WO2024098566A1

WO2024098566A1 - Microfluidic chip for drug delivery system

Info

Publication number: WO2024098566A1
Application number: PCT/CN2023/075342
Authority: WO
Inventors: 黄健
Original assignee: 铭汰医药设备(上海)有限公司
Priority date: 2022-11-10
Filing date: 2023-02-10
Publication date: 2024-05-16
Also published as: CN115591594A

Abstract

The present application relates to a microfluidic chip for a drug delivery system, comprising a bottom chip, a top chip, and a sealing film. A mounting recess is formed in the bottom chip, and a protruding portion protrudes from the bottom wall of the mounting recess provided in the bottom chip; the protruding portion is provided with a flow channel for allowing a fluid to flow, the flow channel comprises a mixing flow channel and a plurality of liquid inlet flow channels, liquid inlet ends of the plurality of liquid inlet flow channels are spaced apart, and liquid outlet ends of the plurality of liquid inlet flow channels are gathered with the mixing flow channel; the top chip is mounted on the bottom chip, and a clamping portion located in the mounting recess protrudes from the side of the top chip facing the bottom chip; and the sealing film is sandwiched between the protruding portion and the clamping portion so as to seal the flow channel. According to the present application, the sealing film can be clamped tightly, the possibility of movement of the sealing film is reduced, and the sealing performance of the sealing film for the flow channel is enhanced.

Description

Microfluidic Chips for Drug Delivery Systems

Technical Field

The present application relates to the technical field of microfluidic chips, and in particular to a microfluidic chip for a drug delivery system.

Background technique

Microfluidic chip technology is a kind of technology based on fluid mechanics theory, which integrates the basic operation units of sample preparation, reaction, separation, detection and other basic operation units of biological, chemical and medical analysis processes into a micrometer-scale chip, automatically completing the entire analysis process. Due to its huge potential in the fields of biology, chemistry, medicine, etc., it has developed into a new research field that intersects biology, chemistry, medicine, fluid, electronics, materials, mechanics and other disciplines.

The usual chip structure is made of multiple layers of glass or acrylic pressed together, with micro channels carved out in the middle layer. This method is costly and cannot be mass-produced. In order to achieve mass production, the current method is to make smooth bottom chips and top chips, carve channels on the bottom chip, and laminate the sealing film between the bottom chip and the top chip, pressing them tightly. In this way, the sealing of the microfluidic chip mainly depends on the top chip pressing the sealing film to seal the channel, but the sealing film and the channel are difficult to match accurately, resulting in insufficient airtightness.

Summary of the invention

In order to improve the sealing performance of a microfluidic chip, the present application provides a microfluidic chip for a drug delivery system.

The microfluidic chip for a drug delivery system provided in this application adopts the following technical solution:

A microfluidic chip for a drug delivery system, comprising:

A bottom chip, wherein the bottom chip is provided with a mounting groove, and a protrusion is provided on the bottom wall of the mounting groove; a flow channel for fluid flow is provided on the protrusion, and the flow channel includes a mixing flow channel and a plurality of liquid inlet flow channels, and the liquid inlet ends of the plurality of liquid inlet flow channels are arranged at intervals, and the liquid outlet ends of the plurality of liquid inlet flow channels are all merged with the mixing flow channel;

A top chip is mounted on the bottom chip, a clamping portion is convexly provided on a side of the top chip facing the bottom chip, and the clamping portion is located in the mounting groove; and

A sealing film is sandwiched between the protruding portion and the clamping portion to seal the flow channel.

By adopting the above technical scheme, the bottom chip is provided with a mounting groove, and the top chip is provided with a clamping portion located in the mounting groove, so as to facilitate positioning of the mounting position of the top chip; a protrusion is provided on the bottom chip, and a flow channel is provided on the protrusion, so that when the sealing film is placed between the bottom chip and the top chip, the protrusion on the bottom chip and the clamping portion on the top chip can press the sealing film; relative to the surfaces of the bottom chip and the top chip facing the sealing film, which are both arranged in a flat surface, a protrusion is provided on the bottom chip, and a clamping portion is provided on the top chip, which helps to clamp the sealing film, reduce the possibility of movement of the sealing film, and enhance the sealing performance of the sealing film to the flow channel.

