Double-core microbead production process and application based on cone tip matching three-dimensional microfluidic chip

Abstract

The application belongs to the technical field of double-core microbead preparation, and particularly relates to a double-core microbead production process based on a cone tip matching three-dimensional microfluidic chip and application. The production process comprises the following steps: (1) raw material conveying: conveying the required materials through different pipelines to the cone tip matching three-dimensional microfluidic chip under insulation conditions; (2) material flow shearing: shearing the required materials in the cone tip matching three-dimensional microfluidic chip to obtain double-core droplets; (3) cooling and forming; and (4) product collection. The cone tip matching three-dimensional microfluidic chip structure can be used for accurately producing double-core microbeads, can realize accurate wrapping of the double-core microbeads, can realize accurate regulation of the particle size of the double-core microbeads, and can provide double-core microbeads with high structural consistency and high yield. Meanwhile, the continuous production of the double-core microbeads can realize stable, rapid and large-scale preparation, so that the microbeads can be widely applied in the fields of medicine, cosmetics, food and the like.

Description

Technical Field

[0001] This invention belongs to the field of dual-core microbead preparation technology, specifically relating to the production process and application of dual-core microbeads based on cone-tip matched three-dimensional microfluidic chips. Background Technology

[0002] Dual-core microbeads are microbead structures consisting of two independent inner cores encapsulated within a single outer shell. These inner cores can differ in color and composition. This design not only significantly enhances the visual appeal of products but also integrates multiple functions. For example, in skincare products, dual-core microbeads can simultaneously load active ingredients with both anti-aging and whitening effects; in pharmaceuticals, they can encapsulate both anti-inflammatory and antibacterial drugs for synergistic treatment; and in food, they can encapsulate different bacterial strains, preventing cross-contamination. Dual-core microbeads have broad application prospects in cosmetics, food, and many other fields.

[0003] Traditional methods for preparing microspheres have not yielded ideal results when used to fabricate binuclear microspheres. For example, the emulsion method relies on the self-assembly of microspheres at the two-phase interface, a process that is random and difficult to precisely control in terms of nucleus positioning and encapsulation. Spray drying involves atomizing droplets and rapidly drying them, but the high-temperature instantaneous curing cannot achieve a precise dual-core-shell structure. Phase separation methods utilize solubility changes to induce polymer precipitation, but the kinetics are complex, making it extremely difficult to stably form a regular binuclear morphology. Furthermore, none of these methods can achieve precise encapsulation of binuclear microspheres; therefore, binuclear microspheres represent a significant market gap and development potential.

[0004] Currently, most microbead products on the market are single-layer microbeads, with a few being double-layer microbeads with a single-pack structure or multiple microbeads per pack. However, these microbeads have a core of the same composition. For example, Chinese patent CN120515349B, "A Microbead Production Process Based on Microfluidic Technology with Adjustable Internal Phase and Its Application," can only produce multiple microbeads per pack with a core of the same composition.

[0005] Patent CN102327761B discloses a polymer composite microsphere and its preparation method. The microsphere comprises a core and a shell, forming a core-shell structure. The core consists of two hemispherical polymer droplets, and the shell consists of polymer droplets incompatible with the core. The interface between the two hemispheres is bonded together through reaction, charge interaction, or specific interaction, and cannot be independent. This structure allows for material exchange and prevents independent encapsulation of substances by the upper and lower hemispheres. The microsphere structure in this patent is not a binuclear microsphere but a mononuclear microsphere, except that the core layer is divided into two parts (two hemispheres). Furthermore, this method only applies to the preparation of polymer composite microspheres and limits the core to a water-soluble polymer and the shell layer to an oil-soluble (organic) polymer. The patent also... The bispherical structure lacks stability; the two hemispherical components easily mix and cannot exist independently. The polymers used in both hemispheres are water-soluble / hydrophilic (e.g., sodium alginate, chitosan, PEG), and the solvents are miscible polar solvents such as water and alcohol. The two hemispherical materials have similar thermodynamic properties and lack strong repulsion to maintain a long-term interface; molecular diffusion is inevitable. The so-called "reaction, charge, or specific interaction" bonding is thermodynamically very fragile and easily destroyed. The droplet structure lacks long-term stability: any minute environmental changes (e.g., temperature, pH, ionic strength, external stress) can weaken the secondary interactions (charge, hydrogen bonds, etc.) upon which it depends, disrupting the hemispherical interface bonding and causing the two hemispheres to mix. This patent uses a two-dimensional planar structure, with the core and shell channels in the same plane. The diameter and structure of the microbeads are controlled by the structure of the microtube reactor and the preparation parameters, resulting in poor operational flexibility.

[0006] The two different components in dual-core microbeads (such as anti-aging and whitening, anti-inflammatory and antibacterial) may have chemical or physical incompatibilities. If they come into contact before storage or use, it may lead to inactivation, reaction, or degradation of the components. Precise encapsulation ensures that the two components are completely isolated before release; at the same time, precise encapsulation can extend shelf life and ensure safe use. In addition, dual-core microbeads are often distinguished by color. If the encapsulation is not independent, there may be adhesion or core misalignment, resulting in color mixing between the two cores or leakage of core material, which will damage the aesthetics of the design and the quality of the product.

[0007] Therefore, how to achieve stable, rapid, and large-scale preparation of dual-core microbeads, especially ensuring the consistency of the structure of each microbead, high yield, and precise encapsulation, remains the core challenge for current industrialization. Summary of the Invention

[0008] The purpose of this invention is to provide a manufacturing process and application for dual-core microbeads based on a cone-tip matched three-dimensional microfluidic chip. By using a cone-tip matched three-dimensional microfluidic chip structure that can be used to precisely produce dual-core microbeads, and combining it with metal 3D printing technology to process the 3D microfluidic chip, precise encapsulation of dual-core microbeads can be achieved, enabling precise control of the particle size of the dual-core microbeads and providing dual-core microbeads with high structural consistency and high yield. At the same time, continuous production of dual-core microbeads can be achieved, enabling stable, rapid, and large-scale preparation, so as to realize the wide application of microbeads in multiple fields such as medicine, cosmetics, and food.

