Lipid nanoparticle mixing preparation device integrated with bubble catcher

Abstract

The utility model discloses a lipid nanoparticle mixing preparation device integrated with a bubble trap, which belongs to the technical field of lipid nanoparticle preparation and comprises a jet mixer shell, a first liquid inlet channel is arranged at the upper end of the jet mixer shell, a first bubble trap is arranged on the surface of the first liquid inlet channel, and a second liquid inlet channel is arranged on the surface of the first bubble trap. A second liquid inlet channel is arranged on one side of the jet mixer shell, a second bubble trap is arranged on the surface of the second liquid inlet channel, a positioning installation assembly is arranged on the side, away from the second liquid inlet channel, of the jet mixer shell, a liquid drainage pipe is arranged at the bottom end of the jet mixer shell, and a third liquid inlet channel is arranged on one side of the liquid drainage pipe. A third bubble trap is arranged on the surface of the third liquid inlet channel; according to the utility model, the bubble trap is arranged to carry out defoaming treatment on fluid before entering the jet mixer, so that accurate flow and accurate proportion mixing of an organic phase and a water phase are ensured.

Description

Technical Field

[0001] The utility model belongs to the technical field of lipid nanoparticle preparation, and in particular relates to a lipid nanoparticle mixing preparation device with an integrated bubble trap. Background Art

[0002] RNA can play a variety of powerful functions in the body, such as translating proteins, interfering with gene expression, mediating protein interactions, regulating gene transcription or translation, etc. RNA has unique advantages such as a wide range of expression, high safety, easy large-scale production, and low cost. However, there are many challenges in delivering RNA to the clinic: RNA chains are negatively charged, and the cell membrane surface is also negatively charged. Electrostatic repulsion makes it difficult for RNA molecules to pass through the cell membrane and enter the cell; RNA molecules, especially linear mRNA molecules, are extremely easy to degrade, and a variety of enzymes in the body can quickly degrade them; mRNA molecules have strong immunogenicity and are easily identified as exogenous nucleic acids to activate immune responses. As a drug that works stably in the body, RNA also requires a safe, effective and stable delivery system. LNP is a non-viral vector delivery system based on lipid materials that can carry nucleic acids and small molecule drugs into cells. RNA therapy has shown potential in various medical applications, including viral vaccines, cancer immunotherapy, and gene editing. LNP encapsulates and protects RNA from nuclease cleavage, improving the stability of RNA molecules. The preparation method of lipid nanoparticles is to mix a lipid ethanol solution with an acidic aqueous buffer solution containing nucleotides. The lipid ethanol solution is usually called the oil phase, and the nucleotide buffer is usually called the aqueous phase. The two phases are mixed through a specific mixer, and the positive and negative charges of the lipids and nucleotides in the two phases are used to achieve self-assembly to form particles of tens to hundreds of nanometers. The particle size can be changed by adjusting the flow rate and ratio of the two phases.

[0003] The existing lipid nanoparticle mixing and preparation device does not have a bubble trap to defoam the liquid before mixing when in use. The shear stress caused by the bubbles may cause damage to the biological sample, affect the effect of lipid nanoparticle mixing and preparation, make the oil-water ratio difficult to control, and make it inconvenient to install and position the jet mixer shell, wasting working time. Utility Model Content

[0004] In order to solve the problems raised in the above background technology, the utility model provides a lipid nanoparticle mixing preparation device with an integrated bubble trap, which has the characteristics of convenient defoaming and easy installation.

[0005] To achieve the above-mentioned purpose, the utility model provides the following technical solutions: a lipid nanoparticle mixing and preparation device with an integrated bubble trap, comprising a jet mixer shell, a first liquid inlet channel is arranged at the upper end of the jet mixer shell, a first bubble trap is arranged at the liquid inlet end of the first liquid inlet channel, a second liquid inlet channel is arranged at one side of the jet mixer shell, a second bubble trap is arranged at the liquid inlet end of the second liquid inlet channel, a positioning and mounting assembly is arranged at the side of the jet mixer shell away from the second liquid inlet channel, a drain pipe is arranged at the bottom end of the jet mixer shell, a third liquid inlet channel is arranged at one side of the drain pipe, and a third bubble trap is arranged at the liquid inlet end of the third liquid inlet channel.

