A multi-core emulsion droplet preparation chip, modification method and emulsion droplet preparation system

Abstract

The present application provides a multi-core emulsion droplet preparation chip, a modification method and an emulsion droplet preparation system, wherein the multi-core emulsion droplet preparation chip includes a first glass chip and a second glass chip, a first microchannel is opened inside the first glass chip, and a second microchannel is opened inside the second glass chip. In the multi-core emulsion droplet preparation process, the first microchannel and the second microchannel are subjected to corresponding hydrophilic and hydrophobic modification treatments respectively, and then the first glass chip and the second glass chip are spliced ​​and docked to form the required multi-core emulsion droplet preparation chip. Compared with related technologies, the multi-core emulsion droplet preparation chip has a simple production process, a high yield, a convenient and reliable modification operation, and significantly improved performance.

Description

Technical Field

[0001] The present invention relates to the technical field of microfluidic chips, and further to a multi-core emulsion droplet preparation chip, a modification method and an emulsion droplet preparation system. Background Art

[0002] Droplet microfluidics is a non-continuous flow microfluidic technology that uses two immiscible liquid phases to produce dispersed microdroplets for experimental operations. As an important branch of microfluidic chip research, it realizes the flow control of droplets in tiny channels and builds a new platform for biological and medical research.

[0003] In the related art, microfluidic chips are mostly made of glass because of its good optical properties, chemical inertness, thermal stability and reusability. At present, the multi-core emulsion droplet microfluidic chip prepared by glass microfluidic technology is mainly assembled from glass capillaries after hydrophilic and hydrophobic surface modification. Its production process is cumbersome, reproducible, and difficult to achieve industrialization; other types of chips such as polydimethylsiloxane chips and polymethyl methacrylate chips can also prepare multi-core emulsion droplets, but because the use process of such chips is to pass multiphase fluid into the integrated chip channel, the chip channel needs to be locally hydrophilic and hydrophobic modified, and this local modification process is relatively cumbersome, which also limits its wide application. Therefore, the inventor believes that the development of a multi-core emulsion droplet preparation chip with simple development, convenient modification operation and good performance will have a profound impact on the development of microfluidic chip technology. Summary of the Invention

[0004] The purpose of this application is to provide a multi-core emulsion droplet preparation chip, a modification method and an emulsion droplet preparation system to address the deficiencies and defects in the existing technology.

[0005] The technical solutions provided in this application are as follows:

[0006] In one aspect, the present application provides a multi-core emulsion droplet preparation chip, comprising:

[0007] a first glass chip having a first microchannel defined therein; an inner phase liquid inlet and an intermediate phase liquid inlet defined on one side of the first glass chip; a single emulsion liquid outlet defined on a side of the first glass chip adjacent to the inner phase liquid inlet, the inner phase liquid inlet, the intermediate phase liquid inlet, and the single emulsion liquid outlet all being in communication with the first microchannel;

[0008] a second glass chip, wherein a second microchannel is defined within the second glass chip; an external phase liquid inlet and a multi-core emulsion liquid outlet are defined on one side of the second glass chip; a single emulsion liquid inlet is defined on a side of the second glass chip adjacent to the side where the external phase liquid inlet is defined, wherein the external phase liquid inlet, the multi-core emulsion liquid outlet, and the single emulsion liquid inlet are all connected to the second microchannel;

[0009] When in use, the first glass chip and the second glass chip are arranged side by side, the inner phase liquid inlet, the middle phase liquid inlet, the outer phase liquid inlet, and the multi-core emulsion liquid outlet are located on the same side, and the single emulsion liquid outlet is docked with and connected to the single emulsion liquid inlet.

[0010] A multi-core emulsion droplet preparation chip provided in the present application is provided, a first microchannel is opened inside the first glass chip, and a second microchannel is opened inside the second glass chip, and then the first microchannel of the first glass chip and the second microchannel of the second glass chip are subjected to corresponding hydrophilic and hydrophobic treatments; thereafter, the first glass chip and the second glass chip are placed side by side, and the inner phase liquid inlet, the intermediate phase liquid inlet, the outer phase liquid inlet, and the multi-core emulsion liquid outlet are kept on the same side, and the single emulsion liquid outlet is docked and connected with the single emulsion liquid inlet, and the corresponding materials are respectively introduced from the inner phase liquid inlet, the intermediate phase liquid inlet, and the outer phase liquid inlet, and then the required multi-core emulsion droplets can be output at the multi-core emulsion liquid outlet. In this way, by opening microchannels inside two glass chips respectively, and then docking the two glass chips after hydrophilic and hydrophobic treatment to form a whole multi-core emulsion droplet preparation chip, the technology of forming a glass microfluidic chip by splicing glass capillaries after hydrophilic and hydrophobic surface modification and the operation of local modification of integrated chip channels in related technologies are replaced. The production process of the multi-core emulsion droplet preparation chip is simple, the modification operation is convenient, and the yield is high; at the same time, the performance of use is also stably guaranteed.

[0011] In some embodiments, the first microchannel includes a middle phase main channel and an inner phase main channel;

[0012] One end of the mesophase main channel is connected to the mesophase liquid inlet, and the other end is connected to the first channel junction. The mesophase main channel is divided into a mutually independent first mesophase sub-channel and a second mesophase sub-channel at the first channel junction. The first mesophase sub-channel and the second mesophase sub-channel are respectively located on both sides of the mesophase main channel.

[0013] One end of the internal phase main channel is connected to the internal phase liquid inlet hole, and the other end is connected to the first fluid confocal shear hole. The first intermediate phase sub-channel and the second intermediate phase sub-channel are connected to the first fluid confocal shear hole perpendicularly with the internal phase main channel, and the first fluid confocal shear hole has a cross-shaped structure; the first fluid confocal shear hole extends in a direction away from the internal phase main channel and forms a single emulsion main channel, and the end of the single emulsion main channel away from the first fluid confocal shear hole is connected to the single emulsion liquid outlet hole.

[0014] In some embodiments, the intermediate phase inlet, the internal phase inlet, and the single emulsion outlet are located on the same straight line.