Optionally, a plurality of annular mixing grooves are recessed in the mixing flow channel, and the plurality of annular mixing grooves are spaced apart and connected in sequence along the direction of the mixing flow channel, and are staggered in a direction perpendicular to the mixing flow channel.

By adopting the above technical solution, the fluid flows into the mixing channel through the liquid inlet channel to be mixed, and the mixed fluid is divided by the annular mixing groove and then mixed again, which can promote more uniform mixing of the fluid.

Optionally, the mixing channel is arranged in a curved shape.

By adopting the above technical solution, the length of the mixing flow channel is increased. On the one hand, the reaction time between the fluids can be extended to ensure that the reaction between the fluids occurs completely in the flow channel, so that what flows out of the mixing flow channel is the finished product after the reaction; on the other hand, the flow rate of the fluid in the mixing flow channel is reduced, which has a pressure relief effect, so that the finished product flows out of the mixing flow channel smoothly.

Optionally, the length of at least one of the liquid inlet flow channels is different from that of the other liquid inlet flow channels, and the liquid inlet flow channel with a larger length is arranged in a curved shape.

By adopting the above technical solution, a fluid with a higher flow rate can be injected into a liquid inlet channel with a longer length, and a fluid with a lower flow rate can be injected into a liquid inlet channel with a shorter length, so that different fluids can flow to the mixing channel at the same time, reducing the phenomenon of cross contamination of fluids during liquid injection.

Optionally, the bottom chip and the top chip are made of stainless steel.

By adopting the above technical solution, the bottom chip and the top chip made of stainless steel will not react with the fluid and can carry fluid with a higher flow rate, thus realizing a pilot-level microfluidic chip.

Optionally, the outer peripheral surface of the bottom chip is provided with a plurality of liquid inlets connected one-to-one with the liquid inlet end and a liquid outlet connected with the liquid outlet end.

By adopting the above technical solution, the liquid inlet and the liquid outlet are both connected to the pipeline, and the liquid inlet and the liquid outlet are located on the outer peripheral surface of the bottom chip, which can avoid affecting the placement of the bottom chip and the sealing performance of the sealing film, thereby ensuring the stability of the reaction in the chip.

Optionally, the bottom chip is provided with a plurality of milling channels protruding from the bottom wall of the mounting groove, the plurality of milling channels are spaced apart and arranged around the flow channel, the milling channels close to the flow channel are parallel to the flow channel, the milling channels on the inner side wall of the mounting groove close to the bottom chip are parallel to the inner side wall, and the top of the milling channels and the clamping portion jointly clamp the sealing film.

By adopting the above technical solution, the installation groove on the bottom chip can be formed by milling, and a milling track can be reserved on the bottom chip while processing the installation groove. The milling track and the clamping part clamp the sealing film, which can further help clamp the sealing film, reduce the possibility of movement of the sealing film, and enhance the sealing performance of the sealing film to the flow channel. The milling track close to the flow channel is parallel to the flow channel, and the milling track close to the inner wall is parallel to the inner wall, so that the milling track close to the flow channel can be spliced with the milling track close to the inner wall, which can improve the processing efficiency of the milling track on the bottom chip.

Optionally, two liquid inlet flow channels are provided, and the two liquid inlet flow channels converge at an end point of the mixing flow channel.

By adopting the above technical solution, one liquid inlet flow channel is injected with water phase, and the other liquid inlet flow channel is injected with organic phase. The water phase and the organic phase are combined at the end of the mixing flow channel to cause a self-assembly reaction.

Optionally, the angle between the two liquid inlet channels at the intersection is less than or equal to 90°.

By adopting the above technical solution, when injecting fluid into one of the liquid inlet channels, the fluid does not have a flow component flowing to the other liquid inlet channel, thereby reducing the cross contamination of the fluid during liquid injection.

Optionally, the liquid inlet channel includes a first liquid inlet channel and a second liquid inlet channel, the depth of the first liquid inlet channel is greater than the depth of the second liquid inlet channel, the position of the top chip relative to the first liquid inlet channel protrudes toward the bottom chip to form a seal extending into the upper part of the first liquid inlet channel to seal the upper part of the first liquid inlet channel, the thickness of the seal is the same as the depth of the second liquid inlet channel, and the depth of the mixing channel at one end close to the liquid inlet channel is the same as the depth of the first liquid inlet channel.

