A nucleic acid lipid nanoparticle integrated manufacturing device

Abstract

The utility model relates to a nucleic acid lipid nano particle integration preparation device, it includes device casing and sets up in the pretreatment module, mixing module, postprocessing module and monitoring module in device casing, the pretreatment module includes first pretreatment device, second pretreatment device, third pretreatment device and fourth pretreatment device, the mixing module includes the first mixing device for the lipid solution and nucleic acid solution mixture obtains the first preliminary mixture, with first mixing device and third pretreatment device and the second mixing device for the preliminary mixture and dilution buffer mixture obtains the intermediate mixture of intercommunication, the postprocessing module includes the temporary storage device for the temporary storage intermediate mixture, the ultrafiltration device for the concentration of intermediate mixture and carries out liquid change, with the filter sterilization device of ultrafiltration device intercommunication, the monitoring module includes the pressure monitoring device for monitoring first mixing device, second mixing device, ultrafiltration device and filter sterilization device pressure.

Description

Technical Field

[0001] This invention belongs to the field of nucleic acid drug preparation technology, specifically relating to an integrated preparation device for nucleic acid lipid nanoparticles. Background Technology

[0002] Nucleic acid drugs, using small nucleic acid molecules in various forms such as messenger RNA (mRNA) and small interfering RNA (siRNA) as active ingredients, have become a frontier in biomedicine due to their ability to achieve precise treatment by regulating gene expression. mRNA drug molecules guide cells to synthesize target proteins and are widely used in infectious disease vaccines, cancer vaccines, and intracellular protein replacement therapies (such as enzyme replacement). Meanwhile, siRNA, antisense oligonucleotides (ASO), and other drug molecules silence the expression of pathogenic genes, providing novel solutions for treating hereditary rare diseases and metabolic disorders.

[0003] However, nucleic acid molecules, especially single-stranded RNA, possess inherent biochemical instability. RNA molecules are prone to self-hydrolysis under physiological conditions and are extremely sensitive to ubiquitous nucleases, leading to rapid inactivation in the extracellular environment. Secondly, naked nucleic acids carry a high density of negative charges, making it difficult to cross the equally negatively charged lipid barrier of the cell membrane, resulting in extremely low intracellular delivery efficiency. Furthermore, exogenous nucleic acid molecules are easily recognized by the body's innate immune system (such as Toll-like receptors, TLRs), potentially triggering unintended immune responses that not only weaken therapeutic efficacy but also pose safety risks. These inherent instabilities and delivery barriers severely limit their clinical application.

[0004] Lipid nanoparticles (LNPs), as efficient and biodegradable non-viral delivery carriers, have shown significant potential and broad application prospects in the field of nucleic acid drug delivery. LNPs can efficiently encapsulate nucleic acid molecules (such as mRNA, siRNA, etc.) in their hydrophilic core, forming a stable core-shell structure, protecting RNA from the influence of extracellular RNases, and assisting in the in vivo delivery of RNA.

[0005] Currently, laboratory-scale preparation of nucleic acid lipid nanoparticles largely relies on traditional multi-step, batch processing procedures. This process typically includes: solution preparation and filtration of components such as the lipid organic phase and the nucleic acid aqueous phase; encapsulation and initial dilution of nanoparticles using microfluidics and other technologies; sampling of intermediate products and mid-level analysis of key quality attributes (such as encapsulation efficiency and particle size); ultrafiltration and concentration; and final pre-filtration and sterile filtration. This process suffers from inherent drawbacks such as cumbersome operation, high dependence on human operators, dispersed equipment occupying large spaces, and numerous open steps leading to a high risk of contamination. More importantly, existing technologies lack an integrated preparation device with a rational structural layout and highly integrated functional modules. This results in poor coordination between process units, making it difficult to achieve closed, automated, and controllable continuous production. This severely restricts the efficiency, reproducibility, and compliance of nucleic acid lipid nanoparticle preparation, and also poses a significant obstacle to its transformation from laboratory to large-scale production. Utility Model Content

[0006] The purpose of this invention is to provide an integrated preparation device with a reasonable structural layout and highly integrated functional modules, which can realize the closed, automatic, and controllable continuous production of nucleic acid lipid nanoparticles.

