High-flux micro-fluidic chip

By designing a high-throughput microfluidic chip, the consistency and particle size distribution problems of naltrexone-loaded microspheres during the preparation process were solved, and efficient and uniform microsphere production was achieved to meet industrial needs.

CN223404960UActive Publication Date: 2025-10-03PEKING UNIV NANCHANG INNOVATION RES INST
View PDF 0 Cites 0 Cited by

Patent Information

Application Number
CN202521345633.6
Authority / Receiving Office
CN · China
Patent Type
Utility models(China)
Current Assignee / Owner
Filing Date
2025-06-30
Publication Date
2025-10-03
Estimated Expiration
2035-06-30

AI Technical Summary

Technical Problem

The existing technology for preparing naltrexone-loaded microspheres has problems such as poor batch reproducibility, wide particle size distribution, low drug encapsulation efficiency, and difficulty in controlling process parameters. In addition, the throughput of conventional microfluidic chips is low, making it difficult to meet the needs of industrial production.

Method used

A high-throughput microfluidic chip was designed. By integrating dispersed phase flow channels, continuous phase flow channels, and microsphere flow channels within the chip matrix, and setting up multiple microsphere formation units within a limited space, a hierarchical flow channel design was adopted to achieve efficient preparation of naltrexone-loaded microspheres, improving yield and consistency.

Benefits of technology

The preparation efficiency and yield of naltrexone-loaded microspheres were significantly improved, with small batch differences, meeting the needs of industrial production, and ensuring high consistency and particle size uniformity of the microspheres through an independent microsphere formation unit.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN223404960U_ABST
    Figure CN223404960U_ABST
Patent Text Reader

Abstract

The utility model relates to a high-flux micro-fluidic chip in the technical field of drug delivery, which comprises a chip substrate, a dispersed phase flow channel, a continuous phase flow channel and a microsphere flow channel are integrated in the chip substrate, and the surface of the chip substrate is provided with a dispersed phase inlet, a continuous phase inlet and a plurality of microsphere outlets. The dispersion phase flow channel comprises a dispersion phase main flow channel and a dispersion phase branch flow channel, the continuous phase flow channel comprises a continuous phase main flow channel and a continuous phase branch flow channel, the microsphere flow channel comprises a plurality of microsphere main flow channels, and each microsphere main flow channel is at least correspondingly provided with a pair of dispersion phase branch flow channel and continuous phase branch flow channel; and a plurality of microsphere forming units are arranged between each pair of dispersed phase branch flow channel and continuous phase branch flow channel and the corresponding microsphere main flow channel. According to the high-flux micro-fluidic chip, the preparation efficiency of the naltrexone drug-loaded microspheres can be improved, the yield of the naltrexone drug-loaded microspheres is increased, and the industrial production requirement is met.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] The present application relates to the field of drug delivery technology, and in particular to a high-throughput microfluidic chip. Background Art

[0002] Naltrexone is an opioid receptor antagonist primarily used to treat alcohol and drug dependence by blocking the euphoric effects of opioids and reducing the risk of relapse. However, its short half-life and frequent dosing limit its clinical application, thus the development of long-acting sustained-release formulations is of great significance. Naltrexone-loaded microspheres, a novel sustained-release drug delivery system, utilize biodegradable materials (such as PLGA) as drug carriers. The microsphere structure enables sustained, controlled release of the drug over periods of weeks to months, significantly improving patient compliance.

[0003] Currently, the industrial production of naltrexone-loaded microspheres primarily relies on traditional preparation processes such as emulsification-solvent evaporation or spray drying. However, these methods have significant technical limitations: poor batch-to-batch reproducibility and difficulty ensuring product uniformity; a wide range of microsphere size distribution; low drug encapsulation efficiency; and difficulty controlling process parameters, which can easily lead to burst or incomplete drug release. These technical deficiencies severely restrict the stability of product quality and the reliability of clinical efficacy.