[0009] To achieve the above objectives, the present invention provides the following technical solution: a dual-core microbead manufacturing process based on a cone-tip matched three-dimensional microfluidic chip, comprising the following steps:

[0010] (1) Raw material transportation: The required materials are transported to the cone tip matching three-dimensional microfluidic chip through different pipelines under heat preservation conditions;

[0011] (2) Material shearing: The required material is sheared in the cone-tip matched three-dimensional microfluidic chip to obtain a dual-core droplet; the cone-tip matched three-dimensional microfluidic chip includes an inner phase inlet pipe 1, an inner phase inlet pipe 2, an intermediate phase inlet pipe 1, an intermediate phase inlet pipe 2, an outer phase inlet pipe 1, an outer phase inlet pipe 2, a shearing section 1, a shearing section 2, and an outlet pipe. The shearing section 1 is connected to the inner phase inlet pipe 1, the inner phase inlet pipe 2, the intermediate phase inlet pipe 1, and the intermediate phase inlet pipe 2. The shearing section 2 is connected to the outer phase inlet pipe 1, the outer phase inlet pipe 2, and the outlet pipe; the inner phase 1 in the inner phase inlet pipe 1 and the inner phase 2 in the inner phase inlet pipe 2 are sheared by the intermediate phase 1 in the intermediate phase inlet pipe 1 and the intermediate phase 2 in the intermediate phase inlet pipe 2 to obtain an inner phase droplet 1 and an inner phase droplet 2. The inner phase droplet 1 and the inner phase droplet 2 continue to flow and are finally sheared by the outer phase 1 in the outer phase inlet pipe 1 and the outer phase 2 in the outer phase inlet pipe 2 to obtain a dual-core droplet;

[0012] (3) Cooling and molding: After cooling the binuclear droplets, a cooling medium is used to cool and solidify them to form binuclear microbeads;

[0013] (4) Product collection: The dual-core microbead particles and the cooling medium are separated to obtain dual-core microbeads.

[0014] The three-dimensional microfluidic chip structure of this invention is easy to design and fabricate, forming a staggered arrangement that allows for rapid fabrication of dual-core microspheres. The three-dimensional structure enables uniform encapsulation of the inner phase. The chip of this invention features an intermediate phase inlet tube 1, an intermediate phase inlet tube 2, an outer phase inlet tube 1, and an outer phase inlet tube 2. The intermediate phase 1 in intermediate phase inlet tube 1 and the intermediate phase 2 in intermediate phase inlet tube 2 are the same liquid. After mixing in the shearing section 1, they are sheared to obtain inner phase droplets 1 and 2. The inner phase droplets 1 and 2 continue to flow. The outer phase 1 in outer phase inlet tube 1 and the outer phase 2 in outer phase inlet tube 2 are also the same liquid. After mixing in the shearing section 2, the inner phase droplets 1 and 2 are sheared to obtain dual-core microspheres. This invention, through its chip design, uses two streams of both the intermediate and outer phases. The intermediate phase can be split to shear the two inner phases, and the outer phase is divided into two paths, allowing for better shearing of the intermediate phase.

[0015] Preferably, the inner diameter of inner phase inlet pipe 1 and inner phase inlet pipe 2 is a, and the interval between adjacent outlets of inner phase inlet pipe 1 and inner phase inlet pipe 2 is b. <b≤2a。

[0016] Preferably, the angle between the adjacent outlets of the inner phase inlet pipe 1 and the inner phase inlet pipe 2 is θ, where 15° < θ < 20°.

[0017] The included angle between the inner phase inlet pipe 1 and the inner phase inlet pipe 2 of this invention needs to be within the optimal range. If the angle is too small, the two inner phases will directly coalesce at the inner phase outlet; if the angle is too large, the inner phases will be too far apart, failing to form a double encapsulation, and instead, two single-encapsulated droplets will flow out in parallel. If the angle is inappropriate, even if encapsulation can occur initially, the resulting core walls will be too thin, eventually mixing into a homogeneous phase and failing to form binucleated microspheres. Regardless of whether the inner phases are two aqueous solutions or oil solutions, they are miscible, which is a common problem in existing technologies (such as CN102327761B). The included angle of the inner phase pipes allows the intermediate phase to be better guided along the inner phase pipes to encapsulate the inner phase, while also preventing the coalescence of the two inner phase fluids due to the impact of the intermediate phase fluid.

[0018] Preferably, the shearing section 1 has a frustum-shaped structure, the inner diameter of the outlet of the shearing section 1 is d, the inner diameter of the outlet of the shearing section 2 is D, and the horizontal distance between the plane where the outlets of the inner phase inlet pipe 1 and the inner phase inlet pipe 2 are located and the outlet of the shearing section 2 is m; d≤D / 2.

[0019] Preferably, the horizontal distance between the plane where the outlets of the inner phase inlet pipe 1 and the inner phase inlet pipe 2 are located and the outlet of the shear section 2 is m, 1.5cm≤m≤2.1cm.