[0007] To achieve the above objectives, the technical solution adopted by this utility model is as follows: An integrated nucleic acid lipid nanoparticle preparation device includes a device housing and a pretreatment module, a mixing module, a post-treatment module, and a monitoring module disposed within the device housing. The pretreatment module includes a first pretreatment device independently configured for filtering lipid solutions and pumping them into the mixing module, a second pretreatment device for filtering nucleic acid solutions and pumping them into the mixing module, a third pretreatment device for filtering dilution buffer and pumping it into the mixing module, and a fourth pretreatment device for filtering exchange buffer and pumping it into the post-processing module. The mixing module includes a first mixing device connected to the first pretreatment device and the second pretreatment device for mixing the lipid solution and the nucleic acid solution to obtain a preliminary mixture, and a second mixing device connected to the first mixing device and the third pretreatment device for mixing the preliminary mixture with the dilution buffer to obtain an intermediate mixture. The post-processing module includes a temporary storage device connected to the second mixing device for temporarily storing the intermediate mixture, an ultrafiltration device connected to the temporary storage device and the fourth pre-treatment device for concentrating and changing the liquid in the intermediate mixture, and a filtration and sterilization device connected to the ultrafiltration device. The monitoring module includes a pressure monitoring device for monitoring the pressure of the solution on the inner wall of the first mixing device, the second mixing device, the ultrafiltration device, and the filtration and sterilization device.

[0008] In some embodiments, the first mixing device and the second mixing device are connected by a pipe equipped with a first three-way valve, the second mixing device and the temporary storage device are connected by a pipe equipped with a second three-way valve, and the first three-way valve and the second three-way valve are also connected to a waste liquid storage container disposed outside the device housing via waste liquid pipes.

[0009] In some embodiments, the permeation end of the ultrafiltration device is also connected to the waste liquid storage container via a waste liquid pipe equipped with a flow meter.

[0010] In some embodiments, the first pretreatment device and the first mixing device are connected by a pipe equipped with a first pump. The second pretreatment device and the first mixing device are connected by a pipe equipped with a second pump. The third pretreatment device and the second mixing device are connected by a pipeline equipped with a third pump. The fourth pretreatment device and the ultrafiltration device are connected by a pipeline equipped with a fourth pump. The ultrafiltration device and the filtration and sterilization device are connected by a pipeline equipped with a fifth pump. The temporary storage device and the ultrafiltration device are connected by a pipeline equipped with a sixth pump.

[0011] Furthermore, the first pump, the second pump, the third pump, the fourth pump, and the fifth pump are each independently a peristaltic pump or a diaphragm pump.

[0012] In some embodiments, the first pretreatment device, the second pretreatment device, the third pretreatment device, and the fourth pretreatment device each include a liquid inlet device, a filtration device, and a liquid storage device connected sequentially from top to bottom. The liquid storage device is equipped with a temperature control device and a stirring device, and the liquid storage device is equipped with a sampling port and / or connected to a central control quality inspection device, a one-way vent, or a one-way vent device.

[0013] In some embodiments, the filtration device is a filter with replaceable capacity and membrane material.

[0014] In some embodiments, the first mixing device and the second mixing device are microfluidic mixing devices having two inlets and one outlet, respectively.

[0015] In some preferred embodiments, the microfluidic mixing device is the lipid nanoparticle mixer of patent CN220968881U.

[0016] In some embodiments, the ultrafiltration device is a tangential flow ultrafiltration device with a detachable membrane package, and the membrane package accessories with appropriate molecular weight cutoff and loading capacity are selected according to the particle size and feed amount of nucleic acid lipid nanoparticles.

[0017] In some embodiments, the pressure monitoring device is connected to the inlet and outlet of the first mixing device and the second mixing device, to the inlet, permeation, and reflux end of the ultrafiltration device, and to the inlet of the filtration and sterilization device.

[0018] In some embodiments, the monitoring module further includes a control panel disposed on the device housing, the control panel being electrically connected to the device in the integrated nucleic acid lipid nanoparticle preparation device.

[0019] In some embodiments, the temporary storage device is provided with a sampling port and / or connected to a central control quality inspection device, a one-way vent, or a one-way ventilation device.

[0020] In some embodiments, the temporary storage device is equipped with a temperature control device, a stirring device, and a weighing device.

[0021] In some embodiments, the filtration and sterilization device is connected via a pipe to a product storage container disposed inside or outside the device housing.

