MRNA (messenger ribonucleic acid) production device

Abstract

The utility model belongs to the technical field of mRNA (messenger Ribonucleic Acid) production and manufacturing, and discloses an mRNA production device and a quality control method. The mRNA production device provided by the utility model comprises a production tank, a reaction bag, a containing component, a stirring component, a detection component and an automatic sample injector, wherein the reaction bag is structured to form a detection vessel, the containing component has an indirect transmission function, and the detection component is used for detecting IVT reaction liquid. According to the method, the reaction conditions are accurately controlled, the good uniformity of the reaction solution is kept, the adopted real-time monitoring method and the adopted solution homogenization mode have extremely small damage to the mRNA structure, the problems existing in large-scale industrial production of mRNA in the prior art are effectively solved, and the method has good application prospects.

Description

Technical Field

[0001] This invention belongs to the technical field of mRNA production and manufacturing, and particularly relates to an mRNA production apparatus. Background Technology

[0002] mRNA drugs and / or vaccines refer to substances that deliver mRNA encoding one or more proteins into cells, where they react directly in the cytoplasm to produce the corresponding proteins, altering the body's metabolism or inducing a specific immune response. mRNA drugs and / or vaccines are highly favored due to their high safety profile, short development cycle, and low-cost production.

[0003] Currently, structurally complete and sequence-correct mRNA can be successfully prepared under laboratory conditions, but only trace amounts of mRNA can be obtained. However, in the industrial-scale production of mRNA, as the reaction system expands, factors such as pH, enzyme activity, substrate concentration, product concentration, temperature, and the homogeneity of the reaction solution have a significant impact on the efficiency and quality of mRNA synthesis. Furthermore, existing methods for maintaining the homogeneity of the reaction solution lead to increased shear forces within the solution as the reaction system expands, resulting in more significant damage to the mRNA structure. This severely limits the realization of large-scale industrial production of mRNA and presents considerable limitations. Utility Model Content

[0004] The purpose of this invention is to provide an mRNA production device that precisely controls reaction conditions and maintains good homogeneity of the reaction solution by real-time monitoring of the reaction process. Furthermore, the real-time monitoring method and solution homogenization method used cause minimal damage to the mRNA structure, effectively solving the problems existing in the prior art for achieving large-scale industrial production of mRNA, and has good application prospects.

[0005] Specifically, the mRNA production apparatus provided by this utility model includes: a production tank, wherein a heat-conducting liquid is disposed inside the production tank; a reaction bag, wherein the reaction bag includes a flexible bag body and a transparent rigid part, the transparent rigid part being structured to form a detection dish, the detection dish being connected to the flexible bag body to receive the reaction liquid; a containment assembly, wherein the containment assembly includes an elastic connector and a placement plate, the elastic connector being connected to the peripheral wall of the production tank, the placement plate being connected to the elastic connector to be suspended inside the production tank, and the reaction bag being disposed on the placement plate; and a stirring assembly, wherein the stirring assembly drives the heat-conducting liquid to flow to carry... The moving plate shakes, and the stirring assembly remains in a non-contact state with the reaction bag and the plate; the detection assembly includes an optical detector, a pH detector, and a temperature detector; the pH detector and the temperature detector are disposed on the reaction bag; the optical detector includes an emitter and a receiver, which are disposed opposite to each other on both sides of the detection dish, and the detection light emitted by the emitter passes through the detection dish and is received by the receiver; the autosampler is connected to the reaction bag, and the detection assembly and the autosampler are signal-connected to control the injection of IVT raw materials.

[0006] Furthermore, the transparent rigid part is structured to form a detection dish protruding from the reaction bag, and the transmitter and receiver are spaced apart on the placement plate to form a snap-fit ​​groove, into which the detection dish snaps.

[0007] Furthermore, the transparent rigid part is structured to form multiple receiving grooves recessed in the reaction bag, and a detection dish is formed between two adjacent receiving grooves. The transmitter and receiver are respectively snapped into two adjacent receiving grooves.

[0008] Furthermore, the volume of the reaction bag is 50-5000 mL; the volume of the detection dish is 0.1-5 mL; and the optical path length of the detection dish is 0.001-10 mm.

[0009] Furthermore, the reaction bag also includes a fixed rigid part disposed on the outer periphery, and the fixed rigid part and the storage plate are connected by bolts to place the reaction bag on the storage plate.

[0010] Furthermore, one end of the elastic connector is connected to the top wall of the production tank, and the shelf is connected to the end of the elastic connector away from the top wall of the production tank, so that the elastic connector is in a stretched state.