[0020] In the present invention, a < b ≤ 2a. By precisely controlling the magnitudes of a and b, it is ensured that the W1+W2 / O droplets formed after the double internal phase is sheared by the middle phase will not collide and coalesce; 15° < θ < 20°. By controlling the included angle θ at the double internal phase inlet, the flow focusing of the W1+W2 / O droplets is ensured; 1.5 cm ≤ m ≤ 2.1 cm. By controlling the length of m, the secondary shear frequency is regulated to ensure the precise encapsulation of the double-core microbeads. Taking the preparation of W1+W2 / O / W double-core microbeads as an example, if the distance m between the middle phase and the outer phase outlet is too long, W1 / O and W2 / O are prone to a large amount of convergence in the narrow channel of the middle phase, resulting in coalescence; the shorter m is, the closer the internal phase is to the cone mouth, and it is easy to touch the wall and cause inability to shear; d ≤ D / 2. By controlling the magnitudes of d and D, it is ensured that the W1+W2 / O droplets can be sheared by the outer phase to form W1+W2 / O / W double-core droplets.

[0021] For d and m of the present invention, optimal parameters are required. Specifically, d and D directly affect the second shear. The larger d and D are, the larger the diameter of the double-core microbeads is. At the same time, the larger d is, the greater the shearing force required. Taking the preparation of W1+W2 / O / W double-core microbeads as an example, if m is too long, W1 / O and W2 / O are prone to a large amount of convergence in the narrow channel of the middle phase, resulting in coalescence; the shorter m is, the closer the internal phase is to the cone mouth, and it is easy to touch the wall and cause inability to shear.

[0022] Preferably, the flow rates of the internal phase 1 and the internal phase 2 are both ν1, the flow rates of the middle phase 1 and the middle phase 2 are both ν2, and the flow rates of the outer phase 1 and the outer phase 2 are both ν3. The ratio of ν2 / ν1 ≥ 10; 4 ≤ the ratio of ν3 / ν2 ≤ 30.

[0023] Through experiments, it is found that the flow rates of the internal phase and the middle phase affect the size of the microbeads inside the double-core microbeads, and the flow rate of the outer phase affects the size of the outer layer of the microbeads. Only within a specific range can the flow rates of the three affect the shearing force and the shear frequency to achieve the precise encapsulation of the double-core microbeads.

[0024] Preferably, the plane where the internal phase inlet tube 1 and the internal phase inlet tube 2 are located is perpendicular to the plane where the middle phase inlet tube 1 and the middle phase inlet tube 2 are located.

[0025] The plane where the internal phase inlet tube 1 and the internal phase inlet tube 2 of the present invention are located is perpendicular to the plane where the middle phase inlet tube 1 and the middle phase inlet tube 2 are located, which can enhance the ability of the fluid to separate the two internal phase fluid flows during shearing, avoid the coalescence of the inner cores, and obtain qualified double-encapsulated microbeads.

[0026] Experiments revealed that the preparation of binuclear microspheres requires addressing issues such as the synchronous generation of the binuclear cores, precise encapsulation of the binuclear cores, and core positional offset (e.g., asymmetric distribution). The challenge in precisely encapsulating binuclear microspheres in this invention lies in the synchronization and matching of shear forces. In the microfluidic preparation of binuclear microspheres, shear force is the core physical mechanism for achieving precise droplet generation, size control, and precise encapsulation. Furthermore, shear force is closely related to the channel structure design of the microfluidic chip and the product formulation system design. This invention, through precise design of the microfluidic chip structure, ensures the generation of high-quality binuclear microspheres. Taking the preparation of W1+W2 / O / W droplets as an example: First, the shearing frequencies of the two inner phase fluids are completely synchronized: During the first shearing in shearing section 1 (intermediate phase shearing the two inner phases), it must be ensured that two independent, uniformly sized inner phase droplets W1 / O / W and W2 / O / W are generated in the chip in a highly synchronized manner within a very short time interval; Second, during the second shearing in shearing section 2 (external phase shearing the intermediate phase), the shearing of the external phase fluid precisely intersects with the W1 / O / W and W2 / O / W droplets, which can ensure that the intermediate phase breaks just as it encapsulates the two cores.

[0027] Preferably, the cone-tip matched three-dimensional microfluidic chip is a three-dimensional structure, printed by 3D printing technology, and the material of the cone-tip matched three-dimensional microfluidic chip is metal.

[0028] More preferably, the microfluidic chip is made of 316L stainless steel. The equipment used is a microbead / microcapsule synthesizer (Moge Microfluidics Technology Co., Ltd., a commercially available product), and the cone-tip matching three-dimensional microfluidic chip is directly installed onto this equipment.

[0029] The insulation conditions are 30-90℃, preferably 70℃.

[0030] When preparing W1+W2 / O / W type microspheres: External phase: Aqueous phase W1, an aqueous solution of one or more combinations of emulsifier, polymer, thickener, and pigment; Aqueous phase W2, an aqueous solution of one or more combinations of emulsifier, polymer, thickener, and pigment; Intermediate phase: Oil phase O, an oil of one or more combinations of solid fat, liquid oil, thickener, emulsifier, oil-soluble active ingredient, and pigment; Internal phase: Aqueous phase W3, an aqueous solution of one or more combinations of thickener, emulsifier, water-soluble active ingredient, various water-soluble carriers, and pigment.

[0031] When preparing O1+O2 / W / O type microspheres: External phase: oil phase O1, an oil containing one or more combinations of solid oil, liquid oil, thickener, emulsifier, and pigment; oil phase O2, an oil containing one or more combinations of solid oil, liquid oil, thickener, emulsifier, and pigment; Intermediate phase: aqueous phase W, an aqueous solution containing one or more combinations of thickener, emulsifier, water-soluble active ingredient, various water-soluble carriers, and pigment; Internal phase: oil phase O3, an oil containing one or more combinations of solid oil, liquid oil, thickener, emulsifier, oil-soluble active ingredient, and pigment.

