CN103240043B - Preparation method of monodisperse multicomponent multiple emulsion - Google Patents

Abstract

The invention relates to a method for preparing monodisperse multi-component multiple emulsions, the process steps: (1) preparing dispersed phase and continuous phase fluid; (2) preparing monodisperse multi-component multiple emulsion droplets: the step (1) The prepared component fluids are injected into different droplet generators of the microfluidic device to form emulsion droplets, and the emulsion droplets formed in different droplet generators are contacted in the enlarged chamber, and the emulsion liquid formed in one droplet generator Droplets spread onto the emulsion droplets formed in another droplet generator to form multiple emulsion droplets; (3) Collect monodisperse multicomponent multiple emulsions.

Description

A kind of preparation method of monodisperse multi-component multiple emulsion

technical field

The invention belongs to the field of preparation of monodisperse multiple emulsions, in particular to a method for preparing monodisperse multi-component multiple emulsions by using microfluidic technology.

Background technique

Multiple Emulsions, also known as Emulsions of Emulsions, is a combination of oil-in-water (O/W) and water-in-oil (Water-in-Oil, W) /O) type emulsion further emulsifies the composite emulsion formed in another continuous phase. Oil droplets containing water droplets are suspended and dispersed in the water phase to form emulsions called water-in-oil-in-water (W/O/W) type double emulsions, and water droplets containing oil droplets are suspended in oil phases to form emulsions It is an oil-in-water-in-oil (O/W/O) type double emulsion, which is a three-phase system. The W/O/W type emulsion is redispersed in oil to form a water-in-oil-in-oil (W/O/W/O) type triple emulsion, and the O/W/O type emulsion is redispersed in water to form a water Oil-in-water-in-oil (O/W/O/W) triple emulsion. In the same way, four, five or even more heavy emulsions can also be formed. Multi-component multiple emulsions have a variety of complex structures that can protect the active substances embedded in them, so they are widely used in the embedding of nutrients and food additives, drug delivery systems, chemical separation, template synthesis and microreactors, etc. field.

The preparation method of the multiple emulsion reported at present has following several: (1) integral multi-step emulsification method, as utilizing mechanical agitation, colloid mill, ultrasonic wave and homogenizer etc. to realize by the difference of shearing force and oil-water two-phase interfacial tension emulsification. This method is relatively simple to operate, and can prepare multiple emulsions quickly and in large quantities, but because the shear force in the entire system is uneven, it is difficult to finely control, so the particle size distribution of multiple emulsions prepared by this method is relatively wide, and It is difficult to control the structure and size of multiple emulsions. (2) Multi-step membrane emulsification method, that is, pressurize the dispersed phase liquid to make it pass through a porous membrane with equal pore size, form micro-droplets and disperse into the continuous phase to form a primary emulsion, and use the primary emulsion as the dispersed phase, Pressurize it through a porous membrane to make a multiple emulsion. This method can prepare multiple emulsions in large quantities, and the dispersed phase of the prepared multiple emulsions is better than that prepared by the overall multi-step emulsification method, but it still cannot accurately control the internal structure of the multiple emulsions, such as the number of droplets contained. (3) The emulsification method of microfluidic technology, that is, the use of multiphase fluids to perform multiple shear emulsification in microchannels to form multiple emulsions. This method can precisely control the size and structure of multiple emulsions, and the prepared multiple emulsions have good monodispersity. However, it is difficult to prepare a multi-component emulsion with an ultra-thin wall structure. At the same time, this method requires multiple shear emulsifications in the microchannel and has poor stability.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies in the prior art and provide a method for preparing monodisperse multi-component multiple emulsions through mutual infiltration between emulsion droplets. This method can not only accurately control the size and internal structure of multiple emulsions, but also can prepare Multi-component emulsion with ultra-thin wall structure.

The preparation method of monodisperse multi-component multiple emulsion of the present invention, processing step is as follows:

(1) Preparation of dispersed phase and continuous phase fluid

Preparation of the first dispersed phase fluid: Add the water-soluble emulsifier to deionized water at normal pressure and room temperature and stir to form the first dispersed phase fluid. The mass ratio of the water-soluble emulsifier to deionized water is 0.005 to 0.01: 1;

Preparation of the second dispersed phase fluid: Add the oil-soluble emulsifier into the soybean oil at normal pressure and room temperature and stir evenly to form the second dispersed phase fluid. The amount of the oil-soluble emulsifier is 0.005-0.02g per 1ml of soybean oil ;

Preparation of the third dispersed phase fluid: under normal pressure and room temperature, n-octanol and soybean oil are uniformly mixed at a volume ratio of 1:3 to obtain a mixed solution, then an oil-soluble emulsifier is added to the mixed solution, and stirred evenly to form the third Dispersed phase fluid, the amount of the oil-soluble emulsifier is 0.005-0.02g per 1ml of the mixed solution of n-octanol and soybean oil;

Preparation of the fourth dispersed phase fluid: the same as the preparation method of the third dispersed phase fluid;

Preparation of the fifth dispersed phase fluid: the same as the preparation method of the second dispersed phase fluid;

The preparation of the 6th disperse phase fluid: under normal pressure, room temperature, photoinitiator 2-hydroxyl-2-methylpropiophenone is added ethoxylated trimethylolpropane triacrylate (its number average molecular weight Mn is 692) In, stir uniformly to form the sixth dispersed phase fluid, the volume ratio of the 2-hydroxyl-2-methylpropiophenone and ETPTA is 1:100;

Preparation of continuous phase fluid: add surfactant to simethicone oil at normal pressure and room temperature and stir evenly to form continuous phase fluid, the mass ratio of the surfactant to simethicone oil is 0.005-0.01:1;

(2) Preparation of monodisperse multi-component multiple emulsion droplets

Prepare monodisperse multicomponent multiple emulsion droplets using one of the following methods:

Method 1: Preparation of monodisperse multi-component water-in-oil-in-oil emulsion droplets

The second dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into different liquid inlets of the first single-stage droplet generator of the microfluidic device to form monodisperse oil-in-oil emulsion droplets, and at the same time, the step (1) The first dispersed phase fluid and the continuous phase fluid of preparation are respectively injected into different liquid inlets of the second single-stage droplet generator of the microfluidic device to form monodisperse water-in-oil emulsion droplets; the formed oil-in-oil emulsion The droplet and the water-in-oil emulsion droplet enter the collection tube of the microfluidic device together with the continuous phase fluid. When the oil-in-oil emulsion droplet contacts the water-in-oil emulsion droplet in the enlarged chamber of the collection tube, the oil-in-oil emulsion The oil emulsion droplet spreads onto the water-in-oil emulsion droplet to form a monodisperse multi-component water-in-oil emulsion droplet;

The flow rate (Q _B ) of the first dispersed phase fluid is 100 to 300 μL/h, the flow rate (Q _A1 ) of the second dispersed phase fluid is 20 to 80 μL/h, and the continuous phase fluid is in the first single stage The flow rate (Q _C1 ) in the droplet generator is 40-200 μL/h, and the flow rate (Q _C2 ) in the second single-stage droplet generator is 200-500 μL/h;