[0011] Furthermore, the shelf is tilted.

[0012] Furthermore, the shelf is configured as a grid structure.

[0013] Furthermore, the stirring assembly includes a magnetic stirring assembly and / or a mechanical stirring assembly.

[0014] Furthermore, the magnetic stirring assembly includes a magnetic stirring platform and a magnetic rotor. The production tank is disposed on the magnetic stirring platform, and the magnetic rotor is disposed inside the production tank to drive the flow of the heat transfer liquid. The magnetic rotor is kept in a non-contact state with the reaction bag, the placement plate, and the detection assembly.

[0015] Furthermore, the mechanical stirring assembly includes a stirring rod and an agitator motor. The agitator motor drives the stirring rod to rotate. The stirring rod is inserted into the production tank to drive the flow of the heat transfer fluid. The stirring rod and the flexible reaction bag and the placement plate are kept in a non-contact state.

[0016] Furthermore, the optical detector includes one or more of a Fourier transform infrared spectrometer, an in-situ Raman spectrometer, and a particle image analyzer.

[0017] Furthermore, a temperature controller is also installed inside the production tank.

[0018] Beneficial effects:

[0019] The mRNA production apparatus provided by this utility model mainly comprises two parts. The first part consists of a container assembly and a stirring assembly for maintaining solution homogeneity during the IVT reaction. The stirring assembly agitates the heat transfer fluid in the production tank, and the internal shear force generated by the flow of the heat transfer fluid acts on the placement plate, causing it to shake. The elastic connector generates a reaction force under the shaking of the placement plate, thereby optimizing and adjusting the movement state of the placement plate. The shaking of the placement plate causes the reaction bag placed on it to shake. The transmission action of the heat transfer fluid and the container assembly homogenizes the solution in the reaction bag, and the flow mode of the solution in the reaction bag does not generate too much internal shear force, thus effectively reducing the damage to the mRNA structure during the solution homogenization process; the second part... It consists of a detection component for real-time monitoring of the reaction process and an autosampler for precise control of reaction conditions. A detection dish is structurally formed on the reaction bag to serve as a container for optical detection. The solution in the detection dish is updated in real time by the containment and stirring components with minimal impact on optical detection. Then, optical detectors, pH detectors, and temperature detectors are used to detect the solution in the detection dish to obtain real-time information such as raw material concentration, solution aging state, phosphate concentration, mRNA production, pH value, and temperature. Based on the obtained real-time information, the autosampler is fed back to adjust the raw material concentration, pH value, and temperature to precisely control the reaction conditions and achieve good mRNA preparation results in the scaled-up IVT reaction system. Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the structure of the mRNA production apparatus provided in the first embodiment of this utility model;

[0021] Figure 2 for Figure 1 AA section view;

[0022] Figure 3 This is a schematic diagram of the structure of the reaction bag in the first embodiment of this utility model;

[0023] Figure 4 This is a schematic diagram of the structure of the reaction bag of the mRNA production apparatus in the second embodiment of this utility model;

[0024] Figure 5 This is a schematic diagram of the structure of the reaction bag of the mRNA production apparatus in the third embodiment of this utility model;

[0025] Figure 6 This is a schematic diagram of the structure of the reaction bag of the mRNA production apparatus in the fourth embodiment of this utility model;

[0026] Figure 7 This is a schematic diagram of the installation structure of the reaction bag and the containing assembly provided in the first embodiment of this utility model;

[0027] Figure 8 An exploded view of the installation structure of the reaction bag and containing assembly provided in the first embodiment of this utility model;

[0028] Figure 9 for Figure 2 A magnified structural diagram of part B in the middle section.

[0029] Reference numerals: 1. Production tank; 2. Reaction bag; 21. Transparent rigid part; 22. Fixed rigid part; 23. Flexible bag body; 3. Containment assembly; 31. Spring; 32. Placement plate; 4. Mechanical stirring assembly; 41. Stirring rod; 42. Stirring motor; 5. Detection assembly; 51. Optical detector; 52. pH detector; 53. Temperature detector; 6. Automatic sampler; 7. Detection dish; 8. Containment tank; 9. Transmitter; 10. Receiver. Detailed Implementation

[0030] Although the present invention can be readily embodied in various forms, only some specific embodiments are shown in the accompanying drawings and will be described in detail in this specification. It is understood that this specification should be regarded as an exemplary illustration of the principles of the present invention and is not intended to limit the present invention to what is described herein.

