An mRNA biopharmaceutical device lipid nanoparticle preparation mixing device
By using a micro-stirring mechanism and spiral groove in the mixing device during mRNA vaccine preparation, the problem of uneven mixing was solved, achieving efficient and uniform LNP preparation while reducing energy consumption and structural complexity.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- HEFEI AFANA BIOTECHNOLOGY CO LTD
- Filing Date
- 2025-06-10
- Publication Date
- 2026-07-03
AI Technical Summary
In the existing technology, the mixing uniformity is insufficient during the LNP preparation process of mRNA vaccines, especially when the fluid flow rate is low or the mixing chamber size is large. Simple impact is difficult to overcome diffusion limitations, resulting in uneven mixing.
A mixing device for preparing lipid nanoparticles using mRNA biopharmaceutical equipment is presented. The device includes a mixing channel, a micro-stirring mechanism, and a spiral groove. Through the combined action of an impeller and a stirring paddle, a self-driven mixing system is formed by utilizing fluid dynamics and mechanical stirring, which enhances turbulence and shear force and ensures mixing uniformity.
It improves the mixing efficiency and quality of LNP preparation, solves the problems of long mixing time and insufficient uniformity, and reduces equipment energy consumption and structural complexity.
Smart Images
Figure CN224442807U_ABST
Abstract
Description
Technical Field
[0001] This utility model belongs to the field of biological agent equipment technology, specifically relating to a lipid nanoparticle preparation and mixing device for mRNA biological agents. Background Technology
[0002] Besides inactivated antigens, a large portion of vaccine drugs are mRNA vaccines. These mRNA vaccines work by transcribing mRNA in the human body to produce immunogenic target proteins, thereby preventing or treating various diseases.
[0003] The preparation process of mRNA drugs is roughly as follows: First, Escherichia coli is cultured as a vector, and then concentrated through a hollow fiber column to obtain a high concentration of E. coli culture. Next, the stock solution is obtained through fermentation, alkaline lysis, filtration and clarification. The stock solution is then purified by chromatography to obtain a plasmid DNA template. The template is digested with enzymes and transcribed in vitro to obtain mRNA. Finally, the mRNA is encapsulated using lipid nanoparticle (LNP) technology to obtain the mRNA vaccine product.
[0004] LNP-mRNA is prepared by mixing ionizable cationic lipids, phospholipids, cholesterol, and PEG lipids with mRNA using microfluidic technology to form stable and highly efficient delivery nanoparticles.
[0005] Currently, the most common method for preparing LNPs in mRNA vaccines is microfluidic mixing or rapid liquid-phase mixing. The core principle is to achieve rapid turbulent mixing of the lipid organic phase (such as lipids dissolved in ethanol) and the aqueous phase (buffer solution containing mRNA) by controlling the liquid flow rate, and to utilize the self-assembly of lipids in the aqueous phase to form nanoparticles.
[0006] In existing technologies, the main method relies on a liquid pump to drive two fluids to collide at high speed in a microchannel or mixing chamber, achieving mixing through fluid dynamics. While this can meet general mixing requirements, in practical applications, when the fluid velocity is low or the mixing chamber size is large, simple collisions may not be able to overcome diffusion limitations, resulting in insufficient mixing uniformity.
[0007] To address the aforementioned issues, this application proposes an mRNA biopharmaceutical preparation and mixing device for lipid nanoparticles. Utility Model Content
[0008] To address the aforementioned problems in the existing technology, this invention provides a lipid nanoparticle preparation and mixing device for mRNA biological agents, which is convenient to use and provides uniform mixing.
[0009] To achieve the above objectives, this utility model provides the following technical solution: a lipid nanoparticle preparation and mixing device for mRNA biopharmaceuticals, comprising a mixing channel, wherein a first injection port for injecting a lipid ethanol solution and a second injection port for injecting an mRNA aqueous solution are respectively fixed on the mixing channel, and further comprising a micro-stirring mechanism, wherein the micro-stirring mechanism includes:
[0010] A rotating rod, which is rotatably mounted within the mixing channel;
[0011] The impeller is fixed on the rotating rod and faces the second injection port.
