Removal structure of oil phase of hydrogel microsphere with core-shell structure

Abstract

The invention discloses a shell-core structure hydrogel microsphere oil phase removing structure which comprises a substrate, a separation cavity is formed in the substrate, a separation assembly is arranged on the substrate, and the separation assembly is arranged in the separation cavity; a first inlet pipe and a second inlet pipe which are communicated with the separation cavity are arranged on the base plate, and the first inlet pipe and the second inlet pipe are arranged on the two sides of the separation assembly respectively; a first outlet pipe and a second outlet pipe are arranged at one end, deviating from the first inlet pipe and the second inlet pipe, of the separation cavity; the first outlet pipe and the second outlet pipe are arranged on the two sides of the separation assembly respectively. According to the micro-fluidic chip, the oil phase of the microspheres is automatically removed, the microspheres are replaced from the oil phase to the liquid phase, and the microsphere filtering condition is optimized.

Description

Technical Field

[0001] The present application relates to the field of microfluidics, and in particular to a structure for removing the oil phase of a core-shell structured hydrogel microsphere. Background Art

[0002] After the hydrogel microspheres are solidified, the oil phase needs to be effectively removed to facilitate the subsequent growth of loaded cells and differentiation of organoids. The conventional method for removing the oil phase from hydrogel microspheres is centrifugation and filtration. However, this long-term and multi-step filtration method is not conducive to the high-throughput automated preparation of organoids. Summary of the invention

[0003] In order to solve the problems existing in the prior art, the present application provides a structure for removing the oil phase of core-shell structured hydrogel microspheres.

[0004] In order to realize the automated oil phase removal of microspheres, we designed a microfluidic chip to displace microspheres from the oil phase to the liquid phase and optimized the conditions for microsphere filtration.

[0005] In the present application, in a certain sense, the first liquid is the hydrogel microspheres, and the second liquid is the cleaning liquid.

[0006] The specific technical solutions of this application are as follows:

[0007] 1. A core-shell hydrogel microsphere oil phase removal structure, comprising a substrate, a separation cavity is formed on the substrate, a separation component is arranged on the substrate, and the separation component is arranged in the separation cavity;

[0008] A first inlet pipe and a second inlet pipe, both of which are connected to the separation chamber, are arranged on the substrate;

[0009] A first outlet pipe and a second outlet pipe are arranged 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 arranged on both sides of the separation component respectively.

[0010] 2. According to the removal structure of item 1, the separation component separates the separation chamber into a first chamber and a second chamber, and the first chamber and the second chamber are independent chambers respectively;

[0011] Preferably, the first outlet pipe is in communication with the first chamber, and the second outlet pipe is in communication with the second chamber;

[0012] Further preferably, the separation chamber is a long strip structure, and the length dimension of the separation chamber is much larger than the width dimension;

[0013] Further preferably, the ratio between the length dimension and the width dimension of the separation chamber is 1:10-30; preferably, the ratio between the length dimension and the width dimension of the separation chamber is 1:15-20.

[0014] Further preferably, the two ends of the separation component are respectively located close to the two ends of the separation chamber in the length direction;

[0015] Further preferably, both the first inlet pipe and the second inlet pipe are communicated with the first chamber.

[0016] 3. According to the removal structure described in item 1 or 2, the first inlet pipe is connected to a first tank body, in which a first liquid containing microspheres is stored, and the first liquid enters the separation chamber from the first inlet pipe; the first outlet pipe is connected to a third tank body, and the microspheres containing force in the separation chamber flow from the first outlet pipe into the third tank body.

[0017] 4. According to any one of items 1 to 3, the first liquid is an oil phase liquid containing microspheres.

[0018] 5. According to the removal structure described in any one of items 1 to 4, a second tank body is connected to the second inlet pipe, a second liquid is contained in the second tank body, and the second liquid enters the separation chamber from the second inlet pipe.

[0019] 6. According to the removal structure described in item 5, the second liquid is a solution containing an active agent, and preferably, the second liquid is a solution insoluble in the first liquid.

[0020] 7. According to the removal structure of item 3, the first liquid and the second liquid are located on the same side of the separation component in the separation chamber.

[0021] 8. According to the removal structure described in any one of items 1 to 7, the separation component includes an isolation block with both ends connected to the inner wall of the separation chamber; a plurality of isolation blocks are provided, and the isolation blocks are arranged in sequence along the length direction of the substrate.

