Removal structure of oil phase of hydrogel microsphere with core-shell structure
By utilizing a microfluidic chip structure and optimized microsphere filtration conditions, the automation problem of oil phase removal from hydrogel microspheres was solved, achieving efficient and complete oil phase removal, which is suitable for high-throughput preparation of organoids.
Patent Information
- Application Number
- CN202423251298.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-27
- Publication Date
- 2025-12-09
- Estimated Expiration
- 2034-12-27
AI Technical Summary
Existing methods for removing the oil phase from hydrogel microspheres require long time and multiple steps, making it difficult to achieve high-throughput automated preparation of organoids.
A microfluidic chip structure was designed to achieve automated replacement of microspheres from the oil phase to the liquid phase through a separation chamber and separation components, optimize microsphere filtration conditions, and achieve efficient removal of the oil phase by using an isolation block and liquid flow rate control.
This technology enables automated oil phase removal from hydrogel microspheres, reducing the likelihood of microsphere breakage, improving oil phase removal efficiency and microsphere integrity, and is suitable for high-throughput production.
Smart Images
Figure CN223641861U_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of microfluidics, and more particularly to a structure for removing the oil phase from core-shell structured hydrogel microspheres. Background Technology
[0002] After solidification, hydrogel microspheres require effective removal of the oil phase to facilitate subsequent cell growth and organoid differentiation. Conventional methods for oil phase removal from hydrogel microspheres include centrifugation and filtration. However, this time-consuming and multi-step filtration approach is not conducive to high-throughput automated organoid preparation. Utility Model Content
[0003] To address the problems existing in the prior art, this application provides a structure for removing the oil phase of core-shell structured hydrogel microspheres.
[0004] To achieve automated oil phase removal of microspheres, we designed a microfluidic chip to displace microspheres from the oil phase into the liquid phase and optimized the microsphere filtration conditions.
[0005] In this application, the first liquid is, in a certain sense, the hydrogel microspheres, and the second liquid is the cleaning solution.
[0006] The specific technical solution of this application is as follows:
[0007] A structure for removing the oil phase of core-shell structured hydrogel microspheres includes a substrate, a separation cavity formed on the substrate, a separation component disposed on the substrate, and the separation component disposed in the separation cavity.
[0008] A first inlet pipe and a second inlet pipe, both of which are in communication with the separation cavity, are provided on the substrate.
[0009] A first outlet pipe and a second outlet pipe are provided at one end of the separation chamber away from the first inlet pipe and the second inlet pipe; the first outlet pipe and the second outlet pipe are respectively provided on both sides of the separation assembly.
[0010] In one specific embodiment, the separation component divides the separation chamber into a first chamber and a second chamber, wherein the first chamber and the second chamber are independent chambers;
[0011] Preferably, the first outlet pipe is connected to the first chamber, and the second outlet pipe is connected to the second chamber;
[0012] More preferably, the separation cavity has an elongated shape, and the length dimension of the separation cavity is much larger than the width dimension;
[0013] More preferably, the ratio of the length to the width of the separation cavity is 1:10 to 30; more preferably, the ratio of the length to the width of the separation cavity is 1:15 to 20.
[0014] More preferably, the two ends of the separation component are located near the two ends of the separation chamber in the length direction;
[0015] More preferably, both the first inlet pipe and the second inlet pipe are connected to the first chamber.
[0016] In one specific embodiment, the first inlet pipe is connected to a first tank containing a first liquid containing microspheres, and the first liquid enters the separation chamber from the first inlet pipe; a third tank is connected to the first outlet pipe, and the microspheres in the separation chamber flow from the first outlet pipe into the third tank.
[0017] In one specific embodiment, the first liquid is an oil-phase liquid containing microspheres.
[0018] In one specific embodiment, a second inlet pipe is connected to a second tank containing a second liquid, which enters the separation chamber from the second inlet pipe.
[0019] In one specific embodiment, the second liquid is a solution containing an active agent; preferably, the second liquid is a solution insoluble in the first liquid.
[0020] In one specific embodiment, the first liquid and the second liquid are located on the same side of the separation assembly in the separation chamber.