[0032] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows:

[0033] 1. This invention provides a dual-core microbead production process based on a cone-tip matched three-dimensional microfluidic chip. By precisely designing the chip structure, 3D printing technology is used to process a 3D microfluidic chip that can precisely encapsulate two layers of microbeads, enabling continuous and stable production of dual-core microbeads and achieving rapid and precise control of the microbead particle size.

[0034] 2. This invention can prepare dual-core microbeads that can achieve a combination design of outer and inner layer functions, improve the visual effect of microbead products, and enrich the functions of microbead products; based on the dual-core structure of microbeads, a combination design of appearance color and practical function can be achieved, enriching the functions of microbead products, and providing a new type of functional microbead product;

[0035] 3. The core and shell of the microbeads of this invention can be water-soluble polymers and small molecules, such as PVA, xanthan gum, carbomer, sodium hyaluronate, sodium chloride, etc.; or they can be oil-soluble polymers and small molecules, such as hydrogenated poly(C6-20 olefins) (and) HDI / trimethylolhexyl lactone crosslinked polymers, hydrogenated castor oil and IPDI copolymers, etc. This broadens the range of binuclear microbeads.

[0036] 4. The dual-core microbeads of the present invention are completely independent. Through the encapsulation and protection of the solidified shell, the two cores are physically isolated in space. They are not affected by ambient temperature, pH, or ionic strength, and have long-term stability. Compared with the existing technology, which mainly relies on unclear physical or chemical interactions between materials, they are more reliable.

[0037] 5. The diameter of the microspheres in this invention is controlled by the fluid flow rates of the inner phase, intermediate phase and outer phase, which gives the production process extremely high dynamic adjustment capability. It can quickly respond to the production needs of microspheres of different particle sizes on the same chip platform, ensuring the continuity, stability and ease of operation of the process. Attached Figure Description

[0038] Figure 1 This is a schematic diagram of the manufacturing process for dual-core microbeads based on a cone-tip matched three-dimensional microfluidic chip;

[0039] Figure 2 A schematic diagram of the shearing process for the production of dual-core microbeads based on a cone-tip matched three-dimensional microfluidic chip;

[0040] Figure 3 A cross-sectional schematic diagram of a three-dimensional microfluidic chip for matching a cone tip;

[0041] Figure 4 A physical image of a 3D microfluidic chip for matching the cone tip;

[0042] Figure 5 Microscopic images of the binuclear microbeads prepared in Example 1;

[0043] Figure 6 The images show microscopic images of the binuclear microbeads prepared in Comparative Example 1. The top image shows the initial internal phase before aggregation, and the bottom image shows the later internal phase after complete aggregation.

[0044] Figure 7 Microscopic images of the binuclear microbeads prepared for Comparative Example 2;

[0045] Figure 8 Microscopic image of the binuclear microbeads prepared for Comparative Example 3;

[0046] Figure 9 Microscopic images of the binuclear microbeads prepared for Comparative Example 4;

[0047] Figure 10 Microscopic images of the binuclear microbeads prepared for Comparative Example 5;

[0048] Figure 11 Microscopic images of the binuclear microbeads prepared for Comparative Example 6;

[0049] Figure 12 Microscopic images of the dual-core microbeads prepared in Example 2;

[0050] Figure 13 Microscopic images of the binuclear microbeads prepared in Example 3;

[0051] Figure 14 Microscopic images of the dual-core microbeads prepared in Example 4;

[0052] Figure 15 Microscopic images of the dual-core microbeads prepared in Example 5;

[0053] Figure 16 Microscopic images of the binuclear microbeads prepared in Example 6.

[0054] In the figure, (1) Inner phase inlet pipe 1; (2) Inner phase inlet pipe 2; (3) Intermediate phase inlet pipe 1; (4) Intermediate phase inlet pipe 2; (5) Outer phase inlet pipe 1; (6) Outer phase inlet pipe 2; (7) Outlet pipe; (8) Shear section 1; (9) Shear section 2. Detailed Implementation

[0055] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0056] Please see Figure 1-4 The dual-core microbead manufacturing process based on a cone-tip matched three-dimensional microfluidic chip includes the following steps:

[0057] (1) Raw material transportation: The required materials are transported to the cone tip matching three-dimensional microfluidic chip through different pipelines under heat preservation conditions;

[0058] (2) Material shearing: The required material is sheared within the cone-tip matched three-dimensional microfluidic chip to obtain a dual-core droplet; the cone-tip matched three-dimensional microfluidic chip includes an inner phase inlet pipe 1 (1), an inner phase inlet pipe 2 (2), an intermediate phase inlet pipe 1 (3), an intermediate phase inlet pipe 2 (4), an outer phase inlet pipe 1 (5), an outer phase inlet pipe 2 (6), a shearing section 1 (8), a shearing section 2 (9), and an outlet pipe (7). The shearing section 1 (8) is connected to the inner phase inlet pipe 1 (1), the inner phase inlet pipe 2 (2), the intermediate phase inlet pipe 1 (3), and the intermediate phase inlet pipe 2 (4). The shearing section 2 (9) is connected to the outer phase inlet pipe 1 (5), the outer phase inlet pipe 2 (6), and the outlet pipe (7). The inner phase 1 in the inner phase inlet pipe 1 (1) and the inner phase 2 in the inner phase inlet pipe 2 (2) are sheared by the intermediate phase inlet pipe 1 (3). Intermediate phase 1 and intermediate phase 2 in intermediate phase inlet pipe 2 (4) are sheared to obtain inner phase droplet 1 and inner phase droplet 2. Inner phase droplet 1 and inner phase droplet 2 continue to flow and are finally sheared by outer phase 1 in outer phase inlet pipe 1 (5) and outer phase 2 in outer phase inlet pipe 2 (6) to obtain binucleate droplets. The inner diameter of inner phase inlet pipe 1 (1) and inner phase inlet pipe 2 (2) is a, the interval between adjacent parts of the outlet of inner phase inlet pipe 1 (1) and inner phase inlet pipe 2 (2) is b, the included angle between adjacent parts of the outlet of inner phase inlet pipe 1 (1) and inner phase inlet pipe 2 (2) is Ɵ, the shearing part 1 (8) is a frustum structure, the inner diameter of the outlet of shearing part 1 (8) is d, the inner diameter of the outlet of shearing part 2 (9) is D, and the horizontal distance between the plane where the outlet of inner phase inlet pipe 1 (1) and inner phase inlet pipe 2 (2) is located and the outlet of shearing part 2 (9) is m.