[0006] Preferably, the positioning and mounting assembly includes a fixing plate, a clamping plate, a buffer device, a screw and an abutment plate, wherein a fixing plate is symmetrically arranged on one side of the jet mixer housing, a screw is arranged between the fixing plates, a clamping plate is symmetrically arranged on the surface of the screw, a buffer device is arranged on the surface of the clamping plate, and an abutment plate is arranged at one end of the buffer device.

[0007] Preferably, a guide rod is further provided between the fixing plates corresponding to the clamping plates, and one side of the abutting plate is provided as an arc-shaped surface.

[0008] Preferably, a bearing seat is provided inside the fixing plate corresponding to the screw rod, and a rotating sleeve is provided on the bottom end surface of the screw rod.

[0009] Preferably, the buffer device includes a damping slider, a buffer spring, a connecting rod and a guide seat, wherein a guide seat is arranged on the surface of the clamping plate, a damping slider is arranged inside the guide seat, a connecting rod is arranged at the bottom end of the damping slider, and a buffer spring is sleeved on the surface of the connecting rod.

[0010] Preferably, a damping pad is provided on the upper end surface of the guide seat, and the bottom end of the connecting rod is mounted on the abutment plate by brazing.

[0011] Compared with the prior art, the beneficial effects of the utility model are:

[0012] 1. The utility model performs defoaming treatment on the fluid before entering the jet mixer by arranging a bubble trap, thereby minimizing the accidental introduction of bubbles into the fluid, effectively avoiding the blockage of bubbles in the downstream of the small-size channel, and thus enabling the lipid ethanol solution and the nucleotide buffer to be evenly mixed, so that the particle size distribution of the lipid nanoparticles is uniform, the mixing effect of the lipid ethanol solution and the nucleotide buffer is improved, and the quality of the finished lipid nanoparticles is improved. Before the diluent is added through the third liquid inlet channel, the bubbles are also eliminated through the third bubble trap, thereby improving the accurate proportion of the dilution and mixing, ensuring the product qualification rate, ensuring the flow accuracy, and the accurate proportion of the organic phase and the aqueous phase.

[0013] 2. The utility model provides a positioning installation component, so that the jet mixer housing can be installed and positioned before use, thereby ensuring the convenience of installation, improving installation efficiency, saving human resources, and performing shock absorption when vibration occurs, thereby ensuring the stability of the jet mixer housing during use and improving the quality of use of the equipment. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 It is a structural schematic diagram of the utility model;

[0015] Figure 2 This is a rear view of the structure of the utility model;

[0016] Figure 3 It is a schematic diagram of the structure of the buffer device of the utility model.

[0017] In the figure: 1. positioning and mounting assembly; 11. fixing plate; 12. clamping plate; 13. buffer device; 131. damping pad; 132. damping slider; 133. buffer spring; 134. connecting rod; 135. guide seat; 14. screw rod; 15. abutment plate; 2. first liquid inlet channel; 3. first bubble trap; 4. second bubble trap; 5. second liquid inlet channel; 6. third bubble trap; 7. third liquid inlet channel; 8. discharge pipe; 9. jet mixer housing. DETAILED DESCRIPTION

[0018] The following will be combined with the drawings in the embodiments of the utility model to clearly and completely describe the technical solutions in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0019] See also Figure 1-3 The utility model provides the following technical solutions: a lipid nanoparticle mixing and preparation device with an integrated bubble trap, comprising a jet mixer shell 9, a first liquid inlet channel 2 is arranged at the upper end of the jet mixer shell 9, a first bubble trap 3 is arranged at the liquid inlet end of the first liquid inlet channel 2, a second liquid inlet channel 5 is arranged at one side of the jet mixer shell 9, a second bubble trap 4 is arranged at the liquid inlet end of the second liquid inlet channel 5, a positioning and mounting component 1 is arranged at the side of the jet mixer shell 9 away from the second liquid inlet channel 5, a drain pipe 8 is arranged at the bottom end of the jet mixer shell 9, a third liquid inlet channel 7 is arranged at one side of the drain pipe 8, and a third bubble trap 6 is arranged at the liquid inlet end of the third liquid inlet channel 7.