[0021] In one specific embodiment, the separation component includes an isolation block with both ends connected to the inner wall of the separation chamber; multiple isolation blocks are provided, and the isolation blocks are arranged sequentially along the length direction of the substrate.
[0022] In one specific embodiment, the plurality of isolation blocks are spaced apart.
[0023] In one specific embodiment, the spacing between the isolation blocks is 50 to 200 μm; preferably, the spacing between the isolation blocks is 75 to 150 μm; more preferably, the spacing between the isolation blocks is 100 μm.
[0024] In one specific embodiment, 90 to 150 isolation blocks are provided; preferably, 100 to 120 isolation blocks are provided; more preferably, 107 isolation blocks are provided.
[0025] In one specific embodiment, the length and width of the isolation block are equal. Preferably, the length and width of the isolation block are 100-300 μm; more preferably, the length and width of the isolation block are 150-250 μm; and even more preferably, the length and width of the isolation block are 200 μm.
[0026] In one specific embodiment, there is an angle between the extending direction of the isolation blocks and the central axis of the separation cavity; preferably, the angle is 1°.
[0027] In one specific embodiment, the ratio of the flow rate of the first liquid to the flow rate of the second liquid is 1:12.5 to 150.
[0028] In one specific embodiment, the flow rate of the first liquid is 1 to 12 μL / min;
[0029] The flow rate of the second liquid is 100–300 μL / min; preferably, the flow rate of the second liquid is 120–200 μL / min; more preferably, the flow rate of the second liquid is 150 μL / min.
[0030] In one specific embodiment, a first pump is provided between the first inlet pipe and the first tank, and a second pump is provided between the second inlet pipe and the second tank. Preferably, both the first pump and the second pump are precision injection pumps.
[0031] Beneficial effects
[0032] This application presents a core-shell structure for removing the oil phase from hydrogel microspheres, enabling automated oil phase removal from the microspheres. This is achieved by displacing the microspheres from the oil phase into the liquid phase in a microfluidic chip, and the microsphere filtration conditions are optimized. After injecting the filtered microsphere solution into the chip, no secondary filtration of the oil phase was observed, and no oil phase adhered to the surface of the filtered microspheres. Attached Figure Description
[0033] Figure 1 This is the overall diagram of the removed structure in this application;
[0034] Figure 2 This is a schematic diagram of the structure removed in this application;
[0035] Figure 3 This is a schematic diagram of the removed structural cross-section in this application.
[0036] In the diagram, 1 is the first inlet pipe; 2 is the second inlet pipe; 3 is the first outlet pipe; 4 is the second outlet pipe; 5 is the separation chamber; 6 is the isolation block; 7 is the first tank; 8 is the second tank; 9 is the third tank; and 10 is the fourth tank. Detailed Implementation
[0037] The present application will now be described in detail. While specific embodiments of the present application are shown, it should be understood that the present application can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the present application and to fully convey the scope of the present application to those skilled in the art.
[0038] It should be noted that certain terms are used in the specification and claims to refer to specific components. Those skilled in the art will understand that different terms may be used to refer to the same component. This specification and claims do not distinguish components based on differences in terminology, but rather on differences in function. The terms "comprising" or "including" used throughout the specification and claims are open-ended and should be interpreted as "comprising but not limited to." The following descriptions in the specification are preferred embodiments for carrying out this application; however, these descriptions are for the purpose of understanding the general principles of the specification and are not intended to limit the scope of this application. The scope of protection of this application shall be determined by the appended claims.
[0039] refer to Figure 1 and Figure 2 This application provides a structure for removing the oil phase from core-shell structured hydrogel microspheres. It includes a substrate, on which a separation cavity 5 is formed, and a separation component is disposed on the substrate within the separation cavity 5; the separation component divides the separation cavity 5 into two independent chambers.
[0040] After solidification, the oil phase of core-shell structured hydrogel microspheres needs to be removed.
[0041] The core-shell structured hydrogel microspheres can flow in the separation chamber 5, where a cleaning solution that removes the oil phase from the hydrogel microspheres also flows.