By adopting the above technical solution, the fluid flowing in the first liquid inlet flow channel is the first fluid, and the fluid flowing in the second liquid inlet flow channel is the second fluid. The first fluid flows at the bottom of the first liquid inlet flow channel, and the second fluid is located above the first fluid. When the first fluid and the second fluid flow to the mixing flow channel, the second fluid mixes with the first fluid under the action of gravity, and the mixing effect of the first fluid and the second fluid can be improved during the flow process. At the same time, the depth of the end of the mixing flow channel is the same as the depth of the first liquid inlet flow channel, so that the end of the mixing flow channel can completely accommodate the first fluid and the second fluid flowing in, and the first fluid and the second fluid will not be squeezed when they meet, thereby reducing the phenomenon of cross contamination of the fluid during liquid inlet.

Optionally, the mixing channel includes a first channel, a second channel and a third channel in sequence along the flow direction, the first channel has the same depth as the first liquid inlet channel, the third channel has a depth smaller than the first channel, the second channel is located between the first channel and the third channel, and in the direction from the first channel to the third channel, the depth of the second channel gradually decreases from the same depth as the first channel to the same depth as the third channel.

By adopting the above technical solution, the first fluid and the second fluid gradually flow to the third flow channel after merging, and the squeezing effect in the second flow channel and the third flow channel can further promote the mixing of the first fluid and the second fluid.

Optionally, a Tesla valve is provided on the second flow channel.

By adopting the above technical solution, the first fluid and the second fluid will be squeezed when flowing to the second flow channel. A Tesla valve is arranged on the second flow channel to prevent the mixed fluid from flowing back to the first flow channel, thereby avoiding the generation of a flow component toward the first liquid inlet flow channel or the second liquid inlet flow channel, thereby reducing the phenomenon of cross-contamination of the fluid during liquid inlet.

Optionally, a fourth flow channel is provided between the second flow channel and the third flow channel, the depth of the fourth flow channel is greater than the depth of the third flow channel, and the bottom chip is provided with a bottom wall of the fourth flow channel protruding toward the top chip to form a plurality of The invention further comprises a plurality of first protrusions arranged at intervals, the distance between the first protrusion and the top chip is the same as the depth of the third flow channel, the top chip protrudes toward the bottom chip to form a plurality of second protrusions arranged at intervals, the distance between the second protrusion and the bottom wall of the fourth flow channel provided on the bottom chip is the same as the depth of the third flow channel, the first protrusion and the second protrusion are alternately arranged in the direction of the fourth flow channel and their projections on the direction of the fourth flow channel partially overlap, and the spacing between the first protrusion and the second protrusion in the direction of the fourth flow channel is the same as the depth of the third flow channel.

By adopting the above technical solution, a serpentine flow channel with ups and downs is formed in the fourth flow channel, which can promote more uniform mixing of the fluid.

In summary, the present application includes at least one of the following beneficial technical effects:

1. The bottom chip is provided with a mounting groove, and the top chip is provided with a clamping portion in the mounting groove, so as to facilitate positioning of the mounting position of the top chip; the sealing film is placed between the bottom chip and the top chip, and the protrusion on the bottom chip and the clamping portion on the top chip can press the sealing film, which helps to clamp the sealing film, reduce the possibility of movement of the sealing film, and enhance the sealing performance of the sealing film to the flow channel.

2. The fluid flows into the mixing channel through the liquid inlet channel for mixing. The mixed fluid is then divided and mixed again through the annular mixing groove, which can promote more uniform mixing of the fluid.

3. There are two liquid inlet channels, and the angle formed between the ends of the two liquid inlet channels close to the mixing channel is less than or equal to 90°, so as to reduce the cross contamination of the fluid during liquid inlet.

4. The depth of the first liquid inlet channel is greater than that of the second liquid inlet channel. The first fluid flows at the bottom of the first liquid inlet channel, and the second fluid is located above the first fluid. When the first fluid and the second fluid flow to the mixing channel, the second fluid mixes with the first fluid under the action of gravity, and the mixing effect of the first fluid and the second fluid can be improved during the flow process. The depth of the end of the mixing channel is the same as the depth of the first liquid inlet channel, so that the end of the mixing channel can completely accommodate the first fluid and the second fluid flowing in, and the first fluid and the second fluid will not be squeezed when they meet, thereby reducing the phenomenon of cross contamination of the fluid during liquid inlet.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a schematic diagram of the structure of a microfluidic chip for a drug delivery system in Example 1 of the present application;