[0004] Microfluidics, with its precise fluid control and monodispersity advantages, has become an emerging method for preparing drug-loaded microspheres. By manipulating the two-phase flow rates and chip structure, microfluidics can produce microspheres with uniform particle size and high encapsulation efficiency. However, conventional microfluidic chips currently suffer from low throughput, making them difficult to meet the needs of industrial production. Utility Model Content

[0005] In view of the problems existing in the background technology, the present application provides a high-throughput microfluidic chip, which can improve the preparation efficiency of naltrexone-loaded microspheres and increase the yield of naltrexone-loaded microspheres to meet the needs of industrial production.

[0006] According to one aspect of the present invention, a high-throughput microfluidic chip is provided, comprising a chip substrate, wherein a dispersed phase flow channel, a continuous phase flow channel and a microsphere flow channel are integrated in the chip substrate, and a dispersed phase inlet, a continuous phase inlet and a plurality of microsphere outlets are provided on the surface of the chip substrate; the dispersed phase flow channel comprises a dispersed phase main channel connected to the dispersed phase inlet, and the dispersed phase main channel is provided with a plurality of dispersed phase branch channels arranged in parallel; the continuous phase flow channel comprises a continuous phase main channel connected to the continuous phase inlet, and the continuous phase main channel is provided with a plurality of continuous phase branch channels arranged in parallel; the microsphere flow channel comprises a plurality of microsphere main channels, the number of the microsphere main channels is equal to the number of the microsphere outlets, and the microsphere main channels are connected to the microsphere outlets one by one; each of the microsphere main channels is provided with at least a pair of dispersed phase branch channels and continuous phase branch channels; and a plurality of microsphere forming units are provided between each pair of the dispersed phase branch channels and the continuous phase branch channels and the corresponding microsphere main channels.

[0007] In some embodiments of the present invention, the microsphere forming unit includes: a dispersed phase direct flow channel, one end of which is connected to the dispersed phase branch channel; a continuous phase direct flow channel, one end of which is connected to the continuous phase branch channel, and the other end intersects with the dispersed phase direct flow channel to form a microsphere formation site; a microsphere direct flow channel, one end of which is connected to one end of the microsphere formation site, and the other end is connected to the microsphere main flow channel.

[0008] In some embodiments of the present invention, for each microsphere forming unit, there is one dispersed phase straight flow channel and two continuous phase straight flow channels; or there is one dispersed phase straight flow channel and one continuous phase straight flow channel.

[0009] In some embodiments of the present invention, there are two or more microsphere main channels.

[0010] In some embodiments of the present invention, a pair of dispersed phase branch flow channels and continuous phase branch flow channels are respectively provided on both sides of each microsphere main flow channel.

[0011] In some embodiments of the present invention, two or more microsphere main channels are arranged in parallel and at intervals.

[0012] In some embodiments of the present invention, two adjacent microsphere main channels share a continuous phase branch channel.

[0013] In some embodiments of the present invention, two or more microsphere forming units are provided between each pair of the dispersed phase branch channel and the continuous phase branch channel and the corresponding microsphere main channel.

[0014] In some embodiments of the present invention, the microsphere main flow channel is parallel to the corresponding dispersed phase branch flow channel and continuous phase branch flow channel and is arranged at intervals.

[0015] In some embodiments of the present invention, the dispersed phase branch channel is provided between the microsphere main channel and the continuous phase branch channel.

[0016] The embodiments of the present application provide a high-throughput microfluidic chip. This high-throughput microfluidic chip, through precisely designed dispersed phase flow channels, continuous phase flow channels, and microsphere flow channels, enables the arrangement of dozens or even hundreds of microsphere-forming units within the limited space of a chip substrate. This not only enables the efficient preparation of naltrexone-loaded microspheres and significantly increases the yield of naltrexone-loaded microspheres, but also ensures that the naltrexone-loaded microspheres formed by each independent microsphere-forming unit have high consistency and minimal variability between batches, thus meeting the requirements for industrialized production of naltrexone-loaded microspheres. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Various other advantages and benefits will become apparent to those skilled in the art upon reading the detailed description of the preferred embodiment below. The accompanying drawings are for illustration purposes only and are not to be considered as limiting the present application. The same reference symbols are used throughout the drawings to represent the same components. In the drawings:

[0018] Figure 1 This is a schematic diagram of the overall structure of the high-throughput microfluidic chip of this application;

