Flow velocity self-calibration lipid nanoparticle mixing preparation system

Abstract

The utility model discloses a lipid nanoparticle mixing preparation system with a self-calibration flow rate. The system comprises a first infusion assembly, a second infusion assembly and a third infusion assembly, a first mixer and a second mixer; calibrating a central control host; each liquid conveying assembly comprises a liquid storage device, a plunger pump and a flow velocity sensor which are sequentially connected, a first weighing meter is connected between the flow velocity sensor of the first liquid conveying assembly and the first mixer, and a second weighing meter is connected between the flow velocity sensor of the second liquid conveying assembly and the first mixer; a third weighing meter is connected between the flow velocity sensor of the third infusion assembly and the second mixer, and the first weighing meter, the second weighing meter and the third weighing meter are connected to the calibration central control host. And a self-calibration function is set, so that each flow velocity sensor can be calibrated, and the accuracy and stability of process parameters in production can be maintained.

Description

Technical Field

[0001] The utility model relates to the technical field of biomedical equipment, and in particular to a lipid nanoparticle mixing preparation system with self-calibration of flow rate. Background Art

[0002] Lipid nanoparticles (LNPs) are being developed as delivery vehicles for active pharmaceutical ingredients. These tiny lipid vesicles can encapsulate unstable drugs and deliver them to the interior of cells, reducing the likelihood of them being broken down in the bloodstream, thereby prolonging the drug's presence in the body and enhancing its efficacy.

[0003] However, the preparation of lipid nanoparticles still faces some challenges. For example, after a predetermined period of operation, the flow rate metering device may deviate, resulting in errors in the preparation process. The particle size, encapsulation efficiency and other physical and chemical properties of lipid nanoparticles are easily affected by the preparation process, which leads to poor batch consistency of the prepared lipid nanoparticles; therefore, technicians in this field urgently need to develop a reliable, efficient, and self-calibrated lipid nanoparticle mixing preparation system. Utility Model Content

[0004] In order to solve the above problems existing in the prior art, the utility model provides a lipid nanoparticle mixing preparation system with self-calibration of flow rate, which solves the problem that the flow rate metering equipment is prone to deviation after long-term use.

[0005] The purpose of the utility model can be achieved through the following technical solutions:

[0006] A lipid nanoparticle mixing preparation system with self-calibration of flow rate, comprising:

[0007] A first infusion assembly, a second infusion assembly, and a third infusion assembly;

[0008] a first mixer and a second mixer;

[0009] Calibrate the central control host;

[0010] The infusion assembly includes a reservoir, a plunger pump and a flow rate sensor connected in sequence, the first mixer and the second mixer respectively include a first input end, a second input end and an output end, the first input end of the first mixer is connected to the first infusion assembly, the second input end of the first mixer is connected to the second infusion assembly, the first input end of the second mixer is connected to the output end of the first mixer, and the second input end of the second mixer is connected to the third infusion assembly;

[0011] A first weighing meter is connected between the flow rate sensor of the first infusion component and the first mixer, a second weighing meter is connected between the flow rate sensor of the second infusion component and the first mixer, a third weighing meter is connected between the flow rate sensor of the third infusion component and the second mixer, and the first weighing meter, the second weighing meter and the third weighing meter are connected to the calibration central control host.

[0012] Preferably, the first weighing meter, the second weighing meter and the third weighing meter all include a liquid storage tank, a liquid inlet, a liquid outlet, a density sensor and a weighing sensor.

[0013] Preferably, a first reflux pump is arranged between the first weighing meter and the reservoir of the first infusion component, a second reflux pump is arranged between the second weighing meter and the reservoir of the second infusion component, and a third reflux pump is arranged between the third weighing meter and the reservoir of the third infusion component.

[0014] Preferably, the first mixer and the second mixer are T-type mixers.

[0015] Preferably, the reservoir of the first infusion component, the reservoir of the second infusion component, and the reservoir of the third infusion component respectively store an mRNA solution, a lipid solution, and a dilution solution.

[0016] Preferably, the lipid nanoparticle mixing preparation system with self-calibration of flow rate further comprises a product collector, which is connected to the output end of the second mixer.