[0042] refer to Figure 1 and Figure 2 The separation component is located in the separation chamber 5. The hydrogel microspheres and the cleaning liquid flow together in the separation chamber 5 and then pass through the separation component. The hydrogel microspheres are blocked by the separation component, while the cleaning liquid and oil phase pass through the separation component, so that the hydrogel microspheres and oil phase are separated; thereby achieving the purpose of removing the oil phase from the hydrogel microspheres.
[0043] refer to Figure 1 and Figure 2 A first inlet pipe 1 and a second inlet pipe 2, both of which are in communication with the separation chamber 5, are provided on the substrate.
[0044] The first inlet pipe 1 and the second inlet pipe 2 are used to inject cleaning fluid and hydrogel microspheres into the separation chamber 5, respectively.
[0045] A first outlet pipe 3 and a second outlet pipe 4 are provided at one end of the separation chamber 5 away from the first inlet pipe 1 and the second inlet pipe 2; the first outlet pipe 3 and the second outlet pipe 4 are respectively provided on both sides of the separation assembly.
[0046] refer to Figure 1 and Figure 2 The separation component separates the liquid from the hydrogel microspheres in the separation chamber 5. Then, the hydrogel microspheres and liquid in the separation chamber 5 can be discharged from the first outlet pipe 3 and the second outlet pipe 4, respectively, thereby achieving the removal of the oil phase from the hydrogel microspheres.
[0047] refer to Figure 1 and Figure 2 The hydrogel microspheres and the cleaning solution flow in the separation chamber 5. After contacting the separation component, the hydrogel microspheres are blocked by the separation component and then flow along the edge of the separation component. The cleaning solution and the oil phase washed off the hydrogel microspheres will then pass through the separation component and continue to flow forward, thereby achieving the cleaning of the hydrogel microspheres by the cleaning solution and the separation and removal of the oil phase from the hydrogel microspheres.
[0048] refer to Figure 1 and Figure 2 In the separation chamber 5, a separation component is used to separate the hydrogel microspheres from the liquid containing the cleaning solution and the oil phase. Therefore, as the hydrogel flows through the separation chamber 5, the cleaning solution effectively washes and removes the oil phase from the hydrogel microspheres. Compared to the centrifugation method used in the prior art for oil phase removal, the technical solution in this application causes less damage to the hydrogel microspheres, allowing the hydrogel to retain a more intact morphology after oil phase removal and reducing the possibility of microsphere breakage. Furthermore, the removal of the oil phase is achieved after the hydrogel microspheres flow through the separation chamber 5. By controlling the flow rate of the hydrogel microspheres, the rate of oil phase removal can be controlled, significantly improving the oil phase removal efficiency of the hydrogel microspheres.
[0049] refer to Figure 1 and Figure 2 The separation assembly divides the separation chamber 5 into a first chamber and a second chamber, each of which is an independent chamber.
[0050] The separation component divides the separation chamber 5, ensuring that the hydrogel microspheres remain intact in either the first or second chamber after entering. After being cleaned with a cleaning solution to remove the oil phase from the microspheres, the cleaning solution flows through the separation component into the other chamber and out of separation chamber 5. This separation ensures the hydrogel microspheres are completely isolated in either the first or second chamber, while the other chamber contains only the oil phase and cleaning solution, thus reducing the possibility of oil phase contamination between the microspheres and the cleaning solution. The cleaning solution containing the oil phase also reduces the likelihood of residual hydrogel microspheres within the separation chamber, thereby minimizing leakage.
[0051] refer to Figure 1 and Figure 2 Preferably, the first outlet pipe 3 is connected to the first chamber, and the second outlet pipe 4 is connected to the second chamber;
[0052] refer to Figure 1 and Figure 2 In one specific embodiment, the first outlet pipe 3 and the second outlet pipe 4 are located on opposite sides of the separation assembly through communication with the first chamber and the second chamber. Therefore, when the hydrogel microspheres and the oil phase are discharged from the first outlet pipe 3 and the second outlet pipe 4 respectively, the separation of the hydrogel microspheres and the oil phase is achieved.
[0053] In one specific embodiment, the hydrogel microspheres enter the first chamber, and the cleaning solution after cleaning the oil phase enters the second chamber.