FIG2 is a schematic top view of the bottom chip in FIG1 ;

FIG3 is a schematic diagram of the structure of the top chip in FIG1 ;

FIG4 is a schematic top view of the bottom chip in the microfluidic chip for drug delivery system in Example 2 of the present application;

Fig. 5 is a schematic cross-sectional view of A-A' in Fig. 4;

Fig. 6 is a schematic cross-sectional view of B-B' in Fig. 4;

FIG7 is a partial enlarged schematic diagram of point D in FIG6;

FIG8 is a partial enlarged schematic diagram of point C in FIG4;

FIG9 is a schematic cross-sectional view of the mixing channel in FIG4 ;

10 is a schematic cross-sectional view of a mixing channel in a microfluidic chip for a drug delivery system according to Example 3 of the present application;

FIG11 is a partial enlarged schematic diagram of point E in FIG10;

12 is a schematic top view of the bottom chip in the microfluidic chip for drug delivery system in Example 4 of the present application;

Fig. 13 is a schematic cross-sectional view of F-F' in Fig. 12 .

Explanation of the reference numerals: 1. bottom chip; 11. mounting groove; 12. protrusion; 13. liquid inlet; 14. liquid outlet; 15. first protrusion; 16. milling channel; 2. top chip; 21. clamping portion; 22. seal; 23. second protrusion; 3. sealing film; 4. flow channel; 41. mixing flow channel; 41a. annular mixing groove; 411. first flow channel; 412. second flow channel; 413. third flow channel; 414. fourth flow channel; 42. liquid inlet flow channel; 42a. first liquid inlet flow channel; 42b. second liquid inlet flow channel; 43. Tesla valve.

Detailed ways

The present application is further described in detail below in conjunction with Figures 1-13.

The embodiment of the present application discloses a microfluidic chip for a drug delivery system.

Referring to Figure 1, the microfluidic chip for drug delivery system includes a bottom chip 1, a top chip 2 and a sealing film 3. The bottom chip 1 is provided with a mounting groove 11, and a protrusion 12 is protruding from the bottom wall of the mounting groove 11, and a flow channel 4 for fluid flow is provided on the protrusion 12. Referring to Figure 2, the flow channel 4 includes a mixing flow channel 41 and a plurality of liquid inlet flow channels 42, and the liquid inlet ends of the plurality of liquid inlet flow channels 42 are arranged at intervals, and the liquid outlet ends of the plurality of liquid inlet flow channels 42 are all merged with the mixing flow channel 41. The number of liquid inlet channels can be two or more than three, which is specifically set according to the number of fluids to be reacted, and the positions where each liquid inlet flow channel 42 merges with the mixing flow channel 41 can be the same or different, which is specifically set according to the reaction sequence.

The top chip 2 is mounted on the bottom chip 1. Referring to FIG3 , a clamping portion 21 is convexly provided on the side of the top chip 2 facing the bottom chip 1, and the clamping portion 21 is located in the mounting groove 11. The sealing film 3 is sandwiched between the bottom chip 1 and the top chip 2 to seal the flow channel 4. The bottom chip 1 and the top chip 2 can be connected by bolts, adhesives, clamps, welding, etc.

The bottom chip 1 is provided with a mounting groove 11, and the top chip 2 is provided with a clamping portion 21 located in the mounting groove 11, so as to facilitate positioning of the mounting position of the top chip 2; a protrusion 12 is provided on the bottom chip 1, and a flow channel 4 is provided on the protrusion 12, so that when the sealing film 3 is placed between the bottom chip 1 and the top chip 2, the protrusion 12 on the bottom chip 1 and the clamping portion 21 on the top chip 2 can press the sealing film 3; the sealing film 3 covers the flow channel 4 to seal the flow channel 4, and the fluids participating in the reaction are injected into a plurality of liquid inlet channels 42, and the fluids converge in the mixing flow channel 41 to react, and the finished product after the reaction flows out of the mixing flow channel 41. Relative to the surfaces of the bottom chip 1 and the top chip 2 facing the sealing film 3 are both flat, a protrusion 12 is provided on the bottom chip 1, and a clamping portion 21 is provided on the top chip 2, which helps to clamp the sealing film 3 and reduce The possibility of movement of the sealing film 3 is reduced, thereby enhancing the sealing performance of the sealing film 3 on the flow channel 4.

