Novel fixed bed bioreactor
By designing components such as supports, film rolls, stirring rotors, and filters in the fixed-bed reactor, the problems of complex operation and poor process scale-up in small-scale applications have been solved, achieving efficient biological culture and high product yield, simplifying the operation process, and improving the ease of use of the equipment.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- TONGTENG INNOVATION (SUZHOU) CO LTD
- Filing Date
- 2025-04-30
- Publication Date
- 2026-04-10
AI Technical Summary
Existing fixed-bed reactors are complex to operate in small-scale applications and have poor compatibility with reactor process scale-up. They ignore the advantages of three-dimensional culture mode in small-scale applications, resulting in complex equipment structure, inconvenient operation, and difficulty in fully utilizing the advantages of high specific area culture.
The design incorporates a support frame at the bottom of the tank, a built-in membrane and stirring rotor, a side filter, and a bottom stirring unit to achieve efficient biological culture and filtration separation. The stirring rotor ensures uniform mixing of the culture medium, the filter facilitates the removal of metabolic waste, and the stirring unit provides stable power. The overall structure is compact and reasonable.
It improves the efficiency and quality of biological culture, simplifies the operation process, enhances the stability and product yield of biological culture, and facilitates maintenance and upkeep, making full use of the advantages of the three-dimensional culture system.
Smart Images
Figure CN224105807U_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of bioreactor, in particular to a novel fixed bed bioreactor. BACKGROUND
[0002] At present, cell culture and product preparation in the field of biotechnology are mainly applied to the traditional two-dimensional culture system with culture bottles, culture dishes and cell factories in small scale. However, with the expansion of production demand from small-scale process development to industrial scale, the three-dimensional culture system production platform based on bioreactor plays an important role. The fixed bed reactor filled with solid carrier material inside the reactor changes the preparation method of cell culture, antibody, exosome and virus vector. Compared with the traditional bioreactor, the fixed bed bioreactor carrier can capture and immobilize cells, and the stirring device only drives the medium to infiltrate the carrier without direct contact with the cells on the carrier, avoiding the cell shear force damage caused by stirring in the experiment.
[0003] At present, the fixed bed reactor is mainly considered for large-scale preparation, and various real-time sensors are equipped in the equipment. The structure is usually very complex and the operation is more troublesome. Moreover, the equipment has strict space and environmental cleanliness requirements. After small-scale process development, the process amplification of the reactor is also poor. These usage restrictions exist widely in the use of fixed bed reactors, and the current research and use of fixed bed reactors only consider the large-scale application method and problem, obviously ignoring the high specific area culture advantage of the three-dimensional culture mode itself which can also play an advantage in small scale. SUMMARY
[0004] In order to improve the complex structure of the existing fixed bed reactor and the problem of complex operation in small-scale application, the present application provides a novel fixed bed bioreactor.
[0005] The novel fixed bed bioreactor provided by the present application adopts the following technical scheme:
[0006] A novel fixed bed bioreactor, comprising a tank body, an end cover is arranged at the top end of the tank body, a culture assembly is arranged in the tank body, the culture assembly comprises a support, the support is installed at the bottom of the tank body, a film winding is arranged in the support, and a stirring rotor is arranged in the support below the film winding; a plurality of filters communicating with the inside of the tank body are arranged on the side of the tank body, and a stirring main machine for driving the stirring rotor is arranged below the tank body.
[0007] By adopting the technical scheme, the bracket is installed at the bottom of the tank body, the built-in film is combined with the stirring rotor, the side filter and the bottom stirring main machine are designed, efficient biological culture and filtration separation can be realized, the film provides sufficient biological attachment area, the stirring rotor ensures uniform mixing of the culture solution and promotes mass transfer, the filter facilitates discharge of metabolic waste and replacement of the culture solution, and the stirring main machine provides stable power, the overall structure design is compact and reasonable, and the efficiency and quality of biological culture are effectively improved, and operation and maintenance are facilitated.
[0008] Optionally, the bracket comprises a base, a shell, a supporting plate and a cover plate, the base is provided with a sink, the shell is fixedly connected in the sink, the shell comprises a stirring cavity and a culture chamber inside, the stirring rotor is arranged in the stirring cavity, the film is arranged in the culture chamber, a limiting ring is arranged on the inner wall of the shell at the intersection of the stirring cavity and the culture chamber, the supporting plate is embedded in the shell and is pressed on the limiting ring, the film is arranged on the supporting plate, and the cover plate is embedded in the shell and is located above the film.