[0015] In some embodiments, the second microchannel includes a single emulsion main channel and an external phase main channel;

[0016] One end of the external phase main channel is connected to the external phase liquid inlet hole, and the other end is connected to the second channel junction. The external phase main channel is divided into a mutually independent external phase first sub-channel and an external phase second sub-channel at the second channel junction.

[0017] One end of the single emulsion main channel is connected to the single emulsion inlet, and the other end is connected to the second fluid confocal shearing port. The first external phase sub-channel and the second external phase sub-channel are vertically connected to the single emulsion main channel at the second fluid confocal shearing port, and the second fluid confocal shearing port is formed into a cross-shaped structure.

[0018] The single emulsion main channel passes through the second fluid confocal shear cut and extends along its own length to form a liquid outlet channel, and one end of the liquid outlet channel away from the second fluid confocal shear cut is connected to the multi-core emulsion liquid outlet hole.

[0019] In some embodiments, the external phase liquid inlet, the single emulsion side liquid inlet, and the multi-core emulsion liquid outlet are located on the same straight line.

[0020] On the other hand, the present application provides a multi-core emulsion droplet preparation system, comprising any of the multi-core emulsion droplet preparation chips described above;

[0021] The chip adapter further comprises a placement table, the placement table being a flat plate structure, the middle portion of the upper surface of which is provided with a chip slot along a first direction, the first glass chip and the second glass chip being sequentially inserted into the chip slot along the first direction, with the end portion providing the single emulsion outlet being kept in contact with the end portion providing the single emulsion inlet, and the side portion providing the inner phase inlet and the side portion providing the outer phase inlet facing the opening of the chip slot;

[0022] First adjusting members are provided on both sides of the placement table in the first direction, and the first adjusting members are used to assist the single emulsion outlet and the single emulsion inlet to communicate in a straight line;

[0023] A second adjusting member is provided at one end of the placement table in the first direction, and the second adjusting member is used to assist the second glass chip to abut against the first glass chip, so that the single emulsion outlet and the single emulsion inlet are docked and sealed.

[0024] A multi-core emulsion droplet preparation system provided by the present application, after the first microchannel and the second microchannel have undergone corresponding hydrophilic-hydrophobic modification treatments, the first glass chip and the second glass chip are sequentially embedded in the chip groove along the first direction, and the end face of the first glass chip with a single emulsion outlet hole and the end face of the second glass chip with a single emulsion inlet hole are kept close to each other; then, the second adjusting member is adjusted so that the single emulsion outlet hole of the first glass chip and the single emulsion inlet hole of the second glass chip are located in the same straight line along the first direction; thereafter, the first adjusting member is adjusted again so that the end face of the first glass chip with a single emulsion outlet hole and the end face of the second glass chip with a single emulsion inlet hole are pressed against each other along the first direction, and the single emulsion outlet hole and the single emulsion inlet hole are sealed and docked, thereby realizing the splicing of the first glass chip and the second glass chip to form a complete multi-core emulsion droplet preparation chip. The overall structure of the chip adapter is simple, and the first glass chip and the second glass chip are easy to splice together, which helps to further ensure the convenience of the production process and modification process of the multi-core emulsion droplet preparation chip, improve the yield of the multi-core emulsion droplet preparation chip, and effectively ensure the performance of the multi-core emulsion droplet preparation chip when preparing multi-core emulsion droplets; at the same time, it helps to improve the preparation efficiency of the corresponding multi-core emulsion droplets.

[0025] In some embodiments, each of the first adjusting members includes two first adjusting bolts, the axes of the two first adjusting bolts are perpendicular to the first direction, and the two first adjusting bolts are arranged in parallel and spaced apart; the two first adjusting bolts are arranged corresponding to the first glass chip and the second glass chip,

[0026] The threaded ends of the two first adjusting bolts are threaded through the corresponding side walls of the chip slot, then extend into the chip slot and abut against the middle of the side wall of the corresponding first glass chip or the corresponding second glass chip.

[0027] Through the multi-core emulsion droplet preparation system provided by the present application, in actual application, the first glass chip and the second glass chip are sequentially embedded in the chip slot along the first direction, and the end face of the first glass chip with the single emulsion outlet hole and the end face of the second glass chip with the single emulsion inlet hole are kept close to each other along the first direction; the two first adjusting bolts are screwed until the inner phase inlet hole, the intermediate phase inlet hole, the outer phase inlet hole, and the multi-core emulsion outlet hole are located in the same straight line along the first direction, thereby achieving the single emulsion outlet hole of the first glass chip and the single emulsion inlet hole of the second glass chip being located in the same straight line along the first direction; the first adjusting member has a simple structure and is easy to operate, which helps to improve the splicing efficiency of the first glass chip and the second glass chip and saves the company's production costs.

[0028] In some embodiments, one end of the placement platform located in the first direction is open and forms a mounting opening, and the dimension of the mounting opening along the direction perpendicular to the first direction is larger than the dimension of the chip slot along the direction perpendicular to the first direction;

[0029] The second adjusting member includes a fixing block, one end of which is adapted to the shape of the mounting opening and is provided with a plug, the plug being embedded in the mounting opening and sliding relative to the inner wall of the mounting opening along a first direction; an end of the plug facing away from the fixing block presses against an end of the second glass chip facing away from the first glass chip;

[0030] The second adjusting member further includes a second adjusting bolt, the threaded end of which passes through the fixing block and the placing platform in sequence along the first direction and is threadably engaged with the fixing block and the placing platform.

[0031] A multi-core emulsion droplet preparation system provided by the present application, in the initial state, the fixed block is set at the installation port through the first adjusting bolt, and the plug is embedded in the installation port; after the single emulsion outlet and the single emulsion inlet are located in the same straight line along the first direction, the second adjusting bolt is tightened until the end of the plug away from the fixed block is pressed against the end of the second glass chip away from the first glass chip, thereby achieving a sealed connection between the single emulsion outlet and the single emulsion inlet; the second adjusting part has a simple structure, and the adjustment operation is convenient and fast, which helps to further improve the preparation efficiency of the corresponding multi-core emulsion droplet preparation chip and further save the company's production costs.

[0032] In some embodiments, an elastic gasket is provided between the first glass chip and the second glass chip, a through hole is provided in the middle of the elastic gasket, and the through hole is sealed and connected to the single emulsion outlet and the single emulsion inlet.