[0019] Figure 2 This is a schematic diagram of the dispersed phase inlet, continuous phase inlet and microsphere outlet arranged on the surface of the chip substrate of the present application;

[0020] Figure 3 Schematic diagram of the arrangement of dispersed phase flow channels, continuous phase flow channels and microsphere flow channels within the chip matrix of the present application;

[0021] Figure 4 This is a partial diagram of a flow-focusing microfluidic chip of the present application;

[0022] Figure 5 This is a schematic diagram of a flow focusing microsphere formation unit of the present application;

[0023] Figure 6 This is a schematic diagram of the generation of naltrexone-loaded microspheres corresponding to a flow focusing structure of the present application;

[0024] Figure 7 This is a partial diagram of a cross-flow microfluidic chip of the present application;

[0025] Figure 8 This is a schematic diagram of a cross-flow microsphere formation unit of the present application;

[0026] Figure 9 This is a schematic diagram of the formation of naltrexone-loaded microspheres corresponding to a cross-flow structure of the present application;

[0027] Figure 10 is a scanning electron micrograph of naltrexone-loaded microspheres prepared in the present application;

[0028] Figure 11 is a particle size distribution diagram of the naltrexone-loaded microspheres prepared in this application;

[0029] Figure 12 This is the in vitro release graph of the naltrexone-loaded microspheres prepared in this application at 45°C.

[0030] The reference numerals in the accompanying drawings represent the following: 1. chip substrate; 2. dispersed phase inlet; 3. continuous phase inlet; 4. microsphere outlet; 5. dispersed phase main channel; 6. dispersed phase branch channel; 7. dispersed phase direct channel; 8. continuous phase main channel; 9. continuous phase branch channel; 10. continuous phase direct channel; 11. microsphere main channel; 12. microsphere direct channel; 13. microsphere formation site; 14. dispersed phase solution; 15. continuous phase solution; 16. naltrexone droplet microspheres. DETAILED DESCRIPTION

[0031] It should be clear that the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.

[0032] When the following description refers to the accompanying drawings, unless otherwise indicated, the same numbers in different drawings represent the same or similar elements. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present application. Instead, they are merely examples of devices and methods consistent with certain aspects of the present application, as detailed in the appended claims.

[0033] In the description of this application, it should be understood that the terms "first", "second", etc. are used for descriptive purposes only and should not be understood as indicating or implying relative importance. For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood according to specific circumstances. In addition, in the description of this application, unless otherwise specified, "multiple" refers to two or more. "And / or" describes the association relationship of associated objects, indicating that three relationships may exist. For example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone. The character " / " generally indicates that the previous and subsequent associated objects are in an "or" relationship.

[0034] The high-throughput microfluidic chip provided in the embodiments of the present application is described below with reference to the accompanying drawings.

[0035] The present application discloses a high-throughput microfluidic chip. Figure 1-Figure 3 As shown, the high-throughput microfluidic chip includes a chip substrate 1, in which dispersed phase flow channels, continuous phase flow channels and microsphere flow channels are integrated. A dispersed phase inlet 2, a continuous phase inlet 3 and several microsphere outlets 4 are provided on the surface of the chip substrate 1.

[0036] The dispersed phase flow channel includes a dispersed phase main channel 5 connected to the dispersed phase inlet 2, and the dispersed phase main channel 5 is provided with a number of dispersed phase branch channels 6 arranged in parallel; the continuous phase flow channel includes a continuous phase main channel 8 connected to the continuous phase inlet 3, and the continuous phase main channel 8 is provided with a number of continuous phase branch channels 9 arranged in parallel; the microsphere flow channel includes a number of microsphere main channels 11, and the number of microsphere main channels 11 is equal to the number of microsphere outlets 4, and the microsphere main channels 11 are connected to the microsphere outlets 4 one by one.

[0037] Each microsphere main channel 11 is provided with at least one pair of dispersed phase branch channels 6 and continuous phase branch channels 9 ; and a plurality of microsphere forming units are provided between each pair of dispersed phase branch channels 6 and continuous phase branch channels 9 and the corresponding microsphere main channel 11 .

