Multistage fine-adjustable coaxial capillary micro-fluidic chip and emulsion preparation method

Abstract

The invention discloses a multistage fine-adjustable modular coaxial capillary micro-fluidic chip and an emulsion preparation method, and belongs to the technical field of micro-fluidic chips. The chip comprises a focusing capillary tube, a collecting capillary tube, a square capillary tube, a sliding rail base module, a feeding module and a liquid inlet platform module. Focusing capillary tubes are inserted into the first and second side connectors of the liquid inlet platform, square capillary tubes are inserted into the second and third side connectors of the liquid inlet platform, and a collecting capillary tube is inserted into the right connector of the third liquid inlet platform; and the focusing capillary tube and the collecting capillary tube jointly extend into the square capillary tube. The whole forms a single-stage chip module, and a plurality of single-stage modules are connected in series through a rubber hose to form a multi-stage chip which is used for preparing complex micro-droplets and the like. The device adopts a split type modular structural design, and has the advantages that the assembly is convenient, the standardization can be realized, and the preparation efficiency of complex micro-droplets is improved. And the precise 3D printing technology is combined, mold opening is not needed, flexible machining of parts is achieved, and cost is reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of preparing single emulsion, double emulsion and complex droplets by microfluidic chip, and specifically relates to a multi-level fine-tunable coaxial capillary microfluidic chip and an emulsion preparation method. Background Art

[0002] In recent years, due to the rapid development of microfluidic technology, coaxial capillary microfluidic chips have been widely used in the production of core-shell microcapsules. For example, double emulsions, a core-shell structure, have higher flexibility and controllability, and play an important role in many processes such as directional release, functional material preparation, and food additive encapsulation. They have been widely used in many industries such as fusion energy, chemical engineering, and medicine.

[0003] The coaxial capillary microfluidic chip includes a focusing capillary with a conical head, a collecting capillary with a flat head and a square capillary connecting the two. The focusing capillary and the collecting capillary are coaxially arranged in the square capillary and separated by a distance. In traditional microfluidic devices, the circular capillary and the square capillary are prone to coaxial alignment. The existing microfluidic chips are mainly integrated PDMS chips and detachable mechanical structure chips. The main disadvantages of the integrated PDMS chip are: fixed structure, not easy to disassemble, replace and clean, complex processing technology, complex surface modification of the channel, and the bonded channel is prone to leakage under high pressure, and some organic solvents will swell with the bonding structure. The main disadvantages of the existing detachable mechanical structure chip are: poor sealing, solution leakage when preparing droplets, which seriously affects the experiment; when adjusting the coaxial distance of the capillary, the existing technology mostly adopts hand-push or spiral feeding, and the accuracy and distance cannot be well controlled. These factors will greatly affect the generation of core-shell structure capsules. In addition, traditional chip manufacturing usually uses epoxy glue to fix, which cannot be fine-tuned. If the experiment fails, the chip needs to be remade. In short, the main challenges of existing microfluidic chips are accurate alignment and strict sealing to ensure no leakage and fluid intercommunication, which requires high manufacturing precision.

[0004] Based on the above technical background, the researchers improved the existing preparation process of coaxial glass capillary microfluidic chips, using modular ideas to ensure the accurate coaxial arrangement of the round tubes in the square capillary, and also realized the detachable and repeated use of the chip. Its characteristics are that specific basic functional modules can be selected according to specific needs to realize the assembly of specific structures. At the same time, each connection is more solid, which improves the efficiency of making microfluidic chips, reduces the risk of leakage at the liquid inlet joint, and realizes the formation of multi-layer nested complex emulsions. Summary of the invention

[0005] In view of the deficiencies of the prior art described above, the object of the present invention is to provide a split modular multi-stage fine-tunable coaxial capillary microfluidic chip and an emulsion preparation method, which divides the overall structure into a slide rail base module, a feed module and a liquid inlet platform module. Each module acts simultaneously, which can realize the coaxial spacing adjustment of the capillary and the preparation of a variety of complex droplets. This quickly reconstructible modular microfluidic device consists of basic functional modules, each of which has a unified standard interface for easy assembly. Printing by 3D printer makes the manufacturing process simple and efficient, and the flow channel size can be easily controlled. Through various combinations of different modules, a variety of different functions can be achieved without repeating the manufacturing process. A single module can also be taken out for testing and analysis.