[0009] By adopting the technical scheme, the bracket adopts the combined structure of the base, the shell, the supporting plate and the cover plate, the fixed connection of the base sink and the shell enhances the stability of the bracket, the partition design of the stirring cavity and the culture chamber ensures that the stirring of the culture solution in the stirring cavity does not interfere with the biological culture on the film in the culture chamber, and the cooperation of the cover plate and the supporting plate ensures that the film is stably installed and provides a good attachment space for the biological, and the cover plate protects the film. This structure design not only realizes effective separation of the stirring and mixing and biological culture functions, but also ensures the structural reliability of the culture assembly, which is conducive to improving the orderliness of the biological culture process and the culture effect.
[0010] Optionally, a plurality of through holes are formed in the base, the supporting plate and the cover plate.
[0011] By adopting the technical scheme, the plurality of through holes formed in the base, the supporting plate and the cover plate can effectively promote the circulation of the culture solution between the parts of the bracket, so that the culture solution in the stirring cavity can smoothly enter the culture chamber, ensure that the biological on the film can fully contact the nutrients and oxygen, improve the material exchange efficiency, facilitate timely discharge of metabolic products, maintain the stability of the culture environment, ensure efficient biological culture, and reduce the overall weight of the bracket to some extent, facilitating installation and disassembly.
[0012] Optionally, a plurality of supporting columns are fixedly connected to the bottom of the base, and a plurality of limiting holes corresponding to the supporting columns are formed in the bottom of the tank body.
[0013] By adopting the technical scheme, the support column arranged below the base cooperates with the limiting hole at the bottom of the tank body, which can accurately position the position of the support in the tank body, ensure the accuracy of the installation of the culture assembly, make the stirring rotor, the membrane rolling part and other parts in the suitable working position, on the other hand, after the support column is inserted into the limiting hole, the stability of the connection between the support and the tank body can be enhanced, the shaking and displacement of the support when the stirring main machine drives the stirring rotor to work can be avoided, the smooth and orderly biological culture process can be ensured, and the adverse effects of unstable parts on the biological culture effect can be reduced.
[0014] Optionally, the height dimension of the support column is greater than the depth dimension of the limiting hole, so that a gap is formed between the base and the bottom of the tank body.
[0015] By adopting the technical scheme, the direct contact between the base and the bottom of the tank body is effectively avoided, the flow of the culture solution is prevented from being hindered by the base, the smooth circulation of the culture solution at the bottom of the tank body is ensured, and the overall mass transfer efficiency is improved; the existence of the gap also facilitates the discharge of residual culture solution, metabolic waste and the like, avoids the accumulation of the residual culture solution, metabolic waste and the like between the base and the bottom of the tank body, and reduces the pollution risk; meanwhile, the gap provides a certain activity buffer space for the support column, which is helpful to absorb the vibration generated in the stirring process, further enhances the stability of the support after installation, and creates a better environment for biological culture
[0016] Optionally, a sampling port is arranged through the end cover, and the sampling port is connected with a sampling tube.
[0017] By adopting the technical scheme, during the culture process, the researcher does not need to open the end cover, but can directly extract the culture solution sample in the tank body through the sampling tube, the risk of pollution caused by the entry of external microorganisms into the tank body is reduced, the information such as the biological growth state, the nutrient component concentration, the metabolic product accumulation and the like in the culture solution can be obtained in real time, the culture conditions can be adjusted in time, the culture process can be optimized, the success rate and the quality of biological culture are improved, and the culture process is more scientific and controllable.
[0018] Optionally, the filter is a butterfly filter.
[0019] By adopting the technical scheme, the butterfly structure of the butterfly filter can provide a larger filtering area, compared with a general filter, the air inside and outside the tank body can be exchanged more efficiently; the butterfly design makes the operation of the filter during installation and disassembly more convenient, facilitates the quick replacement of the filtering part, and maintains the continuous and stable operation of the bioreactor; meanwhile, the connection mode of the butterfly filter and the side edge of the tank body is compact, saves space, and has smaller resistance when fluid passes through, which can guarantee the smooth circulation of the gas inside and outside the tank body, and is helpful to optimize the material exchange and environmental control in the biological culture process.
