WO2022240193A1 - 지질 나노 입자 제조용 칩, 이를 포함하는 지질 나노 입자 제조 시스템 및 지질 나노 입자 제조 방법 - Google Patents
지질 나노 입자 제조용 칩, 이를 포함하는 지질 나노 입자 제조 시스템 및 지질 나노 입자 제조 방법 Download PDFInfo
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- WO2022240193A1 WO2022240193A1 PCT/KR2022/006749 KR2022006749W WO2022240193A1 WO 2022240193 A1 WO2022240193 A1 WO 2022240193A1 KR 2022006749 W KR2022006749 W KR 2022006749W WO 2022240193 A1 WO2022240193 A1 WO 2022240193A1
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- Prior art keywords
- flow path
- raw material
- lipid nanoparticles
- dilution
- chip
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Definitions
- the present invention relates to a chip for preparing lipid nanoparticles, a system for preparing lipid nanoparticles including the chip for preparing lipid nanoparticles, and a method for preparing lipid nanoparticles, and more particularly, to manufacturing lipid nanoparticles containing active ingredients such as mRNA. It relates to a lipid nanoparticle preparation chip, a lipid nanoparticle preparation system including the lipid nanoparticle preparation chip, and a lipid nanoparticle preparation method including the active ingredient.
- mRNA messenger RNA
- mRNA messenger RNA
- mRNA messenger RNA
- the advantage of mRNA therapeutics is that they do not have to be delivered to the nucleus compared to DNA, and they are not inserted into the genome, so they do not cause permanent genetic diseases, so they are highly safe.
- mRNA can have various sizes depending on the protein it expresses, and exists as a single strand.
- mRNA is in the limelight as a next-generation gene therapy, since it is single-stranded, its stability is very low, so it is rapidly degraded by nucleases in the blood and rapidly excreted from the body through the kidneys. It is known.
- an object of the present invention is to provide a chip for preparing lipid nanoparticles for preparing lipid nanoparticles.
- Another object of the present invention is to provide a lipid nanoparticle manufacturing system including the lipid nanoparticle manufacturing chip.
- Another object of the present invention is to provide a method for preparing lipid nanoparticles.
- a chip for producing lipid nanoparticles is a mixer unit for forming a mixed solution by mixing a first raw material containing an active ingredient and a second raw material containing a lipid, A dilution unit connected to the mixer unit and diluting the mixed solution using a diluent, and a concentrating unit connected to the dilution unit and concentrating Lipid Nanoparticles (LNP) from the diluted mixed solution to obtain a concentrated solution. do.
- the enrichment unit includes a main flow path connected to the dilution unit, an ion exchange channel in contact with the main flow path, a buffer solution channel spaced apart from the main flow path and in contact with the ion exchange channel, and the main flow path. It may include a lipid nanoparticle obtaining flow path connected to and obtaining the concentrate, and a recovery flow path connected to the main flow path and recovering solutions other than the concentrate.
- the ion exchange channel of the enrichment unit may have a V-shape disposed above or below the main flow path and having an appendix disposed in a flow direction on a plane.
- the lipid nanoparticle collection passage and the recovery passage have a smaller cross-sectional area than the main passage and may be disposed parallel to each other.
- the mixer unit is connected to a first raw material supply passage through which the first raw material is supplied, a second raw material supply passage through which the second raw material is supplied, and the first and second raw material supply passages. It may include a mixed flow path that becomes.
- the dilution unit includes a first flow path connected to the mixing flow path of the mixer unit, a dilution flow path providing the dilution solution, and a dilution space connected to the dilution flow path and the first flow path. can do.
- the active ingredient may be a nucleic acid.
- the active ingredient may be any one of mRNA, miRNA, siRNA, DNA and CRISPR.
- the first raw material may include mRNA and water
- the second raw material may include lipid and ethanol
- the diluent may include deionized water.
- a lipid nanoparticle manufacturing system is a first raw material supply unit for supplying a first raw material, a second raw material supply unit for supplying a second raw material, the first raw material and the first raw material supply unit.