[0006] The technical solution of the present invention is summarized as follows:

[0007] The present invention provides a multi-stage fine-tunable coaxial capillary microfluidic chip, comprising: a slide rail base, characterized in that: a first liquid inlet platform, a second liquid inlet platform and a third liquid inlet platform are slidably mounted on the slide rail base;

[0008] A microfluidic connector 1 is movably installed on the top of the liquid inlet platform 1, a microfluidic connector 2 is movably installed on the lower right side, and a connecting magnetic sheet 1 is fixedly connected on the left side;

[0009] A microfluidic joint 3 is movably installed on the upper part of the liquid inlet platform 2, a microfluidic joint 4 is movably installed on the lower left part, and a square fixing groove 1 is opened on the lower right part;

[0010] A microfluidic connector 5 is movably mounted on the right side of the liquid inlet platform 3, a square fixing groove 2 is provided at the lower left side, and a connector hole is provided at the top, on which a microfluidic connector 6 or a microfluidic connector without a hole can be movably mounted;

[0011] One end of the square capillary extends into the square fixing groove 1, and the other end extends into the square fixing groove 2, and the square capillary is fixed in a suitable position;

[0012] One end of the focusing capillary is fixedly installed in the microfluidic connector 2, and the other end is movably installed in the microfluidic connector 4 and extends into the square capillary;

[0013] One end of the collecting capillary is fixedly installed in the microfluidic connector 5 and extends into the square capillary;

[0014] The slide rail base is movably mounted with a clamping nut 1, a clamping nut 2 and a clamping nut 3, and base slide grooves are provided inside the two sides of the slide rail base; a distance adjustment support is fixedly mounted on the slide rail base, a feed push rod is movably mounted on the distance adjustment support, a distance adjustment knob is movably mounted on the rear end of the feed push rod, and a magnetic sheet 2 is nested and fixedly connected to the front end;

[0015] The focusing capillary, the square capillary and the collecting capillary are kept coaxially, and the connecting magnetic sheet 1 and the connecting magnetic sheet 2 are kept coaxially aligned.

[0016] Preferably, the clamping nuts two and three fix the liquid inlet platform two and the liquid inlet platform three at appropriate positions on the slide rail base, and fit the connecting magnetic sheet one and the connecting magnetic sheet two tightly. The distance adjustment knob is adjusted so that the feed push rod pushes the liquid inlet platform one to move forward. After moving to the appropriate position, it is fixed to the slide rail base by the clamping nut one. The microfluidic connector four and the microfluidic connector five are tightened and the square convex groove one and the square convex groove two are glued to make them sealed and fixed.

[0017] Preferably, a discrete phase injection pump is arranged on the microfluidic connector one, and a continuous phase injection pump is arranged on the microfluidic connector three. The connector hole can select a movable microfluidic connector six or a non-porous microfluidic connector according to whether liquid is introduced to generate different types of droplets.

[0018] Preferably, one end of the connecting hose is connected to the collecting capillary, and the other end is connected to the microfluidic connector 1 of the next-level fine-tunable coaxial capillary microfluidic chip, so that the single-level fine-tunable coaxial capillary microfluidic chip is assembled into a two-level fine-tunable coaxial capillary microfluidic chip, which can be connected in sequence to form more levels.

[0019] Preferably, the focusing capillary and the collecting capillary are both circular in cross section, and at their opposite ends, the focusing capillary has a tapered opening, and the collecting capillary has a flat opening, and the other ends of both are flat openings.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] 1. The present invention provides a multi-stage fine-tunable coaxial capillary microfluidic chip, whose overall structure adopts split modularization. The modular assembly method is convenient for disassembly, the square tube has a high reuse rate, and the service life of the equipment is increased.

[0022] 2. The present invention sets a slide rail base module. The standardized flow channel block and the slide rail base module can ensure geometric coaxial centering. The base slide groove allows the liquid inlet platform to move and adjust the distance in the same dimension, which is beneficial to the coaxial centering distance adjustment of the focusing capillary and the collecting capillary, and integrates the entire structure.

[0023] 3. The present invention sets a feed module, and by turning the distance adjustment knob, the feed push rod pushes the liquid inlet platform to move. The movement of the liquid inlet platform realizes the coaxial distance adjustment of the focusing capillary and the collecting capillary in the square tube, and can perform real-time adjustment to obtain the relative distance between the two circular tubes required for the experiment, thereby ensuring real-time adjustment of the emulsion particle size and reducing the trial and error cost. The distance adjustment device in the present invention is not limited to a micrometer, and can be realized by piezoelectric ceramics and a precision translation stage.