[0054] refer to Figure 1 and Figure 2 More preferably, both the first inlet pipe 1 and the second inlet pipe 2 are connected to the first chamber.
[0055] Hydrogel microspheres containing the oil phase and cleaning solution enter the first chamber from the first inlet pipe 1 and the second inlet pipe 2, respectively. After the cleaning solution removes the oil phase from the hydrogel microspheres, it enters the second chamber through the separation component. The hydrogel microspheres are blocked in the first chamber by the separation component, thereby achieving the separation of the oil phase and the hydrogel microspheres.
[0056] refer to Figure 1 and Figure 2 More preferably, the separation cavity 5 has a long strip-shaped structure, and the length dimension of the separation cavity 5 is much larger than the width dimension;
[0057] The first inlet pipe 1 and the second inlet pipe 2 are both located at one end of the separation chamber 5 along its length, while the first outlet pipe 3 and the second outlet pipe 4 are located at the other end of the separation chamber 5 along its length. Therefore, in the separation chamber 5, the hydrogel microspheres and the cleaning solution will flow from one end of the separation chamber 5 to the other end along its length, increasing the length of the separation chamber 5 and thus increasing the clear path length between the cleaning solution and the hydrogel microspheres; reducing oil phase residue on the hydrogel microspheres, so that the cleaning solution can clean the hydrogel microspheres more thoroughly.
[0058] At the same time, reducing the width dimension of the separation chamber 5 reduces the diffusion of hydrogel microspheres and cleaning fluid in the separation chamber 5 in the width direction, allowing the cleaning fluid to more fully fuse and clean the hydrogel microspheres; simultaneously, it allows the cleaning fluid and hydrogel microspheres to flow simultaneously in the length direction, increasing the cleaning effect of the cleaning fluid on the hydrogel microspheres.
[0059] More preferably, the ratio of the length to the width of the separation cavity 5 is 1:10 to 30; more preferably, the ratio of the length to the width of the separation cavity is 1:15 to 20.
[0060] Specifically, the ratio between the length and width of the separation cavity is: 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30.
[0061] refer to Figure 1 and Figure 2 More preferably, the two ends of the separation component are located near the two ends of the separation cavity 5 in the length direction;
[0062] refer to Figure 1 and Figure 2 When the separation component divides the separation chamber 5, it divides the separation chamber 5 along the length direction, increasing the length of the force component in the separation chamber 5, thereby increasing the length of the isolation filtration path of the separation component for the hydrogel microspheres, so as to increase the filtration efficiency.
[0063] On the other hand, the separation chamber 5 is isolated along its length, and the separation component is also a long strip structure. The first and second chambers obtained by the division are also long strips. Therefore, when the hydrogel microspheres and the cleaning liquid flow along the length of the separation chamber 5, they will flow along the separation component at the same time. Then the separation component will block the hydrogel microspheres in the first chamber, and the cleaning liquid and oil phase will pass through the separation component and enter the second chamber. As the hydrogel microspheres and the cleaning liquid flow in the separation chamber 5, the hydrogel microspheres and the oil phase will be gradually cleaned and separated. Setting the separation component and the separation chamber 5 as a long structure can increase the cleaning distance and cleaning time of the cleaning liquid on the hydrogel microspheres, thereby increasing the cleaning effect of the cleaning liquid on the hydrogel microspheres.
[0064] refer to Figure 1 The first inlet pipe 1 is connected to a first tank 7, which contains a first liquid containing hydrogel microspheres. The first liquid enters the separation chamber 5 from the first inlet pipe 1. The first outlet pipe 3 is connected to a third tank 9, and the hydrogel microspheres separated in the separation chamber 5 flow from the first outlet pipe 3 into the third tank 9.
[0065] refer to Figure 1 A second tank 8 is connected to the second inlet pipe 2. The second tank 8 contains a second liquid, which enters the separation chamber 5 from the second inlet pipe 2.