[0038] By using the high-throughput microfluidic chip of the present technical solution, a layout of a dispersed phase main channel 5 with multiple dispersed phase branch channels 6, a continuous phase main channel 8 with multiple continuous phase branch channels 9 and a multi-microsphere main channel 11 is formed in the chip substrate 1, the dispersed phase branch channels 6 and the continuous phase branch channels 9 are grouped with the microsphere main channel 11, and a multi-microsphere forming unit is set between the grouped dispersed phase branch channels 6 and the continuous phase branch channels 9 and the microsphere main channel 11, so that when preparing naltrexone-loaded microspheres, the dispersed phase and the continuous phase can be injected through the dispersed phase inlet 2 and the continuous phase inlet 3 respectively, so that ... The dispersed phase enters each dispersed phase branch channel 6 through the dispersed phase main channel 5 and then enters each microsphere forming unit, so that the continuous phase enters each continuous phase branch channel 9 through the continuous phase main channel 8 and then enters each microsphere forming unit. After the dispersed phase and the continuous phase form naltrexone-loaded microspheres in each microsphere forming unit, they merge into the corresponding microsphere main channel 11 and are sent out from the corresponding microsphere outlet 4. The utility model realizes the arrangement of a large number of microsphere forming units in the chip substrate 1 based on the hierarchical design of the flow channel, thereby greatly improving the preparation efficiency of naltrexone-loaded microspheres and increasing the output of naltrexone-loaded microspheres, thereby meeting the needs of industrial production.

[0039] In some embodiments of the present invention, Figure 4 and Figure 5As shown, the microsphere forming unit includes a dispersed phase direct flow channel 7, a continuous phase direct flow channel 10 and a microsphere direct flow channel 12; one end of the dispersed phase direct flow channel 7 is connected to the dispersed phase branch channel 6; one end of the continuous phase direct flow channel 10 is connected to the continuous phase branch channel 9, and the other end intersects with the dispersed phase direct flow channel 7 to form a microsphere forming point 13; one end of the microsphere direct flow channel 12 is connected to one end of the microsphere forming point 13, and the other end is connected to the microsphere main channel 11.

[0040] In this embodiment, the dispersed phase used to prepare naltrexone-loaded microspheres enters the dispersed phase direct flow channel 7 through the dispersed phase branch channel 6, and the continuous phase enters the continuous phase direct flow channel 10 through the continuous phase branch channel 9. The continuous phase squeezes / cuts the dispersed phase at the microsphere formation area 13 to form naltrexone-loaded microspheres. The naltrexone-loaded microspheres then enter the microsphere direct flow channel 12 along with the continuous phase and merge into the microsphere main flow channel 11, thereby finally obtaining naltrexone-loaded microspheres at the microsphere outlet 4.

[0041] It should be noted that, in the present invention, the last section of the continuous phase direct current channel 10 can be vertically connected to the dispersed phase direct current channel 7, that is, at the upstream position near the microsphere formation point 13, the flow direction of the dispersed phase in the dispersed phase direct current channel 7 is perpendicular to the flow direction of the continuous phase in the continuous phase direct current channel 10, and at least a section of the microsphere direct current channel 12 near the microsphere formation point 13 is collinearly connected to the dispersed phase direct current channel 7.

[0042] In some embodiments of the present invention, for each microsphere forming unit, there is one dispersed phase straight flow channel 7 and two continuous phase straight flow channels 10; or there is one dispersed phase straight flow channel 7 and one continuous phase straight flow channel 10.

[0043] like Figure 4 and Figure 5 As shown, two continuous phase direct current channels 10 are connected to a dispersed phase direct current channel 7 to form a cross structure, thereby obtaining a microsphere forming unit for preparing naltrexone-loaded microspheres by a flow focusing method. The process of forming naltrexone droplet microspheres 16 by a dispersed phase solution 14 and a continuous phase solution 15 is as shown in FIG. Figure 6 shown.

[0044] like Figure 7 and Figure 8 As shown, a continuous phase straight channel 10 is connected to a dispersed phase straight channel 7 to form a T-shaped structure, thereby obtaining a microsphere forming unit for preparing naltrexone-loaded microspheres by a cross-flow method. The process of forming naltrexone droplet microspheres 16 by a dispersed phase solution 14 and a continuous phase solution 15 is as shown in FIG. Figure 9 shown.