[0022] 9. According to the removal structure described in item 8, a plurality of the isolation blocks are arranged with intervals therebetween.

[0023] 10. According to the removal structure described in item 8, the spacing between the isolation blocks is 50 to 200 μm; preferably, the spacing between the isolation blocks is 75 to 150 μm; further preferably, the spacing between the isolation blocks is 100 μm.

[0024] 11. According to the removal structure described in item 8, the number of the isolation blocks is 90 to 150; preferably, the number of the isolation blocks is 100 to 120; further preferably, the number of the isolation blocks is 107.

[0025] 12. According to the removal structure described in item 8, the length and width of the isolation block are equal. Preferably, the length and width of the isolation block are 100-300 μm; further preferably, the length and width of the isolation block are 150-250 μm; further preferably, the length and width of the isolation block are 200 μm.

[0026] 13. According to the removal structure described in item 8, there is an angle between the extension direction of the isolation block arrangement and the central axis of the separation chamber; preferably, the angle is 1°.

[0027] 14. According to any one of items 1 to 13, the ratio of the flow rate of the first liquid to the flow rate of the second liquid is 1:12.5-150.

[0028] 15. The removal structure according to any one of items 1 to 14, wherein 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.

[0030] 16. According to the removal structure described in any one of items 1 to 15, a first pump is provided between the first inlet pipe and the first tank body, and a second pump is provided between the second inlet pipe and the second tank body. Preferably, both the first pump and the second pump are precision injection pumps.

[0031] Beneficial Effects

[0032] The core-shell hydrogel microsphere oil phase removal structure of the present application realizes the automated oil phase removal of the microspheres, replaces the microspheres from the oil phase to the microfluidic chip in the liquid phase, and optimizes the conditions for microsphere filtration. After the filtered microsphere solution is injected into the chip, it is found that there is no secondary filtration of the oil phase, and there is no oil phase attached to the surface of the filtered microspheres. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the overall diagram of the removal structure of this application;

[0034] Figure 2 It is a schematic diagram of the removal structure of this application;

[0035] Figure 3 It is a schematic diagram of the cross-section of the structure removed in this application.

[0036] In the figure, 1, first inlet pipe; 2, second inlet pipe; 3, first outlet pipe; 4, second outlet pipe; 5, separation chamber; 6, isolation block; 7, first tank body; 8, second tank body; 9, third tank body; 10, fourth tank body. DETAILED DESCRIPTION

[0037] The present application is described in detail below. Although 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 by the embodiments described herein. On the contrary, 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 words are used in the specification and claims to refer to specific components. Those skilled in the art should understand that technicians may use different nouns to refer to the same component. This specification and claims do not use the difference in nouns as a way to distinguish components, but use the functional differences of components as the criterion for distinction. As mentioned throughout the specification and claims, "including" or "comprising" are open-ended terms and should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present application, but the description is based on the general principles of the specification and is not intended to limit the scope of the present application. The scope of protection of the present application shall be determined by the attached claims.

[0039] refer to Figure 1 and Figure 2 The present application provides a structure for removing the oil phase of a core-shell structure hydrogel microsphere. It includes a substrate, a separation cavity 5 is provided on the substrate, a separation component is provided on the substrate, and the separation component is provided in the separation cavity 5; the separation component separates the separation cavity 5 into two independent chambers;

[0040] After the core-shell structured hydrogel microspheres are solidified, the oil phase needs to be removed.

[0041] The core-shell structured hydrogel microspheres can flow in the separation chamber 5 , and a cleaning liquid capable of removing the oil phase on the hydrogel microspheres also flows in the separation chamber 5 .

[0042] refer to Figure 1 and Figure 2 The separation component is located in the separation chamber 5, and the hydrogel microspheres and the cleaning liquid flow together in the separation chamber 5, and then pass through the separation component. The hydrogel microspheres will be blocked by the separation component, and the cleaning liquid and the oil phase will pass through the separation component, so that the hydrogel microspheres are separated from the oil phase; so as to achieve the purpose of removing the oil phase of the hydrogel microspheres.

[0043] refer to Figure 1 and Figure 2, a first inlet pipe 1 and a second inlet pipe 2 are provided on the substrate, both of which are connected to the separation chamber 5;

[0044] The first inlet tube 1 and the second inlet tube 2 are used to inject cleaning liquid 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 in the separation chamber 5 from the hydrogel microspheres, and then the hydrogel microspheres and the 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 of the hydrogel microspheres.