[0066] In this application, the first liquid can be either an oil-phase liquid containing hydrogel microspheres or another phase liquid containing hydrogel microspheres. The second liquid is a cleaning solution used to clean and remove the hydrogel microsphere phase from the first liquid. The separation chamber 5 is used to clean the hydrogel microspheres to obtain the desired hydrogel microsphere solution. Therefore, those skilled in the art can select a suitable phase hydrogel microsphere solution and the corresponding second liquid according to the actual situation.
[0067] Preferably, the first liquid is an oil-phase liquid containing microspheres.
[0068] The second liquid is a solution containing an active agent;
[0069] The second solution is used to remove the oil phase from the first solution. The solution containing surfactants helps to separate the oil phase from the hydrogel microspheres and improves the oil phase removal effect of the hydrogel microspheres.
[0070] When the second solution lacks a surfactant, the hydrogel microspheres struggle to overcome the surface tension at the oil-water interface to facilitate displacement from the oil phase to the water phase, resulting in blockage at the barrier. However, when the second solution contains a surfactant, the hydrogel microspheres can effectively overcome the oil-water interface, allowing displacement from the oil phase to the water phase.
[0071] Preferably, the second liquid is a solution insoluble in the first liquid. More preferably, the second solution is a PBS solution.
[0072] refer to Figure 1 and Figure 2 In one specific embodiment, the first liquid and the second liquid are located on the same side of the separation assembly in the separation chamber 5.
[0073] The first liquid and the second liquid can be located on the same side of the separation assembly in the separation chamber 5, or they can be located on opposite sides of the separation assembly. Preferably, the first liquid and the second liquid are located on the same side of the separation assembly in the separation chamber 5; that is, the first liquid and the second liquid enter the first chamber or the second chamber simultaneously.
[0074] refer to Figure 1 and Figure 2 The separation component includes an isolation block 6 with both ends connected to the inner wall of the separation chamber 5; multiple isolation blocks 6 are provided, and the isolation blocks 6 are arranged sequentially along the length direction of the substrate.
[0075] refer to Figure 2 and Figure 3 The hydrogel microspheres are blocked by isolation blocks 6. The isolation blocks 6 have gaps between them, and the size of these gaps is smaller than the size of the hydrogel microspheres. Therefore, when the hydrogel microspheres flow in the separation chamber 5, they are blocked by the isolation blocks 6, while the oil phase and cleaning fluid flow through the gaps between the isolation blocks 6, thus achieving separation of the hydrogel microspheres from the oil phase. Using isolation blocks 6 to block the hydrogel microspheres has the advantage of a regular shape, reducing damage to the microspheres. Furthermore, the isolation blocks 6 can be manufactured using the same material as the substrate, allowing them to be integrally formed. This strengthens the connection between the isolation blocks 6 and the substrate, while also reducing manufacturing costs. The integrally formed substrate and isolation blocks 6 also help to accelerate manufacturing, reduce substrate processing time, and improve manufacturing efficiency.
[0076] refer to Figure 2 and Figure 3 Multiple isolation blocks 6 are spaced apart.
[0077] The isolation blocks 6 are evenly distributed, and the distance between two adjacent isolation blocks 6 is equal. Therefore, the isolation blocks 6 can play the same blocking role for the hydrogel microspheres. At the same time, when the flow of hydrogel microspheres is blocked by the isolation blocks 6, the hydrogel microspheres can also flow or roll smoothly on the isolation blocks 6, reducing the possibility of hydrogel microspheres being stuck at the isolation blocks 6, so that the hydrogel microspheres can be smoothly discharged from the separation chamber 5, reducing the residue of hydrogel microspheres.
[0078] The spacing between the isolation blocks 6 is 50 to 200 μm; preferably, the spacing between the isolation blocks 6 is 75 to 150 μm; more preferably, the spacing between the isolation blocks 6 is 100 μm.
[0079] Specifically, the spacing between the isolation blocks 6 is: 50μm, 55μm, 60μm, 65μm, 70μm, 75μm, 80μm, 85μm, 90μm, 95μm, 100μm, 105μm, 110μm, 115μm, 120μm, 125μm, 130μm, 135μm, 140μm, 145μm, 150μm, 155μm, 160μm, 165μm, 170μm, 175μm, 180μm, 185μm, 190μm, 195μm, and 200μm.