Method 2: Preparation of monodisperse multi-component oil-in-water-in-oil emulsion droplets

The third dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into different liquid inlets of the first single-stage droplet generator of the microfluidic device to form monodisperse oil-in-oil emulsion droplets, and at the same time, the step (1) The first dispersed phase fluid and the continuous phase fluid of preparation are injected into the different liquid inlets of the second single-stage droplet generator of microfluidic device respectively to form monodisperse water-in-oil emulsion droplet; Formed water-in-oil emulsion The droplet and the oil-in-oil emulsion droplet enter the collection tube of the microfluidic device together with the continuous phase fluid. When the water-in-oil emulsion droplet contacts the oil-in-oil emulsion droplet in the enlarged chamber of the collection tube, the oil-in-oil emulsion The water emulsion droplets promptly spread onto the oil-in-oil emulsion droplets to form monodisperse multi-component oil-in-water-in-oil emulsion droplets;

The flow rate (Q _B ) of the first dispersed phase fluid is 100 to 150 μL/h, the flow rate (Q _A2 ) of the third dispersed phase fluid is 50 to 90 μL/h, and the continuous phase fluid is in the first single stage The flow rate (Q _C1 ) in the droplet generator is 100-150 μL/h, and the flow rate (Q _C2 ) in the second single-stage droplet generator is 200-400 μL/h;

Method 3: Preparation of monodisperse multi-component oil-in-water-in-oil emulsion droplets with different oil cores

The third dispersed phase fluid, the fourth dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into different liquid inlets of the first single-stage droplet generator of the microfluidic device to form two kinds of monodisperse oil-in-oil Emulsion droplets, while injecting the first dispersed phase fluid and the continuous phase fluid prepared in step (1) into different liquid inlets of the second single-stage droplet generator of the microfluidic device to form monodisperse water-in-oil emulsion droplets; The formed two kinds of monodisperse oil-in-oil emulsion droplets and monodisperse water-in-oil emulsion droplets enter the collection tube of the microfluidic device together with the continuous phase fluid. When the droplets are contacted in the enlarged chamber of the collecting tube, the water-in-oil emulsion droplets spread onto the two kinds of oil-in-oil emulsion droplets to form monodisperse multi-component water-in-oil emulsion droplets with different oil nuclei;

The flow rate (Q _A2 ) of the third dispersed phase fluid is 20 μL/h, the flow rate (Q _A3 ) of the fourth dispersed phase fluid is 20 μL/h, and the flow rate (Q _B ) of the first dispersed phase fluid is 150 μL/h, the flow rate (Q _C1 ) of the continuous phase fluid in the first single-stage droplet generator is 200 μL/h, and the flow rate (Q _C2 ) in the second single-stage droplet generator is 400 μL/h ;

Or use the following method to prepare monodisperse multi-component oil-in-water-in-oil different oil-core emulsion droplets:

The fourth dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into different liquid inlets of the single-stage droplet generator of the microfluidic device to form oil-in-oil emulsion droplets, and at the same time, the step (1) is prepared The third dispersed phase fluid is used as the internal phase, the first dispersed phase fluid is used as the intermediate phase, and the continuous phase fluid is used as the external phase, respectively injected into different liquid inlets of the two-stage droplet generator of the microfluidic device to form oil-in-water-in-oil emulsion droplets The formed oil-in-water-in-oil emulsion droplet and oil-in-oil emulsion droplet enter the collection tube of the microfluidic device together with the continuous phase fluid, when the oil-in-water-in-oil emulsion droplet and the oil-in-oil emulsion droplet are in the The water layer of the oil-in-water-in-oil emulsion droplet spreads on the oil-in-oil emulsion droplet to form a monodisperse multi-component oil-in-water-in-oil emulsion droplet of different oil nuclei;

The flow rate (Q _B ) of the first dispersed phase fluid is 150 μL/h, the flow rate (Q _A2 ) of the third dispersed phase fluid is 150 μL/h, and the flow rate (Q _A3 ) of the fourth dispersed phase fluid is 50-200 μL/h, the flow rate (Q _C4 ) of the continuous phase fluid in the single-stage droplet generator is 100-300 μL/h, and the flow rate (Q _C3 ) in the two-stage droplet generator is 300 μL/h ;

Method 4: Preparation of monodisperse multi-component oil-in-oil-in-water-in-oil emulsion droplets

The fifth dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into different liquid inlets of the single-stage droplet generator of the microfluidic device to form oil-in-oil emulsion droplets, and at the same time, the step (1) is prepared The third dispersed phase fluid is used as the internal phase, the first dispersed phase fluid is used as the intermediate phase, and the continuous phase fluid is used as the external phase, respectively injected into different liquid inlets of the two-stage droplet generator of the microfluidic device to form oil-in-water-in-oil emulsion droplets The formed oil-in-water-in-oil emulsion droplet and oil-in-oil emulsion droplet enter the collection pipe of the microfluidic device together with the continuous phase fluid, when the oil-in-oil emulsion droplet and the oil-in-water-in-oil emulsion droplet are in The oil-in-oil emulsion droplets are spread on the oil-in-water-in-oil emulsion droplets to form monodisperse multi-component oil-in-oil-in-water-in-oil emulsion droplets;

The flow rate (Q _B ) of the first dispersed phase fluid is 100-150 μL/h, the flow rate (Q _A2 ) of the third dispersed phase fluid is 150 μL/h, and the flow rate (Q _A4 ) is 150-200 μL/h, the flow rate (Q _C4 ) of the continuous phase fluid in the single-stage droplet generator is 200-220 μL/h, and the flow rate (Q _C3 ) in the two-stage droplet generator is 300 ~500μL/h;

(3) Collect monodisperse multi-component multiple emulsions

The monodisperse multicomponent multiple emulsion droplets formed in step (2) together with the continuous phase are introduced into the collection container through the output pipe of the microfluidic device, and a corresponding type of monodisperse multicomponent multiple emulsion is obtained.

In the above method, the water-soluble emulsifier is sodium lauryl sulfate or an addition polymer of polypropylene glycol and ethylene oxide.

In the above method, the oil-soluble emulsifier is glycerol polyricinoleate or a condensation product of alkylphenol and ethylene oxide.

In the above method, the surfactant is a mixture (DowCorning) of trimethylsiloxane and cyclomethicone, and the volume ratio of trimethylsiloxane to cyclomethicone is 1:1 .

In the above method, the fourth dispersed-phase fluid and the fifth dispersed-phase fluid described in the step can also contain dyes, the effect of the dyes is to dye the droplets, and the amount added is limited for the convenience of observation, and various soluble liquids can be used Dye from soybean oil, preferably F Red300.

The outer diameter of the emulsion droplets in the monodisperse multi-component multiple emulsion prepared by the above method is 100-500 μm.