[0047] refer to Figure 1 and Figure 2 The hydrogel microspheres and the cleaning liquid flow in the separation chamber 5, and then after contacting the separation component, the hydrogel microspheres will be blocked by the separation component, and then the hydrogel microspheres will flow along the edge of the separation component, and then the cleaning liquid and the oil phase cleaned from the hydrogel microspheres will continue to flow forward through the separation component, thereby achieving the cleaning of the hydrogel microspheres by the cleaning liquid, and the separation and removal of the oil phase and the hydrogel microspheres.

[0048] refer to Figure 1 and Figure 2 , a separation component is used in the separation chamber 5 to separate the hydrogel microspheres from the liquid containing the cleaning liquid and the oil phase. Therefore, during the flow of the hydrogel in the separation chamber 5, the cleaning liquid cleans and removes the oil phase on the hydrogel microspheres. Compared with the centrifugal method for removing the oil phase in the prior art, the technical solution in the present application is less harmful to the hydrogel microspheres, so that the hydrogel can retain a more complete shape after the oil phase is removed, reducing the possibility of damage to the hydrogel microspheres. Furthermore, after the hydrogel microspheres flow through the separation chamber 5, the oil phase is removed. By controlling the flow rate of the hydrogel microspheres, the speed at which the hydrogel microspheres remove the oil phase can be controlled; the oil phase removal efficiency of the hydrogel microspheres is significantly improved.

[0049] refer to Figure 1 and Figure 2 , the separation component separates the separation chamber 5 into a first chamber and a second chamber, and the first chamber and the second chamber are independent chambers respectively;

[0050] The separation component separates the separation chamber 5, so that after the hydrogel microspheres enter the separation chamber 5, they can be completely retained in the first chamber or the second chamber, and then after being cleaned by the cleaning liquid and the oil phase is removed from the hydrogel microspheres, the cleaning liquid after cleaning the oil phase will pass through the separation component into another chamber and flow out of the separation chamber 5; the separation component partition makes the hydrogel microspheres completely isolated in the first chamber or the second chamber, and in the other chamber, there are only the oil phase and the cleaning liquid, thereby reducing the possibility of mixing the hydrogel microspheres with the oil phase. When the cleaning liquid with the oil phase flows out of the separation chamber 5, the possibility of hydrogel microspheres remaining inside it is reduced; thereby reducing the leakage of the hydrogel microspheres.

[0051] refer to Figure 1 and Figure 2 Preferably, the first outlet pipe 3 is in communication with the first chamber, and the second outlet pipe 4 is in communication with the second chamber;

[0052] refer to Figure 1 and Figure 2 In one embodiment, the first outlet pipe 3 and the second outlet pipe 4 are located on both sides of the separation component by being connected to the first chamber and the second chamber. Therefore, the hydrogel microspheres and the oil phase can be discharged from the first outlet pipe 3 and the second outlet pipe 4 respectively, thereby achieving separation of the hydrogel microspheres and the oil phase.

[0053] In a 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 , further preferably, the first inlet pipe 1 and the second inlet pipe 2 are both connected to the first chamber.

[0055] The hydrogel microspheres containing the oil phase and the cleaning liquid enter the first chamber from the first inlet pipe 1 and the second inlet pipe 2 respectively. Then, after the cleaning liquid clears the oil phase on 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 separation of the oil phase and the hydrogel microspheres.

[0056] refer to Figure 1 and Figure 2 , further preferably, the separation chamber 5 is a long strip structure, and the length direction dimension of the separation chamber 5 is much larger than the width direction dimension;

[0057] The first inlet pipe 1 and the second inlet pipe 2 are both located at one end of the separation chamber 5 in the length direction, and the first outlet pipe 3 and the second outlet pipe 4 are located at the other end of the separation chamber 5 in the length direction. Therefore, in the separation chamber 5, the hydrogel microspheres and the cleaning liquid will flow from one end to the other end in the length direction of the separation chamber 5, increasing the length of the separation chamber 5 and thus increasing the clear path length of the cleaning liquid and the hydrogel microspheres; reducing the oil phase residue on the hydrogel microspheres, so that the cleaning liquid can clean the hydrogel microspheres more cleanly.