[0024] 4. The present invention sets a liquid inlet platform module and can adjust in real time whether the liquid inlet platform 3 is inletting liquid by selecting a porous or non-porous microfluidic connector, thereby realizing the preparation of multiple droplets, reducing the number of types of liquid inlet platforms of microfluidic chips, and improving standardization.

[0025] 5. The present invention combines multi-stage chips by connecting hoses. The multi-stage modular structure can not only satisfy that the single-stage chip modules correspond to their respective single emulsion and double emulsion working conditions, but can also be combined with each other and used flexibly to produce a variety of complex droplets that meet the requirements, which is simple and efficient.

[0026] 6. The chip of the present invention is easy to assemble and disassemble, requires less consumables, and can be mass-produced. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 1 is a schematic diagram of a single-stage chip structure of a coaxial capillary microfluidic chip provided by an embodiment of the present invention;

[0028] Figure 2 This is a single-stage chip front view of a coaxial capillary microfluidic chip proposed by the present invention;

[0029] Figure 3 The present invention proposes Figure 2 The local structural cross-section of

[0030] Figure 4 It is a structural diagram of the feeding module proposed by the present invention;

[0031] Figure 5 It is a schematic diagram of the secondary chip structure of a coaxial capillary microfluidic chip proposed by the present invention;

[0032] Figure 6 It is a schematic diagram of the three-level chip structure of a coaxial capillary microfluidic chip proposed by the present invention;

[0033] Figure 7 This is a physical picture of a single emulsion droplet obtained from the experiment of the present invention;

[0034] Figure 8 This is a physical picture of a single-core double emulsion droplet obtained from the experiment of the present invention;

[0035] Fig. 9This is a real picture of the double-core double-emulsion droplet obtained from the experiment of the present invention;

[0036] Fig.10 This is a real picture of the triple-core double emulsion droplet obtained in the experiment of the present invention.

[0037] Legend: 1. Slide rail base; 101. Pressing nut one; 102. Pressing nut two; 103. Pressing nut three; 104. Base slide; 2. Liquid inlet platform one; 201. Microfluidic connector one; 202. Microfluidic connector two; 203. Connecting magnetic sheet one; 3. Liquid inlet platform two; 301. Microfluidic connector three; 302. Microfluidic connector four; 303. Square fixing groove one; 4. Liquid inlet platform three; 401. Connector hole; 402. Microfluidic connector five; 403. Square fixing groove two; 404. Microfluidic connector six; 405. Microfluidic connector without hole; 5. Pitch adjustment support; 501. Pitch adjustment knob; 502. Feed push rod; 503. Connecting magnetic sheet; 6. Focusing capillary; 7. Square capillary; 8. Collecting capillary; 9. Connecting hose. DETAILED DESCRIPTION

[0038] To make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described in detail below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other implementation methods obtained by ordinary technicians in this field without creative work belong to the scope of protection of the present invention.

[0039] Embodiment 1:

[0040] like Figure 1 As shown, a multi-stage fine-tunable coaxial capillary microfluidic chip of the present invention comprises: a slide rail base 1, on which a liquid inlet platform 1 2, a liquid inlet platform 2 3 and a liquid inlet platform 3 4 are slidably mounted;

[0041] A clamping nut 101, a clamping nut 2 102 and a clamping nut 3 103 are movably mounted on the slide rail base 1, and base slide grooves 104 are opened inside the two sides of the slide rail base 1;

[0042] A microfluidic connector 201 is movably installed on the top of the liquid inlet platform 2, a microfluidic connector 202 is movably installed on the lower right side, and a connecting magnetic sheet 203 is fixedly connected on the left side;

[0043] A microfluidic connector 3 301 is movably installed above the second liquid inlet platform 3, a microfluidic connector 4 302 is movably installed at the lower left side, and a square fixing groove 1 303 is opened at the lower right side;

[0044] A microfluidic connector 5 402 is movably mounted on the right side of the liquid inlet platform 3 4, a square fixing groove 2 403 is provided at the lower left side, and a connector hole 401 is provided at the top, on which a microfluidic connector 6 404 and a non-porous microfluidic connector 405 can be movably mounted;

[0045] One end of the square capillary tube 7 extends into the square fixing groove 1 303, and the other end extends into the square fixing groove 2 403, and the square capillary tube 7 moves to a suitable position;

[0046] One end of the collecting capillary 8 is installed in the microfluidic connector 5 402, extending into the square capillary 7 and fixed thereto;

[0047] The square fixing groove 1 303 and the square fixing groove 2 403 are sealed by glue, so that the liquid inlet platform 2 3 and the liquid inlet platform 3 4 become a whole; after sliding it to a suitable position on the slide rail base 1, it is fixed on the slide rail base 1 by the clamping nut 2 102 and the clamping nut 3 103;