[0020] Specifically, the positioning and mounting assembly 1 includes a fixing plate 11, a clamping plate 12, a buffer device 13, a screw 14 and an abutment plate 15, wherein the fixing plate 11 is symmetrically arranged on one side of the jet mixer housing 9, the screw 14 is arranged between the fixing plates 11, the clamping plate 12 is symmetrically arranged on the surface of the screw 14, the buffer device 13 is arranged on the surface of the clamping plate 12, and the abutment plate 15 is arranged at one end of the buffer device 13.

[0021] By adopting the above technical solution, the jet mixer housing 9 can be installed and positioned before use, and the rotating sleeve at the bottom end of the rotating screw 14 can be rotated to rotate it. At the same time, the two sets of clamping plates 12 slide along the guide rod to move away from or approach each other, and then the jet mixer housing 9 is installed in the equipment protection box through the clamping action of the abutment plate 15, thereby ensuring the convenience of installation, improving installation efficiency, and saving human resources.

[0022] Specifically, guide rods are further provided between the fixing plates 11 corresponding to the clamping plates 12 , and one side of the abutting plate 15 is provided as an arc-shaped surface.

[0023] By adopting the above technical solution, the clamping effect of the abutting plate 15 is improved, and the stability of the movement of the clamping plate 12 is ensured.

[0024] Specifically, a bearing seat is provided inside the fixing plate 11 corresponding to the screw rod 14 , and a rotating sleeve is provided on the bottom end surface of the screw rod 14 .

[0025] By adopting the above technical solution, the convenience of using the screw rod 14 is improved and the adjustment efficiency is guaranteed.

[0026] Specifically, the buffer device 13 includes a damping slider 132, a buffer spring 133, a connecting rod 134 and a guide seat 135, wherein the guide seat 135 is arranged on the surface of the clamping plate 12, the damping slider 132 is arranged inside the guide seat 135, the bottom end of the damping slider 132 is arranged with a connecting rod 134, and the surface of the connecting rod 134 is sleeved with a buffer spring 133.

[0027] By adopting the above technical solution, when vibration occurs, the buffer spring 133 is vibrated under force, causing the damping slider 132 to move inside the guide seat 135 and process the elastic potential energy of the buffer spring 133, thereby ensuring that the shock absorption effect can be achieved, ensuring the stability of the jet mixer housing 9 during use, improving the quality of equipment use, and ensuring production efficiency.

[0028] Specifically, a damping pad 131 is provided on the upper end surface of the guide seat 135 , and the bottom end of the connecting rod 134 is mounted on the abutment plate 15 by brazing.

[0029] By adopting the above technical solution, the use strength of the connecting rod 134 and the abutment plate 15 is improved, and the use quality of the equipment is guaranteed.

[0030] The first bubble trap 3, the second bubble trap 4 and the third bubble trap 6 in the utility model are existing known public technologies, and the selected model is: LVF-3526.