[0058] At the same time, the size of the separation chamber 5 in the width direction is reduced, and the diffusion of the hydrogel microspheres and the cleaning liquid in the separation chamber 5 in the width direction is reduced, so that the cleaning liquid can be more fully fused and cleaned with the hydrogel microspheres; at the same time, the cleaning liquid and the hydrogel microspheres can flow simultaneously in the length direction; and the clearing effect of the cleaning liquid on the hydrogel microspheres is increased.

[0059] Further preferably, the ratio between the length dimension and the width dimension of the separation chamber 5 is 1:10-30; preferably, the ratio between the length dimension and the width dimension of the separation chamber is 1:15-20.

[0060] Specifically, the ratio between the length dimension and the width dimension of the separation chamber 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 , further preferably, the two ends of the separation component are respectively located near the two ends of the separation chamber 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 to increase the filtration efficiency.

[0063] On the other hand, the separation chamber 5 is isolated in the length direction, and the separation component is also a long strip structure. The first chamber and the second chamber obtained by division are also long strips. Therefore, when the hydrogel microspheres and the cleaning liquid flow in the separation chamber 5 along the length direction, they will flow along the separation component at the same time, and then the separation component will block the hydrogel microspheres in the first chamber, and the cleaning liquid and the oil phase will pass through the separation component into the second chamber, and 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; and setting the separation component and the separation chamber 5 into a longer structure can increase the cleaning distance and cleaning time of the hydrogel microspheres by the cleaning liquid, 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 body 7, in which a first liquid containing hydrogel microspheres is stored, and 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 body 9, and the hydrogel microspheres separated in the separation chamber 5 flow from the first outlet pipe 3 into the third tank body 9.

[0065] refer to Figure 1 The second inlet pipe 2 is connected to a second tank body 8 , and the second tank body 8 contains a second liquid. The second liquid enters the separation chamber 5 from the second inlet pipe 2 .

[0066] In the present application, the first liquid can be either an oil phase liquid containing hydrogel microspheres or other phase liquid containing hydrogel microspheres. The second liquid is a cleaning liquid, which is used to clean and remove the phase of hydrogel microspheres in 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 hydrogel microsphere solution of a suitable phase according to actual conditions and select a corresponding second liquid.

[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 in the first solution. The solution containing the active agent helps to separate the oil phase from the hydrogel microspheres, thereby improving the oil phase removal effect of the hydrogel microspheres.

[0070] When there is no surfactant in the second solution, it is difficult for the hydrogel microspheres to break through the surface tension of the oil-water interface to achieve the displacement of the oil phase to the water phase, and blockage will occur at the fence. When the second solution is a solution containing a surfactant, the hydrogel microspheres can well break through the oil-water interface and displace from the oil phase to the water phase.

[0071] Preferably, the second liquid is a solution that is insoluble in the first liquid. Further preferably, the second solution is a PBS solution.

[0072] refer to Figure 1 and Figure 2 In a specific embodiment, the first liquid and the second liquid are located on the same side of the separation component in the separation chamber 5.

[0073] The first liquid and the second liquid can be located at the same side of the separation component in the separation chamber 5, and the first solution and the second solution can also be located at the two sides of the separation component. Preferably, the first liquid and the second liquid are located at the same side of the separation component in the separation chamber 5; that is, the first liquid and the second liquid enter the first chamber or the second chamber at the same time.

[0074] refer to Figure 1 and Figure 2 The separation component includes an isolation block 6 whose two ends are connected to the inner wall of the separation chamber 5; a plurality of isolation blocks 6 are provided, and the isolation blocks 6 are arranged in sequence along the length direction of the substrate.

[0075] refer to Figure 2 and Figure 3 , the isolation blocks 6 are used to block the hydrogel microspheres. There are gaps between the isolation blocks 6, and the size of the gaps is smaller than the size of the hydrogel microspheres. Therefore, when the hydrogel microspheres flow in the separation chamber 5, the hydrogel microspheres will be blocked by the isolation blocks 6, while the oil phase and the cleaning liquid will flow through the gaps between the isolation blocks 6, thereby achieving the separation of the hydrogel microspheres from the oil phase. The isolation blocks 6 are used to block the hydrogel microspheres. Since the isolation blocks 6 are of regular shape, the damage to the hydrogel microspheres by the isolation blocks 6 can be reduced. At the same time, the isolation blocks 6 can be made of the same material as the substrate during manufacturing. Therefore, the isolation blocks 6 and the substrate are integrally formed, which can not only strengthen the connection strength of the isolation blocks 6, but also reduce the production cost of the substrate and the isolation blocks 6. The integrally formed substrate and isolation block 6 also help to speed up the manufacturing process, reduce the processing time of the substrate, and improve manufacturing efficiency.