[0048] One end of the focusing capillary 6 is fixedly installed in the microfluidic connector 202, and the other end is movably installed in the microfluidic connector 4 302 and extends into the square capillary 7;

[0049] The focusing capillary 6, the square capillary 7 and the collecting capillary 8 are kept coaxially, and the connecting magnetic sheet 1 203 and the connecting magnetic sheet 2 503 are kept coaxially aligned;

[0050] The slide rail base 1 is fixedly mounted with a distance adjustment support 5, and a feed push rod 502 is movably mounted on the distance adjustment support 5. The rear end of the feed push rod 502 is movably mounted with a distance adjustment knob 501, and the front end is nested and fixed with a connecting magnetic sheet 2 503. The connecting magnetic sheet 1 203 and the connecting magnetic sheet 2 503 are tightly fitted to realize the simultaneous movement of the feed module and the liquid inlet platform 1 2. The distance adjustment knob 501 is adjusted to make the feed push rod 502 push the liquid inlet platform 1 2 to move forward. After moving to a suitable position, the liquid inlet platform 1 2 is fixed to the slide rail base 1 by tightening the nut 101, and the microfluidic connector 4 302 and the microfluidic connector 5 402 are tightened.

[0051] The coaxial distance adjustment of the focusing capillary 6 and the collecting capillary 8 in the square capillary 7 is achieved by moving the liquid inlet platform 2. The relative distance between the focusing capillary 6 and the collecting capillary 8 is adjusted to 100-150 μm with an accuracy of 2 μm. The adjustment can be performed in real time to obtain the relative distance between the two circular tubes required for the experiment, thereby ensuring real-time adjustment of the emulsion particle size and reducing the trial and error cost.

[0052] Embodiment 2:

[0053] like Figure 1 , 5As shown in Figure 6, based on the first embodiment, the present invention provides a technical solution: the microfluidic connector 1 201 and the microfluidic connector 3 301 are fixed liquid inlets, a discrete phase injection pump is arranged on the microfluidic connector 1 201, and a continuous phase injection pump is arranged on the microfluidic connector 3 301. The connector hole 401 can be installed with a microfluidic connector 6 404 or a non-porous microfluidic connector 405 according to whether liquid is introduced. If the non-porous microfluidic connector 405 is installed on the connector hole 401, the liquid inlet is closed, and the two microfluidic connectors are simultaneously introduced to generate single emulsion droplets. The relevant single emulsion droplets generated in the experiment are shown in Figure 6. Figure 7 If the microfluidic connector six 404 is installed on the connector hole 401, a continuous phase injection pump can be set on the microfluidic connector six 404, and the three microfluidic connectors are simultaneously fed with liquid to generate double emulsion droplets. The various double emulsions generated in the experiment are as follows Figure 8-10 shown.

[0054] One end of the connecting hose 9 is connected to the collecting capillary 8, and the other end is connected to the microfluidic connector 1 201 of the next-stage fine-tunable coaxial capillary microfluidic chip, together forming a multi-stage fine-tunable coaxial capillary microfluidic chip. The microfluidic connector 6 404 or the non-porous microfluidic connector 405 is installed through the connector hole 401 on each single-stage microfluidic chip, which can realize the preparation of various complex droplets, such as Figure 8-10 The specific contents are described in the table below. The attached table is as follows:

[0055]

[0056] Working principle:

[0057] (1) Build a high-speed microscopic imaging system: First, use two supporting devices to fix the high-speed CCD and microscope on the optical experimental platform respectively, and then connect the CCD to the computer;

[0058] (2) Building the chip experimental section: Fix the coaxial capillary microfluidic chip device on a three-dimensional mobile platform and place a cold light source on the back of the chip as an auxiliary light source;

[0059] (3) Build a fluid input device and connect the polyethylene tube and syringe to the corresponding chip inlet;

[0060] (4) Start the injection pump and check the sealing of each phase pipeline and chip;

[0061] (5) Turn on the high-speed camera system, computer and auxiliary light source, and adjust the relative position of the chip and the microscope by adjusting the three-dimensional mobile platform so that the chip is roughly in the center of the microscope field of view;

[0062] (6) Adjust the intensity and distance of the auxiliary light source, as well as the CCD focal length and shooting speed to ensure that the photos taken have sufficient clarity;

[0063] (7) After ensuring the tightness, start the continuous phase injection pump. When the continuous phase fluid fills the entire channel, turn on the dispersed phase injection pump. Droplet preparation can be observed in the microchannel. After the observed flow phenomenon is stable for at least 5 minutes, use a high-speed CCD to record it in real time and save it to the computer.