[0017] The beneficial effects of the present invention are:

[0018] The utility model discloses a lipid nanoparticle mixing preparation system with self-calibration of flow rate. The system is provided with a self-calibration function through a flow rate sensor and a weighing meter, and can calibrate each flow rate sensor, which helps to maintain the accuracy and stability of process parameters in production, thereby ensuring the flow rate accuracy of various types of solutions, and further ensuring the ratio of lipids and active ingredients, achieving the purpose of improving the consistency within and between batches. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to facilitate understanding by those skilled in the art, the present invention is further described below with reference to the accompanying drawings.

[0020] Figure 1 It is a schematic diagram of the overall structure of the first embodiment of the utility model;

[0021] Figure 2 It is a structural schematic diagram of a weighing meter according to a first embodiment of the utility model;

[0022] Figure 3 It is a schematic diagram of the overall structure of the second embodiment of the utility model.

[0023] Description of main component symbols:

[0024] 101, a first liquid reservoir; 102, a second liquid reservoir; 103, a third liquid reservoir;

[0025] 201, a first plunger pump; 202, a second plunger pump; 203, a third plunger pump;

[0026] 301, a first flow velocity sensor; 302, a second flow velocity sensor; 303, a third flow velocity sensor;

[0027] 311, pressure sensor; 312, second pressure sensor; 313, third pressure sensor;

[0028] 401, a first weighing meter; 402, a second weighing meter; 403, a third weighing meter;

[0029] 41. Liquid storage tank; 42. Liquid inlet; 43. Liquid outlet; 44. Density sensor; 45. Weighing sensor;

[0030] 501, a first mixer; 502, a second mixer;

[0031] 601, a first reflux pump; 602, a second reflux pump; 603, a third reflux pump;

[0032] 7. Calibrate the central control host;

[0033] 8. Product collector;

[0034] 901, first stop valve; 902, second stop valve; 903, third stop valve;

[0035] 1001, first control valve; 1002, second control valve; 1003, third control valve;

[0036] 1101, first reflux valve; 1102, second reflux valve; 1103, third reflux valve. DETAILED DESCRIPTION

[0037] In order to make the technical personnel in this field better understand the present application scheme, the following will be combined with the attached Figure 1-2 , a clear and complete description of the technical solutions in the embodiments of the utility model is given.

[0038] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "provided with", "connected", etc. should be understood in a broad sense. For example, "connected" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be an indirect connection through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0039] As a first embodiment of the present invention, a lipid nanoparticle mixing preparation system with self-calibration of flow rate comprises:

[0040] A first infusion assembly, a second infusion assembly, and a third infusion assembly;

[0041] A first mixer 501 and a second mixer 502;

[0042] Calibrate the central control host 7;

[0043] The infusion component includes a reservoir, a plunger pump and a flow rate sensor connected in sequence. The first mixer 501 and the second mixer 502 respectively include a first input end, a second input end and an output end. The first input end of the first mixer 501 is connected to the first infusion component, the second input end of the first mixer 501 is connected to the second infusion component, the first input end of the second mixer 502 is connected to the output end of the first mixer 501, the second input end of the second mixer 502 is connected to the third infusion component, and the flow rate sensor is electrically connected to the calibration central control host 7.

[0044] The first infusion assembly includes a first liquid reservoir 101, a first plunger pump 201 and a first flow rate sensor 301;

[0045] The second infusion assembly includes a second fluid reservoir 102, a second plunger pump 202 and a second flow rate sensor 302;

[0046] The third infusion assembly includes a third liquid reservoir 103, a third plunger pump 203 and a third flow rate sensor 303;

[0047] A first weighing meter 401 is connected between the first flow rate sensor 301 and the first mixer 501, a second weighing meter 402 is connected between the second flow rate sensor 302 and the first mixer 501, a third weighing meter 403 is connected between the third flow rate sensor 303 and the second mixer 502, and the first weighing meter 401, the second weighing meter 402 and the third weighing meter 403 are connected to the calibration central control host 7.