[0020] In summary, the present application has at least one of the following beneficial technical effects:
[0021] 1. By installing a bracket at the bottom of the tank, embedding a membrane and a stirring rotor, combining a side filter and a bottom stirring host design, efficient biological culture and filtration separation can be achieved. The membrane provides sufficient biological attachment area, the stirring rotor ensures uniform mixing of the culture medium and promotes mass transfer, the filter facilitates the discharge of metabolic waste and the replacement of the culture medium, and the stirring host provides stable power. The overall structure design is compact and reasonable, fully utilizes the advantages of three-dimensional culture system, and obtains more high-yield biological products, while facilitating operation and maintenance.
[0022] 2. The partition design of the stirring cavity and the culture chamber ensures that the stirring rotor fully mixes the culture medium in the stirring cavity without disturbing the biological membrane in the culture chamber, ensuring the stability of the culture environment. BRIEF DESCRIPTION OF DRAWINGS
[0023] Fig. 1 is a structural schematic diagram of the fixed bed bioreactor of the present application.
[0024] Fig. 2 is an exploded view of the fixed bed bioreactor of the present application.
[0025] Fig. 3 is a sectional view of the fixed bed bioreactor of the present application.
[0026] Fig. 4 is a sectional view of the culture assembly of the present application.
[0027] Reference signs: 1, tank; 11, limiting hole; 2, end cover; 21, sampling port; 3, culture assembly; 31, bracket; 311, base; 3111, sink; 3112, support column; 312, shell; 3121, stirring cavity; 3122, culture chamber; 3123, limiting ring; 313, supporting plate; 314, cover plate; 315, through hole; 32, membrane; 33, stirring rotor; 4, filter; 5, stirring host; 6, sampling tube. DETAILED DESCRIPTION
[0028] The embodiments of the present application will be described in detail below, and examples of the embodiments are shown in the accompanying drawings.
[0029] In the description of the present application, the description of the terms "certain embodiments", "one embodiment", "some embodiments", "illustrative embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in connection with the described embodiments or examples are included in at least one embodiment or example of the present application. In the present description, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.
[0030] The embodiment of the application discloses a novel fixed bed bioreactor, referring to Figs. 1 to 4 , comprising a tank body 1, an end cover 2, a culture assembly 3, a filter 4 and a stirring main machine 5, the end cover 2 is buckled at the top opening of the tank body 1, the culture assembly 3 is fixedly connected at the bottom of the tank body 1, the culture assembly 3 comprises a bracket 31 installed at the bottom of the tank body 1, the bracket 31 is a hollow structure, a membrane roll 32 is installed in the bracket 31, a stirring rotor 33 is installed in the bracket 31 and below the membrane roll 32, and the stirring rotor 33 is a magnetic rotor; the filters 4 are symmetrically installed at the two sides of the tank body 1 and communicated with the inside of the tank body 1, the filters 4 are used for guaranteeing smooth circulation of gas inside and outside the tank body 1 and helping to optimize material exchange and environmental control in the biological culture process; the tank body 1 is placed on the stirring main machine 5, the stirring main machine 5 is used for driving the stirring rotor 33, and the stirring main machine 5 is a magnetic stirrer.
[0031] The bracket 31 comprises a base 311, an outer shell 312, a supporting plate 313 and a cover plate 314, the upper side of the base 311 is provided with a sink 3111, the outer shell 312 is a hollow cylindrical structure, the outer shell 312 is fixedly connected in the sink 3111, the inside of the outer shell 312 comprises a stirring cavity 3121 and a culture chamber 3122, the inner diameter size of the stirring cavity 3121 is greater than that of the culture chamber 3122, the stirring rotor 33 is arranged in the stirring cavity 3121, and the membrane roll 32 is arranged in the culture chamber 3122; the inner wall of the outer shell 312 is inwardly protruded at the intersection of the stirring cavity 3121 and the culture chamber 3122 to form a limiting ring 3123, the supporting plate 313 is embedded in the outer shell 312 and is press-connected on the limiting ring 3123, the membrane roll 32 is placed on the supporting plate 313, and the cover plate 314 is embedded in the outer shell 312 and above the membrane roll 32.
[0032] A plurality of through holes 315 are formed in the base 311, the supporting plate 313 and the cover plate 314, so as to promote the flow of the culture solution between the parts of the bracket 31.
[0033] A plurality of support columns 3112 are fixedly connected to the lower side of the base 311 and are uniformly distributed in the circumferential direction, and a plurality of limiting holes 11 corresponding to the support columns 3112 are formed in the bottom of the tank body 1.
[0034] The height size of the support column 3112 is greater than the depth size of the limiting hole 11, so that a gap is formed between the base 311 and the bottom of the tank body 1.