[0080] The isolation block 6 is provided in 90 to 150 units; preferably, the isolation block 6 is provided in 100 to 120 units; more preferably, the isolation block 6 is provided in 107 units.
[0081] Specifically, the number of isolation blocks 6 is as follows: 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 135, 140, 145, 150.
[0082] The isolation block 6 has equal length and width. Preferably, the length and width of the isolation block 6 are 100-300 μm; more preferably, the length and width of the isolation block 6 are 150-250 μm; and even more preferably, the length and width of the isolation block 6 are 200 μm.
[0083] Specifically, the length and width of the isolation block 6 are: 100μm, 105μm, 110μm, 115μm, 120μm, 125μm, 130μm, 135μm, 140μm, 145μm, 150μm, 155μm, 160μm, 165μm, 170μm, 175μm, 180μm, 185μm, 190μm, 1 95μm, 200μm, 205μm, 210μm, 215μm, 220μm, 225μm, 230μm, 235μm, 240μm, 245μm, 250μm, 255μm, 260μm, 265μm, 270μm, 275μm, 280μm, 285μm, 290μm, 295μm, 300μm.
[0084] refer to Figure 1 and Figure 2 The extending direction of the isolation blocks 6 is at an angle to the central axis of the separation cavity 5;
[0085] refer to Figure 2 and Figure 3 In one specific embodiment, the isolation block 6 of the separation component is located at one end of the separation cavity 5 along the length direction and near the edge along the width direction, while the isolation block 6 at the other end along the length direction is located near the middle along the width direction of the separation cavity 5.
[0086] refer to Figure 1 and Figure 2 In short, one end of the separation component is located at the edge of one end of the separation cavity 5, and the other end of the separation component is located at the middle of the other end of the separation cavity 5.
[0087] This results in the separation assembly having an angle with the central axis of the separation chamber 5.
[0088] refer to Figure 1 When the isolation block 6 is set, it is inclined relative to the central axis of the separation chamber 5. After the hydrogel microspheres enter the separation chamber 5, they will flow along the isolation block 6. With the injection of cleaning fluid, the cleaning fluid will clean the oil phase on the hydrogel microspheres, thereby achieving the removal of the oil phase on the hydrogel microspheres.
[0089] refer to Figure 2 and Figure 3 The separation assembly is tilted. A first liquid enters the first chamber through the first inlet pipe 1; a second liquid enters the first chamber through the second inlet pipe 2. The hydrogel microspheres then flow continuously within the first chamber until they exit through the first outlet pipe 3. The first outlet pipe 3 is centrally symmetrical to the first inlet pipe 1, allowing the hydrogel microspheres to flow along the tilted isolation blocks 6. The second liquid, after entering the first chamber through the second inlet pipe 2, flows forward without being blocked by the isolation blocks 6, then flows directly to the other end of the separation chamber 5 along its length, exiting through the second outlet pipe 4. Similarly, the second inlet pipe 2 and the second outlet pipe 4 are centrally symmetrically positioned. By centrally symmetrically positioning the first and second inlet pipes 1 and 2, and the second inlet pipe 2 and the second outlet pipe 4, the flow directions of the first and second liquids in the separation chamber 5 intersect. This allows the second liquid to flush the first liquid, and the hydrogel microspheres in the first liquid are blocked by the isolation blocks 6, thus achieving oil phase removal from the hydrogel microspheres.
[0090] refer to Figure 1 and Figure 2Preferably, the angle between the extending direction of the isolation blocks 6 and the central axis of the separation cavity 5 is 0.1 to 3°.
[0091] Specifically, the angle between the extending direction of the isolation blocks 6 and the central axis of the separation cavity 5 is 0.1°, 0.2°, 0.3°, 0.4°, 0.5°, 0.6°, 0.7°, 0.8°, 0.9°, 1°, 1.1°, 1.2°, 1.3°, 1.4°, 1.5°, 1.6°, 1.7°, 1.8°, 1.9°, 2°, 2.1°, 2.2°, 2.3°, 2.4°, 2.5°, 2.6°, 2.7°, 2.8°, 2.9°, and 3°.