- a chip for preparing lipid nanoparticles including a mixer unit for mixing raw materials, a dilution unit for diluting the mixed solution, and a concentration unit for concentrating lipid nanoparticles from the diluted mixture to obtain a concentrated solution, providing a dilution solution to the chip for preparing lipid nanoparticles. and a recovery unit for recovering a solution other than the concentrate from the chip for producing the lipid nanoparticles.
- the enrichment unit of the chip for producing lipid nanoparticles includes a main flow path connected to the dilution unit, an ion exchange channel in contact with the main flow path, and spaced apart from the main flow path and in contact with the ion exchange channel. It may include a buffer solution channel, a lipid nanoparticle collection channel connected to the main channel to obtain the concentrate, and a recovery channel connected to the main channel to recover solutions other than the concentrate.
- the ion exchange channel of the enrichment part of the chip for producing lipid nanoparticles is disposed above or below the main flow path and has a v-shape so that the tip is disposed in the direction of flow of the fluid on a plane.
- the dilution unit of the chip for producing lipid nanoparticles includes a first flow path connected to the mixer unit, a dilution flow path providing the dilution solution, and a dilution flow path connected to the first flow path. Dilution space may be included.
- a lipid nanoparticle manufacturing method includes preparing a first raw material containing an active ingredient and a second raw material containing a lipid, the first raw material and It may include mixing the second raw material to form lipid nanoparticles containing mRNA, and a post-processing step of manufacturing a final product by filtering and filling a solution containing the lipid nanoparticles into individual containers.
- the step of forming the lipid nanoparticles is performed on a chip for producing lipid nanoparticles having a flow path, and the mixing step of mixing the first raw material and the second raw material to form a mixed solution, the mixed solution using a diluent It may include a dilution step of diluting, and a concentration step of obtaining a concentrated solution by concentrating the lipid nanoparticles from the diluted mixed solution.
- the concentration step of the formation of lipid nanoparticles is performed by applying a voltage to a buffer solution channel connected to an ion exchange channel in contact with the flow path of the chip for preparing lipid nanoparticles, so that the solution in the flow path is By forming an ion-rich zone and an ion-depleted zone, the lipid nanoparticles containing the active ingredient can be concentrated in a specific region within the flow path.
- the chip for producing lipid nanoparticles is connected to a mixer unit and the mixer unit for mixing the first raw material and the second raw material to form the mixed solution, and the mixed solution using the diluent. It may include a dilution unit for diluting, and a concentration unit connected to the dilution unit and concentrating the lipid nanoparticles from the diluted mixed solution.
- the enrichment unit of the chip for producing lipid nanoparticles includes a main flow path connected to the dilution unit, an ion exchange channel in contact with the main flow path, and spaced apart from the main flow path and in contact with the ion exchange channel. It may include a buffer solution channel, a lipid nanoparticle collection channel connected to the main channel to obtain the concentrate, and a recovery channel connected to the main channel to recover solutions other than the concentrate.
- lipid nanoparticle production since mixing, dilution, and concentration for lipid nanoparticle production are all performed on a chip for lipid nanoparticle production, it is easy to control the size and uniformity of lipid nanoparticles, thereby producing high-quality lipid nanoparticles can do.
- FIG. 1 is a schematic diagram of a lipid nanoparticle production system according to an embodiment of the present invention.
- FIG. 2 is a view showing various examples of a mixer unit of a chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- FIG. 3 is a view showing various examples of a dilution unit of a chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- FIG. 4 is a view for explaining the enrichment part of the chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- FIG. 5 is a view showing various examples of an enrichment unit of a chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- FIG. 6 is a view showing an embodiment of an enrichment unit of a chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- FIG. 7 is a view for explaining the fluid flow and concentrating effect according to the shape of the divorce exchange part of the concentrating part of the chip for producing lipid nanoparticles according to an embodiment of the present invention.
- FIG. 8 is a flowchart showing a method for preparing lipid nanoparticles according to an embodiment of the present invention.
- FIG. 9 is a flowchart showing in detail the steps of preparing LNPs on a chip in the method for preparing lipid nanoparticles of FIG. 8 .
- FIG. 1 is a schematic diagram of a lipid nanoparticle production system according to an embodiment of the present invention.