[0033] In a multi-core emulsion droplet preparation system provided by the present application, the elastic gasket is used to improve the sealing between the single emulsion outlet and the single emulsion inlet, thereby reducing the probability of leakage between the first glass chip and the second glass chip.

[0034] In some embodiments, the multi-core emulsion droplet preparation system further includes a fixture, the fixture including a first clamping plate and a second clamping plate that are adapted to each other; the middle portion of the first clamping plate near the second clamping plate is recessed inward to form a receiving groove for accommodating the chip adapter, and the shape of the receiving groove is adapted to the shape of the chip adapter;

[0035] The first splint is hinged to the second splint, and a locking piece is provided at one end of the first splint away from the hinge point between the first splint and the second splint, and the locking piece is used to lock the first splint and the second splint so that the second splint can be detachably covered with the accommodating groove.

[0036] The multi-core emulsion droplet preparation system provided by this application is provided with a first clamping plate and a second clamping plate that are hinged. In actual application, after the chip adapter is installed in the receiving slot, the staff only needs to buckle the first clamping plate and the second clamping plate and lock them with a locking member to achieve the stable installation of the chip adapter and the multi-core emulsion droplet preparation chip inside the fixture. Using this method, the overall structure of the fixture is simple, low-cost, and easy to disassemble, thereby effectively improving the convenience of installing the multi-core emulsion droplet preparation chip in the corresponding fixture.

[0037] At the same time, the present application also provides a method for modifying a multi-core emulsion droplet preparation chip, which is applied to any of the multi-core emulsion droplet preparation chips described above, comprising:

[0038] introducing a hydrophobic reagent into the first microchannel or the second microchannel of the first glass chip to perform a hydrophobic treatment;

[0039] A strong base reagent is introduced into the second microchannel or the first microchannel of the second glass chip to perform surface modification and increase the surface energy.

[0040] Through the modification method of a multi-core emulsion droplet preparation chip provided in the present application, the multi-core emulsion droplet preparation chip is set as a first glass chip and a second glass chip that are independent of each other. When modifying them, it is only necessary to perform hydrophilic and hydrophobic treatment on the first glass chip and the second glass chip separately; the modification operation is convenient and accurate, which effectively guarantees the performance of the corresponding multi-core emulsion droplet preparation chip and improves the yield of the corresponding multi-core emulsion droplets.

[0041] In some embodiments, the hydrophobic agent includes methoxysilane, ethoxysilane, or chlorosilane;

[0042] The strong alkaline reagent includes sodium hydroxide and potassium hydroxide.

[0043] Compared with the prior art, the multi-core emulsion droplet preparation chip, modification method, and emulsion droplet preparation system provided in this application have at least one of the following beneficial effects:

[0044] 1. In the present application, a first microchannel is opened inside a first glass chip, a second microchannel is opened inside a second glass chip, and a complete multi-core emulsion droplet preparation chip is formed by connecting the first glass chip and the second glass chip in series. The multi-core emulsion droplet preparation chip has a simple manufacturing process and a high yield, which effectively reduces the production cost of the enterprise. At the same time, when the multi-core emulsion droplet preparation chip is modified, it is only necessary to perform corresponding hydrophilic and hydrophobic treatments on the first microchannel of the first glass chip and the second microchannel of the second glass chip respectively. The modification operation is convenient and time-saving. Multiple glass chips can be processed at the same time with good processing effect, which effectively guarantees the use performance of the corresponding multi-core emulsion droplet preparation chip and the yield of the corresponding multi-core emulsion droplets.

[0045] 2. In the present application, by setting a first adjusting member and a second adjusting member on the chip adapter, accurate docking of the single emulsion outlet hole of the first glass chip and the single emulsion inlet hole of the second glass chip is achieved. The structure is simple and the adjustment operation is convenient, which helps to improve the preparation efficiency of the corresponding multi-core emulsion droplet preparation chip and save the production cost of the multi-core emulsion droplet preparation system.

[0046] At the same time, due to the setting of the first adjustment part and the second adjustment part, the corresponding chip adapter can be suitable for first glass chips and second glass chips of different models and sizes, which can meet the preparation requirements of various models of multi-core emulsion droplet preparation chips, effectively expanding the application scope of the multi-core emulsion droplet preparation system and enhancing its practicality.

[0047] 3. In the present application, the first clamp and the second clamp are hingedly connected, and a locking member is used to lock the two. The clamp has a simple structure, a small size, and is easy to carry and disassemble, which effectively improves the convenience of installing the multi-core emulsion droplet preparation chip in the corresponding clamp, thereby significantly improving the efficiency of the corresponding multi-core emulsion droplet preparation. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] The preferred implementation scheme will be described below in a clear and understandable manner with reference to the accompanying drawings to further illustrate the above-mentioned characteristics, technical features, advantages and implementation methods of this solution.

[0049] Figure 1 This is an exploded view of the overall structure of the multi-core emulsion droplet preparation chip preparation system according to the embodiment of the present application;

[0050] Figure 2 This is a diagram showing a state in which a first glass chip and a second glass chip are clamped in a chip adapter;

[0051] Figure 3 This is a plan view of the first microchannel layout according to an embodiment of the present application;

[0052] Figure 4 This is a plan view of the second microchannel layout according to an embodiment of the present application;

[0053] Figure 5 This is an exploded view of an embodiment of the present application showing a chip adapter being clamped into a fixture;

[0054] Figure 6 This is a schematic diagram of the double-emulsion micro-droplet generation process in the multi-core emulsion droplet preparation chip according to the embodiment of the present application;

[0055] Figure 7 This is a schematic diagram of the final product in the multi-core emulsion droplet preparation chip according to the embodiment of the present application.