[0092] The flow rate of the first liquid is 1–12 μL / min.
[0093] Specifically, the flow rates of the first liquid are 1 μL / min, 2 μL / min, 3 μL / min, 4 μL / min, 5 μL / min, 6 μL / min, 7 μL / min, 8 μL / min, 9 μL / min, 10 μL / min, 11 μL / min, and 12 μL / min.
[0094] refer to Figure 1 The flow rate of the second liquid in the separation chamber 5 is 100-300 μL / min; preferably, the flow rate of the second liquid in the separation chamber 5 is 120-200 μL / min; more preferably, the flow rate of the second liquid in the separation chamber 5 is 150 μL / min.
[0095] Specifically, the flow rates of the second liquid in separation chamber 5 are: 100 μL / min, 105 μL / min, 110 μL / min, 115 μL / min, 120 μL / min, 125 μL / min, 130 μL / min, 135 μL / min, 140 μL / min, 145 μL / min, 150 μL / min, 155 μL / min, 160 μL / min, 165 μL / min, 170 μL / min, 175 μL / min, 180 μL / min, 185 μL / min, 190 μL / min, and 195 μL / min. / min, 200μL / min, 205μL / min, 210μL / min, 215μL / min, 220μL / min, 225μL / min, 230μL / min, 235μL / min, 240μL / min, 245μL / min, 25 0μL / min, 255μL / min, 260μL / min, 265μL / min, 270μL / min, 275μL / min, 280μL / min, 285μL / min, 290μL / min, 295μL / min, 300μL / min.
[0096] The ratio of the flow rate of the first liquid to the flow rate of the second liquid is 1:12.5 to 150.
[0097] refer to Figure 1 A first pump (not shown in the figure) is provided between the first inlet pipe 1 and the first tank 7, and a second pump (not shown in the figure) is provided between the second inlet pipe 2 and the second tank 8. Preferably, both the first pump and the second pump are precision injection pumps.
[0098] In summary, this application provides a structure for removing the oil phase from core-shell structured hydrogel microspheres. In use, a first liquid enters the first chamber of the separation chamber 5 from the first inlet pipe 1, and a second liquid enters the first chamber of the separation chamber 5 from the second inlet pipe 2. The first and second liquids then mix and flow continuously forward along the length of the separation chamber 5. The hydrogel microspheres in the first liquid are blocked by the isolation block 6, causing them to remain in the first chamber. The second liquid and the oil phase in the first liquid pass through the isolation block 6 during flow and enter the second chamber. The hydrogel microspheres are then discharged from the first outlet pipe 3, which communicates with the first chamber, and collected in the third tank 9. The second liquid and the oil phase in the first liquid then flow from the second outlet pipe 4 into the fourth tank 10 for collection.
[0099] In addition, when collecting hydrogel microspheres in the third tank 9, it cannot be ruled out that some of the first liquid will simultaneously enter the third tank 9.
[0100] Example
[0101] This application provides a structure for removing the oil phase from core-shell structured hydrogel microspheres, including a substrate, which is a plate-like structure with a length of 5 cm and a width of 3 cm. A first inlet pipe 1, a second inlet pipe 2, a first outlet pipe 3, and a second outlet pipe 4 are all pipes with a diameter of 500 μm. A separation chamber 5 is disposed inside the substrate, and isolation blocks 6 are disposed within the separation chamber 5. Each isolation block 6 is a block-like structure with a length and width of 200 μm. A total of 107 isolation blocks 6 are disposed in the separation chamber 5, and all isolation blocks 6 are evenly arranged sequentially. The distance between any two adjacent isolation blocks 6 is 100 μm; the angle between the arrangement direction of the isolation blocks 6 and the central axis of the substrate or the separation chamber 5 is 1°.
[0102] The substrate and the isolation block 6 are integrally formed, and a separation cavity 5 is formed inside the substrate. The substrate and the isolation block 6 are made of PDMS material.
[0103] The separation chamber 5 has a length dimension of 35.7 mm and a width dimension of 1.9 mm.
[0104] The first liquid is an alginate-matrix-oil dual hydrogel microsphere solution. The second liquid is a PBS solution containing a certain amount of surfactant.