- FIG. 2 is a view showing various examples of a mixer unit of a chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- FIG. 3 is a view showing various examples of a dilution unit of a chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- FIG. 4 is a view for explaining the enrichment part of the chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- the lipid nanoparticle manufacturing system includes a first raw material providing unit 10 including mRNA, a second raw material providing unit 20 including lipid (Lipid), a dilution solution providing unit 30, It includes a lipid nanoparticle acquisition unit 40, a first recovery unit 50, a second recovery unit 60, and a lipid nanoparticle manufacturing chip 100.
- the first raw material supply unit 10 stores the first raw material and provides the first raw material to the chip 100 for producing lipid nanoparticles.
- the first raw material may be a solution containing mRNA.
- the first raw material may include mRNA and water.
- the second raw material supply unit 20 stores the second raw material and provides the second raw material to the chip 100 for producing lipid nanoparticles.
- the second raw material may be a solution containing lipid.
- the second raw material may include lipids and ethanol.
- the lipid nanoparticle preparation chip 100 may mix, dilute, and concentrate the first raw material and the second raw material to prepare a lipid nanoparticle concentrate containing mRNA.
- the chip 100 for preparing lipid nanoparticles includes a mixer unit 110, a dilution unit 120, and a concentration unit 130.
- the mixer unit 110 may mix the first raw material and the second raw material to prepare a mixed pressure solution.
- a microfluidic mixer commonly used in a microchannel such as a chaotic mixer or a herringbone mixer, may be used.
- a liquid mixture containing lipid nanoparticles can be prepared by self-aligning of lipid and mRNA at the interface of the two fluids through mixing of the first raw material and the second raw material in the flow path.
- the mixer unit 110 includes a first raw material supply channel 112 through which the first raw material is supplied, a second raw material supply channel 114 through which the second raw material is supplied, A mixing passage 116 connected to the first and second raw material supply passages may be included.
- the first raw material supply passage 112 and the second raw material supply passage 114 meet each other at the merging point JP so that the first raw material and the second raw material may be mixed.
- the dilution unit 120 may dilute the mixed solution.
- the dilution unit 120 includes a first flow path 123 connected to the mixing flow path 116 of the mixer unit 110, a dilution flow path 122 providing the dilution solution, and the dilution flow path 122 and the dilution flow path 122.
- a dilution space 124 connected to the first flow path 123 may be included.
- the dilution space 124 may have various shapes, such as a line shape (see FIG. 3(a)), a serpentine chamber shape (see FIG. 3(b)), and the like.
- the dilution solution providing unit 30 may provide the dilution solution through the dilution passage 122 of the dilution unit 120 of the chip 100 for preparing lipid nanoparticles.
- the diluent may include deionized water.
- the solution mixed in the mixing unit 110 contains the solvent of the second raw material, for example, ethanol at a high concentration, dilution to a desired concentration is required.
- the concentration of the ethanol may be lowered to a desired level while passing through the dilution unit 120 .
- the dilution unit 120 may be implemented in the flow path structure of the mixing unit 110 . That is, a structure in which the first raw material, the second raw material, and the diluting liquid are input may be possible by configuring the mixing and diluting unit so that the mixer unit and the dilution unit are implemented simultaneously rather than sequentially.
- the concentration unit 130 may concentrate the lipid nanoparticles from the mixed solution diluted in the dilution unit 120 to obtain a concentrated solution.
- the enrichment unit 130 is spaced apart from the main flow path 132 connected to the dilution unit 120, an ion exchange channel (IM) in contact with the main flow path 132, and the main flow path 132, and the ion exchange Buffer solution channels 134a and 134b in contact with the channel IM, connected to the main flow path 132, and a lipid nanoparticle obtaining flow path 136 for obtaining the concentrate, and connected to the main flow path 132, Recovery channels 138a and 138b for recovering solutions other than the concentrate may be included.
- the ion exchange channel (IM) may be a charged nanochannel for exchanging cations or anions made of a nanoporous material.
- lipid nanoparticles having a size of 100 nm or less may be separated and concentrated using an ion concentration polarization (ICP) phenomenon.
- ICP ion concentration polarization
- ICP ion depletion zone
- buffer solution channels 134a and 134b through which the buffer solution flows, are formed on both sides of the second direction D2 of the main flow path 132 through which the fluid flows along the first direction D1, and both sides
- ions move through the ion exchange channel IM, and an ion depletion zone (see IDZ in FIG. 8) is formed along the second direction D2.