[0056] Description of reference numerals:

[0057] 101, first glass chip; 1010, mesophase inlet; 1011, first channel junction; 1012, internal phase inlet; 1013, first fluid confocal shearing opening; 1014, single emulsion outlet; 1015, mesophase main channel; 1016, first mesophase branch channel; 1017, second mesophase branch channel; 1018, internal phase main channel; 1019, first single emulsion main channel; 102, second glass chip; 1020, single emulsion inlet; 1021, second fluid confocal shearing opening; 1022, multi-core emulsion outlet; 1023 , second channel joint; 1024, external phase liquid inlet hole; 1025, second single emulsion main channel; 1026, external phase first branch channel; 1027, external phase second branch channel; 1028, liquid outlet channel; 1029, external phase main channel; 2, chip adapter; 201, placement table; 202, chip slot; 203, fixing block; 204, second adjusting bolt; 205, first adjusting bolt; 3, elastic gasket; 4, single emulsion; 5, multi-core emulsion droplet; 6, clamp; 601, first splint; 602, second splint; 603, flexible joint; 604, locking piece. DETAILED DESCRIPTION

[0058] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the specific implementation methods of the present application will be described below with reference to the accompanying drawings. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings and other implementation methods can be obtained based on these drawings without inventive work.

[0059] To simplify the drawings, only the parts relevant to this application are schematically shown in each figure. They do not represent the actual structure of the product. In addition, to simplify the drawings and facilitate understanding, in some figures, only one of the components with the same structure or function is schematically depicted or labeled. In this document, "one" not only means "only one" but also "more than one."

[0060] As we all know, droplet microfluidics, as an important branch of microfluidic chip research, has built a new platform for biological, medical and other research by realizing the flow control of droplets in tiny channels.

[0061] At present, in the relevant technology, microfluidic chips are mostly made of glass materials, and are mainly assembled from glass capillaries after hydrophilic and hydrophobic surface modification. The production process is cumbersome, with poor repeatability and difficult to industrialize. Other types of chips such as polydimethylsiloxane chips can also prepare multi-core emulsion droplets. Since multiphase fluids need to be passed into the integrated chip channels during use, the chip channels need to be locally hydrophilic and hydrophobic modified. However, the local modification process is relatively cumbersome, which also limits its wide application.

[0062] In one embodiment, referring to the accompanying drawings Figures 1 to 5 A multi-core emulsion droplet preparation chip includes two completely disconnected glass chips, namely, a first glass chip 101 and a second glass chip 102 spliced ​​together; wherein, a first microchannel is opened inside the first glass chip 101, and a second microchannel is opened inside the second glass chip 102. During the manufacturing process of the multi-core emulsion droplet preparation chip, the first microchannel and the second microchannel are subjected to corresponding hydrophilic and hydrophobic modification treatments respectively, and then the first glass chip 101 and the second glass chip 102 are spliced ​​and docked to form the required multi-core emulsion droplet preparation chip. Compared with related technologies, the multi-core emulsion droplet preparation chip has a simple manufacturing process, a high yield, and a convenient and reliable modification operation, which can significantly improve its performance.

[0063] Specifically, an internal phase inlet 1012 and an intermediate phase inlet 1010 are defined on one side of the first glass chip 101. A single emulsion outlet 1014 is defined on the side of the first glass chip 101 adjacent to the side with the internal phase inlet 1012. The internal phase inlet 1012, intermediate phase inlet 1010, and single emulsion outlet 1014 are all connected to the first microchannel. Similarly, an external phase inlet 1024 and a multi-core emulsion outlet 1022 are defined on one side of the second glass chip 102. A single emulsion inlet 1020 is defined on the side of the second glass chip 102 adjacent to the side with the external phase inlet 1024. The external phase inlet 1024, multi-core emulsion outlet 1022, and single emulsion inlet 1020 are all connected to the second microchannel.

[0064] The first microchannel and the second microchannel are subjected to corresponding hydrophilic-hydrophobic modification treatments respectively. Then, the first glass chip 101 and the second glass chip 102 are arranged side by side, and the inner phase liquid inlet hole 1012, the intermediate phase liquid inlet hole 1010, the outer phase liquid inlet hole 1024 and the multi-core emulsion liquid outlet hole 1022 are kept on the same side, and the single emulsion liquid outlet hole 1014 is connected to the single emulsion liquid inlet hole 1020. The corresponding materials are introduced from the inner phase liquid inlet hole 1012, the intermediate phase liquid inlet hole 1010 and the outer phase liquid inlet hole 1024 respectively. After that, the required multi-core emulsion droplets 5 can be output at the multi-core emulsion liquid outlet hole 1022.

[0065] In one embodiment, based on the above embodiment, referring to Figures 1 to 3 Specifically, in this embodiment of the present application, the first glass chip 101 and the second glass chip 102 both have a rectangular sheet structure; and the inner phase liquid inlet hole 1012 and the intermediate phase liquid inlet hole 1010 are spaced apart and opened in the middle position of one side of the thickness direction of the first glass chip 101, and are arranged in sequence along the length direction of the first glass chip 101, and the single emulsion liquid outlet hole 1014 is opened at one end of the length direction of the first glass chip 101.

[0066] Further, refer to Figure 3 The first microchannel includes an intermediate phase main channel 1015 and an internal phase main channel 1018; wherein, one end of the intermediate phase main channel 1015 is connected to the intermediate phase liquid inlet 1010, and the other end is connected to the first channel joint 1011, and the intermediate phase main channel 1015 is divided into two at the first channel joint 1011, forming an independent intermediate phase first sub-channel 1016 and an intermediate phase second sub-channel 1017; in this embodiment of the present application, the intermediate phase main channel 1015 is arranged on the center line of the first glass chip 101 in the width direction and the thickness direction, and the intermediate phase first sub-channel 1016 and the intermediate phase second sub-channel 1017 are respectively located on both sides of the intermediate phase main channel 1015, and are arranged corresponding to the two sides of the width direction of the first glass chip 101.

[0067] One end of the internal phase main channel 1018 is connected to the internal phase liquid inlet hole 1012, and the other end is connected to the first fluid confocal shear opening 1013. The intermediate phase first sub-channel 1016 and the intermediate phase second sub-channel 1017 are connected to the first fluid confocal shear opening 1013 vertically with the internal phase main channel 1018, and the first fluid confocal shear opening 1013 has a cross-shaped structure; the first fluid confocal shear opening 1013 extends in a direction away from the internal phase main channel 1018 and forms a first single emulsion main channel 1019, and the end of the first single emulsion main channel 1019 away from the first fluid confocal shear opening 1013 is connected to the single emulsion liquid outlet hole 1014.