[0031] Therefore, a feature pointed out in this specification is used to describe one feature of one embodiment of the present invention, and does not imply that every embodiment of the present invention must have the described feature. Furthermore, it should be noted that this specification describes many features. Although certain features may be combined to illustrate possible system designs, these features may also be used in other combinations not explicitly stated. Therefore, unless otherwise stated, the described combinations are not intended to be limiting.

[0032] In the embodiments shown in the accompanying drawings, the directional indications (such as up, down, left, right, front, and back) used to explain the structure and movement of the various elements of this invention are relative rather than absolute. These descriptions are appropriate when these elements are in the positions shown in the drawings. If the descriptions of the positions of these elements change, these directional indications also change accordingly.

[0033] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Where specific techniques or conditions are not specified in the embodiments, they shall be performed in accordance with the techniques or conditions described in the literature in this field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0034] Please see Figure 1 and Figure 2 . Figure 1 This is a schematic diagram of the structure of the mRNA production device according to the first embodiment of this utility model. Figure 2 yes Figure 1 A cross-sectional view of AA. The mRNA production apparatus provided in the first embodiment includes: a production tank 1, a reaction bag 2, a containment assembly 3, a mechanical stirring assembly 4, a detection assembly 5, and an autosampler 6.

[0035] Please see Figure 3 . Figure 3 This is a schematic diagram of the reaction bag 2 in the first embodiment. Specifically, the reaction bag 2 includes a transparent rigid part 21, a fixed rigid part 22, and a flexible bag body 23. The transparent rigid part 21 is structurally formed into a detection dish 7 protruding from the reaction bag 2. The detection dish 7 is connected to the interior of the reaction bag 2 to receive the IVT reaction solution, and the volume of the detection dish is 3 mL, the optical path is 3 mm, and the volume of the reaction bag is 100 mL. The fixed rigid part 22 is protruding from the side of the flexible bag body 23 away from the transparent rigid part (that is, the fixed rigid part 22 is located on the outer periphery of the reaction bag 2), and the fixed rigid part 22 is structurally formed into a first mounting hole to realize the installation of the reaction bag 2 on the receiving assembly 3. The flexible bag body 23 has a feed port, which is connected to the autosampler 6 through a pipe.

[0036] In this invention, the transparent rigid portion 21 can be structured to form the detection dish 7 in a manner that is not limited to the method provided in the first embodiment. Those skilled in the art can make adaptive choices according to actual needs, and this invention does not impose any particular limitations on it. Please refer to... Figure 4 . Figure 4 This is a schematic diagram of the structure of the reaction bag 2 of the mRNA production apparatus according to the second embodiment of the present invention. The mRNA production apparatus of the second embodiment is basically the same as that of the first embodiment, except that in the reaction bag 2 of the second embodiment, the transparent rigid part 21 is structured to form a plurality of receiving grooves 8 recessed in the flexible bag body 23 for placing the detection component 5, and the detection dish 7 is formed by surrounding two adjacent receiving grooves 8.

[0037] In this invention, the number of detection dishes formed by the structured transparent rigid portion 21 can be, but is not limited to, the number shown in the first embodiment. Those skilled in the art can make adaptive choices according to actual needs, and this invention does not impose any particular limitation on it. Please refer to... Figure 5 . Figure 5 This is a schematic diagram of the structure of the reaction bag of the mRNA production apparatus according to the third embodiment of the present invention. The mRNA production apparatus of the third embodiment is basically the same as that of the first embodiment, except that in the reaction bag 2 of the third embodiment, the transparent rigid part 21 is structured to form a plurality of detection dishes 7 that protrude from the flexible bag body 23 and are spaced apart, and an installation space is formed between two adjacent detection dishes for placing the detection component 5.

[0038] In this invention, the position of the fixing rigid part 22 on the flexible bag body 23 can be, but is not limited to, the position shown in the first embodiment. Those skilled in the art can make adaptive choices according to actual needs. Please refer to... Figure 6 . Figure 6 This is a schematic diagram of the structure of the reaction bag of the mRNA production apparatus according to the fourth embodiment of the present invention. The mRNA production apparatus of the fourth embodiment is basically the same as that of the fourth embodiment, except that in the reaction bag 2 of the fourth embodiment, a fixing rigid part 22 is also provided on the side of the reaction bag 2 near the transparent rigid part 21, so as to achieve a more stable installation of the reaction bag 2 on the receiving component 3.