- lipid nanoparticles having an electro-dense core are concentrated in the center of the main flow path 132, and pass through the lipid nanoparticle acquisition flow path 136.
- the cation component is used as a driving source of the ion concentration polarization phenomenon and is discharged to the outside of the chip through the main channel 132 and the ion exchange channel IM through the buffer solution channels 134a and 134b.
- the remaining positive cation component is affected by the ion depletion region and the electric field formed at the interface of the ion depletion region, and the path is set according to the properties of the particle to the lipid nanoparticle acquisition channel 136 and the recovery channel 138a, 138b and can be moved selectively.
- the concentration of lipid nanoparticles increases in the fluid passing through the lipid nanoparticle collection channel 136, and fluids other than the lipid nanoparticles can be recovered in the recovery channels 138a and 138b.
- mixing to prepare lipid nanoparticles, dilution to dilute a solvent such as ethanol, and concentration to increase lipid nanoparticle concentration can all be performed on the chip 100 for preparing lipid nanoparticles.
- the ion exchange channel (IM) may have various shapes (see FIGS. 5 and 6 ), and for example, the ion exchange channel (IM) is disposed above or below the main flow path 132 and is I on a plane. It may have a V-shape so that the attachment is disposed in the direction of flow of the ruler or fluid.
- a sum of widths of the recovery passages 138a and 138b in the second direction D2 may be smaller than the width of the main passage 132 .
- the recovery passages 138a and 138b may have an I-shaped channel structure as a whole since the main passage 132 is divided into three passages and formed in parallel.
- the area occupied by the enrichment unit 130 is reduced, space integration efficiency is improved compared to a structure in which channels are radially formed, fluid flow is improved, and operation is possible with low power, thereby improving production efficiency.
- the same or superior efficiency can be obtained with lower power consumption compared to the conventional structure in which the ion depletion zone is generated on both sides and the ion depletion zone is formed only on one side of the flow path, and it can be used as an on/off valve by adjusting the power. . (See (b) of FIG. 8)
- the main flow path is divided into three branches, including one lipid nanoparticle obtaining flow path and two recovery flow paths, is described, but is not limited thereto.
- the main passage may be divided into 5 or 7 branches, and the size and width of each of the divided passages may be different.
- the chip 100 for preparing the lipid nanoparticles may be manufactured by various known methods. For example, it may be formed by stacking a plurality of substrates having grooves corresponding to passages. For example, an ion exchange channel may be formed on a lower substrate, and an upper substrate having a groove formed on a lower surface may be formed by bonding to the lower substrate, but is not limited thereto.
- various substrates capable of forming a flow path pattern such as a glass substrate, a plastic substrate, a silicon substrate, etc. Methods may be used, and various known methods such as a laser bonding method, a thermal compression method, an adhesion method, and a lamination method may be used for bonding of a plurality of substrates.
- the fluid is controlled in a laminar flow state, and thus lipid nanoparticles It is easy to control the size and uniformity of the lipid nanoparticles of high quality.
- the bulk size manufacturing method in which turbulence cannot be controlled, it is difficult to control the size and uniformity of lipid nanoparticles because fine fluid control is impossible.
- the conventional lipid nanoparticle manufacturing method using the chip method only the mixing of mRNA and lipid is performed on the chip, and the steps for diluting organic solvents such as ethanol and concentrating the lipid nanoparticles require separate processes. Since it proceeds in the bulk size through the process, it is not easy to control the lipid nanoparticle manufacturing process compared to the present invention.
- lipid nanoparticles in the case of a solution containing lipid nanoparticles in the initial stage manufactured on a microfluidics chip, the flow rate conditions in the manufacturing stage, in particular, the ratio of the organic phase in which lipids are dissolved in ethanol to the aqueous phase (Flow Rate Ratio) ), a certain concentration of ethanol is necessarily included. Since the concentration of ethanol contained is an unstable state that can affect the lipid of nanoparticles in the early stages, effective post-process application has a great effect on the production of stable lipid nanoparticles. Through the bulk size process, lipid nanoparticles at an early stage are discharged to the outside of the chip and may not maintain stability until diluted in bulk size through a tubing line. However, according to embodiments of the present invention, lipid nanoparticles Since mixing, dilution, and concentration of nanoparticles are all performed on a chip (on chip process), this problem can be solved.