[0012] A stirring paddle, which is fixed to the rotating rod.
[0013] Preferably, the micro-stirring mechanism further includes:
[0014] The spiral blades are fixed at equal intervals on the rotating rod, and the spiral blades are fixed on the rotating rod and located between the two sets of the stirring blades.
[0015] Preferably, the rotating rod is rotatably mounted within the mixing channel using a mounting bracket, wherein the mounting bracket includes:
[0016] An outer fixing ring is fixed within the mixing channel;
[0017] An inner fixing ring, wherein the inner fixing ring is located inside the outer fixing ring and is coaxial with the outer fixing ring;
[0018] Multiple fixing rods are used to fix the inner fixing ring to the outer fixing ring.
[0019] The bearing is used to rotatably connect the rotating rod to the inner fixed ring.
[0020] Preferably, the mounting brackets are arranged in two sets at intervals, and the impeller is located between the two sets of mounting brackets.
[0021] Preferably, the outer fixing ring near the stirring paddle is a semi-circular ring-shaped component with the arc opening facing downwards.
[0022] Preferably, the mixing channel includes a detachably connected mixing tube, an installation tube, and a plug, and the first injection port is fixed on the mixing tube, and the second injection port is fixed on the installation tube.
[0023] Preferably, one end of the mounting pipe is connected to the mixing pipe via a flange, and the other end is connected to the plug via a flange.
[0024] Preferably, a spiral groove is formed on the inner wall of the mixing tube.
[0025] Compared with the prior art, the beneficial effects of this utility model are:
[0026] In this invention, a micro-stirring mechanism is used in conjunction with the inner wall of the spiral groove to actively introduce mechanical stirring during fluid flow, thereby enhancing turbulence and shear force. This solves the defects of long mixing time and insufficient uniformity caused by diffusion limitation, and improves the efficiency and quality of LNP preparation.
[0027] Other additional advantages and benefits of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Attached Figure Description
[0028] The accompanying drawings are provided to further illustrate the present invention and form part of the specification. They are used together with the embodiments of the present invention to explain the present invention, but do not constitute a limitation thereof. In the drawings:
[0029] Figure 1 This is a schematic diagram of the structure of this utility model;
[0030] Figure 2 This is a cross-sectional structural diagram of the present invention;
[0031] Figure 3 This is an isometric structural diagram of the micro stirring mechanism in this utility model;
[0032] Figure 4 This is a schematic diagram of the hybrid tube isometric structure of this utility model.
[0033] In the diagram: 1. Mixing channel; 11. Mixing pipe; 111. Spiral groove; 12. Mounting pipe; 13. Plug; 2. No. 1 injection port; 3. No. 2 injection port; 4. Micro stirring mechanism; 41. Rotating rod; 42. Mounting bracket; 421. Outer fixing ring; 422. Inner fixing ring; 423. Fixing rod; 424. Bearing; 43. Impeller; 44. Stirring paddle; 45. Spiral blade. Detailed Implementation
[0034] The technical solutions of the present utility model will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present utility model, and not all embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present utility model.
[0035] Please see Figures 1-4The present invention provides the following technical solution: a lipid nanoparticle preparation mixing device for mRNA biological agents, including a mixing channel 1, wherein a first injection port 2 for injecting lipid ethanol solution and a second injection port 3 for injecting mRNA aqueous solution are fixed on the mixing channel 1, and further includes a micro stirring mechanism 4, wherein the micro stirring mechanism 4 includes a rotating rod 41, an impeller 43 and a stirring paddle 44.
[0036] Furthermore, by Figures 1-3 As shown in this embodiment, the rotating rod 41 is rotatably installed in the mixing channel 1, the impeller 43 is fixed on the rotating rod 41 and faces the second injection port 3, and the stirring paddle 44 is fixed on the rotating rod 41. With the above scheme, when in use, the lipid ethanol solution is injected into the mixing channel 1 through the first injection port 2 at a constant flow rate using an injection pump. At the same time, the mRNA aqueous solution (buffer containing mRNA) is injected into the mixing channel 1 at a constant flow rate.