[0068] In this embodiment of the present application, the intermediate phase main channel 1015, the internal phase main channel 1018 and the first single emulsion main channel 1019 are all arranged in a straight line and extend in the same direction, so that the intermediate phase liquid inlet hole 1010, the internal phase liquid inlet hole 1012 and the single emulsion liquid outlet hole 1014 are located on the same straight line.

[0069] Reference Figure 4 The second microchannel includes a second single emulsion main channel 1025 and an external phase main channel 1029; in this embodiment of the present application, the second single emulsion main channel 1025 is arranged on the center line of the center line of the width direction and the thickness direction of the second glass chip 102; wherein, one end of the external phase main channel 1029 is connected to the external phase liquid inlet hole 1024, and the other end is connected to the second channel joint 1023, and the external phase main channel 1029 is divided into two at the second channel joint 1023, and forms an independent external phase first sub-channel 1026 and an external phase second sub-channel 1027, and the external phase first sub-channel 1026 and the external phase second sub-channel 1027 are respectively located on both sides of the second single emulsion main channel 1025, and are arranged corresponding to the two sides of the width direction of the second glass chip 102. One end of the second single emulsion main channel 1025 is connected to the single emulsion inlet 1020, and the other end is connected to the second fluid confocal shear 1021. The first external phase sub-channel 1026 and the second external phase sub-channel 1027 are perpendicularly connected to the second single emulsion main channel 1025 at the second fluid confocal shear 1021, forming the overall structure of the second fluid confocal shear 1021 into a cross. After passing through the second fluid confocal shear 1021, the second single emulsion main channel 1025 extends along its length to form an outlet channel 1028. Alternatively, the second fluid confocal shear 1021 extends in a direction away from the second single emulsion main channel 1025 to form an outlet channel 1028. The end of the outlet channel 1028 facing away from the second fluid confocal shear 1021 is connected to the multi-core emulsion outlet 1022.

[0070] In this embodiment of the present application, the second single emulsion main channel 1025, the external phase main channel 1029, and the liquid outlet channel 1028 are all arranged in a straight line and extend in the same direction, so that the external phase liquid inlet 1024, the single emulsion liquid inlet 1020, and the multi-core emulsion liquid outlet 1022 are located on the same straight line. This allows the intermediate phase liquid inlet 1010, the internal phase liquid inlet 1012, the single emulsion liquid outlet 1014, the external phase liquid inlet 1024, the single emulsion liquid inlet 1020, and the multi-core emulsion liquid outlet 1022 to be located on the same straight line after the first glass chip 101 and the second glass chip 102 are assembled, thereby reducing liquid flow resistance. Furthermore, in this embodiment of the present application, the width of the first microchannel and the second microchannel ranges from 10 to 1000 μm.

[0071] In practical applications, the fluid in the first microchannel is used to form the first fluid confocal shear opening 1013 to form a single emulsion 4, and the formed single emulsion 4 passes through the second fluid confocal shear opening 1021 in the second microchannel to form a double emulsion.

[0072] In one embodiment, based on the above embodiment, specifically, referring to Figures 1 to 5 A multi-core emulsion droplet preparation system includes the multi-core emulsion droplet preparation chip described in the above embodiment; in order to realize the serial splicing of the first glass chip 101 and the second glass chip 102, the multi-core emulsion droplet preparation system also includes a chip adapter 2. In this embodiment of the present application, the chip adapter 2 is a rectangular plate-shaped structure; the chip adapter 2 includes a placement table 201 for mounting the multi-core emulsion droplet preparation chip, referring to Figure 1 and Figure 2 A chip slot 202 is provided in the middle of the placement table 201 extending along the first direction for accommodating a multi-core emulsion droplet preparation chip; in this embodiment of the present application, the first direction is set as the length direction of the chip adapter 2; the first glass chip 101 and the second glass chip 102 are both embedded in the chip slot 202 in sequence along the first direction, and the end portion of the single emulsion outlet hole 1014 and the end portion of the single emulsion inlet hole 1020 are kept docked along the first direction, and the side portion of the inner phase inlet hole 1012 and the side portion of the outer phase inlet hole 1024 are arranged toward the opening of the chip slot 202.

[0073] At the same time, refer to Figure 2 The placement platform 201 is also provided with a first adjusting member and a second adjusting member, wherein a group of first adjusting members are provided on both sides of the placement platform 201 in the first direction, respectively, for assisting the single emulsion outlet hole 1014 and the single emulsion inlet hole 1020 to be connected in a straight line; and the second adjusting member is provided at one end of the placement platform 201 in the first direction, and the second adjusting member is used to assist the second glass chip 102 to abut against the first glass chip 101, so that the single emulsion outlet hole 1014 and the single emulsion inlet hole 1020 are docked and sealed and connected.

[0074] Reference Figure 1 Specifically, in this embodiment of the present application, any group of first adjusting members includes two first adjusting bolts 205, and the two first adjusting bolts 205 are arranged parallel to the chip adapter 2, and the axial directions of the two first adjusting bolts 205 are parallel and spaced, and are arranged perpendicular to the first direction; and the threaded ends of the two first adjusting bolts 205 are threaded through the corresponding side walls of the chip slot 202, and then extend into the chip slot 202, and abut against the middle of the side wall of the corresponding first glass chip 101 or the second glass chip 102.

[0075] In this embodiment of the present application, the second adjustment member includes a fixed block 203, which is an overall rectangular block structure, and the length of the fixed block 203 is approximately equal to the width of the adapter. The end of the placement platform 201 located in the first direction is open and forms a mounting opening. The dimension of the mounting opening perpendicular to the first direction, i.e., the dimension along the width of the chip adapter 2, is greater than the dimension of the chip slot 202 along the width of the chip adapter 2. A plug is provided in the middle of one end of the fixed block 203 in the width direction. The shape of the plug is adapted to the shape of the mounting opening, and the length of the plug extends along the first direction. After the fixed block 203 is installed on the placement platform 201 at the end of the mounting opening, the plug is embedded in the mounting opening and can slide relative to the inner wall of the mounting opening along the first direction until the end of the plug facing away from the fixed block 203 abuts against the end wall of the second glass chip 102 facing away from the first glass chip 101.