- FIG. 5 is a view showing various examples of an enrichment unit of a chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- FIG. 5 shows a case in which the ion exchange channel IM has an I-shape extending in a second direction D2 perpendicular to the first direction D1 in which the main flow path 132 extends. has been When viewed from the side, the ion exchange channel IM has a predetermined height on the lower side of the main flow path 132 in a third direction D3 perpendicular to the first and second directions D1 and D2. can be formed to have
- Figure 5 (b) is an embodiment in which the ion exchange channel (IM) is formed in a V shape
- Figure 5 (c) is an embodiment in which two V-shaped ion exchange channels (IM1, IM2) are formed
- Figure 5 (d) is an embodiment in which an I-shaped ion exchange channel (IM1) and a V-shaped ion exchange channel (IM2) are sequentially formed
- (e) of FIG. 5 is a V-shaped ion exchange channel (IM)
- FIG. 6 is a view showing an embodiment of an enrichment unit of a chip for preparing lipid nanoparticles of the lipid nanoparticle manufacturing system of FIG. 1 .
- the ion exchange channels IM1 and IM2 are formed on the upper and lower surfaces of the main flow path 132, and the ion depletion zone can be formed more efficiently.
- FIG. 7 is a view for explaining the fluid flow and concentrating effect according to the shape of the divorce exchange part of the concentrating part of the chip for producing lipid nanoparticles according to an embodiment of the present invention.
- FIG. 7 (a) is a diagram showing the fluid flow and concentrating effect of the I-shaped ion exchange channel
- FIG. 7 (b) is a diagram showing the fluid flow and concentrating effect of the V-shaped ion exchange channel.
- Figure 7 (c) is the result of the power consumption comparison experiment according to the channel shape
- Figure 7 (d) is an experiment confirming that the concentration of lipid nanoparticles can be controlled (valve effect) according to the applied voltage / current is the drawing shown
- 7(e) is a view showing an experiment confirming that the particle separation direction can be changed according to the formation of an electric field.
- the enrichment unit of the chip for preparing seismic nanoparticles not only has a function of concentrating the lipid nanoparticles, but also has a form of an on/off valve to turn on/off the obtained lipid nanoparticles. It can be controlled as, and if necessary, it is possible to obtain the required particles not only through the lipid nanoparticle obtaining channel but also through the recovery channel.
- FIG. 8 is a flowchart showing a method for preparing lipid nanoparticles according to an embodiment of the present invention.
- 9 is a flowchart showing in detail the step of preparing lipid nanoparticles on a chip of the method for preparing lipid nanoparticles of FIG. 8 .
- the method for preparing lipid nanoparticles may include preparing raw materials (S100), preparing lipid nanoparticles on a chip (S200), and post-processing (S300).
- a first raw material including mRNA and a second raw material including lipid may be prepared.
- lipid nanoparticles containing mRNA may be formed by mixing the first raw material and the second raw material.
- a final product may be prepared by diafiltration of the solution containing the lipid nanoparticles, additional concentration to a required concentration, and filling into individual containers.
- the step of forming the lipid nanoparticles is performed on a chip for preparing lipid nanoparticles on which a channel is formed, and may include a mixing step (S110), a dilution step (S120), and a concentration step (S130). have.
- the chip for preparing the lipid nanoparticles the chip for lipid nanoparticles described in FIG. 1 may be used.
- the chip for preparing the lipid nanoparticles may include a mixer unit, a dilution unit, and a concentration unit.
- a mixed solution may be formed by mixing the first raw material and the second raw material.
- the mixing step (S110) may be performed in the mixer unit of the chip for preparing the lipid nanoparticles.
- the mixed solution may be diluted using a dilution solution.
- the dilution step (S120) may be performed in the dilution unit of the chip for preparing the lipid nanoparticles.
- a concentrate may be obtained by concentrating the lipid nanoparticles from the diluted mixed solution.
