CN107201301B - Multistage shaking type bioreactor - Google Patents

Multistage shaking type bioreactor Download PDF

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Publication number
CN107201301B
CN107201301B CN201710330464.2A CN201710330464A CN107201301B CN 107201301 B CN107201301 B CN 107201301B CN 201710330464 A CN201710330464 A CN 201710330464A CN 107201301 B CN107201301 B CN 107201301B
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shaking
flat plate
multistage
cylinder
sleeve
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CN107201301A (en
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张玮
张孝杨
陈冰冰
项敬来
郑三龙
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Zhejiang University of Technology ZJUT
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Zhejiang University of Technology ZJUT
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/14—Bags
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/28—Constructional details, e.g. recesses, hinges disposable or single use
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/48—Holding appliances; Racks; Supports
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
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  • Sustainable Development (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Clinical Laboratory Science (AREA)
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  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The multistage shaking type bioreactor comprises a multistage shaking type platform for supporting a disposable biological reaction bag, a stepped annular perturber for increasing the turbulence degree of culture solution at the bottom layer of a supporting area of a fixed plate, a driving device for providing driving force and a controller for the driving device, wherein the multistage shaking type platform is fixedly connected with the stepped annular perturber, the driving device is arranged at the multistage shaking type platform, and the control end of the driving device is electrically connected with corresponding pins of the controller; the multistage shaking type platform comprises a polygonal flat plate and a shaking flat plate; the stepped annular perturbator comprises a plurality of coaxially sleeved sleeves and a plurality of multi-stage telescopic cylinders, wherein adjacent sleeves are arranged in a sliding manner to form an annular shape, and the lengths of the sleeves are gradually reduced from inside to outside; the driving device comprises a driving cylinder, a reversing valve and an intermediate relay for controlling the reversing valve to work. The beneficial effects of the invention are as follows: the culture solution bottom layer has large turbulence degree and high gas mass transfer efficiency, and can be amplified to improve the production capacity of the platform.

Description

Multistage shaking type bioreactor
Technical Field
The invention relates to a multistage shaking bioreactor.
Background
Biotechnology, which is an emerging technology, has now demonstrated tremendous economic and social values, and has evolved to the current major fields including genetic engineering, fermentation engineering, cellular engineering, enzyme engineering, protein engineering, etc. These engineering techniques will involve cell metabolism and cell culture, both from technical research to final scale production. The study of bioreactors, which are key devices involved in cell culture, has become one of the important core technologies in biotechnology.
With the development of bioreactor technology, especially disposable technology, disposable bioreactors have been widely used for seed expansion culture, culture of mammalian cells, plant cells and insect cells down to pilot scale, production of monoclonal antibodies, vaccines and recombinant proteins, etc., and gradually expanded to the fields of microbial fermentation, algal culture, etc. The greatest commercial use is for seed expansion culture and for antibody, vaccine, etc. production by cultured mammalian cells.
Among the current types of disposable bioreactors, the wave-mixed type disposable bioreactor was first proposed. The primary component of the wave mixing disposable bioreactor is a sterilized disposable bioreactor bag with the cell bag resting on a shaking platform, the shaking of the platform causing the culture medium to generate waves which provide adequate mixing and oxygen transfer to the culture. Such single-support, integrally swing bioreactors are deficient in terms of wave-making morphology and adjustability and are difficult to provide high quality gas mass transfer processes.
In a shaking platform patent for a bioreactor, the defect of a sit-up type shaking platform is analyzed, and a single-pole shaking platform is provided, so that the wave making capacity of the bioreactor and the adjustable performance of the platform are effectively improved.
However, when the above-mentioned shaking platform faces larger-volume production applications, it is difficult to provide higher-quality wave-making capability, the turbulence degree of the culture solution bottom layer of the supporting area of the fixing plate is small, and the gas mass transfer efficiency is low, which affects the applicability of the platform in a wider application range and limits the scalability of the platform production capability.
Disclosure of Invention
Aiming at the problems that when the existing shaking type platform faces to the production application with larger volume, the wave making capability with higher quality is difficult to provide, the turbulence degree of the culture solution bottom layer in the supporting area of the fixed plate is small, and the gas mass transfer efficiency is low, the invention provides a multistage shaking type bioreactor with large turbulence degree of the culture solution bottom layer and high gas mass transfer efficiency.