[0022] In some embodiments, the pipes in the integrated nucleic acid lipid nanoparticle preparation device are all resistant to acids, alkalis, and organic reagents.

[0023] Due to the application of the above technical solution, this utility model has the following advantages compared with the prior art: The integrated nucleic acid lipid nanoparticle preparation device provided by this utility model integrates multiple modules within the device housing to achieve the entire process of nucleic acid lipid nanoparticle preparation. This not only saves space but also effectively avoids contamination by bacteria, endotoxins, etc., and can effectively reduce batch-to-batch variation, reduce labor costs, and improve the preparation efficiency of nucleic acid lipid nanoparticles. At the same time, the devices in each module are connected by pipes and are relatively independent, which facilitates verification and maintenance by engineers. Attached Figure Description

[0024] To more clearly illustrate the technical solutions of the embodiments of this application, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 This is a schematic diagram of each module in the integrated nucleic acid lipid nanoparticle preparation device of Example 1; Figure 2 This is a schematic diagram of the pretreatment device in the integrated nucleic acid lipid nanoparticle preparation device of Example 1.

[0026] The system comprises: 1. Pretreatment module; 11. First pretreatment device; 12. Second pretreatment device; 13. Third pretreatment device; 14. Fourth pretreatment device; 151. Liquid inlet device; 152. Filtration device; 153. Liquid storage device; 2. Mixing module; 21. First mixing device; 22. Second mixing device; 3. Posttreatment module; 31. Temporary storage device; 32. Ultrafiltration device; 33. Filtration and sterilization device; 4. Monitoring module; 41. Pressure monitoring device; 51. Flow meter; 52. First pump; 53. Second pump; 54. Third pump; 55. Fourth pump; 56. Fifth pump; 57. Sixth pump; 58. First three-way valve; 59. Second three-way valve; 61. Product storage container; 62. Waste liquid storage container. Detailed Implementation

[0027] The technical solution of this utility model will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this utility model. Based on the embodiments of this utility model, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this utility model.

[0028] Example 1: This example provides an integrated preparation device for nucleic acid lipid nanoparticles, which includes a device shell and a pretreatment module 1, a mixing module 2, a post-processing module 3 and a monitoring module 4 disposed within the device shell.

[0029] like Figure 1 As shown, the pretreatment module 1 includes a first pretreatment device 11 for filtering lipid solutions and pumping them into the mixing module 2, a second pretreatment device 12 for filtering nucleic acid solutions and pumping them into the mixing module 2, a third pretreatment device 13 for filtering dilution buffer (e.g., histidine buffer) and pumping it into the mixing module 2, and a fourth pretreatment device 14 for filtering exchange buffer (e.g., Tris-HCl buffer) and pumping it into the post-processing module 3. Figure 2As shown, the first pretreatment device 11, the second pretreatment device 12, the third pretreatment device 13, and the fourth pretreatment device 14 each include a liquid inlet device 151, a filtration device 152, and a liquid storage device 153 connected sequentially from top to bottom. The liquid storage device 153 is equipped with a temperature control device and a stirring device. The liquid storage device 153 has a sampling port and a one-way vent. The sampling port is used for sampling at any time to monitor the reagent status in real time and can be connected to the central control quality inspection device. The filtration device 152 is a filter with replaceable capacity and suitable membrane material.

[0030] like Figure 1 As shown, the mixing module 2 includes a first mixing device 21 connected to the first pretreatment device 11 and the second pretreatment device 12 for mixing lipid solution and nucleic acid solution to obtain a preliminary mixture, and a second mixing device 22 connected to the first mixing device 21 and the third pretreatment device 13 for mixing the preliminary mixture with dilution buffer to obtain an intermediate mixture. In this embodiment, the first mixing device 21 and the second mixing device 22 are connected by a pipe equipped with a first three-way valve 58, and the second mixing device 22 and the temporary storage device 31 are connected by a pipe equipped with a second three-way valve 59. The first three-way valve 58 and the second three-way valve 59 are also connected to a waste liquid storage container 62 located outside the device housing via waste liquid pipes. The first pretreatment device 11 and the first mixing device 21 are connected by a pipe equipped with a first pump 52, the second pretreatment device 12 and the first mixing device 21 are connected by a pipe equipped with a second pump 53, and the third pretreatment device 13 and the second mixing device 22 are connected by a pipe equipped with a third pump 54. In this embodiment, the microfluidic mixing device is the lipid nanoparticle mixer of patent CN220968881U.

