers the opening 12 after the feeding device is installed, the conducting element 3 penetrates through the baffle 8 and then extends out of the opening 12, and a silicone hose port 8a is formed at the part of the conducting element 3, which penetrates through the baffle 8. The first part of the port of the lead through 3 is arranged on the flap 14. The blocking plate 14 is fixed in the middle of the opening 12, and can position the first part of the conducting member 3 to avoid the position of the conducting member 3 relative to the opening 12 from changing. The baffle plate 14 and the baffle plate 8 are mutually compressed after the cover body and the bottle body of the feeding device are closed, the first part and the second part of the conducting piece are hermetically communicated, and the conducting piece 3 is communicated with the first cavity through a silica gel hose 34 fixed on the baffle plate 14. While baffle 8 prevents spillage of the feed liquid in chamber 1 and mixing of the feed liquids in the inadvertent pouring of chamber 1. Baffle 8's material is the elastic material, and elastic material self can warp, and baffle 8 can realize the airtight combination of bottle and lid through elastic deformation, avoids holding the interior liquid of chamber 1 and spills over.

As shown in fig. 4 and 5, the second chamber 22 is a cavity portion formed between the cover body and the baffle 8 and surrounding the outside of the lead-through member 3. The air pressure adjusting device 4 is communicated with the second chamber 22 and is communicated with the first chambers 11 through the part air holes 8b in fig. 6, and the supplied air can enter the corresponding first chambers 11 through the air holes 8b in the baffle plate 8, so that the communication between the second chamber 22 and the first chambers 11 is realized.

The hydrophobic air filter 6 includes a first air filter 61 at the position of the gas exchange passage 21 and a second air filter 62 at the position of the air hole 8 b. The position of the air hole 8b on the baffle 8 is provided with a second hydrophobic air filter membrane 62, the second air filter membrane 62 can realize the effects of hydrophobicity and microorganism isolation, and meanwhile, the liquid in the accommodating cavity 1 is prevented from overflowing. The material and membrane area of the second air filtration membrane 62 are not required, as long as the effects of water repellency, bacteria isolation and ventilation can be satisfied.

The working process is as follows: taking out the material supplementing device, preparing four sterile supplementary solutions of first material supplementing, second material supplementing, glucose, defoaming agent and the like, placing the material supplementing device in the biological safety cabinet, removing the outer package of the material supplementing device after being sterilized by using rays, and placing the material supplementing device in the biological safety cabinet. According to the volume requirements of the four kinds of liquid supplementing, the four kinds of liquid supplementing are respectively placed in a groove with corresponding volume by using a liquid transfer device, and the accommodating cavity 1 and the closing piece 2 are connected. The entire feeding device was removed from the safety cabinet and then connected to a 3L bioreactor via thermoplastic tubing 33 using a tube connector, the feeding device was snapped into the bioreactor's own peristaltic pump. And (3) placing the material supplementing device on the electronic scale, opening a water stop clamp of a pipeline where the first material supplementing device is located, starting the peristaltic pump, and supplementing a proper material liquid. And (5) after finishing the feeding, inserting a 50mL syringe into the syringe interface 41 at the upper part of the bottle cap, and pumping the syringe to finish the backflow of the material liquid. Similarly, the water stop clamp of the pipeline where different feed liquids are placed is opened and closed, so that the feed liquids are added. The feeding device can provide supplement of various feed liquids by only one container, and the mode that 2 aseptic tube connectors are usually needed to be connected is changed into the mode that 4 pipelines are connected by only closing one feeding container. Has the characteristics of simple and convenient use and easy operation.

Although the embodiments of the present invention have been described above, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A feed supplement device, characterized in that the feed supplement device comprises:

the device comprises an accommodating cavity, a first sealing ring and a second sealing ring, wherein a plurality of mutually partitioned first cavities are formed in the accommodating cavity, and each first cavity is provided with an opening on the upper surface of the accommodating cavity;

the plurality of access ends of the conducting piece are respectively communicated with the first chambers;

2. The feeding device as claimed in claim 1, wherein a plurality of the inlets of the conducting member pass through the corresponding openings and out of the accommodating cavity, and then pass through the closing member to form a plurality of outlets.

3. The feeding device of claim 2, wherein said lead-through member comprises a first portion and a second portion, said first portion being disposed within said containment chamber and said second portion being disposed within said closure member, said first portion and said second portion being removably connected.

4. A feeding device as set forth in claim 2, comprising at least one water stop member provided at said outlet end of said conducting member.

5. The feeding device as claimed in claim 2, wherein said gas pressure regulating device is a gas exchange channel for use with a syringe, a nozzle of said syringe communicates with said second chamber through said gas exchange channel, and a plunger of said syringe is disposed outside said closure.

6. The feeding device of claim 1, wherein said air pressure adjusting device comprises a first air filter membrane in the area of the gas exchange channel connected to said second chamber.

7. The feeding device as claimed in claim 1, wherein the plurality of outlet ends of the conducting member form a unified liquid guiding channel outside the second chamber.

8. The feeding device as claimed in claim 2, wherein said holding chamber is a bottle, said closure is a cap, and said closure is screwed on one side of said opening of said holding chamber.

9. The feeding device as claimed in claim 8, wherein the closing member is provided with a baffle integrated with the conducting member in a direction towards the accommodating chamber, the baffle closes the opening, the conducting member penetrates through the baffle, the accommodating chamber is provided with a baffle at the opening of the first part of the conducting member, and the upper part of the access end of the conducting member is fixedly connected to the baffle and forms a channel.

10. The feeding device as claimed in claim 9, wherein the baffle plate and the blocking piece are made of elastic members.

11. The feeding device of claim 1, wherein said access port is located at the bottom of the corresponding first chamber.