The invention relates to a multistage shaking bioreactor, which is characterized in that: the device comprises a multistage shaking platform for supporting a disposable biological reaction bag, a stepped annular perturber for increasing the turbulence degree of culture solution at the bottom layer of a supporting area of a fixed plate, a driving device for providing driving force and a controller for the driving device, wherein the multistage shaking platform is fixedly connected with the stepped annular perturber, the driving device is arranged at the multistage shaking platform, and the control end of the driving device is electrically connected with a corresponding pin of the controller;
the multistage shaking type platform comprises a polygonal flat plate and a shaking flat plate, wherein the number of edges of the polygonal flat plate is even, and a through hole for the stepped annular perturber to pass through is formed in the center of the polygonal flat plate; each side of the polygonal flat plate is correspondingly hinged with one shaking flat plate, wherein two shaking flat plates are in one group, and at least two groups of shaking platforms move simultaneously;
the stepped annular perturbator comprises a plurality of coaxially sleeved sleeves and a multi-stage telescopic cylinder, wherein adjacent sleeves are arranged in a sliding connection manner to form an annular shape, and the length of each sleeve is gradually reduced from inside to outside; except the sleeve at the center, the end surfaces of the bottoms of the other sleeves are provided with blocking plates, the blocking plates are provided with central through holes for the telescopic rods of the multistage telescopic cylinders to pass through, and the apertures of the central through holes of the blocking plates corresponding to the sleeves from inside to outside are gradually increased; the number of expansion stages of the expansion rods of the multistage expansion cylinder is consistent with the number of sleeves, the outermost sleeve corresponds to a first-stage rod body of the expansion rod of the multistage expansion cylinder, the secondary outer sleeve corresponds to a second-stage rod body of the multistage expansion cylinder, and the like, the sleeve positioned at the center corresponds to the highest-stage rod body of the multistage expansion cylinder, the outer end of the highest-stage rod body of the expansion rod of the multistage expansion cylinder is fixedly connected with the bottom of the sleeve positioned at the center, the central through hole aperture of the outermost sleeve is between the outer diameter of the first-stage rod body and the outer diameter of the second-stage rod body, the central through hole aperture of the secondary outer sleeve is between the outer diameter of the second-stage rod body and the outer diameter of the third-stage rod body, and the like; the sleeve stretches along with the multistage telescopic cylinder to form a step which can penetrate out of the polygonal flat plate through hole; the control end of the multistage telescopic cylinder is electrically connected with a corresponding control pin of the controller;
the driving device comprises a plurality of driving cylinders for driving the shaking flat plates, a plurality of reversing valves for controlling the movement directions of the driving cylinders and an intermediate relay for controlling the reversing valves to work, one driving cylinder corresponds to one shaking flat plate, the bottom of the driving cylinder is hinged with the polygonal flat plate, and a telescopic rod of the driving cylinder is hinged with the bottom of the corresponding shaking flat plate, so that the shaking flat plate swings up and down with the surface of the polygonal flat plate as a boundary; the driving cylinders are in one-to-one correspondence with the reversing valves, the air inlets and the air outlets of the driving cylinders are respectively communicated with corresponding passages of the reversing valves, and the control ends of the reversing valves are electrically connected with corresponding control ends of the controller through intermediate relays, so that reversing of the driving cylinders is realized.
The reversing valves are three-position five-way reversing valves, and each reversing valve is provided with an intermediate relay for controlling alternating energization of an A coil and a B coil of the reversing valve.
One end of the shaking flat plate is consistent with the edge of the polygonal flat plate, the other end of the shaking flat plate is a semicircular plate, the included angle between the upper limit position of the shaking flat plate, which swings upwards, and the polygonal flat plate is 60 degrees, and the included angle between the lower limit position of the shaking flat plate, which swings downwards, and the polygonal flat plate is 30 degrees.
The stepped annular perturbator is a fourth-order annular member, namely the stepped annular perturbator comprises 4 sleeves, the multistage telescopic cylinder is a fourth-stage telescopic cylinder, and a mounting part for fixedly connecting with a fourth-stage rod body of the fourth-stage telescopic cylinder is arranged at the bottom of the sleeve positioned at the center.