[0045] In some embodiments of the present invention, Figure 1 and Figure 3 As shown, there are more than two microsphere main channels 11.

[0046] In this embodiment, by setting the number of microsphere main channels 11 to be more than two, the yield of naltrexone-loaded microspheres can be effectively increased. Moreover, by independently setting the microsphere main channel 11 and the microsphere outlet 4, the flexibility in designing the position and number of the dispersed phase main channel 5 and the dispersed phase branch channel 6 as well as the continuous phase main channel 8 and the continuous phase branch channel 9 can be improved, making the overall design of the microfluidic chip more reasonable.

[0047] For example, in some embodiments of the present invention, the number of the microsphere main channels 11 can be designed to be 2, 3, 4, or 5 as needed.

[0048] Specifically, if Figure 1 and Figure 3 As shown, in one embodiment of the present invention, four microball main channels 11 are provided in the chip substrate 1 , and a microball outlet 4 is provided on the surface of the chip substrate 1 corresponding to one end of each microball main channel 11 .

[0049] In some embodiments of the present invention, Figure 1 and Figure 3 As shown, a pair of dispersed phase branch flow channels 6 and continuous phase branch flow channels 9 are provided on both sides of each microsphere main flow channel 11 .

[0050] In this embodiment, by providing a pair of dispersed phase branch channels 6 and continuous phase branch channels 9 on both sides of each microsphere main channel 11, the two pairs of dispersed phase branch channels 6 and continuous phase branch channels 9 share one microsphere main channel 11, which can further improve the yield of naltrexone-loaded microspheres and save the space occupied by the chip substrate 1. With the same output efficiency of naltrexone-loaded microspheres, the microfluidic chip can be smaller and the material cost can be lower.

[0051] For example, Figure 1 and Figure 3 As shown, in one embodiment of the present invention, there are four microsphere main channels 11 in the chip substrate 1, and each microsphere main channel 11 is provided with a pair of dispersed phase branch channels 6 and continuous phase branch channels 9 on both sides.

[0052] In some embodiments of the present invention, Figure 1 and Figure 3 As shown, more than two microsphere main channels 11 are arranged in parallel and at intervals.

[0053] In this embodiment, by arranging a plurality of microsphere main channels 11 in parallel and at intervals, the dispersed phase branch channels 6 and the continuous phase branch channels 9 can be conveniently arranged, making the overall structure more orderly.

[0054] Furthermore, two adjacent microsphere main channels 11 share a continuous phase branch channel 9 .

[0055] For example, Figure 1 and Figure 3 As shown, in one embodiment of the present invention, there are four microsphere main channels 11 in the chip substrate 1, and only one continuous phase branch channel 9 is provided between every two adjacent microsphere main channels 11.

[0056] By rationally arranging the microsphere main channel 11 and grouping two microsphere main channels 11 with a continuous phase branch channel 9, the space occupied by the chip substrate 1 can be further saved, the yield of the microfluidic chip can be further improved, and the volume of the microfluidic chip can be reduced.

[0057] In some embodiments of the present invention, Figure 1 and Figure 4 As shown, two or more microsphere forming units are provided between each pair of dispersed phase branch channel 6 and continuous phase branch channel 9 and the corresponding microsphere main channel 11 .

[0058] By disposing multiple microsphere-forming units between each pair of dispersed phase branch channels 6 and continuous phase branch channels 9 and the corresponding microsphere main channels 11, and by combining the design of the multiple microsphere main channels 11, the number of microsphere-forming units can be maximized, thereby maximizing the production efficiency and yield of naltrexone-loaded microspheres within the limited dimensions of the chip substrate 1.

[0059] Furthermore, in some embodiments of the present invention, corresponding to each group of dispersed phase branch channels 6, continuous phase branch channels 9 and microsphere main channels 11, a layer of microsphere forming units can be set on the side close to the upper surface of the chip substrate 1 and the side close to the lower surface of the chip substrate 1, that is, in the thickness direction of the chip substrate 1, two layers of symmetrically distributed microsphere forming units are provided, so that the number of microsphere forming units can be doubled on the basis of the single-side setting of the chip substrate 1.