[0048] The first flow rate sensor 301 is arranged between the liquid outlet of the first plunger pump 201 and the first mixer 501; the second flow rate sensor 302 is arranged between the liquid outlet of the second plunger pump 202 and the first mixer 501; the third flow rate sensor 303 is arranged between the liquid outlet of the third plunger pump 203 and the second mixer 502, and the first flow rate sensor 301, the second flow rate sensor 302, and the third flow rate sensor 303 are all electrically connected to the calibration central control host 7;

[0049] Among them, the liquid inlet of the first plunger pump 201 is connected to the liquid outlet of the first liquid reservoir 101, the liquid inlet of the second plunger pump 202 is connected to the liquid outlet of the second liquid reservoir 201, the liquid inlet of the third plunger pump 203 is connected to the liquid outlet of the third liquid reservoir 103, the first input end and the second input end of the first mixer 501 are respectively connected to the liquid outlet of the first plunger pump 201 and the second plunger pump 202, and the first input end and the second input end of the second mixer 502 are respectively connected to the output end of the first mixer 501 and the liquid outlet of the third plunger pump 203.

[0050] In this embodiment, the first liquid reservoir 101 stores an mRNA solution, the second liquid reservoir 102 stores a lipid solution, and the third liquid reservoir 103 stores a dilution solution;

[0051] This embodiment is also provided with a first weighing meter 401, a second weighing meter 402, and a third weighing meter 403. The first weighing meter 401 is arranged between the liquid outlet of the first plunger pump 201 and the first mixer 501, the second weighing meter 402 is arranged between the liquid outlet of the second plunger pump 202 and the first mixer 501, and the third weighing meter 403 is arranged between the liquid outlet of the third plunger pump 203 and the second mixer 502.

[0052] The first weighing meter 401, the second weighing meter 402, and the third weighing meter 403 each include a liquid storage tank 41, a liquid inlet 42, a liquid outlet 43, a density sensor 44, and a weighing sensor 45. In this embodiment, the first weighing meter 401, the second weighing meter 402, and the third weighing meter 403 are each provided with four weighing sensors 45, and the four weighing sensors 45 are respectively located at the four corners of the liquid storage tank 41. When liquid flows into the liquid storage tank 41 through the liquid inlet 42, the density sensor 44 obtains the density of the flowing liquid and transmits the value to the calibration central control host 7, and the weighing sensor 45 is subjected to the pressure of the liquid and transmits the value to the calibration central control host 7.

[0053] In this embodiment, a first reflux pump 601 is further provided between the first liquid reservoir 101 and the first weighing scale 401 , a second reflux pump 602 is provided between the second liquid reservoir 102 and the second weighing scale 402 , and a third reflux pump 603 is provided between the third liquid reservoir 103 and the third weighing scale 403 .

[0054] Further, a first stop valve 901 is connected between the liquid outlet of the first plunger pump 201 and the first input end of the first mixer 501, so as to control the liquid to flow from the liquid outlet of the first plunger pump 201 to the first input end of the first mixer 501. A second stop valve 902 is connected between the liquid outlet of the second plunger pump 202 and the second input end of the first mixer 501, so as to control the liquid to flow from the liquid outlet of the second plunger pump 202 to the second input end of the first mixer 501. A third stop valve 903 is connected between the third plunger pump 203 and the second input end of the second mixer 502, so as to control the liquid to flow from the third plunger pump 203 to the second input end of the second mixer 502;

[0055] A first control valve 1001 is connected between the liquid inlet 42 of the first weighing meter 401 and the liquid outlet of the first plunger pump 201, for controlling the liquid to flow from the first plunger pump 201 to the liquid inlet 42 of the first weighing meter 401. A second control valve 1002 is connected between the liquid inlet 42 of the second weighing meter 402 and the liquid outlet of the second plunger pump 202, for controlling the liquid to flow from the second plunger pump 202 to the liquid inlet 42 of the second weighing meter 402. A third control valve 1003 is connected between the liquid inlet 42 of the third weighing meter 403 and the liquid outlet of the third plunger pump 203, for controlling the liquid to flow from the third plunger pump 203 to the liquid inlet 42 of the third weighing meter 403;

[0056] A first reflux valve 1101 is connected between the liquid outlet 43 of the first weighing meter 401 and the first liquid reservoir 101 to control the liquid in the liquid reservoir 41 of the first weighing meter 401 to flow to the first liquid reservoir 101. A second reflux valve 1102 is connected between the liquid outlet 43 of the second weighing meter 402 and the second liquid reservoir 102 to control the liquid in the liquid reservoir 41 of the second weighing meter 402 to flow to the second liquid reservoir 102. A third reflux valve 1103 is connected between the liquid outlet 43 of the third weighing meter 403 and the third liquid reservoir 103 to control the liquid in the liquid reservoir 41 of the third weighing meter 403 to flow to the third liquid reservoir 103. Figure 1 shown.