[0076] At the same time, the second adjusting member also includes a second adjusting bolt 204, and a second adjusting bolt 204 is arranged at each end in the length direction of the fixed block 203, and any second adjusting bolt 204 is arranged parallel to the first direction. The threaded end of the second adjusting bolt 204 passes through the fixed block 203 and the placement platform 201 in sequence along the first direction, and is threadedly matched with the two.

[0077] When making a multi-core emulsion droplet preparation chip, the length directions of the first glass chip 101 and the second glass chip 102 are set parallel to the first direction, and the first glass chip 101 and the second glass chip 102 are sequentially inserted into the chip slot 202 along the first direction, while keeping the end face of the first glass chip 101 with the single emulsion outlet hole 1014 and the end face of the second glass chip 102 with the single emulsion inlet hole 1020 close to each other along the first direction; then, the corresponding first adjusting bolts 205 of the two sets of first adjusting members are tightened until the inner phase inlet hole 1012 and the middle phase inlet hole 1010 are aligned with the outer phase inlet hole 1024. , the multi-core emulsion outlet holes 1022 are located in the same straight line along the first direction, thereby achieving the alignment of the single emulsion outlet holes 1014 of the first glass chip 101 and the single emulsion inlet holes 1020 of the second glass chip 102 along the first direction; thereafter, the second adjusting bolt 204 is tightened until the end of the plug facing away from the fixing block 203 abuts against the end of the second glass chip 102 facing away from the first glass chip 101, thereby achieving a sealed connection between the single emulsion outlet holes 1014 and the single emulsion inlet holes 1020, that is, achieving the serial connection of the first glass chip 101 and the second glass chip 102. The first and second adjusting parts have simple structures, and the adjustment operation is convenient and fast, which helps to improve the efficiency of the multi-core emulsion droplet preparation chip when it is installed on the chip adapter 2, thereby improving the preparation efficiency of the corresponding multi-core emulsion droplet preparation chip and saving enterprise production costs.

[0078] At the same time, in order to reduce the probability of leakage at the docking position between the single emulsion outlet hole 1014 and the single emulsion inlet hole 1020, an elastic gasket 3 is provided between the first glass chip 101 and the second glass chip 102, and a through hole is opened in the middle of the elastic gasket 3, and the through hole is sealed and connected with the single emulsion outlet hole 1014 and the single emulsion inlet hole 1020; and due to the setting of the elastic gasket 3, it helps to reduce the occurrence of wear and tear between the first glass chip 101 and the second glass chip 102 when adjusting the second adjusting member, thereby ensuring the safety of the multi-core emulsion droplet preparation system and extending its service life.

[0079] In the industry, elastic gaskets 3 include fluororubber gaskets, polytetrafluoroethylene (PTFE) gaskets, silicone gaskets and many other types.

[0080] In addition, in order to facilitate the introduction of fluid materials into the corresponding microchannels of the multi-core emulsion droplet preparation chip, in this embodiment of the present application, the multi-core emulsion droplet preparation system also includes a clamp 6; specifically, the clamp 6 includes a first clamp 601 and a second clamp 602, and the first clamp 601 and the second clamp 602 are both flat-plate structures, and the two are adapted to fit together along their own thickness direction, wherein the middle part of the first clamp 601 close to the side of the second clamp 602 is recessed inward and forms a receiving groove, and the shape of the receiving groove is adapted to the outer shape of the chip adapter 2; and, the first clamp 601 and the second clamp 602 are hinged, and a locking piece 604 is provided at the end of the first clamp 601 away from the hinge point between it and the second clamp 602.

[0081] In actual application, after the chip adapter 2 is installed in the receiving groove, the first clamp 601 and the second clamp 602 are fastened together, and the locking member 604 is used to lock the two together, so that the second clamp 602 can be removably covered with the receiving groove, thereby realizing the stable installation of the chip adapter 2 and the multi-core emulsion droplet preparation chip therein in the fixture 6.

[0082] In this embodiment of the present application, a first extension plate is provided at one end of the first splint 601 away from the hinge point between the first splint 601 and the second splint 602, and the first extension plate is located on the side of the first splint 601 close to the opening of the accommodating groove in the thickness direction. The thickness dimension of the first extension plate is smaller than the thickness dimension of the first splint 601, and the width direction of the first extension plate is parallel to the length direction of the first splint 601; correspondingly, a second extension plate is provided at one end of the second splint 602 away from the hinge point between the first splint 601 and the second extension plate is formed on the side of the second splint 602 close to the first splint 601 in the thickness direction, and the first extension plate and the second extension plate can be adapted and buckled along their own thickness direction.

[0083] Reference Figure 5The locking member 604 includes a clip that is rotatably arranged on the side of the first extension plate facing away from the first clamping plate 601 in the width direction; specifically, the clip is generally in the form of a U-shaped strip, one end of which in the length direction is hinged to the other end of the first extension plate in the length direction, and the rotation axis is arranged perpendicular to the first clamping plate 601; the first extension plate is located in the U-shaped opening of the sealing clamp body, and the width dimension of the U-shaped opening of the clip is slightly larger than the total dimension of the first extension plate and the second extension plate in the thickness direction. In this embodiment of the present application, in order to ensure that the clip stably locks the first clamping plate 601 and the second clamping plate 602, the rotational connection method of the clip and the first extension plate is a tight fit connection method. In actual application, after the first clamping plate 601 and the second clamping plate 602 are fastened together, the clip is rotated until the ends of the first extension plate and the second extension plate in the width direction facing away from the first clamping plate 601 are embedded in the U-shaped opening of the clip, thereby achieving the locking of the first clamping plate 601 and the second clamping plate 602.

[0084] Of course, in the embodiment of the present application, the locking member 604 can also be configured as a buckle, a bolt, or other forms, which will not be described in detail here.

[0085] In addition, a plurality of flexible joints 603 are detachably provided on the second clamping plate 602 , and the flexible joints 603 are correspondingly provided with the intermediate phase liquid inlet 1010 , the inner phase liquid inlet 1012 , the outer phase liquid inlet 1024 , and the multi-core emulsion liquid outlet 1022 .