[0059] (3) Cooling and molding: After cooling the binuclear droplets, a cooling medium is used to cool and solidify them to form binuclear microbeads;

[0060] (4) Product collection: The dual-core microbead particles and the cooling medium are separated to obtain microbeads.

[0061] The following examples and comparative examples demonstrate the production of different types of microbeads using the above-described production process. The equipment used is a microbead / microcapsule synthesizer (Morgan Microfluidics Technology Co., Ltd., a commercially available product), and the cone-tip matching three-dimensional microfluidic chip is directly mounted onto this equipment.

[0062] Example 1

[0063] In this embodiment, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases, and octanoic acid-capric triglyceride (GTCC) liquid oil was used for thickening. The chip channel parameters were adjusted, where b>a, 15°≤θ≤20°, d≤D / 2, and 1.5cm≤m≤2.1cm.

[0064] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=1.5mm, D=4mm, and m=1.51cm.

[0065] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA (polyvinyl alcohol) and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer (isophorone diisocyanate copolymer, model: Dachanghuajia Estogel M) and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.01% brilliant blue pigment to external phase 1; Internal phase 2: Prepared by adding 0.1% sunset yellow pigment to external phase 2.

[0066] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the three-dimensional microfluidic chip for material shearing to obtain droplets.

[0067] Cooling and collection: The droplets are added to cold water at 10°C. After cooling, the solidified microbeads are retrieved to obtain a blue-green dual-core microbead product.

[0068] pass Figure 5 It can be seen that the dual-core microbeads prepared in Example 1 are of excellent quality. The transparent oil shell encapsulates two independent cores without any core aggregation. Each core retains its own color and there is no pigment leakage between the cores.

[0069] Comparative Example 1

[0070] In this comparative example, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases, and GTCC liquid grease was used for thickening. The chip channel parameters were adjusted, where b=a, 15°≤θ≤20°, d≤D / 2, and 1.5cm≤m≤2.1cm.

[0071] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.5mm, θ=20°, d=1.5mm, D=4mm, and m=1.5cm.

[0072] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.01% brilliant blue pigment to external phase 1; Internal phase 2: Prepared by adding 0.1% sunset yellow pigment to external phase 2.

[0073] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing.

[0074] pass Figure 6 It can be seen that because the inner phase outlets are too close, the W1 / O droplets and W2 / O droplets rapidly coalesce, making it impossible to obtain the binucleated microbead product. The two cores in the middle are two water droplets of different colors, and their final state can only be either separated or aggregated. Figure 6 The image above shows the intermediate state, which is a semi-circle plus a semi-circle state. It exists for a very short time. After the two water nuclei gather, you will initially see a clear half-and-half color structure. As matter is exchanged, the color will be uniformly mixed and present the same color, eventually showing the state shown in the image below.

[0075] Comparative Example 2

[0076] In this comparative example, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases, and GTCC liquid grease was used for thickening. The chip channel parameters were adjusted, where b>a, θ>20°, d≤D / 2, and 1.5cm≤m≤2.1cm.

[0077] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=21°, d=1.5mm, D=4mm, and m=1.5cm.

[0078] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.01% brilliant blue pigment to external phase 1; Internal phase 2: Prepared by adding 0.1% carmine red pigment to external phase 2.

[0079] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing.

[0080] pass Figure 7 It can be seen that, due to the large angle between the internal phases, W1 / O and W2 / O cannot be encapsulated at the same time, forming two types of microbead products: W1 / O / W and W2 / O / W.

[0081] Comparative Example 3

[0082] In this comparative example, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases, and GTCC liquid grease was used for thickening. The chip channel parameters were adjusted, where b>a, θ<15°, d≤D / 2, and 1.5cm≤m≤2.1cm.

[0083] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=14°, d=1.5mm, D=4mm, and m=1.5cm.

[0084] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.01% brilliant blue pigment to external phase 1; Internal phase 2: Prepared by adding 0.1% carmine red pigment to external phase 2.

[0085] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing.

[0086] pass Figure 8It can be seen that, due to the small angle between the inner phases, W1 and W2 quickly converge into one stream at the inner phase outlet, making it impossible to obtain the dual-core microbead product. Figure 8 The unpolymerized state of the internal phase is an intermediate state. Eventually, the colors will be uniformly mixed to present the same color, which is an internal phase polymerization.

[0087] Comparative Example 4

[0088] In this comparative example, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases, and GTCC liquid grease was used for thickening. The chip channel parameters were adjusted, where b>a, 15°≤θ≤20°, d>D / 2, and 1.5cm≤m≤2.1cm.

[0089] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=2.2mm, D=4mm, and m=1.5cm.

[0090] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.01% brilliant blue pigment to external phase 1; Internal phase 2: Prepared by adding 0.1% sunset yellow pigment to external phase 2.

[0091] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing.