[0057] The first stop valve 901, the second stop valve 902, the third stop valve 903, the first control valve 1001, the second control valve 1002, the third control valve 1003, the first return valve 1101, the second return valve 1102 and the third return valve 1103 can be manual control valves or pneumatic or electric opening / closing control valves.

[0058] In order to avoid the possibility of deviation of the flow rate metering device after a predetermined period of operation, the lipid nanoparticle mixing preparation system with self-calibration of flow rate is provided with a self-calibration function.

[0059] The flow sensor calibration process is as follows:

[0060] The following takes the calibration of the first flow rate sensor 301 as an example. When the first flow rate sensor 301 needs to be calibrated, the first stop valve 901 and the first return valve 1101 are closed, and the first control valve 1001 is opened, so that the output liquid of the first plunger pump 201 does not flow into the first mixer 501, but flows into the liquid storage tank 41 of the first weighing meter 401 from the liquid inlet 42 of the first weighing meter 401. The density sensor 45 of the first weighing meter 401 obtains the true density of the inflowing liquid to avoid the density value being affected by the temperature. The weighing sensor 46 transmits the pressure value to the calibration central control host 7. The calibration central control host 7 obtains the volume of the inflowing liquid by dividing the pressure value by the density value, and divides the volume of the inflowing liquid by a certain interval time to obtain the true flow rate of the liquid in the connecting pipe. And adjust the reading from the first flow rate sensor 301 so that the reading conforms to the calculated actual flow rate;

[0061] When the first flow rate sensor 301 is calibrated, the first control valve 1001 is closed, and the first stop valve 901 and the first reflux valve 1101 are opened. At this time, the liquid in the liquid storage tank 41 of the first weighing meter 401 flows out from the liquid outlet 43 of the first weighing meter 401 and flows back to the first liquid reservoir 101 under the action of the first reflux pump 601.

[0062] The above is the calibration process of the first flow velocity sensor 301 . The calibration processes of the second flow velocity sensor 302 and the third flow velocity sensor 303 are similar to this, so they will not be described in detail here.

[0063] The mixing process of the lipid nanoparticle mixing preparation system with self-calibration of flow rate in this embodiment is as follows:

[0064] When in a mixed state, the first stop valve 901, the second stop valve 902 and the third stop valve 903 are in an open state, and the first control valve 1001, the second control valve 1002, the third control valve 1003, the first return valve 1101, the second return valve 1102 and the third return valve 1103 are in a closed state, and the liquid does not flow into the first weighing meter 401, the second weighing meter 402 and the third weighing meter 403.

[0065] The first plunger pump 201 and the second plunger pump 202 respectively transport the mRNA solution in the first liquid reservoir 101 and the lipid solution in the second liquid reservoir 102 to the first mixer 601 for mixing at a set flow rate, and the flow rate is set according to the preparation process requirements. After the mRNA solution and the lipid solution are mixed, a lipid nanoparticle solution containing lipid nanoparticles is formed, and then the lipid nanoparticle solution is introduced into the first input end of the second mixer through the output end of the first mixer 501. At the same time, the third plunger pump 203 transports the diluted solution in the third liquid reservoir 103 to the second mixer 502 at a set flow rate. The flow rate is set according to the preparation process requirements. The two-phase solution is diluted and mixed in the second mixer 502. Finally, the diluted and mixed solution is introduced into the product collector 8 for storage through the output end of the second mixer 502.

[0066] During the mixing operation, the first flow rate sensor 301, the second flow rate sensor 302 and the third flow rate sensor 303 will monitor the liquid flow rate in the pipeline in real time and transmit the numerical value to the calibration central control host 7. When it is detected that the deviation between the flow rate and the set value exceeds the set threshold, the calibration central control host 7 can send a signal to remind the user to make manual adjustments; the calibration central control host 7 can also directly automatically adjust the first flow rate sensor 301, the second flow rate sensor 302 and the third flow rate sensor 303.