- the enrichment step (S130) may be performed in the enrichment unit of the chip for preparing the lipid nanoparticles.
- the concentrated solution applies a voltage to a buffer solution channel connected to an ion exchange channel in contact with the flow path of the chip for producing lipid nanoparticles to form an ion-rich zone and an ion-depleted zone in the solution within the flow path, including mRNA
- the lipid nanoparticles may be concentrated in a specific region within the flow path.
- first raw material supply unit 20 second raw material supply unit
- diluent supply unit 40 lipid nanoparticle acquisition unit
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Abstract
Description
Claims (17)
- 유효 성분을 포함하는 제1 원료와 지질(lipid)를 포함하는 제2 원료를 혼합하여 혼합액을 형성하는 믹서부;상기 믹서부와 연결되고, 희석액을 이용하여 상기 혼합액을 희석하는 희석부; 및상기 희석부에 연결되고, 희석된 혼합액으로부터 지질 나노 입자(Lipid Nanoparticles; LNP)를 농축하여 농축액을 수득하는 농축부를 포함하는 지질 나노 입자 제조용 칩.
- 제1항에 있어서,상기 농축부는상기 희석부와 연결되는 메인 유로;상기 메인 유로에 접하는 이온 교환 채널;상기 메인 유로와 이격되고, 상기 이온 교환 채널과 접하는 버퍼 솔루션 채널;상기 메인 유로에 연결되고, 상기 농축액을 수득하는 지질 나노 입자 수득 유로; 및상기 메인 유로에 연결되고, 상기 농축액 외의 용액을 회수하기 위한 회수 유로를 포함하는 지질 나노 입자 제조용 칩.
- 제2항에 있어서,상기 농축부의 상기 이온 교환 채널은 상기 메인 유로의 상측 또는 하측에 배치되고 평면상에서 유체의 진행 방향으로 첨부가 배치되도록 v자 형태를 갖는 것을 특징으로 하는 지질 나노 입자 제조용 칩.
- 제2항에 있어서,상기 지질 나노 입자 수득 유로와 상기 회수 유로는 상기 메인 유로 보다 단면적이 작고, 서로 평행하게 배치되는 것을 특징으로 하는 지질 나노 입자 제조용 칩.
- 제1항에 있어서,상기 믹서부는상기 제1 원료가 공급되는 제1 원료 공급 유로, 상기 제2 원료가 공급되는 제2 원료 공급 유로, 상기 제1 및 제2 원료 공급 유로들과 연결되는 혼합 유로를 포함하는 것을 특징으로 하는 지질 나노 입자 제조용 칩.
- 제1항에 있어서,상기 희석부는,상기 믹서부의 상기 혼합 유로와 연결되는 제1 유로;상기 희석액을 제공하는 희석 유로; 및상기 희석 유로 및 상기 제1 유로와 연결되는 희석 공간을 포함하는 것을 특징으로 하는 지질 나노 입자 제조용 칩.
- 제1항에 있어서,상기 유효 성분은 핵산인 것을 특징으로 하는 지질 나노 입자 제조용 칩.
- 제1항에 있어서,상기 유효 성분은 mRNA, miRNA, siRNA, DNA 및 CRISPR 중 어느 하나인 것을 특징으로 하는 지질 나노 입자 제조용 칩.
- 제1항에 있어서,상기 제1 원료는 mRNA 및 물을 포함하고, 상기 제2 원료는 지질(Lipid) 및 에탄올을 포함하고, 상기 희석액은 탈이온수(Deionized water)를 포함하는 것을 특징으로 하는 지질 나노 입자 제조용 칩.
- 제1 원료를 공급하는 제1 원료 공급부;제2 원료를 공급하는 제2 원료 공급부;상기 제1 원료 및 상기 제2 원료를 혼합하여 혼합액을 형성하는 믹서부, 상기 혼합액을 희석하는 희석부 및 희석된 혼합액으로부터 지질 나노 입자를 농축하여 농축액을 수득하는 농축부를 포함하는 지질 나노 입자 제조용 칩;상기 지질 나노 입자 제조용 칩에 희석액을 제공하는 희석액 제공부; 및상기 지질 나노 입자 제조용 칩으로부터 상기 농축액 외의 용액을 회수하는 회수부를 포함하는 지질 나노 입자 제조 시스템.