The preparation method of the monodisperse multi-component multiple emulsion of the present invention is a microfluidic technology emulsification-infiltration method, and the formation of multiple emulsions is based on the principle of mutual infiltration between two or more emulsion droplets: monodisperse multi-component double emulsion See Figure 1 for a schematic diagram of the formation of the immiscible first emulsion droplet 1 and the second emulsion droplet 2 dispersed in another immiscible continuous phase fluid 3. When the spreading coefficient S ₁ >0, the first The emulsion droplet 1 will spread to the second emulsion droplet 2 to form a 2/1/3 type emulsion; when the spreading coefficient S ₂ >0, the second emulsion droplet 2 will spread to the first emulsion droplet 1 Form 1/2/3 type emulsion; spreading coefficient S ₁ =γ ₂₃ -(α ₁ ·γ ₁₃ +γ ₁₂ ), S ₂ =γ ₁₃ -(α ₂ ·γ ₂₃ +γ ₁₂ ), γ _ij is phase i and the interfacial tension between phase j (i≠j=1,2,3), ${\mathrm{\α}}_1={[1+{\left(\frac{R_1}{R_2}\right)}^3]}^{\frac{2}{3}}-{\left(\frac{R_1}{R_2}\right)}^2,{\mathrm{\α}}_2={[1+{\left(\frac{R_2}{R_1}\right)}^3]}^{\frac{2}{3}}-{\left(\frac{R_2}{R_1}\right)}^2,$ _R1 and _R2 are the radii of the first emulsion droplet 1 and the second emulsion droplet 2, respectively. In the present invention, the schematic diagram of the formation of monodisperse multi-component double and triple emulsions is shown in FIG. 2 . Therefore, for any three immiscible fluids, as long as the interfacial tension between the three phases is properly adjusted, monodisperse multi-component multiple emulsions can also be prepared according to the principle of mutual infiltration between emulsion droplets.

According to the present invention, various types of microfluidic devices can be used, such as PDMS devices and glass capillary devices, etc., and the used microfluidic devices have two droplet generators and a common collection tube for droplet contact; A droplet generator prepares two different emulsion droplets, and the emulsion droplets flow through a common collection pipe, and realize mutual infiltration in the collection pipe to prepare more complex emulsions; preferably use a microfluidic device with the following structure: the microfluidic device Including slide glass, upper cover glass, lower cover glass, and injection needle; the number of lower cover glass is at least 7 pieces, and each lower cover glass is fixed on the glass slide at a certain interval to form a microfluidic channel that communicates with each other. The upper cover glass covers the micro flow channel formed by the lower cover glass and is fixed on the lower cover glass. The liquid inlets of the micro flow channel are six or eight, and the collecting tube is provided with an enlarged chamber. There is one liquid outlet; the number of injection needles is the same as the number of microfluidic channel liquid inlets, which are respectively fixed at the liquid inlets of the microfluidic channels, and the outlet tubes of the microfluidic channels are fixed with output tubes (the microfluidic For the construction method of the device, refer to CN102626602A).

The structure of the microfluidic device with two single-stage droplet generators used in the present invention is shown in Figure 3, and the schematic diagrams of the microfluidic channels and the spread of emulsion droplets in the microfluidic channels are shown in Figures 4 to 6. The first microfluidic Road and the second microfluidic channel constitute the first single-stage droplet generator, and the third microfluidic channel and the fourth microfluidic channel constitute the second single-stage droplet generator; what the present invention adopts has a two-stage droplet generator The structure of the microfluidic device with a single-stage droplet generator is shown in Figure 7, and the schematic diagrams of the spreading of emulsion droplets in its microfluidic channel and microfluidic channel are shown in Figure 8 and Figure 9, the fifth microfluidic channel, the first microfluidic channel The six microfluidic channels and the seventh microfluidic channel constitute a two-stage droplet generator, and the eighth microfluidic channel and the ninth microfluidic channel constitute a single-stage droplet generator.

The present invention has the following beneficial effects:

1. The present invention adopts microfluidic technology emulsification-infiltration method to prepare monodisperse multi-component multiple emulsions, which provides a new method for the preparation of monodisperse multi-component multiple emulsions.

2. The method of the present invention can not only accurately control the internal structure and size of the multiple emulsion, but also prepare a multi-component emulsion with an ultra-thin wall structure. In principle, the wall thickness of the multiple emulsion can be a single molecule thickness of.

3. The multiple emulsions prepared by the method of the present invention have good monodispersity, so the method can be used to prepare complex multi-component drugs or synergistic controlled release systems of active substances.

4. The method of the present invention is simple to operate, easy to control and adjust, and can be realized by using conventional equipment, which saves costs and is easy to realize industrial production.

Description of drawings

Fig. 1 is the formation schematic diagram of monodisperse multi-component double emulsion in the method for the present invention;

Fig. 2 is the formation schematic diagram of monodisperse multicomponent double and triple emulsion in the method for the present invention;

Fig. 3 is the structural representation of the microfluidic device that the method for the present invention adopts has two single-stage droplet generators;

4 is a schematic diagram of the microfluidic channel of the microfluidic device described in FIG. 3 and the oil-in-oil emulsion droplet spreading on the water-in-oil emulsion droplet in the microfluidic channel;

Fig. 5 is a microfluidic channel of the microfluidic device described in Fig. 3 and a schematic diagram of the water-in-oil emulsion droplet spreading on the oil-in-oil emulsion droplet in the microfluidic channel;

6 is a schematic diagram of the microfluidic channel of the microfluidic device described in FIG. 3 and the water-in-oil emulsion droplets in the microfluidic channel spreading to different oil-in-oil emulsion droplets at the same time;

Fig. 7 is a structural schematic diagram of a microfluidic device with a two-stage droplet generator and a single-stage droplet generator used in the method of the present invention;

8 is a schematic diagram of the microfluidic channel of the microfluidic device described in FIG. 7 and the oil-in-water-in-oil emulsion droplet spreading on the oil-in-oil emulsion droplet in the microfluidic channel;

Fig. 9 is a schematic diagram of the microfluidic channel of the microfluidic device described in Fig. 7 and the oil-in-oil emulsion droplet spreading on the oil-in-water-in-oil emulsion droplet in the microfluidic channel;

Fig. 10 is a high-speed camera photo of the process of spreading the oil-in-oil emulsion droplet to the water-in-oil emulsion droplet to form a monodisperse multi-component W/O/O emulsion droplet in Embodiment 1 of Example 1;

Fig. 11 is a high-speed camera photo of the oil-in-oil emulsion droplet spreading on the water-in-oil emulsion droplet to form a monodisperse multi-component W/O/O emulsion droplet process in Embodiment 2 of Example 1;

Fig. 12 is a high-speed camera photo of the process of spreading the oil-in-oil emulsion droplet to the water-in-oil emulsion droplet to form a monodisperse multi-component W/O/O emulsion droplet in Embodiment 3 of Example 1;

Figure 13 is an optical microscope photo of the monodisperse multi-component W/O/O emulsion prepared in Embodiment 1 of Example 1;