[0037] Since the No. 2 injection port 3 is directly facing the curved surface of the blades of the impeller 43, the high-speed flowing mRNA aqueous solution will first impact the impeller 43. By utilizing the principle of fluid dynamics, part of the kinetic energy of the liquid is converted into the rotational mechanical energy of the impeller 43. The impeller 43 drives the stirring paddle 44 to rotate synchronously through the rotating rod 41, forming a self-driven hybrid power system. There is no need to configure additional drive devices such as motors, which greatly reduces the energy consumption and structural complexity of the equipment.
[0038] After the impeller 43 starts to rotate, its first function is to initially disperse the mRNA aqueous solution that has just entered the mixing channel 1. The high-speed flowing aqueous solution forms turbulence under the cutting of the blades of the impeller 43, so that the mRNA molecules in the solution are evenly distributed in the liquid phase, avoiding the problem of uneven mixing in the later stage due to excessively high local concentration.
[0039] Next, the stirring paddle 44 at the end of the rotating rod 41 begins to play a mixing role: it breaks the interface layer between the lipid ethanol solution and the mRNA aqueous solution through radial shear force, promoting the rapid diffusion of the two solutions.
[0040] As the two solutions were continuously injected, the ethanol in the lipid ethanol solution, as an organic solvent, was rapidly diluted when mixed with the aqueous phase, resulting in a decrease in the solubility of lipid molecules and the initiation of self-assembly to form nanoscale micelles.
[0041] During the mixing process, the rotation speed of the rotating rod 41 will adaptively adjust with the flow rate of the mRNA aqueous solution: when the flow rate of the second injection port 3 increases, the fluid kinetic energy of the impeller 43 is enhanced, and the rotation speed of the impeller 43 increases accordingly, driving the stirring paddle 44 to shear the mixture at a higher frequency; conversely, when the flow rate decreases, the rotation speed automatically decreases, forming an adaptive mixing intensity adjustment system to meet the strict requirements of mRNA vaccines for carrier particles.
[0042] Preferably, by Figures 1-3 As shown, in this embodiment, the micro-stirring mechanism 4 further includes: a spiral blade 45, two sets of stirring paddles 44 fixed at equal intervals on the rotating rod 41, and the spiral blade 45 fixed on the rotating rod 41 and located between the two sets of stirring paddles 44. With the above scheme, when in use, the spiral direction of the spiral blade 45 is consistent with the rotation direction of the rotating rod 41. When rotating, it applies axial thrust to the mixture through its curved surface structure. Specifically, when the rotating rod 41 rotates clockwise, the lifting surface of the spiral blade 45 pushes the mixture from the front stirring paddle 44 area to the rear stirring paddle 44 area; at the same time, the radial flow generated by the rotation of the rear stirring paddle 44 will squeeze some liquid against the wall of the mixing channel 1, forming a reverse radial backflow. After the two flows are superimposed, a circulation mode of "central axial flow and wall radial backflow" is formed in the mixing channel 1, so that the path of the mixture changes from a straight line to a figure-eight reciprocating flow, which prolongs the residence time of the two-phase fluid in the mixing channel 1 and significantly improves the mixing uniformity.
[0043] Preferably, by Figures 1-3 As shown in this embodiment, the rotating rod 41 is rotatably mounted in the mixing channel 1 using a mounting frame 42. The mounting frame 42 includes an outer fixing ring 421, an inner fixing ring 422, multiple fixing rods 423, and a bearing 424. The outer fixing ring 421 is fixed in the mixing channel 1, and the inner fixing ring 422 is located inside the outer fixing ring 421 and is coaxial with the outer fixing ring 421. The inner fixing ring 422 is fixed in the outer fixing ring 421 using multiple fixing rods 423 that are evenly distributed along the circumferential direction. The rotating rod 41 is rotatably connected to the inner fixing ring 422 using the bearing 424. With the above solution, in use, the outer fixing ring 421, the inner fixing ring 422, and the multiple fixing rods 423 form the main frame to ensure the stability of the rotating rod 41 installed in the mixing channel 1.