The sleeve is a hollow sleeve, and the upper part and the lower part of the sleeve are sealed.
Two rocking plates of the same group are in opposite, adjacent or spaced positions, and the rocking plates of the same group rock upward or downward simultaneously.
The swinging flat plate is driven by the air cylinder to swing at a certain angle, and the swinging angle and frequency can be adaptively adjusted. The stepped annular perturbator is connected with the stepped annular bottom of the disposable bioreactor bag. The movement of each step of the step type annular perturbator drives the step type annular bottom of the disposable biological reaction bag to move, and different movement modes of each step of the step type annular perturbator can cause different turbulence effects in the supporting area of the fixing plate of the disposable biological reaction bag. The stepped annular perturbator is generally designed into four steps, the height of each step is adjustable within a certain range, each step is supported and driven by one cylinder, and the movement of each step of the annular perturbator is realized by the lifting of the cylinder. The swinging of the swinging plate, the movement of each step of the stepped annular perturber and the like are completed by the air cylinder. The change of the angle and frequency of the swing plate needs to adjust the lift of the cylinder and the speed of intake and exhaust. The controller can adaptively control the number of the movable air cylinders according to requirements, and adaptively adjust the lift and the air inlet and outlet speeds of the air cylinders.
The beneficial effects of the invention are as follows: the swinging flat plate is driven by the air cylinder to swing at a certain angle, and the swinging angle and frequency can be adaptively adjusted; the method provides a plurality of shaking states, and enables the turbulence degree of the bottom culture solution to be large through the stepped annular perturbator, so that the method has higher quality wave making capacity when facing larger volume production application, and the culture solution bottom turbulence degree of the central fixed plate supporting area is large, the gas mass transfer efficiency is high, the applicability of a wider application range of a platform is improved, and the scalability of the platform production capacity is improved.
Drawings
FIG. 1 is a two-stage rocking platform of the present invention;
FIG. 2 is a three-level rocking platform of the present invention;
FIG. 3 is a front view of a two-stage shake table;
FIG. 4 is a diagram of an annular perturbator configuration;
FIG. 5 is a diagram of the action of an annular perturbator;
FIG. 6 is a control loop diagram of a single drive cylinder;
FIG. 7 is a schematic diagram of an embodiment of a two-stage rocking bioreactor
Fig. 8 is a schematic diagram of a multicomponent dynamic gas distribution system.
Detailed Description
The invention will be further described with reference to the accompanying drawings
Referring to the drawings:
embodiment 1 the multistage shaking bioreactor comprises a multistage shaking platform 1 for supporting a disposable bioreactor bag, a stepped annular perturber 2 for increasing the turbulence degree of culture solution at the bottom layer of a supporting area of a fixed plate, a driving device for providing driving force and a controller for the driving device, wherein the multistage shaking platform 1 is fixedly connected with the stepped annular perturber 2, the driving device is arranged at the multistage shaking platform 1, and the control end of the driving device is electrically connected with a corresponding pin of the controller;
the multistage shaking type platform 1 comprises a polygonal flat plate 11 and a shaking flat plate 12, wherein the number of edges of the polygonal flat plate 11 is even, and a through hole for a stepped annular perturber to pass through is formed in the center of the polygonal flat plate 11; each side of the polygonal flat plate 11 is correspondingly hinged with one shaking flat plate 12, wherein two shaking flat plates 12 are in one group, and at least two groups of shaking flat plates 12 move simultaneously;
the stepped annular perturbator 2 comprises 4 coaxially sleeved sleeves 21 and multistage telescopic cylinders 22, wherein adjacent sleeves 21 are arranged in a sliding connection mode to form an annular shape, and the lengths of the sleeves 21 are reduced gradually from inside to outside; except the sleeve at the center, the end surfaces of the bottoms of the other sleeves are provided with blocking plates 23, the blocking plates 23 are provided with central through holes for the telescopic rods of the multistage telescopic cylinders 22 to pass through, and the diameters of the central through holes of the blocking plates corresponding to the sleeves from inside to outside are equal in equal difference and gradually increased; the number of expansion stages of the expansion rods of the four-stage telescopic cylinder is consistent with the number of sleeves, the outermost sleeve corresponds to a first-stage rod body of the expansion rod of the multi-stage telescopic cylinder, the secondary outer sleeve