[0039] In this invention, the volume of the reaction bag 2, the volume of the detection dish 7, and the optical path length can be, but are not limited to, the sizes shown in the first embodiment. Those skilled in the art can make adaptive selections according to actual needs, and this invention does not impose any particular limitation on them. In some specific embodiments, the volume of the reaction bag 2 is preferably 50-5000mL, such as 50mL, 80mL, 100mL, 250mL, 500mL, 1000mL, 2500mL, 5000mL, or any value between them; the volume of the detection dish 7 is preferably 0.1-5mL, such as 0.1mL, 0.5mL, 1mL, 3mL, 5mL, or any value between them; the optical path length of the detection dish 7 is preferably 0.001-10mm, such as 0.001mm, 0.005mm, 0.01mm, 0.5mm, 1mm, 5mm, 8mm, 10mm, or any value between them.

[0040] Please see Figure 2 , Figure 7 and Figure 8 . Figure 7 This is a schematic diagram of the installation structure of the reaction bag 2 and the containing component 3 in the first embodiment. Figure 8 This is an exploded view of the installation structure of the reaction bag 2 and the containing assembly 3 in the first embodiment. Specifically, the containing assembly 3 includes a spring 31 and a placement plate 32. One end of the spring 31 is fixedly connected to the inner peripheral wall of the top of the production tank 1, and the spring 31 is arranged vertically. A fixing clip is provided at its lower end, which clamps and fixes the outer peripheral side of the placement plate 32 so that the placement plate 32 is suspended and tilted in the production tank 1. At this time, the spring 31 is in a stretched state under the action of the placement plate 32. The placement plate 32 has a second mounting hole corresponding to the first mounting hole. The side of the reaction bag 2 near the fixing rigid part 22 is fixed to the placement plate 32 through the first mounting hole, the second mounting hole, and bolts passing through both. The reaction bag 2 is further fixed to the placement plate 32 by straps.

[0041] The production tank 1 is filled with water as a heat transfer fluid (not shown in the figure). The placement plate 32 and the reaction bag 2 are completely immersed in the heat transfer fluid. The placement plate 32 is set with a grid structure to increase the contact area between the reaction bag 2 and the heat transfer fluid, thereby achieving a better heat transfer effect.

[0042] In this invention, the spring 31 in the receiving component 3 can also be replaced by an elastic connector with elastic deformation capability, such as a U-shaped spring, a V-shaped spring, or a rubber strip. Those skilled in the art can make an adaptive selection according to actual needs, and this invention does not impose any special limitations on it.

[0043] In this invention, the heat-conducting liquid contained in the production tank 1 can be, but is not limited to, the water shown in the first embodiment, or it can be a liquid with excellent heat conduction capacity, such as heat-conducting oil. Those skilled in the art can make an adaptive choice according to actual needs, and this invention does not impose any particular limitations on it.

[0044] Please see Figure 2 The mechanical stirring assembly 4 includes a stirring rod 41 and a stirring motor 42. The stirring motor 42 is installed at the bottom of the production tank 1 and is connected to the stirring rod 41 in a transmission manner. The end of the stirring rod 41 away from the stirring motor 42 passes through the bottom of the production tank 1 and is at a certain distance from the reaction bag 2 and the storage plate 32 so that the stirring rod 41 always remains in a non-contact state with the reaction bag 2 and the storage plate 32 in the working state.

[0045] In this invention, the mechanical stirring component 4 in the mRNA production device can be replaced by other stirring components that can drive liquid flow, such as a magnetic stirring component. Specifically, the magnetic stirring component includes a magnetic stirring platform and a magnetic rotor. The production tank is placed on the magnetic stirring platform, while the magnetic rotor is placed inside the production tank to drive the flow of the heat transfer liquid. Furthermore, the magnetic rotor remains in a non-contact state with the reaction bag and the placement plate during operation.

[0046] Please see Figure 8 and Figure 9 . Figure 9 for Figure 2 A magnified structural diagram of part B in the diagram. The detection assembly 5 includes an optical detector 51, a pH detector 52, and a temperature detector 53. The optical detector 51 includes an emitter 9 and a receiver 10. The emitter 9 and receiver 10 are fixedly mounted on the placement plate 32 at intervals. When the reaction bag 2 is mounted on the placement plate 32, the detection dish 7 is located in the gap between the emitter 9 and the receiver 10, and the detection light emitted by the emitter 9 passes through the detection dish 7 and is received by the receiver 10. The pH detector 52 and temperature detector 53 are installed inside the reaction bag 2 to detect the temperature and pH value of the solution inside the reaction bag 2 in real time. A temperature controller (not shown in the diagram) is also installed inside the production tank 1 to detect and control the temperature of the heat transfer fluid. The real-time data measured by the optical detector 51 and pH detector 52 is transmitted to the autosampler 6 to control the injection of IVT raw materials, and the temperature data measured by the temperature detector 53 is transmitted to the temperature controller to control the temperature of the solution inside the reaction bag 2 by adjusting the temperature of the heat transfer fluid.