[0035] A sampling port 21 is formed through the end cover 2, the sampling port 21 is connected with a sampling pipe 6, the sampling pipe 6 is a sterile silica gel hose, and the sampling pipe 6 is closed by a clamp jaw.
[0036] The pipeline connected with the filter 4 is arranged obliquely upward, the filter 4 is a butterfly-shaped filter 4, the butterfly-shaped structure of the butterfly-shaped filter 4 can provide a larger filtering area, and the air inside and outside the tank body 1 can be exchanged more efficiently, which is helpful for optimizing the material exchange and environmental control in the biological culture process.
[0037] The stirring main machine 5 can be used to control and adjust the rotating speed in real time, and the stirring main machine 5 can be divided into a single control type for controlling one reactor tank body 1 and a multiple control type for controlling multiple reactor tank bodies 1.
[0038] The implementation principle of the novel fixed-bed bioreactor in the embodiment of the application is as follows: in use, the tank body 1 is sterilized by high-pressure steam, the coiled membrane 32 has a spiral winding structure and is arranged in the support 31, the support 31 is installed at the central position of the bottom of the tank body 1, the filter 4 is installed on the pipeline on the two sides of the tank body 1, and the end cover 2 is buckled on the top end of the tank body 1; the tank body 1 is placed in a rotating machine, and the reactor tank body 1 and the stirring main machine 5 are placed in a carbon dioxide incubator for operation.
[0039] In the biological culture, the culture solution is allowed to flow through the coiled membrane 32, the culture assembly 3 is exposed to air in the form of a waterfall flow falling film by rotating the stirring rotor 33 driven by the stirring main machine 5, and the rotating speed of the stirring main machine 5 can be controlled and adjusted in real time to change the circulation speed of the culture solution in the tank body 1.
[0040] The fixed-bed bioreactor has a simple structure, is easy to operate, has a wide application range, fully utilizes the advantages of the three-dimensional culture system, and can obtain more high-yield biological products.
[0041] Although the embodiments of the application have been shown and described above, it should be understood that the above embodiments are exemplary and cannot be understood as limiting the application, and those skilled in the art can make changes, modifications, replacements and variations to the above embodiments within the scope of the application.
Claims
1. A novel fixed bed bioreactor comprising a tank body (1) provided with an end cap (2) at its top end, characterized in that, The culture assembly (3) is arranged in the tank body (1), the culture assembly (3) comprises a support (31), the support (31) is installed at the bottom of the tank body (1), a film roll (32) is arranged in the support (31), and a stirring rotor (33) is arranged in the support (31) and below the film roll (32); a plurality of filters (4) communicating with the inside of the tank body (1) are arranged on the side of the tank body (1), and a stirring main machine (5) for driving the stirring rotor (33) is arranged below the tank body (1).
2. The novel fixed bed bioreactor according to claim 1, characterized in that, The support (31) comprises a base (311), an outer shell (312), a supporting plate (313) and a cover plate (314), the base (311) is provided with a sink (3111), the outer shell (312) is fixedly connected in the sink (3111), the inner part of the outer shell (312) comprises a stirring cavity (3121) and a culture chamber (3122), the stirring rotor (33) is arranged in the stirring cavity (3121), the film roll (32) is arranged in the culture chamber (3122), a limiting ring (3123) is arranged on the inner wall of the outer shell (312) at the intersection of the stirring cavity (3121) and the culture chamber (3122), the supporting plate (313) is embedded in the outer shell (312) and is pressed on the limiting ring (3123), the film roll (32) is arranged on the supporting plate (313), and the cover plate (314) is embedded in the outer shell (312) and above the film roll (32).
3. The novel fixed bed bioreactor according to claim 2, characterized in that, A plurality of through holes (315) are formed in the base (311), the supporting plate (313) and the cover plate (314).
4. The novel fixed bed bioreactor as claimed in claim 2, wherein, A plurality of supporting columns (3112) are fixedly connected below the base (311), and a plurality of limiting holes (11) corresponding to the supporting columns (3112) are formed in the bottom of the tank body (1).
5. The novel fixed bed bioreactor according to claim 4, characterized in that, The height of the supporting column (3112) is greater than the depth of the limiting hole (11), so that a gap is formed between the base (311) and the bottom of the tank body (1).
6. The novel fixed bed bioreactor as claimed in claim 1, wherein, A sampling port (21) is arranged through the end cover (2), and a sampling pipe (6) is connected to the sampling port (21).
7. The novel fixed bed bioreactor as claimed in claim 1, wherein, The filter (4) is a butterfly filter (4).