[0031] like Figure 1As shown, the post-processing module 3 includes a temporary storage device 31 connected to the second mixing device 22 for temporarily storing intermediate mixtures, an ultrafiltration device 32 connected to the temporary storage device 31 and the fourth pretreatment device for concentrating and changing the intermediate mixture, and a filtration and sterilization device 33 connected to the ultrafiltration device 32. The filtration and sterilization device 33 is connected to a product storage container 61 located inside or outside the device housing via a pipe. The permeate end of the ultrafiltration device 32 is also connected to the waste liquid storage container 62 via a waste liquid pipe equipped with a flow meter 51. The ultrafiltration device 32 is a tangential flow ultrafiltration device with a detachable membrane package. The membrane package accessories with appropriate molecular weight cutoff and loading capacity are selected according to the particle size and feed amount of nucleic acid lipid nanoparticles. The fourth pretreatment device 14 and the ultrafiltration device 32 are connected via a pipe equipped with a fourth pump 55. The ultrafiltration device 32 and the filtration and sterilization device 33 are connected via a pipe equipped with a fifth pump 56. The temporary storage device 31 and the ultrafiltration device 32 are connected via a pipe equipped with a sixth pump 57. The temporary storage device 31 is equipped with a sampling port for sampling at any time to monitor the reagent status in real time. It can be connected to the central control and quality inspection device. The temporary storage device 31 is also equipped with a one-way vent, a temperature control device, a stirring device, and a weighing device. The filtration and sterilization device 33 is connected to the product storage container 61, which is located inside or outside the device housing, through a pipeline.

[0032] like Figure 1 As shown, the monitoring module 4 includes a pressure monitoring device 41 for monitoring the pressure of the solutions in the first mixing device 21, the second mixing device 22, the ultrafiltration device 32, and the filtration and sterilization device 33 on the inner wall of the device, and a control panel mounted on the device housing. The control panel is electrically connected to the device in the integrated nucleic acid lipid nanoparticle preparation device. The pressure monitoring device 41 is connected to the inlet and outlet of the first mixing device 21 and the second mixing device 22, to the inlet, permeation, and reflux ends of the ultrafiltration device 32, and to the inlet of the filtration and sterilization device 33. In this embodiment, the pressure monitoring device 41 is a fully automatic pressure sensor.

[0033] In this embodiment, all pipes in the integrated nucleic acid lipid nanoparticle preparation device are resistant to acids, alkalis, and organic reagents. All pumps used in this embodiment are diaphragm pumps.

[0034] The method for preparing nucleic acid lipid nanoparticles using the integrated nucleic acid lipid nanoparticle preparation apparatus of this embodiment is as follows: Before production, select appropriate models of mixers, ultrafiltration membrane packs, and filters based on production scale and process requirements. During equipment installation, strictly follow the equipment installation instructions to ensure installation accuracy and stability. After installation, conduct a comprehensive commissioning of the equipment and check its operational status.

[0035] A lipid solution was prepared according to the ratio of SM102:DSPC:Cholesterol:DMG-PEG = 50:10:38.5:1.5 (mol%), with a total lipid molar concentration of 21.82 mM. Anhydrous ethanol was used as the solvent. After thorough dissolution, the solution was transferred to the first pretreatment device 11 for filtration and storage. The temperature control device of the storage device 153 was adjusted to maintain the lipid solution temperature at approximately 40°C, and the stirring device of the storage device 153 was adjusted to approximately 100 rpm to prevent lipid precipitation. A suitable amount of liquid was taken from the sampling port for intermediate control, and the concentration of each component was measured to ensure the correct concentration and ratio of the lipid solution.

[0036] The RNA stock solution was dispersed in a 25mM acetate-sodium acetate buffer solution at pH 5.0, with a final RNA concentration of 0.2 mg / mL. After thorough mixing, the solution was transferred to the second pretreatment device 12 for filtration and storage. The temperature control device of the storage device 153 was adjusted to maintain the RNA solution temperature between 2 and 8°C, and the stirring device of the storage device 153 was adjusted to a speed of approximately 50 rpm to prevent rapid RNA degradation. An appropriate amount of liquid was taken from the sampling port for intermediate control, and the RNA concentration and purity were tested to ensure that the RNA was in good condition before mixing.