corresponds to a second-stage rod body of the multi-stage telescopic cylinder, and the like, the sleeve positioned at the center corresponds to a fourth-stage rod body of the four-stage telescopic cylinder, the outer end of the fourth-stage rod body of the expansion rod of the four-stage telescopic cylinder is fixedly connected with the bottom of the sleeve positioned at the center, the aperture of a central through hole of the outermost sleeve is between the outer diameter of the first-stage rod body and the outer diameter of the second-stage rod body, the aperture of a central through hole of the secondary outer sleeve is between the outer diameter of the second-stage rod body and the outer diameter of the third-stage rod body, and the like; the sleeve stretches along with the four-stage telescopic cylinder to form a step which can penetrate out of the polygonal flat plate through hole; the control end of the four-stage telescopic cylinder is electrically connected with a control pin corresponding to the controller; wherein, the rod body with the coarsest diameter of the four-stage telescopic cylinder is defined as a first-stage rod body, and the first-stage rod body 221, the second-stage rod body 222, the third-stage rod body 223 and the fourth-stage rod body 224 are sequentially arranged from bottom to top; the sleeve is defined as a first step 211, a second step 212, a third step 213 and a fourth step 214 in sequence from the inside to the outside;
the driving device comprises a plurality of driving air cylinders 3 for driving the shaking flat plates, a plurality of reversing valves 4 for controlling the movement directions of the driving air cylinders and an intermediate relay for controlling the reversing valves to work, one driving air cylinder corresponds to one shaking flat plate, the bottom of the driving air cylinder is hinged with the polygonal flat plate, and a telescopic rod of the driving air cylinder 3 is hinged with the bottom of the corresponding shaking flat plate 12, so that the shaking flat plate 12 swings up and down with the surface of the polygonal flat plate as a boundary; the driving cylinders are in one-to-one correspondence with the reversing valves 4, the air inlets 31 and the air outlets 32 of the driving cylinders 3 are respectively communicated with corresponding passages of the reversing valves, and control ends of the reversing valves 4 are electrically connected with corresponding control ends of the controller through intermediate relays, so that reversing of the driving cylinders is realized.
The reversing valves 4 are three-position five-way reversing valves, and each reversing valve is provided with an intermediate relay for controlling alternating energization of an A coil 41 and a B coil 42 of the reversing valve.
One end of the shaking flat plate is consistent with the edge of the polygonal flat plate, the other end of the shaking flat plate is a semicircular plate, the included angle between the upper limit position of the shaking flat plate, which swings upwards, and the polygonal flat plate is 60 degrees, and the included angle between the lower limit position of the shaking flat plate, which swings downwards, and the polygonal flat plate is 30 degrees.
The stepped annular perturbator is a fourth-order annular member, namely the stepped annular perturbator comprises 4 sleeves, the multistage telescopic cylinder is a fourth-stage telescopic cylinder, and a mounting part for fixedly connecting with a fourth-stage rod body of the fourth-stage telescopic cylinder is arranged at the bottom of the sleeve positioned at the center.
The sleeve is a hollow sleeve, and the upper part and the lower part of the sleeve are sealed.
Two rocking plates of the same group are in opposite, adjacent or spaced positions, and the rocking plates of the same group rock upward or downward simultaneously.
The swinging flat plate is driven by the air cylinder to swing at a certain angle, and the swinging angle and frequency can be adaptively adjusted. The stepped annular perturbator is connected with the stepped annular bottom of the disposable bioreactor bag. The movement of each step of the step type annular perturbator drives the step type annular bottom of the disposable biological reaction bag to move, and different movement modes of each step of the step type annular perturbator can cause different turbulence effects in the supporting area of the fixing plate of the disposable biological reaction bag. The stepped annular perturbator is generally designed into four steps, the height of each step is adjustable within a certain range, each step is supported and driven by one cylinder, and the movement of each step of the annular perturbator is realized by the lifting of the cylinder. The swinging of the swinging plate, the movement of each step of the stepped annular perturber and the like are completed by the air cylinder. The change of the angle and frequency of the swing plate needs to adjust the lift of the cylinder and the speed of intake and exhaust. The controller can adaptively control the number of the movable air cylinders according to requirements, and adaptively adjust the lift and the air inlet and outlet speeds of the air cylinders.