[0092] pass Figure 9 It can be seen that because the inner diameter of the mesophase cone is too large, the shearing effect of the outer phase is weakened, and the mesophase cannot be sheared to obtain the binucleate microsphere product.

[0093] Comparative Example 5

[0094] In this comparative example, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases, and GTCC liquid grease was used for thickening. The chip channel parameters were adjusted, where b>a, 15°≤θ≤20°, d≤D / 2, and m<1.5cm.

[0095] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=1.5mm, D=4mm, and m=1.4cm.

[0096] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.1% sunset yellow pigment to the external phase solution; Internal phase 2: Prepared by adding 0.1% grape purple pigment to the external phase solution.

[0097] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing.

[0098] pass Figure 10 It can be seen that because the inner phase is too close to the cone opening, the inner phase pipeline touches the wall, preventing the inner phase from being sheared by the intermediate phase.

[0099] Comparative Example 6

[0100] In this comparative example, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases, and GTCC liquid grease was used for thickening. The chip channel parameters were adjusted, where b>a, 15°≤θ≤20°, d≤D / 2, and m>2.1cm.

[0101] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=1.5mm, D=4mm, and m=2.2cm.

[0102] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.1% copper chlorophyll solution to external phase 1; Internal phase 2: Prepared by adding 0.1% carmine red pigment to external phase 2.

[0103] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing.

[0104] pass Figure 11It can be seen that the horizontal distance between the plane where the outlets of the inner phase inlet pipe 1 and the inner phase inlet pipe 2 are located and the outlet of the shear section 2 is too long, which makes W1 / O and W2 / O easy to aggregate in the intermediate phase.

[0105] Example 2

[0106] In this embodiment, W1+W2 / O / W type microspheres were prepared, where W1 and W2 are ordinary internal aqueous phases and GTCC liquid grease is used for thickening.

[0107] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=15°, d=1.4mm, D=3mm, and m=1.5cm.

[0108] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.1% carmine red pigment to external phase 1; Internal phase 2: Prepared by adding 0.1% sunset yellow pigment to external phase 1.

[0109] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 50 mL / min; intermediate phase 1 and intermediate phase 2: 6 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing to obtain droplets.

[0110] Cooling and Collection: The droplets were added to cold water at 10°C. After cooling, the solidified microbeads were collected to obtain the pink orange oil-in-water microbead product. Figure 12 It can be seen that the prepared binuclear microbeads are of excellent quality, the encapsulated core droplets do not aggregate, each droplet is independent, and there is no intermingling of substances.

[0111] Example 3

[0112] In this embodiment, W1+W2 / O / W type microspheres were prepared, where W1 and W2 were internal aqueous phases with added pearlescent powder, and GTCC liquid grease was used for thickening.

[0113] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=18°, d=1.5mm, D=3mm, and m=2.0cm.

[0114] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir and keep warm at 80℃ for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir and keep warm at 70℃ for later use; Internal phase 1: Prepare an aqueous solution of 0.1% ZEN by mass, stir evenly at room temperature, and then add 5% blue pearlescent powder by mass; Internal phase 2: Prepare an aqueous solution of 0.1% ZEN by mass, stir evenly at room temperature, and then add 5% purple pearlescent powder by mass; Material shearing: Flow rate settings: External phase 1 and external phase 2: 100 mL / min; Intermediate phase 1 and intermediate phase 2: 10 mL / min; Internal phase 1 and internal phase 2: 1.2 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing to obtain droplets.

[0115] Cooling and Collection: The droplets were added to cold water at 10°C. After cooling, the solidified microspheres were retrieved to obtain the blue-violet pearlescent dual-core microsphere product. Figure 13 It can be seen that the prepared binuclear microbeads are of excellent quality, the encapsulated core droplets do not aggregate, each droplet is independent, and there is no intermingling of substances.

[0116] Example 4

[0117] In this embodiment, W1+W2 / O / W type microspheres were prepared, where W1 is a normal internal aqueous phase, W2 is an internal aqueous phase with added pearlescent powder, and GTCC liquid grease is used for thickening.

[0118] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=18°, d=1.5mm, D=3mm, and m=2.1cm.

[0119] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Add 0.1% lycopene to external phase 1; Internal phase 2: Prepare an aqueous solution of 0.1% ZEN by mass, stir evenly at room temperature and then add 5% blue pearlescent powder by mass.

[0120] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 6 mL / min; inner phase: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing to obtain droplets.

[0121] Cooling and Collection: The droplets were added to cold water at 10°C. After cooling, the solidified microbeads were retrieved to obtain the powder-water dual-core microbead product. Figure 14 It can be seen that the prepared binuclear microbeads are of excellent quality, the encapsulated core droplets do not aggregate, each droplet is independent, and there is no intermingling of substances.

[0122] Example 5

[0123] In this embodiment, W1+W2 / O / W type microspheres were prepared. W1 and W2 are ordinary internal aqueous phases, and GTCC liquid grease is used for thickening and flow rate adjustment.

[0124] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=1.5mm, D=3mm, and m=2.1cm.

[0125] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.1% copper chlorophyll solution to external phase 1; Internal phase 2: Prepared by adding 0.1% lemon yellow pigment to external phase 2.

[0126] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 30 mL / min; intermediate phase 1 and intermediate phase 2: 5 mL / min; inner phase 1 and inner phase 2: 0.3 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing to obtain droplets.

[0127] Cooling and Collection: Droplets were added to cold water at 10°C. After cooling, the solidified microspheres were retrieved, yielding orange-green binuclear microspheres with an average diameter of 3.0 mm. Figure 15 It can be seen that the prepared binuclear microbeads are of excellent quality, the encapsulated core droplets do not aggregate, each droplet is independent, and there is no intermingling of substances.