- 제10항에 있어서,상기 지질 나노 입자 제조용 칩의 상기 농축부는상기 희석부와 연결되는 메인 유로;상기 메인 유로에 접하는 이온 교환 채널;상기 메인 유로와 이격되고, 상기 이온 교환 채널과 접하는 버퍼 솔루션 채널;상기 메인 유로에 연결되고, 상기 농축액을 수득하는 지질 나노 입자 수득 유로; 및상기 메인 유로에 연결되고, 상기 농축액 외의 용액을 회수하기 위한 회수 유로를 포함하는 것을 특징으로 하는 지질 나노 입자 제조 시스템.
- 제11항에 있어서,상기 지질 나노 입자 제조용 칩의 상기 농축부의 상기 이온 교환 채널은 상기 메인 유로의 상측 또는 하측에 배치되고 평면상에서 유체의 진행 방향으로 첨부가 배치되도록 v자 형태를 갖는 것을 특징으로 하는 지질 나노 입자 제조 시스템.
- 제10항에 있어서,상기 지질 나노 입자 제조용 칩의 상기 희석부는,상기 믹서부와 연결되는 제1 유로;상기 희석액을 제공하는 희석 유로; 및상기 희석 유로 및 상기 제1 유로와 연결되는 희석 공간을 포함하는 것을 특징으로 하는 지질 나노 입자 제조 시스템.
- 유효 성분을 포함하는 제1 원료와 지질(lipid)를 포함하는 제2 원료를 준비하는 단계;상기 제1 원료와 상기 제2 원료를 혼합하여 상기 유효 성분을 포함하는 지질 나노 입자를 형성하는 단계; 및상기 지질 나노 입자를 포함하는 용액을 여과 및 개별 용기에 충전하여 최종 제품을 제조하는 후처리 단계를 포함하고,상기 지질 나노 입자를 형성하는 단계는 유로가 형성된 지질 나노 입자 제조용 칩(chip) 상에서 이루어지고,상기 제1 원료와 상기 제2 원료를 혼합하여 혼합액을 형성하는 혼합 단계;상기 혼합액을 희석액을 이용하여 희석하는 희석 단계; 및희석된 혼합액으로부터 지질 나노 입자를 농축하여 농축액을 수득하는 농축 단계를 포함하는 것을 특징으로 하는 지질 나노 입자 제조 방법.
- 제14항에 있어서,상기 지질 나노 입자 형성 단계의 상기 농축 단계는상기 지질 나노 입자 제조용 칩의 상기 유로에 접하는 이온 교환 채널과 연결된 버퍼 솔루션 채널에 전압을 인가하여, 상기 유로 내의 용액에 이온과다구역 및 이온 공핍구역을 형성하여, 상기 유효 성분을 포함하는 상기 지질 나노입자를 상기 유로 내 특정 영역으로 농축시키는 것을 특징으로 하는 지질 나노 입자 제조 방법.
- 제14항에 있어서,상기 지질 나노 입자 제조용 칩은상기 제1 원료와 상기 제2 원료를 혼합하여 상기 혼합액을 형성하는 믹서부;상기 믹서부와 연결되고, 상기 희석액을 이용하여 상기 혼합액을 희석하는 희석부; 및상기 희석부에 연결되고, 희석된 혼합액으로부터 상기 지질 나노 입자를 농축하는 농축부를 포함하는 것을 특징으로 하는 지질 나노 입자 제조 방법.
- 제16항에 있어서,상기 지질 나노 입자 제조용 칩의 상기 농축부는상기 희석부와 연결되는 메인 유로;상기 메인 유로에 접하는 이온 교환 채널;상기 메인 유로와 이격되고, 상기 이온 교환 채널과 접하는 버퍼 솔루션 채널;상기 메인 유로에 연결되고, 상기 농축액을 수득하는 지질 나노 입자 수득 유로; 및상기 메인 유로에 연결되고, 상기 농축액 외의 용액을 회수하기 위한 회수 유로를 포함하는 것을 특징으로 하는 지질 나노 입자 제조 방법.