Example 1

2 , in this embodiment, two liquid inlet channels 42 are provided, namely a first liquid inlet channel 42a and a second liquid inlet channel 42b. The two liquid inlet channels 42 converge at the end point of a mixing channel 41, wherein one of the liquid inlet channels 42 is injected with an aqueous phase and the other liquid inlet channel 42 is injected with an organic phase. The aqueous phase and the organic phase converge at the end of the mixing channel 41 to undergo a self-assembly reaction.

In order to avoid affecting the sealing performance of the sealing film 3, referring to FIG1, the bottom chip 1 is provided with a plurality of liquid inlets 13 connected one by one with the liquid inlet end and a liquid outlet 14 connected with the liquid outlet end. The liquid inlet 13 is connected to a plunger pump or a syringe through a conduit. Preferably, the liquid inlet 13 and the liquid outlet 14 are arranged on the outer peripheral surface of the bottom chip 1, which can avoid affecting the placement of the bottom chip 1 and ensure the stability of the reaction in the chip. In other embodiments, the liquid inlet 13 and the liquid outlet 14 can also be arranged on the bottom surface of the bottom chip 1.

In this embodiment, the liquid inlet 13 is connected to the plunger pump through a catheter to realize a pilot-scale microfluidic chip. Optionally, the material of the bottom chip 1 and the top chip 2 can be stainless steel, aluminum alloy, etc., as long as it is a hard material that does not react with the fluid, and can carry a fluid with a larger flow rate, for example, the flow rate of the fluid is more than 400ml/min, and the pressure in the flow channel 4 is more than 20 atmospheres.

In an optional embodiment, the angle at the intersection of the two liquid inlet channels 42 is less than or equal to 90°. When fluid is injected into one of the liquid inlet channels 42, the fluid does not have a flow component flowing to the other liquid inlet channel 42, thereby reducing cross-contamination of the fluid during liquid injection.

When injecting fluid, it is necessary to try to make the two fluids flow to the mixing channel 41 at the same time to be combined. On the one hand, it can reduce the waste of fluid, and on the other hand, it can reduce the phenomenon of fluid contamination caused by the fluid in one liquid inlet channel 42 entering the other liquid inlet channel 42.

Each inlet channel 42 can be straight, or curved, such as arc-shaped or serpentine-shaped. In an optional embodiment, the length of at least one inlet channel 42 is different from that of the other inlet channels 42, and the inlet channel 42 with a longer length is arranged in a curved shape, which can reduce the size of the microfluidic chip. Specifically, the length of the second inlet channel 42b is longer than that of the first inlet channel 42a, and the fluid with a higher flow rate is injected into the inlet channel 42 with a longer length, and the fluid with a lower flow rate is injected into the inlet channel 42 with a smaller length, so that different fluids flow to the mixing channel 41 at the same time, which can reduce the phenomenon of cross contamination of fluids during liquid inlet.

The mixing channel 41 is arranged in a curved shape. Increasing the length of the mixing channel 41 can, on the one hand, prolong the reaction time between the fluids, ensure that the reaction between the fluids occurs completely in the channel 4, and the product flowing out of the mixing channel 41 is the product after the reaction; on the other hand, it can reduce the flow rate of the fluid in the mixing channel 41, play a role in pressure relief, and make the product flow smoothly out of the mixing channel 41. out.

In order to improve the mixing degree between fluids and promote the complete reaction of the fluids, referring to FIG. 2 , a plurality of annular mixing grooves 41 a are recessed in the mixing channel 41. The plurality of annular mixing grooves 41 a are arranged at intervals in the direction of the mixing channel 41 and are connected in sequence, and are staggered in a direction perpendicular to the mixing channel 41. The fluid flows into the mixing channel 41 through the liquid inlet channel 42 for mixing. The mixed fluid is then mixed after being diverted by the annular mixing grooves 41 a, which can promote more uniform mixing of the fluids.