[0037] Prepare a 50mM histidine buffer solution with pH 7.7. After thorough mixing, add the solution to the third pretreatment device 13 for filtration and storage. Adjust the temperature control device of the storage device 153 to maintain the temperature of the histidine buffer solution at 2~8℃. Adjust the stirring device of the storage device 153 to a speed of about 100rpm.

[0038] Prepare a 20mM tromethorphan and 20mM sodium chloride buffer solution with pH 7.4. After thorough mixing, add the solution to the fourth pretreatment device 14 for filtration and storage. Adjust the temperature control device of the storage device 153 to maintain the temperature of the Tris-HCl buffer solution at 2~8℃. Adjust the stirring device of the storage device 153 to a speed of about 100 rpm.

[0039] Start the first pump 52, the second pump 53, and the third pump 54 to pump the lipid solution from the first pretreatment device 11 and the RNA solution from the second pretreatment device 12 into the first mixer at rates of 50 mL / min and 150 mL / min, respectively. Discard the first 1 min and the last 30 s. The waste liquid is discharged through the first three-way valve 58 via the waste pipe. The remaining mixture enters the second mixing device 22 through the first three-way valve 58. Simultaneously, the liquid from the third pretreatment device 13 is pumped into the second mixing device 22 at a rate of 600 mL / min to mix with the initial product obtained from the mixture of lipid solution and RNA solution. Discard the first 1 min and the last 30 s. After 30 seconds, the waste liquid is discharged through the waste liquid pipe via the second three-way valve 59. The remaining mixed products enter the temporary storage device 31 for temporary storage through the second three-way valve 59. The temperature control device of the temporary storage device 31 is adjusted to maintain the intermediate product temperature at 2~8℃. The stirring device of the temporary storage device 31 is adjusted to a speed of about 100rpm. An appropriate amount of liquid is taken out from the sampling port of the temporary storage device 31 at any time for central control. The particle size, encapsulation rate and concentration of the intermediate product are detected. The volume of the intermediate product is calculated based on the weight and density of the intermediate product. The pressure of all pipelines in the entire mixing process is monitored by the pressure monitoring device 41. The pressure must not exceed 1 bar.

[0040] Pumps 55, 56, and 57 are activated, and the intermediate product from the temporary storage device 31 is then pumped into the ultrafiltration device 32 for ultrafiltration concentration. Based on central control data, the concentration is reduced to 0.5 mg / mL (based on RNA concentration). The remaining solution volume is calculated based on the difference between the permeate volume measured by flow meter 51 and the total intermediate product volume measured by the temporary storage device 31. Simultaneously, the liquid in the fourth pretreatment device 14 is pumped into the ultrafiltration device 32, replacing the original buffer solution by 8 times. After the replacement, ultrafiltration concentration continues to the required volume. The concentration and replacement ratios are calculated by accumulating the data from flow meter 51. The pressure at the inlet, reflux, and permeate ends of the ultrafiltration system is monitored by pressure monitoring device 41, and the pressure must not exceed 1 bar. The product obtained from ultrafiltration concentration is pumped into the filtration and sterilization device 33 for filtration and sterilization. The pipeline pressure is also monitored by pressure monitoring device 41, and the pressure must not exceed 1 bar.

[0041] The preparation method in this embodiment is only an example, and the specific conditions and parameters involved can be adjusted according to actual needs.

[0042] The above embodiments are only for illustrating the technical concept and features of this utility model, and are intended to enable those skilled in the art to understand the content of this utility model and implement it accordingly. They should not be construed as limiting the scope of protection of this utility model. All equivalent changes or modifications made in accordance with the spirit and essence of this utility model should be included within the scope of protection of this utility model.