[0044] The bearing 424 effectively reduces the rotational resistance of the rotating rod 41, ensuring smoother rotation of the rotating rod 41 and guaranteeing that the micro stirring mechanism 4 can reliably perform the stirring function.
[0045] Preferably, by Figures 1-3 As shown in this embodiment, there are two sets of mounting brackets 42 spaced apart, and the impeller 43 is located between the two sets of mounting brackets 42. With the above scheme, when in use, the two sets of spaced mounting brackets 42 are used to support the rotating rod 41, which has high stability and avoids the problem of the rotating rod 41 tilting due to uneven force on one side, ensuring that the micro stirring mechanism 4 can reliably perform the stirring function.
[0046] Preferably, by Figures 1-3As shown in this embodiment, the outer fixing ring 421 near the stirring paddle 44 is a semi-circular ring-shaped component with the arc opening facing downward. With the above solution, the purpose of this design is to avoid the outer fixing ring 421 from causing mechanical obstruction to the fluid during use.
[0047] Preferably, by Figure 1 and Figure 2 As shown in this embodiment, the mixing channel 1 includes a detachably connected mixing tube 11, an installation tube 12, and a plug 13. The first injection port 2 is fixed on the mixing tube 11, and the second injection port 3 is fixed on the installation tube 12. With the above solution, in use, the traditional integrated mixing channel 1 is prone to blockage due to lipid deposition and nanoparticle adsorption after long-term operation. The mixing channel 1 of this utility model adopts a detachable modular design, which is convenient for disassembly and cleaning. Damaged parts can also be replaced individually, reducing maintenance costs.
[0048] Optionally, by Figure 1 and Figure 2 As shown in this embodiment, one end of the installation pipe 12 is connected to the mixing pipe 11 via a flange, and the other end is connected to the plug 13 via a flange. With the above solution, the flange connection is more stable and has higher sealing performance during use, and it is also easier to disassemble and clean.
[0049] Site selection, by Figure 1 , Figure 2 and Figure 4 As shown in this embodiment, a spiral groove 111 is provided on the inner wall of the mixing tube 11. With the above solution, when the mixed liquid flows through the mixing tube 11, the spiral groove 111 on the inner wall will guide the fluid.
[0050] The radial shear flow generated by the rotation of the agitator 44 and the spiral flow guided by the spiral groove 111 superimpose each other, extending the fluid flow path, prolonging the contact time between the two phases, and significantly improving the mixing uniformity.
[0051] Components not described in detail in this article are existing technologies.
[0052] The working principle and usage process of this utility model: When using the mixing device of this utility model, the lipid ethanol solution is injected into the mixing channel 1 at a constant flow rate through the injection port 2 using an injection pump. At the same time, the mRNA aqueous solution (buffer solution containing mRNA) is injected into the mixing channel 1 at a constant flow rate.
[0053] Since the No. 2 injection port 3 is directly facing the blade surface of the impeller 43, the high-speed flowing mRNA aqueous solution will first impact the impeller 43. By utilizing the principle of fluid dynamics, part of the kinetic energy of the liquid is converted into the rotational mechanical energy of the impeller 43. The impeller 43 drives the stirring paddle 44 to rotate synchronously through the rotating rod 41, forming a self-driven hybrid power system. There is no need to configure additional drive devices such as motors, which greatly reduces the energy consumption and structural complexity of the equipment.
[0054] After the impeller 43 starts to rotate, its first function is to initially disperse the mRNA aqueous solution that has just entered the mixing channel 1. The high-speed flowing aqueous solution forms turbulence under the cutting of the blades of the impeller 43, so that the mRNA molecules in the solution are evenly distributed in the liquid phase, avoiding the problem of uneven mixing in the later stage due to excessively high local concentration.
[0055] Next, the stirring paddle 44 at the end of the rotating rod 41 begins to play a mixing role: it breaks the interface layer between the lipid ethanol solution and the mRNA aqueous solution through radial shear force, promoting the rapid diffusion of the two solutions.
[0056] As the two solutions were continuously injected, the ethanol in the lipid ethanol solution, as an organic solvent, was rapidly diluted when mixed with the aqueous phase, resulting in a decrease in the solubility of lipid molecules and the initiation of self-assembly to form nanoscale micelles.