[0047] In this invention, the optical detector 51 in the detection component 5 is a device that uses optical principles to detect solutions. Those skilled in the art can make adaptive selections according to actual needs. Specific examples include, but are not limited to, one or more of the following: Fourier transform infrared spectrometer, in-situ Raman spectrometer, and particle image analyzer.

[0048] In the first embodiment, the optical detector 51 is configured as a Fourier transform infrared spectrometer; based on the Fourier transform infrared spectrometer, the first embodiment also provides a quality control method for mRNA production.

[0049] In this method, a Fourier transform infrared spectrometer, a pH detector 52, and a temperature detector 53 are used to monitor the solution in the reaction bag in real time to obtain one or more IVT reaction parameters such as raw material concentration, solution aging state, phosphate concentration, mRNA production, pH value, and temperature. Based on the above IVT reaction parameters, the IVT reaction conditions are adjusted.

[0050] More specifically, based on the data measured by the optical detector 51, when the dNTP concentration in the solution in reaction bag 2 decreases to 10-30% of the initial concentration, dNTP and Mg are added to reaction bag 2 via the autosampler 6. 2+ Cap analogues and inorganic pyrophosphatase to 75%–100% of the initial concentration.

[0051] More specifically, it determines whether flocculation and / or precipitation or other aging phenomena have occurred in the solution in reaction bag 2. When aging occurs in the solution in reaction bag 2, Mg is added to reaction bag 2 via the automatic sampler 6. 2+ To 75%–100% of the initial concentration.

[0052] More specifically, based on the data measured by pH detector 52, when the pH value of the solution in reaction bag 2 deviates from the range of 7-8, Tris-HCl buffer or PBS buffer is added to reaction bag 2 through autosampler 6 to adjust the pH value of the solution in reaction bag 2 to maintain it at 7-8.

[0053] More specifically, based on the data measured by the temperature detector 53, when the temperature of the solution in the reaction bag 2 deviates from the preset temperature by more than 0.5℃, the temperature of the heat transfer fluid is changed by the temperature controller to adjust the temperature of the solution in the reaction bag 2, so that the deviation of the real-time temperature of the solution in the reaction bag 2 from the preset reaction temperature is kept at 0 to 0.5℃.

[0054] More specifically, based on the data measured by the optical detector 51, when the concentration of mRNA in the solution in reaction bag 2 is 10-20 mg / mL (that is, the amount of mRNA generated is 10-20 mg / mL), reaction bag 2 is removed from production tank 1, and the IVT reaction is terminated.

[0055] mRNA was prepared using the mRNA production apparatus provided in the first to fourth embodiments, and the quality control methods provided in the first embodiment were used to control the conditions during the preparation process. The total volume of the reaction solution was 20 mL, and the specific amounts of each reactant and the reaction conditions are shown in Table 1.

[0056] Table 1.

[0057]

[0058] The DNA template includes nucleotide fragments with sequences such as SEQ ID NO:1, as shown in Table 2.

[0059] Table 2.

[0060]

[0061]

[0062] (1) Take 50 μL of the final IVT reaction solution and use the RNA purification kit (NEB, catalog number T2050L) according to the instructions to obtain the mRNA purification product.

[0063] (2) The mass of the purified mRNA product was detected using the RNA mode of the Nanodrop micro spectrophotometer (in μg), and the mRNA yield (mg / mL) prepared using the mRNA production apparatus provided in each embodiment was calculated according to the following formula.

[0064] mRNA yield (mg / mL) = X * 21 / 1000

[0065] Where X is the total amount of mRNA obtained after purifying a 50 μL sample of IVT reaction solution.

[0066] (3) The purified mRNA products were detected by capillary electrophoresis (CE), and the integrity (%) of each purified mRNA product was calculated according to the following formula. The integrity (%) of the purified mRNA products provided in each example was calculated according to the following formula.

[0067] mRNA integrity (%) = a / b * 100%

[0068] Where a represents the area of ​​the target RNA (main peak) in the purified mRNA product, and b represents the peak area of ​​all RNAs in the purified mRNA product. The test results are shown in Table 3.