Claims

1. An integrated apparatus for preparing nucleic acid lipid nanoparticles, characterized in that: It includes a device housing and a preprocessing module, a mixing module, a post-processing module, and a monitoring module disposed within the device housing. The pretreatment module includes a first pretreatment device independently configured for filtering lipid solutions and pumping them into the mixing module, a second pretreatment device for filtering nucleic acid solutions and pumping them into the mixing module, a third pretreatment device for filtering dilution buffer and pumping it into the mixing module, and a fourth pretreatment device for filtering exchange buffer and pumping it into the post-processing module. The mixing module includes a first mixing device connected to the first pretreatment device and the second pretreatment device for mixing the lipid solution and the nucleic acid solution to obtain a preliminary mixture, and a second mixing device connected to the first mixing device and the third pretreatment device for mixing the preliminary mixture with the dilution buffer to obtain an intermediate mixture. The post-processing module includes a temporary storage device connected to the second mixing device for temporarily storing the intermediate mixture, an ultrafiltration device connected to the temporary storage device and the fourth pretreatment device for concentrating and changing the intermediate mixture, and a filtration and sterilization device connected to the ultrafiltration device. The monitoring module includes a pressure monitoring device for monitoring the pressure of the solution on the inner wall of the first mixing device, the second mixing device, the ultrafiltration device, and the filtration and sterilization device.

2. The integrated nucleic acid lipid nanoparticle preparation device according to claim 1, characterized in that: The first mixing device and the second mixing device are connected by a pipe equipped with a first three-way valve, and the second mixing device and the temporary storage device are connected by a pipe equipped with a second three-way valve. The first three-way valve and the second three-way valve are also connected to a waste liquid storage container located outside the device housing via waste liquid pipes.

3. The integrated nucleic acid lipid nanoparticle preparation device according to claim 2, characterized in that: The permeation end of the ultrafiltration device is also connected to the waste liquid storage container via a waste liquid pipe equipped with a flow meter.

4. The integrated nucleic acid lipid nanoparticle preparation device according to claim 1, characterized in that: The first pretreatment device and the first mixing device are connected by a pipeline equipped with a first pump. The second pretreatment device and the first mixing device are connected by a pipe equipped with a second pump. The third pretreatment device and the second mixing device are connected by a pipeline equipped with a third pump. The fourth pretreatment device and the ultrafiltration device are connected by a pipeline equipped with a fourth pump. The ultrafiltration device and the filtration and sterilization device are connected by a pipeline equipped with a fifth pump. The temporary storage device and the ultrafiltration device are connected by a pipeline equipped with a sixth pump.

5. The integrated nucleic acid lipid nanoparticle preparation device according to claim 4, characterized in that: The first pump, the second pump, the third pump, the fourth pump, and the fifth pump are each independently a peristaltic pump or a diaphragm pump.

6. The integrated nucleic acid lipid nanoparticle preparation device according to claim 1, characterized in that: The first pretreatment device, the second pretreatment device, the third pretreatment device and the fourth pretreatment device each include a liquid inlet device, a filtration device and a liquid storage device connected in sequence from top to bottom. The liquid storage device is equipped with a temperature control device and a stirring device. The liquid storage device is equipped with a sampling port and / or connected to a central control quality inspection device, a one-way vent or a one-way vent.

7. The integrated nucleic acid lipid nanoparticle preparation device according to claim 1, characterized in that: The first mixing device and the second mixing device are microfluidic mixing devices with two inlets and one outlet, respectively.

8. The integrated nucleic acid lipid nanoparticle preparation device according to claim 1, characterized in that: The ultrafiltration device is a tangential flow ultrafiltration device with a detachable membrane package.

9. The integrated nucleic acid lipid nanoparticle preparation device according to claim 1, characterized in that: The pressure monitoring device is connected to the inlet and outlet of the first mixing device and the second mixing device, to the inlet end, permeation end and reflux end of the ultrafiltration device, and to the inlet end of the filtration and sterilization device. And / or, the monitoring module further includes a control panel disposed on the device housing, the control panel being electrically connected to the device in the integrated nucleic acid lipid nanoparticle preparation device.

10. The integrated nucleic acid lipid nanoparticle preparation device according to claim 1, characterized in that: The temporary storage device is equipped with a sampling port and / or connected to a central control quality inspection device, a one-way ventilation port, or a one-way ventilation device; And / or, the temporary storage device is equipped with a temperature control device, a stirring device, and a weighing device; And / or, the filtration and sterilization device is connected via a pipe to a product storage container disposed inside or outside the device housing; And / or, the pipes in the integrated nucleic acid lipid nanoparticle preparation device are all resistant to acids, alkalis and organic reagents.

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