[0057] During the mixing process, the rotation speed of the rotating rod 41 will adaptively adjust with the flow rate of the mRNA aqueous solution: when the flow rate of the second injection port 3 increases, the fluid kinetic energy of the impeller 43 is enhanced, and the rotation speed of the impeller 43 increases accordingly, driving the stirring paddle 44 to shear the mixture at a higher frequency; conversely, when the flow rate decreases, the rotation speed automatically decreases, forming an adaptive mixing intensity adjustment system to meet the strict requirements of mRNA vaccines for carrier particles.
[0058] In addition, a spiral groove 111 is provided on the inner wall of the mixing tube 11. When the mixed liquid flows through the mixing tube 11, the spiral groove 111 on the inner wall will guide the fluid. The radial shear flow generated by the rotation of the stirring paddle 44 and the spiral flow guided by the spiral groove 111 are superimposed, which prolongs the fluid flow path, prolongs the contact time of the two-phase fluid, and significantly improves the mixing uniformity.
[0059] Finally, it should be noted that the above description is merely a preferred embodiment of this utility model and is not intended to limit the utility model. Although the utility model has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this utility model should be included within the protection scope of this utility model.
Claims
1. An mRNA biologics device lipid nanoparticle preparation mixing device, comprising a mixing channel (1), a first liquid injection port (2) for injecting a lipid ethanol solution and a second liquid injection port (3) for injecting an mRNA aqueous solution are respectively fixed on the mixing channel (1), characterized in that, The system further includes a micro-stirring mechanism (4), wherein the micro-stirring mechanism (4) comprises: Rotating rod (41), the rotating rod (41) is rotatably mounted in the mixing channel (1); Impeller (43), which is fixed on the rotating rod (41) and faces the second injection port (3); A stirring paddle (44) is fixed on the rotating rod (41).
2. The mRNA biologic device lipid nanoparticle preparation mixing device of claim 1, wherein: The micro stirring mechanism (4) further includes: The spiral blade (45) and two sets of the stirring paddles (44) are fixed at equal intervals on the rotating rod (41). The spiral blade (45) is fixed on the rotating rod (41) and located between the two sets of the stirring paddles (44).
3. The mRNA biologic device lipid nanoparticle preparation mixing device of claim 1, wherein: The rotating rod (41) is rotatably mounted in the mixing channel (1) by means of a mounting bracket (42), wherein the mounting bracket (42) comprises: An outer fixing ring (421) is fixed inside the mixing channel (1); An inner fixing ring (422) is located inside the outer fixing ring (421) and is coaxial with the outer fixing ring (421); Multiple fixing rods (423) are used to fix the inner fixing ring (422) to the outer fixing ring (421) by multiple fixing rods (423) that are equally spaced along the circumferential direction; The bearing (424) is used to rotatably connect the rotating rod (41) to the inner fixed ring (422).
4. The mRNA biopharmaceutical device lipid nanoparticle preparation mixing device of claim 3, wherein: The mounting brackets (42) are distributed in two sets at intervals, and the impeller (43) is located between the two sets of mounting brackets (42).
5. The mRNA biopharmaceutical device lipid nanoparticle preparation mixing device of claim 4, wherein: The outer fixing ring (421) near the stirring paddle (44) is a semi-circular ring-shaped component with the arc opening facing downward.
6. The mRNA biopharmaceutical device lipid nanoparticle preparation mixing device of claim 1, wherein: The mixing channel (1) includes a detachably connected mixing tube (11), an installation tube (12), and a plug (13), and the first injection port (2) is fixed on the mixing tube (11), and the second injection port (3) is fixed on the installation tube (12).
7. The mRNA biopharmaceutical device lipid nanoparticle preparation mixing device of claim 6, wherein: One end of the installation pipe (12) is connected to the mixing pipe (11) via a flange, and the other end is connected to the plug (13) via a flange.
8. The mRNA biopharmaceutical device lipid nanoparticle preparation mixing device of claim 7, wherein: A spiral groove (111) is provided on the inner wall of the mixing tube (11).