[0076] refer to Figure 2 and Figure 3 , multiple isolation blocks 6 are arranged at intervals.

[0077] The isolation blocks 6 are evenly arranged, and the spacing between two adjacent isolation blocks 6 is equal. Therefore, the isolation blocks 6 can play the same blocking role on the hydrogel microspheres. At the same time, when the flow of the hydrogel microspheres is blocked by the isolation blocks 6, the hydrogel microspheres can flow or roll smoothly on the isolation blocks 6, reducing the possibility of the hydrogel microspheres being retained at the isolation blocks 6, so that the hydrogel microspheres can be smoothly discharged from the separation chamber 5, reducing the residue of the hydrogel microspheres.

[0078] The spacing between the isolation blocks 6 is 50-200 μm; preferably, the spacing between the isolation blocks 6 is 75-150 μm; further 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 number of the isolation blocks 6 is 90 to 150; preferably, the number of the isolation blocks 6 is 100 to 120; further preferably, the number of the isolation blocks 6 is 107.

[0081] Specifically, the number of the isolation blocks 6 is: 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 length and width of the isolation block 6 are equal. Preferably, the length and width of the isolation block 6 are 100-300 μm; further preferably, the length and width of the isolation block 6 are 150-250 μm; further 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 There is an angle between the extending direction of the isolation blocks 6 and the central axis of the separation chamber 5;

[0085] refer to Figure 2 and Figure 3 In a specific embodiment, the isolation block 6 of the separation component is arranged at one end of the separation chamber 5 in the length direction near the edge of the separation chamber 5 in the width direction, and the isolation block 6 at the other end of the separator in the length direction is arranged near the middle of the separation chamber 5 in the width direction.

[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 chamber 5, and the other end of the separation component is located at the middle of the other end of the separation chamber 5.

[0087] As a result, the separation component as a whole presents a structure with an angle between it and the central axis of the separation chamber 5 .

[0088] refer to Figure 1 When the isolation block 6 is set, it is set at an inclined direction compared 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 the cleaning liquid, the cleaning liquid 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 component is tilted. The first liquid enters the first chamber from the first inlet pipe 1; the second liquid enters the first chamber from the second inlet pipe 2, and then the hydrogel microspheres continue to flow in the first chamber until they are discharged from the first outlet pipe 3, and the first outlet pipe 3 is in a centrally symmetrical position with the first inlet pipe 1, so the hydrogel microspheres will flow along the tilted isolation block 6, and after the second liquid enters the first chamber from the second inlet pipe 2, it will continue to flow forward and will not be blocked by the isolation block 6, and then directly flow into the other end of the separation chamber 5 in the length direction, and discharge the separation chamber 5 at the second outlet pipe 4; similarly, the second inlet pipe 2 and the second outlet pipe 4 are centrally symmetrically arranged. By centrally symmetrically arranging the first inlet pipe 1 and the second inlet pipe 2 and centrally symmetrically arranging the second inlet pipe 2 and the second outlet pipe 4, the flow directions of the first liquid and the second liquid in the separation chamber 5 are crossed; thereby, the second liquid can flush the first liquid, and the hydrogel microspheres in the first liquid are blocked by the isolation block 6, thereby achieving the oil phase removal of 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 chamber 5 is 0.1 to 3°.

[0091] Specifically, the angles between the extension direction of the isolation blocks 6 and the central axis of the separation chamber 5 are 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 rate of the first liquid is 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; further preferably, the flow rate of the second liquid in the separation chamber 5 is 150 μL / min.

[0095] Specifically, the flow rate of the second liquid in the separation chamber 5 is: 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, 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 1:12.5-150.

[0097] refer to Figure 1 A first pump (not shown in the figure) is arranged between the first inlet pipe 1 and the first tank body 7, and a second pump (not shown in the figure) is arranged between the second inlet pipe 2 and the second tank body 8. Preferably, the first pump and the second pump are both precision injection pumps.