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EP22807840.8A EP4241884A4 (en) | 2021-05-11 | 2022-05-11 | CHIP FOR PRODUCING LIPIDNANOPARTICLES, SYSTEM FOR PRODUCING LIPIDNANOPARTICLES THEREFROM AND METHOD FOR PRODUCING LIPIDNANOPARTICLES |
US18/024,743 US20230285312A1 (en) | 2021-05-11 | 2022-05-11 | Lipid nanoparticles manufacturing chip, lipid nanoparticles manufacturing system having the same, and lipid nanoparticles manufacturing method |
CA3194915A CA3194915A1 (en) | 2021-05-11 | 2022-05-11 | Lipid nanoparticles manufacturing chip, lipid nanoparticles manufacturing system having the same, and lipid nanoparticles manufacturing method |
CN202280006768.2A CN116322959B (zh) | 2021-05-11 | 2022-05-11 | 脂质纳米粒子制造用芯片、包含其的脂质纳米粒子制造系统和脂质纳米粒子制造方法 |
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KR20170126944A (ko) * | 2015-02-24 | 2017-11-20 | 더 유니버시티 오브 브리티시 콜롬비아 | 연속 흐름 미세유체 시스템 |
KR20200074832A (ko) * | 2018-12-17 | 2020-06-25 | 광운대학교 산학협력단 | 마이크로채널내의 생체 시료 속도 및 위치제어를 통한 샘플 농축 및 분리 장치 |
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JP4450368B2 (ja) * | 2004-03-04 | 2010-04-14 | 独立行政法人産業技術総合研究所 | マイクロ流路チップの製造方法、マイクロ流路チップ、そのマイクロ流路チップを用いる生体分子の分離方法、およびそのマイクロ流路チップを有する電気泳動装置 |
WO2009120642A1 (en) * | 2008-03-26 | 2009-10-01 | Massachusetts Institute Of Technology | Methods for fabricating electrokinetic concentration devices |
RU2573409C2 (ru) * | 2009-11-04 | 2016-01-20 | Дзе Юниверсити Оф Бритиш Коламбиа | Содержащие нуклеиновые кислоты липидные частицы и относящиеся к ним способы |
FR2984756B1 (fr) * | 2011-12-27 | 2014-02-21 | Commissariat Energie Atomique | Dispositif nano et micro fluidique pour la separation et concentration de particules presentes dans un fluide |
US10983035B2 (en) * | 2018-03-01 | 2021-04-20 | University Of Notre Dame Du Lac | Simultaneous isolation and preconcentration of exosomes by ion concentration polarization method and apparatus |
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- 2022-05-11 CN CN202280006768.2A patent/CN116322959B/zh active Active
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- 2022-05-11 WO PCT/KR2022/006749 patent/WO2022240193A1/ko active Application Filing
- 2022-05-11 CA CA3194915A patent/CA3194915A1/en active Pending
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US20060087048A1 (en) * | 2002-01-14 | 2006-04-27 | Mello Andrew D | Preparation of nanoparticles |
US20170181972A1 (en) * | 2013-10-28 | 2017-06-29 | University Of Maryland, College Park | Microfluidic Liposome Synthesis, Purification and Active Drug Loading |
KR20170126944A (ko) * | 2015-02-24 | 2017-11-20 | 더 유니버시티 오브 브리티시 콜롬비아 | 연속 흐름 미세유체 시스템 |
JP2020536230A (ja) * | 2017-10-03 | 2020-12-10 | アベイルズ メディカル,インコーポレイテッド | レドックス反応に基づいて微生物の濃度及び抗感染剤に対する微生物の感受性を決定する装置、システム、及び方法 |
KR20200074832A (ko) * | 2018-12-17 | 2020-06-25 | 광운대학교 산학협력단 | 마이크로채널내의 생체 시료 속도 및 위치제어를 통한 샘플 농축 및 분리 장치 |
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EP4241884A4 (en) | 2024-03-27 |
EP4241884A1 (en) | 2023-09-13 |
US20230285312A1 (en) | 2023-09-14 |
JP2024515403A (ja) | 2024-04-10 |
CA3194915A1 (en) | 2022-11-17 |
CN116322959B (zh) | 2024-05-03 |
CN116322959A (zh) | 2023-06-23 |
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