Fig. 14 is the high-speed camera photo of the monodisperse multi-component water-in-oil emulsion droplet process of the single-core monodisperse multi-component water-in-oil emulsion droplet that is completely spread on the water-in-oil emulsion droplet in the embodiment 1 of embodiment 2;

Fig. 15 is the high-speed camera photograph of the monodisperse multicomponent water-in-oil emulsion droplet process of the monodisperse multi-component oil-in-oil emulsion droplet process that the oil-in-oil emulsion droplet spreads completely on the water-in-oil emulsion droplet in the embodiment 2 of embodiment 2;

Fig. 16 is the high-speed camera photo of the monodisperse multi-component water-in-oil emulsion droplet process of the monodisperse multi-component water-in-oil emulsion droplet that spreads completely on the water-in-oil emulsion droplet in embodiment 3 of embodiment 2;

Fig. 17 is the high-speed camera photo of the monodisperse multi-component W/O/O emulsion droplet process of mononuclear monodisperse multi-component W/O/O emulsion droplet that spreads completely on the water-in-oil emulsion droplet in embodiment 4 of embodiment 2;

Fig. 18 is the high-speed camera photograph of the monodisperse multi-component W/O/O emulsion droplet process that the oil-in-oil emulsion droplet spreads completely on the water-in-oil emulsion droplet in embodiment 5 of embodiment 2;

Fig. 19 is a high-speed camera photo of the water-in-oil emulsion droplet spreading completely on the oil-in-oil emulsion droplet to form a mononuclear monodisperse multi-component O/W/O emulsion droplet process in Embodiment 1 of Example 3;

Figure 20 is a high-speed camera photo of the water-in-oil emulsion droplet spreading completely on the oil-in-oil emulsion droplet to form a dual-core monodisperse multi-component O/W/O emulsion droplet process in Embodiment 2 of Example 3;

Figure 21 is a high-speed camera photo of the water-in-oil emulsion droplet spreading completely on the oil-in-oil emulsion droplet to form a triple-nuclear monodisperse multi-component O/W/O emulsion droplet process in Embodiment 3 of Example 3;

Fig. 22 is the high-speed camera photo of the water-in-oil emulsion droplet spreading completely on two kinds of oil-in-oil emulsion droplet in embodiment 4 to form monodisperse multi-component water-in-oil multiple emulsion droplet process with different oil nuclei;

Fig. 23 is a high-speed camera photo of the formation process of oil-in-water-in-oil emulsion droplets in Example 5 of the present invention;

24 is a high-speed camera photo of the formation process of oil-in-oil emulsion droplets in Example 5 of the present invention;

Figure 25 is the water layer of the water-in-oil-in-oil emulsion droplet in embodiment 1 of Example 5 completely spreading on the oil-in-oil emulsion droplet to form a monodisperse multi-component water-in-oil-in-oil multiple emulsion droplet with two different oil cores High-speed camera photos of the process;

Figure 26 is the water layer of the water-in-oil-in-oil emulsion droplet in the embodiment 2 of Example 5 completely spreads on the oil-in-oil emulsion droplet to form a monodisperse multi-component water-in-oil package three oil-core multiple emulsion droplet process high-speed camera photos;

Figure 27 is the water layer of the water-in-oil-in-oil emulsion droplet in the embodiment 3 of Example 5 completely spreads on the oil-in-oil emulsion droplet to form a monodisperse multi-component water-in-oil package four oil core multiple emulsion droplet process high-speed camera photos;

Figure 28 is an optical microscope photo of the monodisperse multi-component water-in-oil multiple emulsion with different oil cores prepared in Embodiment 1 of Example 5;

Fig. 29 is the O/W/O/O emulsion liquid containing one oil-in-water-in-oil emulsion droplet that is completely spread on the oil-in-water-in-oil emulsion droplet in embodiment 1 of Example 6 High-speed camera photos of the dripping process;

Figure 30 is the O/W/O/O emulsion containing two oil-in-water emulsion droplets that are completely spread on the oil-in-water emulsion droplets in the second embodiment of Example 6. High-speed camera photos of the droplet process;

Figure 31 is an optical microscope photo of a monodisperse multi-component O/W/O/O emulsion containing an oil-in-water-in-oil emulsion droplet prepared in Embodiment 1 of Example 6;

Figure 32 is a scanning electron micrograph of ethoxylated trimethylolpropane triacrylate microcapsules prepared in Example 7;

33 is a scanning electron micrograph of the wall thickness of ethoxylated trimethylolpropane triacrylate microcapsules prepared in Example 7.

In the figure, 1—first emulsion droplet, 2—second emulsion droplet, 3—continuous phase fluid, 4—third emulsion droplet, 5—glass slide, 6—lower cover glass, 7—epoxy Resin glue, 8—injection needle, 9—upper cover glass, 10—output tube, 11—the first microfluidic channel, 12—the second microfluidic channel, 12-1—the first inlet of the second microfluidic channel 12 Liquid port, 12-2—the second liquid inlet of the second microfluidic channel 12, 13—the third microfluidic channel, 14—the fourth microfluidic channel, 15—the fifth microfluidic channel, 16—the sixth microfluidic channel Road, 17—seventh microfluidic channel, 18—eighth microfluidic channel, 19—ninth microfluidic channel, 20—collection tube.

Detailed ways

The preparation method of the monodisperse multi-component multiple emulsion of the present invention will be further described below by way of examples and in conjunction with the accompanying drawings. In each of the following examples, the Dow Corning749 is a mixture of 50% trimethylsiloxane by volume and 50% cyclomethicone by volume. Dow Corning749 is its trade name and is available from Dow Corning Corporation; the dye F Red300 is a perylene imide compound, F Red300 is its trade name, purchased from BASF Company; the medical soybean oil is a grade for injection, purchased from Tieling Beiya Pharmaceutical Oil Co., Ltd.

Example 1

In this embodiment, a monodisperse multi-component water-in-oil-in-oil (W/O/O) emulsion is prepared by the method of the present invention, and the process steps are as follows:

(1) Preparation of dispersed phase and continuous phase fluid

The preparation of the first dispersed phase fluid: at normal pressure, at room temperature, sodium dodecyl sulfate (SDS) is added in deionized water and stirred to form the first dispersed phase fluid, and the mass ratio of the SDS to deionized water is 0.01: 1;

Preparation of the second dispersed phase fluid: at normal pressure and room temperature, polyglyceryl ricinoleate (PGPR90) is added in the medical soybean oil and stirred to form the second dispersed phase fluid, and the amount of the PGPR90 is in every 1ml medical soybean oil 0.005g;

Preparation of continuous phase fluid: Add Dow Corning749 (DC749) into simethicone oil at normal pressure and room temperature and stir evenly to form a continuous phase fluid. The mass ratio of DC749 to simethicone oil is 0.005:1. The viscosity of methyl silicone oil is 10cSt.