[0060] In some embodiments of the present invention, Figure 1 and Figure 3 As shown, the microsphere main channel 11 is parallel to the corresponding dispersed phase branch channel 6 and continuous phase branch channel 9 and arranged at intervals.

[0061] By arranging the microsphere main channel 11 in parallel with the corresponding dispersed phase branch channel 6 and continuous phase branch channel 9 and at intervals, a larger number of microsphere forming units can be reasonably arranged in the length direction of the dispersed phase branch channel 6 .

[0062] For example, in some embodiments of the present invention, 20-30 microsphere-forming units can be respectively arranged between each pair of dispersed phase branch channel 6 and continuous phase branch channel 9 and the corresponding microsphere main channel 11, and ultimately a high-throughput microfluidic chip with various specifications and configurations of microsphere-forming units such as 48 / 96 / 204 / 404 can be obtained.

[0063] Further, if Figure 1 and Figure 3 As shown, the dispersed phase branch channel 6 is arranged between the microsphere main channel 11 and the continuous phase branch channel 9.

[0064] In some embodiments of the present invention, the chip substrate 1 can be an integrated molding structure. Specifically, the chip substrate 1 including structures such as dispersed phase flow channels, continuous phase flow channels, and microsphere flow channels can be prepared by 3D printing to complete the complex three-dimensional structure of the microfluidic chip of the present invention, realize integrated high-throughput design, and significantly improve the microsphere yield.

[0065] Furthermore, the chip substrate 1 may be made of photosensitive resin.

[0066] After the microfluidic chip of the present invention is prepared by using a photosensitive resin in a 3D printing manner, the microfluidic chip can be cleaned.

[0067] After the microfluidic chip of the utility model is completely manufactured, the dispersed phase inlet 2 and the continuous phase inlet 3 of the microfluidic chip can be connected to the microfluidic pressure control system through external pipes, and the microsphere outlet 4 can be connected to the collection container through external pipes, for example, by connecting to the external pipes through a Peek flat joint and acrylic glue. Then, the dispersed phase solution 14 and the continuous phase solution 15 for preparing the naltrexone-loaded microspheres are prepared, and the preparation of the naltrexone-loaded microspheres is carried out.

[0068] For example, in some embodiments of the present invention, 4 g to 6 g of naltrexone is dissolved in 9 g to 12 g of benzyl alcohol as liquid A, and 6 g to 8 g of PLGA (poly(lactic-co-glycolic acid)) is dissolved in 40 g to 60 g of ethyl acetate as liquid B. The completely dissolved liquids A and B are then mixed evenly to form dispersed phase solution 14. 10 g of PVA (polyvinyl alcohol) is dissolved in 990 mL of water to form continuous phase solution 15. Dispersed phase solution 14 and continuous phase solution 15 are filtered using a microporous filter membrane. Using a microfluidic pressure control system, dispersed phase solution 14 and continuous phase solution 15 are injected into dispersed phase inlet 2 and continuous phase inlet 3, respectively, on the surface of a microfluidic chip at a flow ratio of 1:5 to 1:300. At microsphere formation site 13 within the microfluidic chip, continuous phase solution 15 shears dispersed phase solution 14 to form naltrexone droplet microspheres 16. Naltrexone droplet microspheres 16 were dispersed into a vacuum stirring device containing an ethyl acetate aqueous solution or a PVA aqueous solution and solidified at a stirring speed of 100 r / min and a pressure of -100 mbar for 1 h. The solidified microspheres were washed with ultrapure water and finally freeze-dried to obtain naltrexone-loaded microspheres.