[0064] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to specific details.

Claims

1. A multi-stage fine-tunable coaxial capillary microfluidic chip, comprising: The slide rail base (1) is characterized in that: a liquid inlet platform 1 (2), a liquid inlet platform 2 (3) and a liquid inlet platform 3 (4) are slidably mounted on the slide rail base (1); a microfluidic connector 1 (201) is movably mounted on the top of the liquid inlet platform 1 (2), a microfluidic connector 2 (202) is movably mounted on the lower right side, and a connecting magnetic sheet 1 (203) is fixedly connected on the left side; a microfluidic connector 3 (301) is movably mounted on the top of the liquid inlet platform 2 (3), a microfluidic connector 4 (302) is movably mounted on the lower left side, and a connecting magnetic sheet 1 (203) is fixedly connected on the left side. A square fixing groove 1 (303) is provided at the lower side; a microfluidic connector 5 (402) is movably installed on the right side of the liquid inlet platform 3 (4), a square fixing groove 2 (403) is provided at the lower left side, and a connector hole (401) is provided at the top, and a microfluidic connector 6 (404) or a non-porous microfluidic connector (405) can be movably installed on the connector hole (401); one end of the square capillary (7) extends into the square fixing groove 1 (303), and the other end extends into the square fixing groove 2 (403), and the square capillary (7) (7) is fixed in a suitable position; one end of the focusing capillary (6) is fixedly installed in the microfluidic connector 2 (202), and the other end is movably installed in the microfluidic connector 4 (302) and extends into the square capillary (7); one end of the collecting capillary (8) is fixedly installed in the microfluidic connector 5 (402) and extends into the square capillary (7); a clamping nut 1 (101), a clamping nut 2 (102) and a clamping nut 3 (103) are movably installed on the slide rail base (1), and the slide rail Base slide grooves (104) are provided inside the two sides of the base (1); the slide rail base (1) is fixedly mounted with a distance adjustment support (5), the distance adjustment support (5) is movably mounted with a feed push rod (502), the rear end of the feed push rod (502) is movably mounted with a distance adjustment knob (501), and the front end is nested with a second connecting magnetic sheet (503); the focusing capillary (6), the square capillary (7) and the collecting capillary (8) are kept coaxially, and the first connecting magnetic sheet (203) and the second connecting magnetic sheet (503) are kept coaxially aligned.

2. A multi-stage fine-tunable coaxial capillary microfluidic chip according to claim 1, characterized in that: The clamping nuts 2 (102) and 3 (103) fix the liquid inlet platform 2 (3) and the liquid inlet platform 3 (4) at appropriate positions on the slide rail base (1), and tightly fit the connecting magnetic sheet 1 (203) and the connecting magnetic sheet 2 (503). The distance adjustment knob (501) is adjusted to allow the feed push rod (502) to push the liquid inlet platform 1 (2) to move forward. After moving to an appropriate position, the liquid inlet platform 1 (2) is fixed to the slide rail base (1) by the clamping nut 1 (101). The microfluidic connector 4 (302) claim 5 and the microfluidic connector 5 (402) are tightened and the square convex groove 1 (303) and the square convex groove 2 (403) are glued to make them sealed and fixed.

3. The multi-stage fine-tunable coaxial capillary microfluidic chip according to claim 1, characterized in that: A discrete phase injection pump is arranged on the microfluidic connector one (201), a continuous phase injection pump is arranged on the microfluidic connector three (301), and the connector hole (401) can be used to select a movable microfluidic connector six (404) or a non-porous microfluidic connector (405) according to whether liquid is introduced.

4. A multi-stage fine-tunable coaxial capillary microfluidic chip according to claims 1-3, characterized in that: One end of the connecting hose (9) is connected to the collecting capillary (8), and the other end is connected to the microfluidic connector 1 (201) of the next-level fine-tunable coaxial capillary microfluidic chip, so that the single-level fine-tunable coaxial capillary microfluidic chip is assembled into a two-level fine-tunable coaxial capillary microfluidic chip, which can be connected in sequence to form more levels.

5. The multi-stage fine-tunable coaxial capillary microfluidic chip according to claim 1, characterized in that: The focusing capillary (6) and the collecting capillary (8) are both circular in cross section, and at their opposite ends, the focusing capillary (6) has a conical opening, and the collecting capillary (8) has a flat opening, and the other ends of both are flat openings.

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