[0069] Table 3.

[0070] Group mRNA yield (mg / mL) mRNA integrity (%) First Embodiment 5.9 86.1 Second Embodiment 6.1 85.3 Third Embodiment 5.6 84.7

[0071] As shown in Table 3, the test results indicate that the mRNA production apparatus provided in the first to fourth embodiments of the present invention can achieve the preparation of mRNA at the milligram level, with mRNA yields of 5.9 mg / mL, 6.1 mg / mL, 5.6 mg / mL and 6.3 mg / mL, respectively. Furthermore, the integrity of the obtained mRNA purification products is all above 84.7%, demonstrating good mRNA preparation effect.

[0072] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention without departing from the principles and spirit of the present invention.

Claims

1. An mRNA production apparatus, characterized in that, The mRNA production apparatus includes: A production tank, wherein a heat-conducting liquid is provided inside the production tank; A reaction bag, comprising a flexible bag body and a transparent rigid part, wherein the transparent rigid part is structured to form a detection dish, and the detection dish is connected to the flexible bag body to receive the reaction liquid; The container assembly includes an elastic connector and a shelf, the elastic connector is connected to the peripheral wall of the production tank, the shelf is connected to the elastic connector to be suspended inside the production tank, and the reaction bag is disposed on the shelf. A stirring assembly drives the flow of heat-conducting liquid to cause the placement plate to shake, and the stirring assembly remains in a non-contact state with the reaction bag and the placement plate; The detection assembly includes an optical detector, a pH detector, and a temperature detector; the pH detector and the temperature detector are disposed on the reaction bag; the optical detector includes an emitter and a receiver, which are disposed opposite to each other on both sides of the detection dish, and the detection light emitted by the emitter passes through the detection dish and is received by the receiver; An autosampler is connected to the reaction bag, and the detection component and the autosampler are signal-connected to control the injection of IVT raw materials.

2. The mRNA production apparatus according to claim 1, characterized in that, The transparent rigid part is structured to form a detection dish that protrudes from the reaction bag. The transmitter and receiver are spaced apart on the placement plate to form a snap-fit ​​groove, and the detection dish snaps into the snap-fit ​​groove.

3. The mRNA production apparatus according to claim 1, characterized in that, The transparent rigid part is structured to form multiple receiving slots recessed in the reaction bag, and a detection dish is formed between two adjacent receiving slots. The transmitter and receiver are respectively snapped into two adjacent receiving slots.

4. The mRNA production apparatus according to claim 1, characterized in that, The reaction bag has a volume of 50–5000 mL; the detection dish has a volume of 0.1–5 mL and an optical path length of 0.001–10 mm.

5. The mRNA production apparatus according to claim 1, characterized in that, The reaction bag also includes a fixed rigid part disposed on the outer periphery, and the fixed rigid part and the storage plate are connected by bolts to place the reaction bag on the storage plate.

6. The mRNA production apparatus according to claim 1, characterized in that, One end of the elastic connector is connected to the top wall of the production tank, and the placement plate is connected to the end of the elastic connector away from the top wall of the production tank, so that the elastic connector is in a stretched state. Optionally, the shelf is inclined; Optionally, the shelf is configured as a grid structure.

7. The mRNA production apparatus according to claim 1, characterized in that, The stirring assembly is a magnetic stirring assembly and / or a mechanical stirring assembly.

8. The mRNA production apparatus according to claim 7, characterized in that, The magnetic stirring assembly includes a magnetic stirring table and a magnetic rotor. The production tank is placed on the magnetic stirring table, and the magnetic rotor is placed inside the production tank to drive the flow of the heat transfer fluid. The magnetic rotor is kept in a non-contact state with the reaction bag, the placement plate, and the detection assembly. Optionally, the mechanical stirring assembly includes a stirring rod and a stirring motor. The stirring motor drives the stirring rod to rotate. The stirring rod is inserted into the production tank to drive the flow of the heat transfer fluid. The stirring rod and the mechanical stirring assembly (including the stirring rod and the stirring motor, the stirring motor driving the stirring rod to rotate, the stirring rod being inserted into the production tank to drive the flow of the heat transfer fluid) are kept in a non-contact state with the flexible reaction bag and the placement plate.

9. The mRNA production apparatus according to claim 1, characterized in that, The optical detector includes one or more of the following: Fourier transform infrared spectrometer, in-situ Raman spectrometer, and particle image analyzer.

10. The mRNA production apparatus according to claim 1, characterized in that, A temperature controller is also installed inside the production tank.

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