[0086] Under the buffering seal of the flexible joint 603, the multi-core emulsion droplet chip is fixed in the fixture 6 by the first clamp 601, the second clamp 602 and the locking piece 604; the external liquid is introduced into the liquid inlet 1010, the internal phase liquid inlet 1012 and the external phase liquid inlet 1024 of the first glass chip 101 and the second glass chip 102 through the catheter inserted into the flexible joint 603, and the multi-core emulsion droplets 5 finally formed are discharged from the multi-core emulsion liquid outlet 1022 to the glass chip by the same method.

[0087] Of course, the chip flow channel can be connected to an external power system, which includes an injection pump, a pressure pump, etc.

[0088] In addition, in order to facilitate the staff to observe the operation status in the multi-core emulsion droplet preparation chip channel in real time, observation windows are opened on the first clamping plate 601 and the second clamping plate 602, and the observation windows are set corresponding to the multi-core emulsion droplet preparation chip.

[0089] In actual application, after the first glass chip 101 and the second glass chip 102 are fixed on the chip adapter 2, the chip adapter 2 is clamped in the fixture 6. Driven by the external power system, the two-phase immiscible fluid first produces a single emulsion 4 (W1 / O or O1 / W) at the first fluid confocal shear 1013 of the first glass chip 101, and then enters the second glass chip 102 through the through hole of the elastic gasket 3. The third phase (W2 or O2) also enters the second glass chip 102 at the same time, and the fluid flow rate is adjusted. Finally, multi-core emulsion droplets 5 are prepared at the second fluid confocal shear 1021, and a uniform and non-fused final product multi-core microdroplet emulsion is obtained through pipeline reception.

[0090] The multi-core emulsion droplets 5 in this embodiment of the present application, such as W1 / O / W2 and O1 / W / O2, are obtained by performing different hydrophilic and hydrophobic modifications on the first glass chip 101 and the second glass chip 102, including single-core, double-core, triple-core, etc., which can be adjusted by changing the flow rate ratio of the fluid.

[0091] In one embodiment, based on the above embodiment, specifically, referring to Figures 1 to 7 A method for modifying a multi-core emulsion droplet preparation chip is applied to the multi-core emulsion droplet preparation chip described in the above embodiment; the method comprises the following steps:

[0092] introducing a hydrophobic reagent into the first microchannel of the first glass chip 101 to perform a hydrophobic treatment;

[0093] A strong alkaline reagent is introduced into the second microchannel of the second glass chip 102 to perform surface modification and increase its surface energy.

[0094] The multi-core emulsion droplet preparation chip of this embodiment is modified and used for preparing water-in-oil-in-water (W1 / O / W2) multi-core emulsion droplets 5 .

[0095] Furthermore, in the water-in-oil-in-water (W1 / O / W2) multi-core emulsion droplets 5, the water phase of the inner phase is pure water or an aqueous solution with certain water-soluble solutes added; the oil phase of the middle phase is an alkane, a halogenated hydrocarbon, or a fluorinated oil containing a surfactant, such as mineral oil containing Span 80 or a fluorinated liquid containing a perfluoropolyoxypropylene (PFPE-PEG-PFPE) polymer; and the water phase of the outer phase is an aqueous solution containing a surfactant, such as an aqueous solution containing polyvinyl alcohol or an aqueous solution containing sodium lauryl sulfate.

[0096] In another embodiment, a method for modifying a chip for preparing multi-core emulsion droplets is applied to the chip for preparing multi-core emulsion droplets described in the above embodiment; the method comprises the following steps:

[0097] Introducing a strong alkaline reagent into the first microchannel of the first glass chip 101 to perform surface modification and increase its surface energy;

[0098] A hydrophobic reagent is introduced into the second microchannel of the second glass chip 102 to perform a hydrophobic treatment.

[0099] The multi-core emulsion droplet preparation chip of this embodiment is modified and used for preparing oil-in-water-in-oil (O1 / W / O2) multi-core emulsion droplets 5 .

[0100] Among them, the oil-in-water-in-oil (O1 / W / O2) multi-core microdroplet emulsion, the inner phase oil phase is alkane, halogenated hydrocarbon or fluoro oil, such as tetradecane, dichloromethane; the middle phase water phase is an aqueous solution containing a surfactant, such as an aqueous solution containing polyvinyl alcohol, an aqueous solution containing sodium lauryl sulfate; the outer phase oil phase is an alkane, halogenated hydrocarbon or fluoro oil containing a surfactant, such as a fluoro oil containing perfluoropolyether (PFPE).

[0101] Of course, based on the above embodiments, the number of cores in the water-in-oil-in-water (W1 / O / W2) and oil-in-water-in-oil (O1 / W / O2) multi-core emulsion droplets 5 can be one or more.

[0102] In one embodiment, based on the above embodiment, specifically, the hydrophobic agent includes methoxysilane, ethoxysilane, chlorosilane; such as n-octyltriethoxysilane, triethoxy-1H,1H,2H,2H-tridecafluoro-N-octylsilane and hexamethyldisilane. The strong base agent includes sodium hydroxide and potassium hydroxide. The strong base agent includes sodium hydroxide and potassium hydroxide, such as 2M NaOH ethanol aqueous solution (V water:V ethanol = 1:1).

[0103] It should be noted that the above embodiments can be freely combined as needed. The above description is only a preferred embodiment of the present application. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present application, and these improvements and modifications should also be considered as the scope of protection of the present application.