[0128] Example 6

[0129] In this embodiment, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases. GTCC liquid grease was used for thickening, and the flow rate was adjusted to prepare small-diameter microspheres.

[0130] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=1.5mm, D=3mm, and m=2.1cm.

[0131] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepared by adding 0.1% copper chlorophyll solution to external phase 1; Internal phase 2: Prepared by adding 0.1% lemon yellow pigment to external phase 2.

[0132] Material shearing: Flow rate settings: outer phase 1 and outer phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; inner phase 1 and inner phase 2: 0.6 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing to obtain droplets.

[0133] Cooling and Collection: The droplets were added to cold water at 10°C. After cooling, the solidified microspheres were retrieved, yielding a microsphere product with an average particle size of 2.0 mm. Figure 16 It can be seen that the prepared binuclear microbeads are of excellent quality, the encapsulated core droplets do not aggregate, each droplet is independent, and there is no intermingling of substances.

[0134] Example 7

[0135] In this embodiment, O1+O2 / W / O type microbeads were prepared, where O1 and O2 were GTCC and W was an agar aqueous solution.

[0136] Raw material preparation: External phase 1 and external phase 2: Prepare a white oil dispersion of 5% castor oil / IPDI copolymer by mass, stir and keep warm at 70℃ for later use; Intermediate phase 1 and intermediate phase 2: Prepare an aqueous solution of 0.3% sodium alginate, 0.2% hydroxymethyl cellulose, 2.0% agar, and 0.5% phenoxyethanol by mass, stir and keep warm at 70℃ for later use; Internal phase 1: Prepare a GTCC solution of 0.1% purple oil-soluble pigment by mass; Internal phase 2: Prepare a GTCC solution of 0.1% red oil-soluble pigment by mass; Flow rate settings: External phase 1 and external phase 2: 50 mL / min; Intermediate phase 1 and intermediate phase 2: 6 mL / min; Internal phase: 2 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing to obtain droplets.

[0137] Cooling and Collection: The droplets were added to cold water at 10°C. After cooling, the solidified microspheres were retrieved to obtain the oil-in-water binuclear microsphere product. The binuclear microsphere product prepared in this embodiment has excellent quality; the encapsulated core droplets do not aggregate, each droplet is independent, and there is no intermingling of substances.

[0138] Example 8

[0139] In this embodiment, W1+W2 / O / W type microspheres were prepared. W1 and W2 were ordinary internal aqueous phases, GTCC liquid oil was used for thickening, and the microspheres were added to the emulsion.

[0140] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=1.5mm, D=3mm, and m=2.1cm.

[0141] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepare an aqueous solution of 0.1% xanthan gum and 0.1% carmine by mass, stir at room temperature and keep warm for later use; Internal phase 2: Prepare an aqueous solution of 0.01% sodium hyaluronate and 0.01% brilliant blue by mass; Ceramide moisturizing and repairing emulsion: Prepare an emulsion of 2.5% MONTANOVL, 0.8% A16-18 alcohol, 0.5% beeswax, 2% DC200 / 350, 2% jojoba oil, 3% squalane, and 2% 36% ceramide by mass. 6. A solution of 1% SB-45, 0.3% EG, 0.1% propyl ester, 0.1% BHT, 0.1% 940, 0.05% EDTA-2NA, 3% glycerol, 0.1% xanthan gum, 0.03% HA-TP, 0.1% SG, 0.1% TEA, 0.2% methyl ester, 0.4% phenoxyethanol, 1% betaine, 0.05% ethylhexylglycerin, 5% MG liposomes, 0.02% AYA03969, and the balance water was homogenized and emulsified for later use. Material shearing: Flow rate settings: external phase 1 and external phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; internal phase 1 and internal phase 2: 0.6 mL / min. After setting the flow rate, the feed pump was turned on to deliver each phase to the shearing section for material shearing to obtain droplets.

[0142] Cooling and Collection: Add the droplets to cold water at 10°C. After cooling, scoop up the solidified microbeads, wash them, and add them to the ceramide moisturizing and repairing emulsion. Stir well to evenly disperse the microbeads in the emulsion to obtain a moisturizing microbead emulsion product.

[0143] Example 9

[0144] In this embodiment, W1+W2 / O / W type microbeads were prepared, where W1 and W2 are ordinary internal aqueous phases, GTCC liquid oil is used for thickening, and the microbeads are added to the essence.

[0145] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=1.5mm, D=3mm, and m=2.1cm.

[0146] Raw material preparation: External phase 1 and external phase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir at 80℃ and keep warm for later use; Intermediate phase 1 and intermediate phase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir at 70℃ and keep warm for later use; Internal phase 1: Prepare an aqueous solution of 0.1% xanthan gum and 0.1% carmine by mass, stir and keep warm for later use; Internal phase 2: Prepare an aqueous solution of 0.01% sodium hyaluronate and 0.01% brilliant blue by mass; Ceramide moisturizing and repairing essence: Prepare 0.1% allantoin... A solution containing 0.3% xanthan gum, 0.03% HA-TP, 2% glycerol, 3% propylene glycol, 0.05% EDTA-2NA, 0.15% methyl ester, 1% trehalose, 0.4% phenoxyethanol, 0.01% AYA03969, 0.05% CO-40, 1% MG liposomes, and the remainder water was prepared and stirred well. Material shearing: Flow rate settings: external phase 1 and external phase 2: 80 mL / min; intermediate phase 1 and intermediate phase 2: 7 mL / min; internal phase 1 and internal phase 2: 0.6 mL / min. After setting the flow rates, the feed pump was turned on to deliver each phase to the shearing section for material shearing to obtain droplets.