The implementation principle of a microfluidic chip for a drug delivery system in the present application embodiment is:

The sealing film 3 is placed between the top chip 2 and the bottom chip 1 to connect the top chip 2 and the bottom chip 1. The protrusion 12 on the bottom chip 1 and the clamping part 21 on the top chip 2 clamp the sealing film 3 to achieve the sealing of the flow channel 4 by the sealing film 3. The fluids to be injected are the aqueous phase and the organic phase. The fluid with a larger flow rate is injected into the second liquid inlet flow channel 42b by a plunger pump, and the fluid with a smaller flow rate is injected into the first liquid inlet flow channel 42a, so that the aqueous phase and the organic phase are simultaneously gathered at the end of the mixing flow channel 41, and a self-assembly reaction begins. By providing an annular mixing groove 41a, the laminar flow is formed after multiple restrictions on the fluid, and the speed and uniformity of the mixing and reaction of the aqueous phase and the organic phase can be controlled, thereby improving the uniformity and consistency of the product.

Example 2

The difference between Example 2 and Example 1 is that the widths of various positions in the flow channel 4 in the direction perpendicular to the flow channel 4 are consistent. That is, when the depths of two positions in the flow channel 4 are the same, the cross-sections of the two positions are the same; the greater the depth, the greater the cross-section, and the more fluids can pass through at the same time.

Referring to Fig. 4, the depth of the first liquid inlet channel 42a is greater than the depth of the second liquid inlet channel 42b. Referring to Fig. 5 and Fig. 6, Fig. 5 is a cross-sectional schematic diagram of A-A' in Fig. 4, and Fig. 6 is a cross-sectional schematic diagram of B-B' in Fig. 4. The position of the top chip 2 relative to the first liquid inlet channel 42a protrudes toward the bottom chip 1 to form a seal 22 (refer to Fig. 7) extending into the upper part of the first liquid inlet channel 42a to seal the upper part of the first liquid inlet channel 42a. The thickness of the seal 22 is the same as the depth of the second liquid inlet channel 42b. The sealing film 3 is bent relative to the seal 22 to match the seal 22. The depth of the end of the mixing channel 41 close to the liquid inlet channel 42 is the same as the depth of the first liquid inlet channel 42a.

The fluid flowing in the first liquid inlet channel 42a is the first fluid, and the fluid flowing in the second liquid inlet channel 42b is the second fluid. The first fluid flows at the bottom of the first liquid inlet channel 42a, and the second fluid is located above the first fluid. When the first fluid and the second fluid flow to the mixing channel 41, the second fluid mixes with the first fluid under the action of gravity, and the mixing effect of the first fluid and the second fluid can be improved during the flow. At the same time, the depth of the end of the mixing channel 41 is the same as the depth of the first liquid inlet channel 42a, so that the end of the mixing channel 41 can completely accommodate the first fluid and the second fluid flowing in, and the first fluid and the second fluid will not be squeezed when they meet, thereby reducing the phenomenon of cross contamination of the fluid during liquid inlet.

Further, referring to FIG. 8 , in an optional embodiment, the mixing channel 41 includes a first channel 411 , a second channel 412 and a third channel 413 in the flow direction. Referring to FIG. 9 , the depth of the first channel 411 and the first liquid inlet channel 42a is Similarly, the depth of the third flow channel 413 is smaller than the depth of the first flow channel 411, and the second flow channel 412 is located between the first flow channel 411 and the third flow channel 413. In the direction from the first flow channel 411 to the third flow channel 413, the depth of the second flow channel 412 gradually decreases from the same depth as the first flow channel 411 to the same depth as the third flow channel 413.

After the first fluid and the second fluid merge, they gradually flow to the third flow channel 413 . The squeezing effect of the second flow channel 412 and the third flow channel 413 can further promote the mixing of the first fluid and the second fluid.

In an optional embodiment, referring to FIG. 8 , a Tesla valve 43 is provided on the second flow channel 412. The first fluid and the second fluid are squeezed when flowing to the second flow channel 412. The Tesla valve 43 is provided on the second flow channel 412 to prevent the mixed fluid from flowing back to the first flow channel 411, thereby avoiding the generation of a flow component toward the first liquid inlet flow channel 42a or the second liquid inlet flow channel 42b, thereby reducing the phenomenon of cross contamination of the fluid during liquid inlet.

The first fluid flows in the first liquid inlet channel 42a, and the second fluid flows in the second liquid inlet channel 42b. When the first fluid and the second fluid converge in the mixing channel 41, the second fluid mixes with the first fluid under the action of gravity because the depth of the first fluid is greater than the depth of the second fluid. The mixing effect of the first fluid and the second fluid can be improved during the flow process, and the cross contamination of the fluid during the liquid inlet can be reduced. When the mixed fluid flows through the second channel 412, the depth of the mixing channel 41 gradually decreases, which can further promote the mixing degree of the fluid. The second channel 412 is provided with a Tesla valve 43 to prevent the mixed fluid from flowing back when it is squeezed.