Claims

1. A chip for preparing multi-core emulsion droplets, characterized in that: include: a first glass chip having a first microchannel defined therein; an inner phase liquid inlet and an intermediate phase liquid inlet defined on one side of the first glass chip; a single emulsion liquid outlet defined on a side of the first glass chip adjacent to the side having the inner phase liquid inlet, the inner phase liquid inlet, the intermediate phase liquid inlet, and the single emulsion liquid outlet all being in communication with the first microchannel; a second glass chip, wherein a second microchannel is defined within the second glass chip; an external phase liquid inlet and a multi-core emulsion liquid outlet are defined on one side of the second glass chip; a single emulsion liquid inlet is defined on a side of the second glass chip adjacent to the side where the external phase liquid inlet is defined, wherein the external phase liquid inlet, the multi-core emulsion liquid outlet, and the single emulsion liquid inlet are all connected to the second microchannel; When in use, the first glass chip and the second glass chip are arranged side by side, the inner phase liquid inlet, the middle phase liquid inlet, the outer phase liquid inlet, and the multi-core emulsion liquid outlet are located on the same side, and the single emulsion liquid outlet is connected to and connected to the single emulsion liquid inlet; The first microchannel includes an intermediate phase main channel and an internal phase main channel; One end of the mesophase main channel is connected to the mesophase liquid inlet, and the other end is connected to the first channel junction. The mesophase main channel is divided into a mutually independent first mesophase sub-channel and a second mesophase sub-channel at the first channel junction. The first mesophase sub-channel and the second mesophase sub-channel are respectively located on both sides of the mesophase main channel. One end of the inner phase main channel is connected to the inner phase liquid inlet, and the other end is connected to the first fluid confocal shearing opening. The first intermediate phase sub-channel and the second intermediate phase sub-channel are connected to the inner phase main channel perpendicularly to the first fluid confocal shearing opening, and the first fluid confocal shearing opening is in a cross-shaped structure. The first fluid confocal shear cut extends in a direction away from the internal phase main channel to form a single emulsion main channel, and one end of the single emulsion main channel away from the first fluid confocal shear cut is connected to the single emulsion outlet; The second microchannel includes a single emulsion main channel and an external phase main channel; One end of the external phase main channel is connected to the external phase liquid inlet hole, and the other end is connected to the second channel junction. The external phase main channel is divided into a mutually independent external phase first sub-channel and an external phase second sub-channel at the second channel junction. One end of the single emulsion main channel is connected to the single emulsion inlet, and the other end is connected to the second fluid confocal shearing port. The first external phase sub-channel and the second external phase sub-channel are vertically connected to the single emulsion main channel at the second fluid confocal shearing port, and the second fluid confocal shearing port is formed into a cross-shaped structure. The single emulsion main channel passes through the second fluid confocal shear cut and extends along its own length to form a liquid outlet channel, and one end of the liquid outlet channel away from the second fluid confocal shear cut is connected to the multi-core emulsion liquid outlet hole.

2. A chip for preparing multi-core emulsion droplets according to claim 1, characterized in that: The intermediate phase liquid inlet, the internal phase liquid inlet, and the single emulsion liquid outlet are located on the same straight line.

3. A chip for preparing multi-core emulsion droplets according to claim 1, characterized in that: The external phase liquid inlet, the single emulsion liquid inlet, and the multi-core emulsion liquid outlet are located on the same straight line.

4. A multi-core emulsion droplet preparation system, characterized in that: A chip for preparing multi-core emulsion droplets comprising any one of claims 1 to 3; The chip adapter further comprises a placement table, the placement table being a flat plate structure, the middle portion of the upper surface of which is provided with a chip slot along a first direction, the first glass chip and the second glass chip being sequentially inserted into the chip slot along the first direction, with the end portion providing the single emulsion outlet being kept in contact with the end portion providing the single emulsion inlet, and the side portion providing the inner phase inlet and the side portion providing the outer phase inlet facing the opening of the chip slot; First adjusting members are provided on both sides of the placement table in the first direction, and the first adjusting members are used to assist the single emulsion outlet and the single emulsion inlet to communicate in a straight line; A second adjusting member is provided at one end of the placement table in the first direction, and the second adjusting member is used to assist the second glass chip to abut against the first glass chip, so that the single emulsion outlet and the single emulsion inlet are docked and sealed.

5. A multi-core emulsion droplet preparation system according to claim 4, characterized in that: Each of the first adjusting members includes two first adjusting bolts, the axes of the two first adjusting bolts are perpendicular to the first direction, and the two first adjusting bolts are arranged in parallel and spaced apart; the two first adjusting bolts are arranged corresponding to the first glass chip and the second glass chip, The threaded ends of the two first adjusting bolts are threaded through the corresponding side walls of the chip slot, then extend into the chip slot and abut against the middle of the side wall of the corresponding first glass chip or the corresponding second glass chip.

6. A multi-core emulsion droplet preparation system according to claim 4, characterized in that: One end of the placement platform located in the first direction is open and forms a mounting opening, wherein the dimension of the mounting opening along the direction perpendicular to the first direction is larger than the dimension of the chip slot along the direction perpendicular to the first direction; The second adjusting member includes a fixing block, one end of which is adapted to the shape of the mounting opening and is provided with a plug, the plug being embedded in the mounting opening and sliding relative to the inner wall of the mounting opening along a first direction; an end of the plug facing away from the fixing block presses against an end of the second glass chip facing away from the first glass chip; The second adjusting member further includes a second adjusting bolt, the threaded end of which passes through the fixing block and the placing platform in sequence along the first direction and is threadably engaged with the fixing block and the placing platform.

7. A multi-core emulsion droplet preparation system according to claim 4, characterized in that: An elastic gasket is provided between the first glass chip and the second glass chip. A through hole is provided in the middle of the elastic gasket. The through hole is sealed and connected to the single emulsion outlet and the single emulsion inlet.

8. A multi-core emulsion droplet preparation system according to claim 4, characterized in that: The multi-core emulsion droplet preparation system further includes a fixture, which includes a first clamping plate and a second clamping plate that are adapted to each other; the middle portion of the first clamping plate near the second clamping plate is recessed inward to form a receiving groove for accommodating the chip adapter, and the shape of the receiving groove is adapted to the shape of the chip adapter; The first splint is hinged to the second splint, and a locking piece is provided at one end of the first splint away from the hinge point between the first splint and the second splint, and the locking piece is used to lock the first splint and the second splint so that the second splint can be detachably covered with the accommodating groove.

9. A method for modifying a chip for preparing multi-core emulsion droplets, characterized in that: A chip for preparing multi-core emulsion droplets according to any one of claims 1 to 3, comprising: introducing a hydrophobic reagent into the first microchannel or the second microchannel of the first glass chip to perform a hydrophobic treatment; A strong base reagent is introduced into the second microchannel or the first microchannel of the second glass chip to perform surface modification and increase the surface energy.

10. The method for modifying a chip for preparing multi-core emulsion droplets according to claim 9, characterized in that: The hydrophobic agent includes methoxysilane, ethoxysilane, and chlorosilane; The strong alkaline reagent includes sodium hydroxide and potassium hydroxide.

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