[0069] The surface morphology of the prepared naltrexone-loaded microspheres was observed, the particle size uniformity was tested, the drug loading and encapsulation efficiency was tested, and the in vitro release performance was tested. Figure 10 and Figure 11 The following are scanning electron micrographs and particle size distribution diagrams of naltrexone-loaded microspheres, respectively. The diagrams show that the prepared naltrexone microspheres have a smooth surface and uniform particle size distribution. The average particle size of the naltrexone-loaded microspheres prepared using the high-throughput microfluidic chip of this invention is 85 μm, with an average CV value of 4.9% and an average span value of 0.25. The particle size variation between batches is within 5%. HPLC test results show that the prepared naltrexone-loaded microspheres have a high drug loading of over 30% and a high encapsulation efficiency of over 80%. Figure 12 The prepared naltrexone microspheres exhibited excellent release performance under accelerated release conditions at 45°C in vitro, with 19% release within the first 24 hours and a sustained release period of 7 days. The high-throughput microfluidic chip used in this utility model effectively overcomes the challenges of traditional methods, such as low throughput, uneven particle size, and complex processes. Furthermore, this high-throughput microfluidic chip combines the flexibility of laboratory research and development with the potential for industrial production.

[0070] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A high-throughput microfluidic chip, characterized in that: The chip substrate (1) comprises a dispersed phase flow channel, a continuous phase flow channel and a microsphere flow channel integrated therein, and a dispersed phase inlet (2), a continuous phase inlet (3) and a plurality of microsphere outlets (4) are provided on the surface of the chip substrate (1); The dispersed phase flow channel comprises a dispersed phase main channel (5) connected to the dispersed phase inlet (2), and the dispersed phase main channel (5) is provided with a plurality of dispersed phase branch channels (6) arranged in parallel; The continuous phase flow channel comprises a continuous phase main channel (8) communicating with the continuous phase inlet (3), and the continuous phase main channel (8) is provided with a plurality of parallel arranged continuous phase branch channels (9); The microsphere flow channel includes a plurality of microsphere main channels (11), the number of the microsphere main channels (11) is equal to the number of the microsphere outlets (4), and the microsphere main channels (11) are connected to the microsphere outlets (4) in a one-to-one correspondence. Each of the microsphere main channels (11) is provided with at least one pair of dispersed phase branch channels (6) and continuous phase branch channels (9); A plurality of microsphere forming units are provided between each pair of the dispersed phase branch channel (6) and the continuous phase branch channel (9) and the corresponding microsphere main channel (11).

2. The high-throughput microfluidic chip according to claim 1, characterized in that: The microsphere forming unit comprises: a dispersed phase direct flow channel (7), one end of the dispersed phase direct flow channel (7) being in communication with the dispersed phase branch flow channel (6); A continuous phase direct flow channel (10), one end of the continuous phase direct flow channel (10) is connected to the continuous phase branch flow channel (9), and the other end intersects with the dispersed phase direct flow channel (7) to form a microsphere forming portion (13); A microsphere direct flow channel (12), one end of which is connected to one end of the microsphere forming portion (13), and the other end of which is communicated with the microsphere main flow channel (11).

3. The high-throughput microfluidic chip according to claim 2, characterized in that: For each of the microsphere forming units, the dispersed phase direct current channel (7) is provided with one, and the continuous phase direct current channel (10) is provided with two; or The dispersed phase direct current channel (7) is provided with one, and the continuous phase direct current channel (10) is provided with one.

4. The high-throughput microfluidic chip according to claim 1, characterized in that: There are more than two microsphere main flow channels (11).

5. The high-throughput microfluidic chip according to claim 4, characterized in that: Each of the microsphere main flow channel (11) is provided with a pair of dispersed phase branch flow channels (6) and continuous phase branch flow channels (9) on both sides.

6. The high-throughput microfluidic chip according to claim 5, characterized in that: The two or more microsphere main channels (11) are arranged in parallel and at intervals.

7. The high-throughput microfluidic chip according to claim 6, characterized in that: Two adjacent microsphere main channels (11) share a continuous phase branch channel (9).

8. The high-throughput microfluidic chip according to claim 1, characterized in that: Two or more microsphere forming units are provided between each pair of the dispersed phase branch channel (6) and the continuous phase branch channel (9) and the corresponding microsphere main channel (11).

9. The high-throughput microfluidic chip according to claim 1, characterized in that: The microsphere main flow channel (11) is parallel to and spaced apart from the corresponding dispersed phase branch flow channel (6) and continuous phase branch flow channel (9).

10. The high-throughput microfluidic chip according to claim 9, characterized in that: The dispersed phase branch channel (6) is provided between the microsphere main channel (11) and the continuous phase branch channel (9).