(2) Preparation of monodisperse multi-component W/O/O emulsion droplets

This embodiment uses a microfluidic device with two single-stage droplet generators, the structure of which is shown in Figure 3, including a slide glass 5, an upper cover glass 9, a lower cover glass 6 and an injection needle 8. The schematic diagram of the oil-in-oil emulsion droplet spreading on the water-in-oil emulsion droplet in the flow channel and the microfluidic channel is shown in Figure 4. The first microfluidic channel 11 and the second microfluidic channel 12 constitute the first single-stage droplet generation device, the third microfluidic channel 13 and the fourth microfluidic channel 14 constitute the second single-stage droplet generator, the width of the first microfluidic channel 11 is 80 μm, the width of the second microfluidic channel 12 is 120 μm, and the third microfluidic channel The width of the flow channel 13 is 120 μm, the width of the fourth microfluidic channel 14 is 80 μm, the width of the collecting tube is 200 μm, and the horizontal projection of the enlarged chamber of the collecting tube is an ellipse with a major axis of 2.5 mm and a minor axis of 260 μm, The height of each microfluidic channel is about 150 μm.

The second dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the first microfluidic channel 11 and the second microfluidic channel of the first single-stage droplet generator of the microfluidic device through the syringe 8 connected with the syringe pump 12 Form the monodisperse oil-in-oil emulsion droplet, meanwhile, the first dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the second single-stage droplet of the microfluidic device by the syringe 8 connected with the syringe pump to generate The third microfluidic channel 13 and the fourth microfluidic channel 14 of the device form monodisperse water-in-oil emulsion droplets; the formed oil-in-oil emulsion droplets and water-in-oil emulsion droplets enter the microfluidic device together with the continuous phase fluid When the oil-in-oil emulsion droplet contacts the water-in-oil emulsion droplet in the enlarged chamber of the collection pipe, the oil-in-oil emulsion droplet spreads on the water-in-oil emulsion droplet to form monodisperse multi-group Divide W/O/O emulsion droplets;

Embodiment 1: When the flow rate Q _B of the first dispersed phase fluid = 200 μL/h, the flow rate Q _A1 of the second dispersed phase fluid = 20 μL/h, the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator = 40 μL/h, the flow rate Q _C2 in the second single-stage droplet generator = 300 μL/h, the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet meet in the enlarged chamber of the collecting pipe 20 Each oil-in-oil emulsion droplet is in contact with a water-in-oil emulsion droplet, and the oil-in-oil emulsion droplet spreads on the water-in-oil emulsion droplet to form a monodisperse multicomponent W/O/O emulsion droplet (see Figure 10);

Embodiment 2: When the flow rate Q _B of the first dispersed phase fluid = 150 μL/h, the flow rate Q _A1 of the second dispersed phase fluid = 80 μL/h, the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator =70 μL/h, the flow Q _C2 in the second single-stage droplet generator =300 μL/h, the oil-in-oil emulsion droplets and the water-in-oil emulsion droplets enter the enlarged chamber of the collecting pipe 20 to meet Each oil-in-oil emulsion droplet is in contact with a water-in-oil emulsion droplet, and the oil-in-oil emulsion droplet spreads on the water-in-oil emulsion droplet to form a monodisperse multicomponent W/O/O emulsion droplet (see Figure 11);

Embodiment 3: When the flow rate Q _B of the first dispersed phase fluid is 150 μL/h, the flow rate Q _A1 of the second dispersed phase fluid is 40 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator = 40 μL/h, the flow rate Q _C2 in the second single-stage droplet generator = 500 μL/h, the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet meet in the enlarged chamber of the collecting pipe 20 Each oil-in-oil emulsion droplet is in contact with a water-in-oil emulsion droplet, and the oil-in-oil emulsion droplet spreads on the water-in-oil emulsion droplet to form a monodisperse multicomponent W/O/O emulsion droplet (see Figure 12).

(3) Collect monodisperse multi-component W/O/O emulsion

The monodisperse multi-component W/O/O emulsion droplets formed in the implementation modes 1 to 3 of step (2) are introduced into the collection container together with the continuous phase through the outlet tube 10 of the microfluidic device, and the corresponding monodisperse multi-component W/O/O emulsion droplets are obtained. Components W/O/O Emulsion.

An optical microscope photo of the monodisperse multi-component W/O/O emulsion prepared according to the conditions in Embodiment 1 is shown in FIG. 13 .

Example 2

In this embodiment, a monodisperse multi-component water-in-oil-in-oil (W/O/O) emulsion is prepared by the method of the present invention, and the process steps are as follows:

(1) Preparation of dispersed phase and continuous phase fluid

Preparation of the first dispersed phase fluid: add SDS to deionized water at normal pressure and room temperature and stir evenly to form the first dispersed phase fluid, the mass ratio of the SDS to deionized water is 0.005:1;

Preparation of the second dispersed phase fluid: PGPR90 was added into medical soybean oil at normal pressure and room temperature and stirred evenly to form a second dispersed phase fluid, the amount of PGPR90 was 0.02g per 1ml of medical soybean oil;

Preparation of the fifth dispersed phase fluid: Add PGPR90 to medical soybean oil at normal pressure and room temperature and stir to form a mixed liquid, then add fluorescent dye LR300 to the mixed liquid and stir to form the fifth dispersed phase fluid, the PGPR90 The amount of LR300 is 0.005g per 1ml of medical soybean oil, and the amount of LR300 is 1mg in 1ml of medical soybean oil;

Preparation of continuous phase fluid: Add DC749 into simethicone oil at normal pressure and room temperature and stir evenly to form a continuous phase fluid. The mass ratio of DC749 to simethicone is 0.01:1, and the simethicone The viscosity is 10cSt.

(2) Preparation of monodisperse multi-component W/O/O emulsion droplets

In this embodiment, the microfluidic device for preparing monodisperse multi-component W/O/O emulsion droplets is the same as that in Embodiment 1;

Method 1: The second dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the first microfluidic channel 11 and the second microfluidic channel 11 of the first single-stage droplet generator of the microfluidic device through a syringe connected to a syringe pump. The flow channel 12 forms a monodisperse oil-in-oil emulsion droplet, and at the same time, the first dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the second single-stage droplet of the microfluidic device by a syringe connected to a syringe pump The third microfluidic channel 13 and the fourth microfluidic channel 14 of the generator form monodisperse water-in-oil emulsion droplets; the formed oil-in-oil emulsion droplets and water-in-oil emulsion droplets enter the microfluidics together with the continuous phase fluid The collection pipe 20 of the device, when the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet contact in the enlarged chamber of the collection pipe, the oil-in-oil emulsion droplet promptly spreads on the water-in-oil emulsion droplet to form monodisperse polydispersity. Component W/O/O emulsion droplets;

Embodiment 1: When the flow rate Q _A1 of the second dispersed phase fluid = 50 μL/h, the flow rate Q _B of the first dispersed phase fluid = 200 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator =200 μL/h, the flow rate Q _C2 in the second single-stage droplet generator =200 μL/h, the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet meet in the enlarged chamber of the collecting tube 20 Each oil-in-oil emulsion droplet is in contact with a water-in-oil emulsion droplet, and the oil-in-oil emulsion droplet spreads to the water-in-oil emulsion droplet to form a single-core monodisperse multi-component W/O/O emulsion drop (see Figure 14);