A two-stage rocking platform for supporting disposable bioreactor bags as shown in figure 2. The stepped annular perturbator is removed in figure three. The two-stage rocking platform consists of a stationary quadrilateral plate and two-stage rocking plates, opposite rocking plates 12 (a and a ', B and B') and each forming a set. As shown in fig. 3, the shaking flat plate is driven by the air cylinder to swing at a certain angle, the upper limit position of the shaking flat plate forms 60 degrees with the horizontal plane, the lower limit position of the shaking flat plate forms 30 degrees with the horizontal plane, and the shaking flat plate can swing within the range. Each shaking flat plate is driven by a single air cylinder, the lift of the air cylinder can be changed by changing the upper limit value of the air inflow of the air cylinder, and then the swinging angle of the shaking flat plates can be adjusted within the limit angle range; the frequency of air inlet and outlet of the cylinder is changed, so that the swinging frequency of the swinging plate can be changed.
A stepped annular perturbator for increasing the turbulence of the underlying culture fluid in the support area of the plate, as shown in fig. 4. The stepped annular perturbator is four-step, the structure of each step is shown in fig. 5, and the materials are selected from lighter polytetrafluoroethylene. The lower part of the annular perturbator is provided with a four-stage air cylinder, the annular stage can be in a state shown in fig. 5 under the pushing of the air cylinder, and when waves caused by two stages of shaking plates pass through the annular stage structure, the turbulence degree of the waves is increased, and the gas mass transfer efficiency is improved. The air inlet and outlet speeds of the air cylinders are adjustable, so that turbulence of culture fluid at the bottom layer of the supporting area of the fixed plate caused by the air cylinders can be diversified and qualified.
The control loop for a single cylinder is shown in fig. 6. The driving cylinder selects a double-acting cylinder, the reversing valve is a three-position five-way reversing valve, the two coils A, B are electrified, the valve core moves to the position I, the cylinder rises, the A is powered off, the B is electrified, and the cylinder falls. The coil A, B is controlled to be on-off through the intermediate relay, but the telescopic motion of the air cylinder is realized, the intermediate relay is connected with the controller, and the self-adaptive control of multiple air cylinders can be realized through the programmed design.
Fig. 7 shows an embodiment of a two-stage rocking bioreactor, wherein the controller is a PLC controller, and the PLC controller can be used for self-adaptive adjustment of a cylinder, control the temperature in a disposable bioreactor bag through a heating blanket, control the air supply of a multi-component dynamic air distribution system, control feeding, inoculation, adding defoamer, acid liquor and alkali liquor, collect parameters such as pH, DO concentration, ORP and temperature in the bioreactor bag, and complete the work of communication with an upper computer, data transmission and the like.
Taking fig. 8 as an example, the mixture is air, oxygen, and CO 2 And N 2 Wherein each gas is stored in corresponding steel cylinders, which are respectively an air steel cylinder, an oxygen steel cylinder and CO 2 Steel cylinder and N 2 Steel cylinders, the air outlet pipeline of each steel cylinder is connected with the air inlet of a corresponding rotameter, the air outlet of the rotameter is provided with a corresponding electromagnetic valve and an MFC (mass flow controller), wherein the air steel cylinder and the oxygen steel cylinder are led into a first mixer, and CO 2 Steel cylinder and N 2 The steel cylinders are converged into a second mixer, and finally the first mixer and the second mixer are converged into a third mixer, and the air outlet of the third mixer is used as a total air outlet; wherein the air outlet pipe of the air steel bottle is provided with an electromagnetic valve, the electromagnetic valves are controlled by a PLC, and the MFC is also controlled by the PLC, so that the multi-component dynamic air distribution in the disposable biological reaction bag can be realized.
The embodiments described in the present specification are merely examples of implementation forms of the inventive concept, and the scope of protection of the present invention should not be construed as being limited to the specific forms set forth in the embodiments, but also equivalent technical means that can be conceived by those skilled in the art according to the inventive concept.