[0067] It should be noted that, based on this embodiment, the technicians can also calibrate the first plunger pump 201, the second plunger pump 202, and the third plunger pump 203 according to the readings of the first flow velocity sensor 301, the second flow velocity sensor 302, and the third flow velocity sensor 303. The specific principles are as follows:

[0068] Take the calibration of the first plunger pump 201 as an example. First, determine the target flow value of the first plunger pump 201. Next, start the first plunger pump 201, and adjust the first plunger pump 201 according to the target flow value so that the output flow value of the first plunger pump 201 is consistent with the target flow value. Then, record the output flow value of the first plunger pump 201 and the reading of the first flow rate sensor 301, and perform conversion comparison analysis. Finally, based on the results of the comparison analysis, evaluate the accuracy of the first plunger pump 201, and make corresponding adjustments and corrections.

[0069] It is understandable that the above-mentioned target flow value can be set in multiples to perform multi-point calibration on the first plunger pump 201 .

[0070] It is understandable that the above-mentioned method of regulating, adjusting and correcting the first plunger pump 201 can be manually controlled by a technician or automatically controlled by a computer program.

[0071] The above is the calibration process of the first plunger pump 201 . The calibration processes of the second plunger pump 202 and the third plunger pump 203 are similar to this, so they will not be described in detail here.

[0072] In some embodiments, the first mixer 501 and the second mixer 502 are T-type mixers.

[0073] As a second embodiment of the utility model, the first infusion assembly further includes a first pressure sensor 311 disposed between the first plunger pump 201 and the first mixer 501; the second infusion assembly further includes a second pressure sensor 312 disposed between the second plunger pump 202 and the first mixer 501; the third infusion assembly further includes a third pressure sensor 313 disposed between the third plunger pump 203 and the second mixer 502. The first pressure sensor 311, the second pressure sensor 312 and the third pressure sensor 313 are used to monitor the pressure of the flow path.

[0074] In summary, calibration is an important part of ensuring accurate metering of plunger pumps. Accurate calibration can ensure the accuracy and reliability of plunger pumps during operation. Through calibration, potential problems can be discovered and eliminated, metering errors can be reduced, and production efficiency and product quality can be improved.

[0075] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technical personnel in this field can make some changes or modify the technical contents disclosed above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any brief modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A lipid nanoparticle mixing preparation system with self-calibration of flow rate, characterized in that: include: A first infusion assembly, a second infusion assembly, and a third infusion assembly; a first mixer and a second mixer; Calibrate the central control host; The infusion assembly includes a reservoir, a plunger pump and a flow rate sensor connected in sequence, the first mixer and the second mixer respectively include a first input end, a second input end and an output end, the first input end of the first mixer is connected to the first infusion assembly, the second input end of the first mixer is connected to the second infusion assembly, the first input end of the second mixer is connected to the output end of the first mixer, and the second input end of the second mixer is connected to the third infusion assembly; A first weighing meter is connected between the flow rate sensor of the first infusion component and the first mixer, a second weighing meter is connected between the flow rate sensor of the second infusion component and the first mixer, a third weighing meter is connected between the flow rate sensor of the third infusion component and the second mixer, and the first weighing meter, the second weighing meter and the third weighing meter are connected to the calibration central control host.

2. A lipid nanoparticle mixing preparation system with self-calibration of flow rate according to claim 1, characterized in that: The first weighing meter, the second weighing meter and the third weighing meter all include a liquid storage tank, a liquid inlet, a liquid outlet, a density sensor and a weighing sensor.

3. A lipid nanoparticle mixing preparation system with self-calibration of flow rate according to claim 1, characterized in that: A first reflux pump is arranged between the first weighing meter and the reservoir of the first infusion assembly, a second reflux pump is arranged between the second weighing meter and the reservoir of the second infusion assembly, and a third reflux pump is arranged between the third weighing meter and the reservoir of the third infusion assembly.

4. A lipid nanoparticle mixing preparation system with self-calibration of flow rate according to claim 1, characterized in that: The first mixer and the second mixer are T-type mixers.

5. A lipid nanoparticle mixing preparation system with self-calibration of flow rate according to claim 1, characterized in that: The reservoir of the first infusion component, the reservoir of the second infusion component, and the reservoir of the third infusion component respectively store an mRNA solution, a lipid solution, and a dilution solution.

6. A lipid nanoparticle mixing preparation system with self-calibration of flow rate according to claim 1, characterized in that: The lipid nanoparticle mixing preparation system with self-calibration of flow rate also includes a product collector, which is connected to the output end of the second mixer.

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