[0031] The working principle and use process of the utility model: when the utility model is used, during the preparation process of lipid nanoparticle mixing, the lipid ethanol solution and the nucleotide buffer are respectively introduced into the interior of the jet mixer housing 9 through the first liquid inlet channel 2 and the second liquid inlet channel 5 for mixing, and because the first bubble trap 3 and the second bubble trap 4 are provided, the fluid dynamics caused by the fluid flow and the surface tension caused by the trap wall interact with each other, so that when the fluid with bubbles flows through the hydrophobic valve, the bubbles are discharged through the hydrophobic breathable membrane, and the aqueous liquid is kept in the flow chamber without leakage, ensuring that the lipid ethanol solution and the nucleotide buffer are introduced into the jet mixer housing 9 to the greatest extent possible before the lipid ethanol solution and the nucleotide buffer are introduced into the jet mixer housing 9, and the blockage of bubbles in the downstream of the small-sized channel is effectively avoided, so that the lipid ethanol solution and the nucleotide buffer can be mixed evenly, so that the particle size distribution of the lipid nanoparticles is uniform, the mixing effect of the lipid ethanol solution and the nucleotide buffer is improved, and the quality of the lipid nanoparticles is improved. Before the diluent is added through the third liquid inlet channel 7, the bubbles are also eliminated through the third bubble trap 6, so as to improve the dilution quality and ensure the product qualification rate;

[0032] The jet mixer housing 9 can be installed and positioned before use. The rotating sleeve at the bottom of the rotating screw 14 can be used to rotate it. At the same time, the two sets of clamping plates 12 slide along the guide rod to move away from or close to each other. Then, the jet mixer housing 9 is installed in the equipment protection box through the clamping action of the abutment plate 15, so as to ensure the convenience of installation, improve the installation efficiency, and save human resources. When vibration occurs, the buffer spring 133 is subjected to force vibration, so that the damping slider 132 moves inside the guide seat 135 and processes the elastic potential energy of the buffer spring 133, so as to ensure that the shock absorption effect can be achieved, and the stability of the jet mixer housing 9 during use is ensured, the use quality of the equipment is improved, and the production efficiency is ensured.

[0033] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A lipid nanoparticle mixing and preparation device with an integrated bubble trap, comprising a jet mixer housing, characterized in that: A first liquid inlet channel is arranged at the upper end of the jet mixer housing, a first bubble trap is arranged at the liquid inlet end of the first liquid inlet channel, a second liquid inlet channel is arranged at one side of the jet mixer housing, a second bubble trap is arranged at the liquid inlet end of the second liquid inlet channel, a positioning and mounting assembly is arranged at the side of the jet mixer housing away from the second liquid inlet channel, a drain pipe is arranged at the bottom end of the jet mixer housing, a third liquid inlet channel is arranged at one side of the drain pipe, and a third bubble trap is arranged at the liquid inlet end of the third liquid inlet channel.

2. The lipid nanoparticle mixing and preparation device with integrated bubble trap according to claim 1, characterized in that: The positioning and mounting assembly includes a fixing plate, a clamping plate, a buffer device, a screw and an abutment plate, wherein a fixing plate is symmetrically arranged on one side of the jet mixer housing, a screw is arranged between the fixing plates, a clamping plate is symmetrically arranged on the surface of the screw, a buffer device is arranged on the surface of the clamping plate, and an abutment plate is arranged at one end of the buffer device.

3. The lipid nanoparticle mixing and preparation device with integrated bubble trap according to claim 2, characterized in that: A guide rod is further arranged between the fixing plates corresponding to the clamping plates, and one side of the abutting plate is arranged as an arc surface.

4. The lipid nanoparticle mixing and preparation device with integrated bubble trap according to claim 2, characterized in that: A bearing seat is arranged inside the fixing plate corresponding to the screw rod, and a rotating sleeve is arranged on the bottom end surface of the screw rod.

5. The lipid nanoparticle mixing and preparation device with integrated bubble trap according to claim 2, characterized in that: The buffer device includes a damping slider, a buffer spring, a connecting rod and a guide seat, wherein a guide seat is arranged on the surface of the clamping plate, a damping slider is arranged inside the guide seat, a connecting rod is arranged at the bottom end of the damping slider, and a buffer spring is sleeved on the surface of the connecting rod.

6. The lipid nanoparticle mixing and preparation device with integrated bubble trap according to claim 5, characterized in that: The upper end surface of the guide seat is provided with a damping pad, and the bottom end of the connecting rod is mounted on the abutment plate by brazing.

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