Example 3

10 and 11, the difference between Example 3 and Example 2 is that a fourth flow channel 414 is provided between the second flow channel 412 and the third flow channel 413, the depth of the fourth flow channel 414 is greater than the depth of the third flow channel 413, the bottom chip 1 is provided with a bottom wall of the fourth flow channel 414 protruding toward the top chip 2 to form a plurality of first protrusions 15 arranged at intervals, the distance a between the first protrusion 15 and the top chip 2 is the same as the depth of the third flow channel 413, and the top chip 2 protrudes toward the bottom chip 1 to form a plurality of first protrusions 15 arranged at intervals. The second protrusion 23, the sealing film 3 is bent at a position relative to the second protrusion 23 to match the second protrusion 23, the distance b between the second protrusion 23 and the bottom wall of the fourth flow channel 414 provided on the bottom chip 1 is the same as the depth of the third flow channel 413, the first protrusion 15 and the second protrusion 23 are alternately arranged in the direction of the fourth flow channel 414 and the projections on the direction of the fourth flow channel 414 partially overlap, and the spacing c between the first protrusion 15 and the second protrusion 23 in the direction of the fourth flow channel 414 is the same as the depth of the third flow channel 413.

The fluid flows in the mixing channel 41 to the fourth channel 414. Since the fluid is injected by the plunger pump, the fluid has a relatively large pressure inside. Even if there are the first protrusion 15 and the second protrusion 23 with a blocking effect in the fourth channel 414, the fluid can flow along the up-and-down serpentine flow channel under the pressure of the plunger pump, and the fluid falls from the channel above the first protrusion 15. When the fluid reaches the channel below the second protrusion 23, the fluid is agitated under the action of gravity, which can promote more uniform mixing of the fluid.

Example 4

12 and 13 , Example 4 differs from Example 1 in that a bottom chip 1 is provided with a plurality of milling channels 16 protruding from the bottom wall of the mounting groove 11, and the plurality of milling channels 16 are arranged at intervals and around the flow channel 4, the milling channels 16 close to the flow channel 4 are parallel to the flow channel 4, the milling channels 16 on the inner side wall of the mounting groove 11 close to the bottom chip 1 are parallel to the inner side wall, and the top of the milling channels 16 and the clamping portion 21 jointly clamp the sealing film 3.

The mounting groove 11 on the bottom chip 1 can be formed by milling, and a milling channel 16 can be reserved on the bottom chip 1 while machining the mounting groove 11. The milling channel 16 and the clamping portion 21 clamp the sealing film 3, which can further help clamp the sealing film 3, reduce the possibility of movement of the sealing film 3, and enhance the sealing performance of the sealing film 3 to the flow channel 4. The milling channel 16 close to the flow channel 4 is parallel to the flow channel 4, and the milling channel 16 close to the inner wall is parallel to the inner wall, so that the milling channel 16 close to the flow channel 4 can be spliced with the milling channel 16 close to the inner wall, which can improve the processing efficiency of the milling channel 16 on the bottom chip 1.

The above are all preferred embodiments of the present application, and the protection scope of the present application is not limited thereto. Therefore, any equivalent changes made according to the structure, shape, and principle of the present application should be included in the protection scope of the present application.

Claims

A microfluidic chip for a drug delivery system, characterized in that it comprises:

A bottom chip (1), the bottom chip (1) being provided with a mounting groove (11), the bottom wall of the mounting groove (11) being provided with a protruding portion (12); a flow channel (4) for fluid flow is provided on the protruding portion (12), the flow channel (4) comprising a mixing flow channel (41) and a plurality of liquid inlet flow channels (42), the liquid inlet ends of the plurality of liquid inlet flow channels (42) being arranged at intervals, and the liquid outlet ends of the plurality of liquid inlet flow channels (42) being connected to the mixing flow channel (41);

A top chip (2) is mounted on the bottom chip (1), a clamping portion (21) is convexly provided on a side of the top chip (2) facing the bottom chip (1), and the clamping portion (21) is located in the mounting groove (11); and