Embodiment 2: When the flow rate Q _A1 of the second dispersed phase fluid = 50 μL/h, the flow rate Q _B of the first dispersed phase fluid = 300 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator =100 μL/h, the flow rate Q _C2 in the second single-stage droplet generator =200 μL/h, the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet meet in the enlarged chamber of the collecting tube 20 Each oil-in-oil emulsion droplet is in contact with two water-in-oil emulsion droplets, and the oil-in-oil emulsion droplet spreads to the water-in-oil emulsion droplet to form a dual-core monodisperse multi-component W/O/O emulsion. drop (see Figure 15);

Embodiment 3: When the flow rate Q _A1 of the second dispersed phase fluid = 50 μL/h, the flow rate Q _B of the first dispersed phase fluid = 300 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator =200 μL/h, the flow rate Q _C2 in the second single-stage droplet generator =200 μL/h, the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet satisfy each One oil-in-oil emulsion droplet is in contact with three water-in-oil emulsion droplets, and the oil-in-oil emulsion droplet spreads to the water-in-oil emulsion droplet to form a three-core monodisperse multi-component W/O/O emulsion drop (see Figure 16);

Method 2: The fifth dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the first microfluidic channel 11 and the second microfluidic channel 11 of the first single-stage droplet generator of the microfluidic device through a syringe connected to a syringe pump. The flow channel 12 forms monodisperse oil-in-oil emulsion droplets, while the first dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the second single-stage droplet generator of the microfluidic device by a syringe connected to a syringe pump The third microfluidic channel 13 and the fourth microfluidic channel 14 form monodisperse water-in-oil emulsion droplets; the formed oil-in-oil emulsion droplets and water-in-oil emulsion droplets enter the microfluidic device together with the continuous phase fluid Collecting tube 20, when the oil-in-oil emulsion droplet contacts the water-in-oil emulsion droplet in the enlarged chamber of the collecting tube 20, the oil-in-oil emulsion droplet spreads on the water-in-oil emulsion droplet to form monodisperse multi-group Divide W/O/O emulsion droplets;

Embodiment 1: When the flow rate Q _A4 of the fifth dispersed phase fluid = 80 μL/h, the flow rate Q _B of the first dispersed phase fluid = 150 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator = 150 μL/h, the flow rate Q _C2 in the second single-stage droplet generator = 250 μL/h, the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet meet in the enlarged chamber of the collecting pipe 20 Each oil-in-oil emulsion droplet is in contact with a water-in-oil emulsion droplet, and the oil-in-oil emulsion droplet spreads to the water-in-oil emulsion droplet to form a single-core monodisperse multi-component W/O/O emulsion drop (see Figure 17);

Embodiment 2: When the flow rate Q _A4 of the fifth dispersed phase fluid = 40 μL/h, the flow rate Q _B of the first dispersed phase fluid = 100 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator =100 μL/h, the flow rate Q _C2 in the second single-stage droplet generator =200 μL/h, the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet meet in the enlarged chamber of the collecting tube 20 Each oil-in-oil emulsion droplet is in contact with two water-in-oil emulsion droplets, and the oil-in-oil emulsion droplet spreads to the water-in-oil emulsion droplet to form a dual-core monodisperse multi-component W/O/O emulsion. drop (see Figure 18).

(3) Collect monodisperse multi-component W/O/O emulsion

The monodisperse multi-component W/O/O emulsion droplets formed in step (2) are connected to the continuous phase fluid and introduced into the collection container through the outlet tube 10 of the microfluidic device to obtain the corresponding monodisperse multi-component W/O /O lotion.

Example 3

In this embodiment, a monodisperse multi-component oil-in-water-in-oil (O/W/O) emulsion is prepared by the method of the present invention, and the process steps are as follows:

(1) Preparation of dispersed phase and continuous phase fluid

Preparation of the first dispersed phase fluid: add SDS to deionized water at normal pressure and room temperature and stir evenly to form the first dispersed phase fluid, the mass ratio of the SDS to deionized water is 0.005:1;

Preparation of the third dispersed phase fluid: Mix n-octanol and medical soybean oil at a volume ratio of 1:3 at normal pressure and room temperature to obtain a mixed solution, then add PGPR90 to the mixed solution, and stir to form the third dispersed phase Fluid, the amount of the PGPR90 is 0.005g per 1ml of the mixed solution of n-octanol and medical soybean oil;

Preparation of continuous phase fluid: Add DC749 into simethicone oil at normal pressure and room temperature and stir evenly to form a continuous phase fluid. The mass ratio of DC749 to simethicone is 0.01:1, and the simethicone The viscosity is 10cSt.

(2) Preparation of monodisperse multi-component O/W/O emulsion droplets

The structure of the microfluidic device used in this embodiment is as shown in Figure 3, including a slide glass 5, an upper cover glass 9, a lower cover glass 6 and an injection needle 8, the microfluidic channel and the oil in the microfluidic channel The schematic diagram of the water-in-emulsion droplet spreading onto the oil-in-oil emulsion droplet is shown in Figure 5. The first microfluidic channel 11 and the second microfluidic channel 12 constitute the first single-stage droplet generator, and the third microfluidic channel 13 and the fourth microfluidic channel 14 constitute the second single-stage droplet generator, the width of the first microfluidic channel 11 is 100 μm, the width of the second microfluidic channel 12 is 150 μm, and the width of the third microfluidic channel 13 is 150 μm , the width of the fourth microfluidic channel 14 is 100 μm, and the width of the collecting tube is 180 μm. The horizontal projection of the enlarged chamber of the collecting tube is elliptical, and its major axis is 1.5 mm, and its minor axis is 600 μm. The height of each microfluidic channel is about is 150 μm.

The third dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the first microfluidic channel 11 and the second microfluidic channel of the first single-stage droplet generator of the microfluidic device through a syringe connected to a syringe pump 12 Form the monodisperse oil-in-oil emulsion droplet, at the same time inject the first dispersed phase fluid and the continuous phase fluid prepared in step (1) into the second single-stage droplet generator of the microfluidic device through the syringe connected to the syringe pump The third micro-flow channel 13 and the fourth micro-flow channel 14 form monodisperse water-in-oil emulsion droplets; the formed water-in-oil emulsion droplets and oil-in-oil emulsion droplets enter the collection pipe 20 together with the continuous phase fluid, When the droplet of the water-in-oil emulsion contacts the droplet of the oil-in-oil emulsion in the enlarged chamber of the collecting tube 20, the droplet of the water-in-oil emulsion spreads on the droplet of the oil-in-oil emulsion to form a monodisperse multicomponent O/W /O emulsion droplets;