Claims (4)

1. A multistage shaking bioreactor, characterized in that: the device comprises a multistage shaking platform for supporting a disposable biological reaction bag, a stepped annular perturber for increasing the turbulence degree of culture solution at the bottom layer of a supporting area of a fixed plate, a driving device for providing driving force and a controller for the driving device, wherein the multistage shaking platform is fixedly connected with the stepped annular perturber, the driving device is arranged at the multistage shaking platform, and the control end of the driving device is electrically connected with a corresponding pin of the controller;
the multistage shaking type platform comprises a polygonal flat plate and a shaking flat plate, wherein the number of edges of the polygonal flat plate is even, and a through hole for the stepped annular perturber to pass through is formed in the center of the polygonal flat plate; each side of the polygonal flat plate is correspondingly hinged with one shaking flat plate, wherein two shaking flat plates are in one group, and at least two groups of shaking platforms move simultaneously; two shaking plates of the same group are positioned at opposite, adjacent or spaced positions, and the shaking plates of the same group swing upwards or downwards simultaneously;
the stepped annular perturbator comprises a plurality of coaxially sleeved sleeves and a multi-stage telescopic cylinder, wherein adjacent sleeves are arranged in a sliding connection manner to form an annular shape, and the length of each sleeve is gradually reduced from inside to outside; except the sleeve at the center, the end surfaces of the bottoms of the other sleeves are provided with blocking plates, the blocking plates are provided with central through holes for the telescopic rods of the multistage telescopic cylinders to pass through, and the apertures of the central through holes of the blocking plates corresponding to the sleeves from inside to outside are gradually increased; the number of expansion stages of the expansion rods of the multistage expansion cylinder is consistent with the number of sleeves, the outermost sleeve corresponds to a first-stage rod body of the expansion rod of the multistage expansion cylinder, the secondary outer sleeve corresponds to a second-stage rod body of the multistage expansion cylinder, and the like, the sleeve positioned at the center corresponds to the highest-stage rod body of the multistage expansion cylinder, the outer end of the highest-stage rod body of the expansion rod of the multistage expansion cylinder is fixedly connected with the bottom of the sleeve positioned at the center, the central through hole aperture of the outermost sleeve is between the outer diameter of the first-stage rod body and the outer diameter of the second-stage rod body, the central through hole aperture of the secondary outer sleeve is between the outer diameter of the second-stage rod body and the outer diameter of the third-stage rod body, and the like; the sleeve stretches along with the multistage telescopic cylinder to form a step which can penetrate out of the polygonal flat plate through hole; the control end of the multistage telescopic cylinder is electrically connected with a corresponding control pin of the controller;
the driving device comprises a plurality of driving cylinders for driving the shaking flat plates, a plurality of reversing valves for controlling the movement directions of the driving cylinders and an intermediate relay for controlling the reversing valves to work, one driving cylinder corresponds to one shaking flat plate, the bottom of the driving cylinder is hinged with the polygonal flat plate, and a telescopic rod of the driving cylinder is hinged with the bottom of the corresponding shaking flat plate, so that the shaking flat plate swings up and down with the surface of the polygonal flat plate as a boundary; the driving cylinders are in one-to-one correspondence with the reversing valves, the air inlets and the air outlets of the driving cylinders are respectively communicated with corresponding passages of the reversing valves, and the control ends of the reversing valves are electrically connected with corresponding control ends of the controller through intermediate relays so as to realize reversing of the driving cylinders;
the stepped annular perturbator is a fourth-order annular member, namely the stepped annular perturbator comprises 4 sleeves, the multistage telescopic cylinder is a fourth-stage telescopic cylinder, and a mounting part for fixedly connecting with a fourth-stage rod body of the fourth-stage telescopic cylinder is arranged at the bottom of the sleeve positioned at the center.
2. A multistage shaking bioreactor as set forth in claim 1, wherein: the reversing valves are three-position five-way reversing valves, and each reversing valve is provided with an intermediate relay for controlling alternating energization of an A coil and a B coil of the reversing valve.
3. A multistage shaking bioreactor as set forth in claim 1, wherein: one end of the shaking flat plate is consistent with the edge of the polygonal flat plate, the other end of the shaking flat plate is a semicircular plate, the included angle between the upper limit position of the shaking flat plate, which swings upwards, and the polygonal flat plate is 60 degrees, and the included angle between the lower limit position of the shaking flat plate, which swings downwards, and the polygonal flat plate is 30 degrees.
4. A multistage shaking bioreactor as claimed in claim 3, wherein: the sleeve is a hollow sleeve, and the upper part and the lower part of the sleeve are sealed.
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