[0147] Cooling and Collection: Add the droplets to cold water at 10°C. After cooling, scoop up the solidified microbeads, wash them, and add them to the ceramide moisturizing and repairing essence. Stir well to evenly disperse the microbeads in the essence to obtain the moisturizing and repairing microbead essence product.

[0148] Example 10

[0149] In this embodiment, W1+W2 / O / W type microbeads were prepared. W1 and W2 were ordinary internal aqueous phases, GTCC liquid fat was used for thickening, and the microbeads were added to milk.

[0150] Chip printing: 3D microfluidic chips are fabricated using 316L stainless steel, with a=0.5mm, b=0.8mm, θ=20°, d=1.5mm, D=3mm, and m=2.1cm.

[0151] Raw material preparation: Mesophase 1 and mesophase 2: Prepare an aqueous solution of 5% PVA and 1% Tween 80 by mass, stir and keep warm at 80℃ for later use; Mesophase 1 and mesophase 2: Prepare a GTCC solution of 12% castor oil / IPDI copolymer and 1% Span 80 by mass, stir and keep warm at 70℃ for later use; Inner phase 1 and inner phase 2: Same as outer phase 1; Milk preparation: Pasteurize and ultra-high temperature sterilize raw milk for later use; Material shearing: Flow rate settings: Outer phase 1 and outer phase 2: 60 mL / min; Mesophase 1 and mesophase 2: 6 mL / min; Inner phase 1 and inner phase 2: 0.4 mL / min. After setting the flow rate, turn on the feed pump to deliver each phase to the shearing section for material shearing to obtain droplets.

[0152] Cooling and collection: Add the droplets to cold water at 10°C. After cooling, scoop up the solidified microbeads, wash them, and add them to milk to obtain milk containing microbeads.

[0153] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A dual-core microbead manufacturing process based on a cone-tip matched three-dimensional microfluidic chip, characterized in that, It includes the following steps: (1) Raw material transportation: The required materials are respectively transported to the tip-matched three-dimensional microfluidic chip through different pipelines under heat preservation conditions; (2) Logistics shearing: The required materials are sheared inside the tip-matched three-dimensional microfluidic chip to obtain double-core droplets; the tip-matched three-dimensional microfluidic chip includes an inner phase inlet pipe 1, an inner phase inlet pipe 2, an intermediate phase inlet pipe 1, an intermediate phase inlet pipe 2, an outer phase inlet pipe 1, an outer phase inlet pipe 2, a shearing part 1, a shearing part 2 and an outlet pipe. The shearing part 1 is connected to the inner phase inlet pipe 1, the inner phase inlet pipe 2, the intermediate phase inlet pipe 1 and the intermediate phase inlet pipe 2. The shearing part 2 is connected to the outer phase inlet pipe 1, the outer phase inlet pipe 2 and the outlet pipe; (3) Cooling and forming: After the double-core droplets are cooled down, a cooling medium is used for cooling and solidification to form double-core microbead particles; (4) Product collection: The double-core microbead particles and the cooling medium are separated to obtain double-core microbeads. The inner diameters of the inner phase inlet pipe 1 and the inner phase inlet pipe 2 are a, and the interval between the adjacent parts of the outlets of the inner phase inlet pipe 1 and the inner phase inlet pipe 2 is b, where a < b ≤ 2a. The included angle between the adjacent parts of the outlets of the inner phase inlet pipe 1 and the inner phase inlet pipe 2 is θ, where 15° < θ < 20°. The shearing part 1 is a frustum-shaped structure, the inner diameter of the outlet of the shearing part 1 is d, the inner diameter of the outlet of the shearing part 2 is D, and the horizontal distance length between the plane where the outlets of the inner phase inlet pipe 1 and the inner phase inlet pipe 2 are located and the outlet of the shearing part 2 is m. d ≤ D / 2; 1.5 cm ≤ m ≤ 2.1 cm.

2. The dual-core microbead manufacturing process based on a cone-tip matched three-dimensional microfluidic chip according to claim 1, characterized in that, The flow rates of the inner phase 1 and the inner phase 2 are both ν1, the flow rates of the intermediate phase 1 and the intermediate phase 2 are both ν2, and the flow rates of the outer phase 1 and the outer phase 2 are both ν3. ν2 / ν1 ≥ 10; 4 ≤ ν3 / ν2 ≤ 30.

3. The dual-core microbead manufacturing process based on a cone-tip matched three-dimensional microfluidic chip according to claim 1, characterized in that, The plane where the inner phase inlet pipe 1 and the inner phase inlet pipe 2 are located is perpendicular to the plane where the intermediate phase inlet pipe 1 and the intermediate phase inlet pipe 2 are located.

4. The dual-core microbead manufacturing process based on a cone-tip matched three-dimensional microfluidic chip according to claim 1, characterized in that, The inner phase 1 in the inner phase inlet pipe 1 and the inner phase 2 in the inner phase inlet pipe 2 are sheared by the intermediate phase 1 in the intermediate phase inlet pipe 1 and the intermediate phase 2 in the intermediate phase inlet pipe 2 to obtain inner phase droplets 1 and inner phase droplets 2. The inner phase droplets 1 and the inner phase droplets 2 continue to flow and are finally sheared by the outer phase 1 in the outer phase inlet pipe 1 and the outer phase 2 in the outer phase inlet pipe 2 to obtain double-core droplets.

5. Application of the double-core microbead production process based on the tip-matched three-dimensional microfluidic chip according to any one of claims 1-4 in the preparation of double-core microbeads.

6. The application of the dual-core microbead production process based on a cone-tip matched three-dimensional microfluidic chip as described in claim 5 in the preparation of dual-core microbeads, characterized in that, The double-core microbeads are used in the fields of skin care products, medicine and food.

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