A sealing film (3) is sandwiched between the protruding portion (12) and the clamping portion (21) to seal the flow channel (4).
The microfluidic chip for a drug delivery system according to claim 1, characterized in that a plurality of annular mixing grooves (41a) are concavely provided in the mixing channel (41), and the plurality of annular mixing grooves (41a) are arranged at intervals in the direction of the mixing channel (41) and are connected in sequence, and are staggered in a direction perpendicular to the mixing channel (41); and/or,

The mixing channel (41) is arranged in a curved shape; and/or,

The length of at least one of the liquid inlet channels (42) is different from the lengths of the other liquid inlet channels (42), and the liquid inlet channel (42) with a larger length is arranged in a curved shape.
The microfluidic chip for a drug delivery system according to claim 1, characterized in that the material of the bottom chip (1) and the top chip (2) is stainless steel; and/or,

The outer peripheral surface of the bottom chip (1) is provided with a plurality of liquid inlets (13) connected one-to-one with the liquid inlet ends and a liquid outlet (14) connected with the liquid outlet ends.
The microfluidic chip for a drug delivery system according to claim 1 is characterized in that the bottom wall of the bottom chip (1) having the mounting groove (11) is convexly provided with a plurality of milling channels (16), the plurality of milling channels (16) are spaced apart and arranged around the flow channel (4), the milling channels (16) close to the flow channel (4) are parallel to the flow channel (4), the milling channels (16) on the inner side wall of the mounting groove (11) close to the bottom chip (1) are parallel to the inner side wall, and the top of the milling channels (16) and the clamping portion (21) jointly clamp the sealing film (3).
The microfluidic chip for a drug delivery system according to claim 1, characterized in that two liquid inlet channels (42) are provided, and the two liquid inlet channels (42) converge at an end point of the mixing channel (41).
The microfluidic chip for a drug delivery system according to claim 5, characterized in that the angle at the intersection of the two liquid inlet channels (42) is less than or equal to 90°.
The microfluidic chip for a drug delivery system according to claim 5, characterized in that the liquid inlet flow channel (42) comprises a first liquid inlet flow channel (42a) and a second liquid inlet flow channel (42b), and the depth of the first liquid inlet flow channel (42a) is greater than that of the second liquid inlet flow channel (42b). The second liquid inlet channel (42b) has a large depth, and the position of the top chip (2) relative to the first liquid inlet channel (42a) protrudes toward the bottom chip (1) to form a seal (22) extending into the upper part of the first liquid inlet channel (42a) to seal the upper part of the first liquid inlet channel (42a). The thickness of the seal (22) is the same as the depth of the second liquid inlet channel (42b), and the depth of one end of the mixing channel (41) close to the liquid inlet channel (42) is the same as the depth of the first liquid inlet channel (42a).
The microfluidic chip for a drug delivery system according to claim 7 is characterized in that the mixing channel (41) includes a first channel (411), a second channel (412) and a third channel (413) in sequence along the flow direction, the first channel (411) and the first liquid inlet channel (42a) have the same depth, the third channel (413) has a depth smaller than the first channel (411), the second channel (412) is located between the first channel (411) and the third channel (413), and in the direction from the first channel (411) to the third channel (413), the depth of the second channel (412) gradually decreases from the same depth as the first channel (411) to the same depth as the third channel (413).
The microfluidic chip for a drug delivery system according to claim 8, characterized in that a Tesla valve (43) is provided on the second flow channel (412).
The microfluidic chip for a drug delivery system according to claim 8, characterized in that a fourth flow channel (414) is provided between the second flow channel (412) and the third flow channel (413), the depth of the fourth flow channel (414) is greater than the depth of the third flow channel (413), the bottom chip (1) is provided with a bottom wall of the fourth flow channel (414) protruding toward the top chip (2) to form a plurality of first protrusions (15) arranged at intervals, the distance between the first protrusion (15) and the top chip (2) is the same as the depth of the third flow channel (413), and the top chip (2) is extended toward the The bottom chip (1) protrudes to form a plurality of second protrusions (23) arranged at intervals, the distance between the second protrusions (23) and the bottom wall of the bottom chip (1) provided with the fourth flow channel (414) is the same as the depth of the third flow channel (413), the first protrusions (15) and the second protrusions (23) are alternately arranged in the direction of the fourth flow channel (414) and their projections in the direction of the fourth flow channel (414) partially overlap, and the spacing between the first protrusions (15) and the second protrusions (23) in the direction of the fourth flow channel (414) is the same as the depth of the third flow channel (413).