Embodiment 1: When the flow rate Q _B of the first dispersed phase fluid = 100 μL/h, the flow rate Q _A2 of the third dispersed phase fluid = 50 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator =100 μL/h, the flow Q _C2 in the second single-stage droplet generator =200 μL/h, the water-in-oil emulsion droplet and the oil-in-oil emulsion droplet meet in the enlarged chamber of the collecting pipe 20 Each water-in-oil emulsion droplet is in contact with one oil-in-oil emulsion droplet, and the water-in-oil emulsion droplet spreads to the oil-in-oil emulsion droplet to form a mononuclear monodisperse multi-component O/W/O emulsion drop (see Figure 19);

Embodiment 2: When the flow rate Q _B of the first dispersed phase fluid = 100 μL/h, the flow rate Q _A2 of the third dispersed phase fluid = 80 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator = 150 μL/h, the flow rate Q _C2 in the second single-stage droplet generator = 400 μL/h, the water-in-oil emulsion droplet and the oil-in-oil emulsion droplet meet in the enlarged chamber of the collecting pipe 20 Each water-in-oil emulsion droplet is in contact with two oil-in-oil emulsion droplets, and the water-in-oil emulsion droplet spreads to the oil-in-oil emulsion droplet to form a dual-core monodisperse multi-component O/W/O emulsion drop (see Figure 20);

Embodiment 3: When the flow rate Q _B of the first dispersed phase fluid is 150 μL/h, the flow rate Q _A2 of the third dispersed phase fluid is 90 μL/h, and the flow rate Q _C1 of the continuous phase fluid in the first single-stage droplet generator = 150 μL/h, the flow rate Q _C2 in the second single-stage droplet generator = 200 μL/h, the water-in-oil emulsion droplet and the oil-in-oil emulsion droplet meet in the enlarged chamber of the collecting pipe 20 Each water-in-oil emulsion droplet is in contact with three oil-in-oil emulsion droplets, and the water-in-oil emulsion droplet spreads to the oil-in-oil emulsion droplet to form a three-core monodisperse multi-component O/W/O emulsion Droplets (see Figure 21).

(3) Collect monodisperse multi-component O/W/O emulsion

The monodisperse multicomponent O/W/O emulsion droplets formed in step (2) are introduced into the collection container together with the continuous phase from the output pipe 10 of the microfluidic device, and the corresponding monodisperse multicomponent O/W/O O emulsion.

Example 4

In this embodiment, the method of the present invention is used to prepare monodisperse multi-component oil-in-water-in-oil multiple emulsions with different oil cores, and the process steps are as follows:

Preparation of the first dispersed phase fluid: add SDS to deionized water at normal pressure and room temperature and stir evenly to form the first dispersed phase fluid, the mass ratio of the SDS to deionized water is 0.01:1;

Preparation of the third dispersed phase fluid: Mix n-octanol and medical soybean oil at a volume ratio of 1:3 at normal pressure and room temperature to obtain a mixed solution, then add PGPR90 to the mixed solution, and stir to form the third dispersed phase Fluid, the amount of the PGPR90 is 0.02g per 1ml of the mixed solution of n-octanol and medical soybean oil;

Preparation of the fourth dispersed phase fluid: Mix n-octanol and medical soybean oil at a volume ratio of 1:3 at normal pressure and room temperature to obtain a mixed solution, then add PGPR90 and fluorescent dye LR300 to the mixed solution, the PGPR90 The amount of LR300 is 0.02g per 1ml of the mixed solution, and the amount of LR300 is 1mg in the mixed solution of 1ml of n-octanol and medical soybean oil;

Preparation of continuous phase fluid: Add DC749 into simethicone oil at normal pressure and room temperature and stir evenly to form a continuous phase fluid. The mass ratio of DC749 to simethicone is 0.005:1. The viscosity is 10cSt.

(2) Preparation of monodisperse multi-component oil-in-water-in-oil emulsion droplets with different oil cores

In this embodiment, the microfluidic device for preparing monodisperse multi-component water-in-oil multiple emulsion droplets with different oil cores is the same as in Example 3, and the microfluidic channel and the water-in-oil emulsion droplets in the microfluidic channel spread to different oils at the same time. The schematic diagram on the oil-in-emulsion droplet is shown in Figure 6;

The third dispersed phase fluid, the fourth dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the second microfluidic channel 12 of the first single-stage droplet generator of the microfluidic device by a syringe connected with a syringe pump The first liquid inlet 12-1, the second liquid inlet 12-2 and the first microfluidic channel 11 simultaneously form two kinds of monodisperse oil-in-oil emulsion droplets, and at the same time the first liquid prepared in step (1) The dispersed phase fluid and the continuous phase fluid are respectively injected into the third microfluidic channel 13 and the fourth microfluidic channel 14 of the second single-stage droplet generator of the microfluidic device through a syringe pump to form monodisperse water-in-oil emulsion droplets; the formed Two kinds of monodisperse oil-in-oil emulsion droplets and monodisperse water-in-oil emulsion droplets enter the collection pipe 20 together with the continuous phase fluid and contact in its enlarged chamber. When each of the oil emulsion droplets contacts, the water-in-oil emulsion droplets promptly spread to two kinds of oil-in-oil emulsion droplets to form monodisperse multi-component water-in-oil emulsion droplets with different oil nuclei (see Figure 22); The flow rate of the first dispersed phase fluid Q _B =150 μL/h, the flow rate of the third dispersed phase fluid Q _A2 =20 μL/h, the flow rate of the fourth dispersed phase fluid Q _A3 =20 μL/h, the flow rate of the continuous phase fluid in the first Flow Q _C1 =200 μL/h in the single-stage droplet generator, Q _C2 =400 μL/h in the second single-stage droplet generator;

(3) Collect monodisperse multi-component oil-in-water-in-oil multiple emulsions with different oil cores

The monodisperse multicomponent water-in-oil emulsion droplets formed in step (2) together with the continuous phase are introduced into the collection container through the outlet pipe 10 of the microfluidic device to obtain the monodisperse multicomponent water-in-oil emulsion droplets. Different oil core lotions.

Example 5

In this embodiment, the method of the present invention is used to prepare monodisperse multi-component oil-in-water-in-oil multiple emulsions with different oil cores, and the process steps are as follows:

(1) Preparation of dispersed phase and continuous phase fluid

Preparation of the first dispersed phase fluid: add SDS to deionized water at normal pressure and room temperature and stir evenly to form the first dispersed phase fluid, the mass ratio of the SDS to deionized water is 0.01:1;

Preparation of the third dispersed phase fluid: Mix n-octanol and medical soybean oil at a volume ratio of 1:3 at normal pressure and room temperature to obtain a mixed solution, then add PGPR90 to the mixed solution, and stir to form the third dispersed phase Fluid, the amount of the PGPR90 is 0.005g per 1ml of the mixed solution of n-octanol and medical soybean oil;

Preparation of the fourth dispersed phase fluid: Mix n-octanol and medical soybean oil at a volume ratio of 1:3 at normal pressure and room temperature to obtain a mixed solution, then add PGPR90 and fluorescent dye LR300 to the mixed solution, the PGPR90 The amount of LR300 is 0.005g per 1ml of the mixed solution of n-octanol and medical soybean oil, and the amount of LR300 is 1mg in the mixed solution of 1ml of n-octanol and medical soybean oil;

Preparation of continuous phase fluid: Add DC749 into simethicone oil at normal pressure and room temperature and stir evenly to form a continuous phase fluid. The mass ratio of DC749 to simethicone is 0.01:1, and the simethicone The viscosity is 10cSt.