[0098] In summary, the present application provides a structure for removing the oil phase of core-shell hydrogel microspheres. When in use, the first liquid enters the first chamber of the separation chamber 5 from the first inlet pipe 1, and the second liquid enters the first chamber of the separation chamber 5 from the second inlet pipe 2; then the first liquid and the second liquid are mixed and continue to flow forward along the length direction of the separation chamber 5. The hydrogel microspheres in the first liquid are blocked by the isolation block 6, so that the hydrogel microspheres remain in the first chamber. The second liquid and the oil phase in the first liquid will pass through the isolation block 6 during the flow process and enter the second chamber. After that, the hydrogel microspheres are discharged from the first outlet pipe 3 connected to the first chamber and collected in the third tank body 9. The second liquid and the oil phase in the first liquid flow from the second outlet pipe 4 into the fourth tank body 10 for collection.

[0099] In addition, when the third tank body 9 collects the hydrogel microspheres, it is not excluded that part of the first liquid will enter the third tank body 9 at the same time.

[0100] Example

[0101] The present application provides a structure for removing the oil phase of a core-shell structure hydrogel microsphere, including a substrate, which is a plate-like structure with a length of 5 cm and a width of 3 cm. The first inlet pipe 1, the second inlet pipe 2, the first outlet pipe 3 and the second outlet pipe 4 are all pipes with a diameter of 500 μm. The separation chamber 5 is arranged inside the substrate, and the isolation block 6 is arranged in the separation chamber 5. The isolation block 6 is a block structure with a length and width of 200 μm. There are 107 isolation blocks 6 in the separation chamber 5, and all the isolation blocks 6 are evenly arranged in sequence. The distance between each two adjacent isolation blocks 6 is 100 μm; the angle between the arrangement direction of the isolation block 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 dimension of the separation chamber 5 in the length direction is 35.7 mm; the dimension in the width direction is 1.9 mm.

[0104] The first liquid is alginate-matrix gel-oil double hydrogel microsphere solution, and the second liquid is a PBS solution containing a certain 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 the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A core-shell hydrogel microsphere oil phase removal structure, characterized in that: It comprises a substrate, a separation cavity is formed on the substrate, a separation component is arranged on the substrate, and the separation component is arranged in the separation cavity; A first inlet pipe and a second inlet pipe, both of which are connected to the separation chamber, are arranged on the substrate; A first outlet pipe and a second outlet pipe are arranged 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 arranged on both sides of the separation component respectively.

2. The removal structure according to claim 1, characterized in that: The separation component separates the separation chamber into a first chamber and a second chamber, wherein the first chamber and the second chamber are independent chambers respectively; Preferably, the first outlet pipe is in communication with the first chamber, and the second outlet pipe is in communication with the second chamber; Further preferably, the separation chamber is a long strip structure, and the length dimension of the separation chamber is much larger than the width dimension; Further preferably, the ratio between the length dimension and the width dimension of the separation chamber is 1:10-30; preferably, the ratio between the length dimension and the width dimension of the separation chamber is 1:15-20; Further preferably, the two ends of the separation component are respectively located close to the two ends of the separation chamber in the length direction; Further preferably, both the first inlet pipe and the second inlet pipe are communicated with the first chamber.

3. The removal structure according to claim 1 or 2, characterized in that: The first inlet pipe is connected to a first tank body, in which a first liquid containing microspheres is stored, and the first liquid enters the separation chamber from the first inlet pipe; the first outlet pipe is connected to a third tank body, and the microspheres separated in the separation chamber flow from the first outlet pipe into the third tank body.

4. The removal structure according to any one of claims 1 to 3, characterized in that: The first liquid is an oil phase liquid containing microspheres.

5. The removal structure according to any one of claims 1 to 4, characterized in that: The second inlet pipe is connected to a second tank body, the second tank body contains a second liquid, and the second liquid enters the separation chamber through the second inlet pipe.

6. The removal structure according to claim 5, characterized in that: The second liquid is a solution containing an active agent. Preferably, the second liquid is a solution insoluble in the first liquid.

7. The removal structure according to claim 3, characterized in that: The first liquid and the second liquid are located at the same side of the separation component in the separation chamber.

8. The removal structure according to any one of claims 1 to 7, characterized in that: The separation component comprises an isolation block with both ends connected to the inner wall of the separation chamber; a plurality of the isolation blocks are provided, and the isolation blocks are arranged in sequence along the length direction of the substrate.

9. The removal structure according to claim 8, characterized in that: A plurality of the isolation blocks are arranged at intervals.

10. The removal structure according to claim 8, characterized in that: The spacing between the isolation blocks is 50-200 μm; preferably, the spacing between the isolation blocks is 75-150 μm; further preferably, the spacing between the isolation blocks is 100 μm.

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