[0105] The flow rate of the first liquid is 1–12 μL / min, and the flow rate of the second liquid is 150 μL / min.
[0106] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.
Claims
1. A structure for removing the oil phase of core-shell structured hydrogel microspheres, characterized in that, The device includes a substrate, on which a separation cavity is formed, and on which a separation component is disposed, the separation component being disposed in the separation cavity. A first inlet pipe and a second inlet pipe, both of which are in communication with the separation cavity, are provided on the substrate. A first outlet pipe and a second outlet pipe are provided at one end of the separation chamber away from the first inlet pipe and the second inlet pipe; the first outlet pipe and the second outlet pipe are respectively provided on both sides of the separation assembly.
2. The removal structure according to claim 1, characterized in that, The separation assembly divides the separation chamber into a first chamber and a second chamber, each of which is an independent chamber.
3. The removal structure according to claim 2, characterized in that, The first outlet pipe is connected to the first chamber, and the second outlet pipe is connected to the second chamber.
4. The removal structure according to claim 2, characterized in that, The separation chamber has a long strip-shaped structure, and the length dimension of the separation chamber is much larger than the width dimension.
5. The removal structure according to claim 2, characterized in that, The two ends of the separation component are located near the two ends of the separation chamber in the length direction.
6. The removal structure according to claim 2, characterized in that, Both the first inlet pipe and the second inlet pipe are connected to the first chamber.
7. The removal structure according to claim 1, characterized in that, The first inlet pipe is connected to a first tank containing a first liquid containing microspheres. The first liquid enters the separation chamber from the first inlet pipe. The first outlet pipe is connected to a third tank, and the microspheres in the separation chamber flow from the first outlet pipe into the third tank.
8. The removal structure according to claim 7, characterized in that, The first liquid is an oil-phase liquid containing microspheres.
9. The removal structure according to claim 7, characterized in that, A second inlet pipe is connected to a second tank containing a second liquid, which enters the separation chamber through the second inlet pipe.
10. The removal structure according to claim 9, characterized in that, The second liquid is a solution containing an active agent.
11. The removal structure according to claim 9, characterized in that, The second liquid is a solution that is insoluble in the first liquid.
12. The removal structure according to claim 9, characterized in that, The first liquid and the second liquid are located on the same side of the separation assembly in the separation chamber.
13. The removal structure according to any one of claims 1 to 12, characterized in that, The separation component includes isolation blocks connected to the inner wall of the separation chamber at both ends; multiple isolation blocks are provided, and the isolation blocks are arranged sequentially along the length direction of the substrate.
14. The removal structure according to claim 13, characterized in that, The isolation blocks are spaced apart.
15. The removal structure according to claim 13, characterized in that, The spacing between the isolation blocks is 50–200 μm.
16. The removal structure according to claim 15, characterized in that, The spacing between the isolation blocks is 75–150 μm.
17. The removal structure according to claim 15, characterized in that, The spacing between the isolation blocks is 100 μm.
18. The removal structure according to claim 13, characterized in that, The isolation blocks are configured in numbers of 90 to 150.
19. The removal structure according to claim 13, characterized in that, The isolation blocks are configured in numbers of 100 to 120.
20. The removal structure according to claim 13, characterized in that, There are 107 isolation blocks.
21. The removal structure according to claim 13, characterized in that, The length and width of the isolation block are equal.
22. The removal structure according to claim 13, characterized in that, The length and width of the isolation block are 100-300 μm.
23. The removal structure according to claim 13, characterized in that, The length and width of the isolation block are 150-250 μm.
24. The removal structure according to claim 13, characterized in that, The isolation block has a length and width of 200 μm.
25. The removal structure according to claim 13, characterized in that, There is an angle between the extending direction of the isolation blocks and the central axis of the separation cavity.
26. The removal structure according to claim 25, characterized in that, The included angle is 1°.
27. The removal structure according to claim 9, characterized in that, A first pump is installed between the first inlet pipe and the first tank, and a second pump is installed between the second inlet pipe and the second tank.
28. The removal structure according to claim 27, characterized in that, Both the first pump and the second pump are precision injection pumps.