(2) Preparation of monodisperse multi-component oil-in-water-in-oil emulsion droplets with different oil cores

The microfluidic device used in this embodiment has a structure as shown in Figure 7, including a slide glass 5, an upper cover glass 9, a lower cover glass 6 and an injection needle 8, and the microfluidic channel and the water-in-oil in the microfluidic channel The schematic diagram of the oil-in-emulsion droplet spreading onto the oil-in-oil emulsion droplet is shown in Figure 8. The fifth microfluidic channel 15, the sixth microfluidic channel 16 and the seventh microfluidic channel 17 constitute a two-stage droplet generator, The eighth microfluidic channel 18 and the ninth microfluidic channel 19 constitute a single-stage droplet generator; the width of the fifth microfluidic channel 15 is 90 μm, the width of the sixth microfluidic channel 16 is 115 μm, and the seventh microfluidic channel 17 The width of the eighth microfluidic channel 18 is 150 μm, the width of the ninth microfluidic channel 18 is 90 μm, and the width of the collecting tube is 200 μm. The horizontal projection of the enlarged chamber of the collecting tube is elliptical, and its major axis is 1.8 mm, the minor axis is 600 μm, and the height of each microfluidic channel is about 150 μm.

The fourth dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the ninth microfluidic channel 19 and the eighth microfluidic channel of the single-stage droplet generator of the microfluidic device through a syringe connected to a syringe pump 18 Form the oil-in-oil emulsion droplets (see Figure 24 for the high-speed camera photo of the oil-in-oil emulsion droplet preparation process in Embodiment 1 of this example), and at the same time use the third dispersed phase fluid prepared in step (1) as the internal phase , the first dispersed phase fluid as the intermediate phase, and the continuous phase fluid as the external phase are respectively injected into the fifth microfluidic channel 15 and the sixth microfluidic channel 16 of the two-stage droplet generator of the microfluidic device by a syringe connected to the syringe pump 7. Microflow channel 17 forms oil-in-water-in-oil emulsion droplets (the high-speed camera photo of the preparation process of oil-in-water-in-oil emulsion droplets in Embodiment 1 in this embodiment is shown in Figure 23); the formed oil-in-water-in-oil emulsion droplets The emulsion droplet and the oil-in-oil emulsion droplet enter the collection pipe 20 together with the continuous phase fluid. The water layer of the oil-in-oil emulsion droplet spreads on the oil-in-oil emulsion droplet to form a monodisperse multi-component water-in-oil emulsion droplet with different oil nuclei;

Embodiment 1: When the flow rate of the first dispersed phase fluid Q _B =150 μL/h, the flow rate of the third dispersed phase fluid Q _A2 =150 μL/h, the flow rate of the fourth dispersed phase fluid Q _A3 =50 μL/h, the continuous phase The flow rate Q _C4 of the fluid in the single-stage droplet generator = 100 μL/h, the flow rate Q _C3 = 300 μL/h in the two-stage droplet generator, the oil-in-water-in-oil emulsion droplet and The oil-in-oil emulsion droplet satisfies each oil-in-water-in-oil emulsion droplet contacting with one oil-in-oil emulsion droplet in the enlarged chamber of the collecting pipe 20, and the water layer of the oil-in-water-in-oil emulsion droplet promptly spreads On the oil-in-oil emulsion droplet, two different oil-core emulsion droplets are formed in a monodisperse multi-component water-in-oil emulsion droplet (see Figure 25);

Embodiment 2: When the flow rate of the first dispersed phase fluid Q _B =150 μL/h, the flow rate of the third dispersed phase fluid Q _A2 =150 μL/h, the flow rate of the fourth dispersed phase fluid Q _A3 =200 μL/h, the continuous phase The flow Q _C4 of the fluid in the single-stage droplet generator = 200 μL/h, the flow Q _C3 = 300 μL/h in the two-stage droplet generator, the oil-in-water-in-oil emulsion droplets and The oil-in-oil emulsion droplet satisfies each oil-in-water-in-oil emulsion droplet contacting with two oil-in-oil emulsion droplet in the enlarged chamber of collecting pipe 20, and the water layer of the oil-in-water-in-oil emulsion droplet is Spread on the oil-in-oil emulsion droplet to form monodisperse multi-component water-in-oil package three oil-core emulsion droplet (see Figure 26);

Embodiment 3: When the flow rate of the first dispersed phase fluid Q _B =150 μL/h, the flow rate of the third dispersed phase fluid Q _A2 =150 μL/h, the flow rate of the fourth dispersed phase fluid Q _A3 =200 μL/h, the continuous phase The flow rate Q _C4 of the fluid in the single-stage droplet generator =300 μL/h, the flow rate Q _C3 =300 μL/h in the two-stage droplet generator, the oil-in-water-in-oil emulsion droplets and The oil-in-oil emulsion droplet satisfies each oil-in-water-in-oil emulsion droplet contacting with three oil-in-oil emulsion droplet in the enlarged chamber of collecting pipe 20, and the water layer of oil-in-water-in-oil emulsion droplet is Spread on the oil-in-oil emulsion droplet to form monodisperse multi-component water-in-oil four-oil core emulsion droplet (see Figure 27);

(3) Collect monodisperse multi-component oil-in-water-in-oil multiple emulsions with different oil cores

The monodisperse multicomponent water-in-oil emulsion droplets formed in step (2) together with the continuous phase are introduced into the collection container through the outlet pipe 10 of the microfluidic device to obtain the monodisperse multicomponent water-in-oil emulsion droplets. Different oil core lotions. The optical microscope photos of the monodisperse multi-component water-in-oil emulsion with different oil cores prepared in embodiment 1 are shown in FIG. 28 .

Example 6

In this embodiment, a monodisperse multi-component oil-in-oil-in-water-in-oil (O/W/O/O) emulsion is prepared by the method of the present invention, and the process steps are as follows:

(1) Preparation of dispersed phase and continuous phase fluid

Preparation of the first dispersed phase fluid: add SDS to deionized water at normal pressure and room temperature and stir evenly to form the first dispersed phase fluid, the mass ratio of the SDS to deionized water is 0.01:1;

Preparation of the third dispersed phase fluid: Mix n-octanol and medical soybean oil at a volume ratio of 1:3 at normal pressure and room temperature to obtain a mixed solution, then add PGPR90 to the mixed solution, and stir to form the third dispersed phase Fluid, the amount of the PGPR90 is 0.02g per 1ml of the mixed solution of n-octanol and medical soybean oil;

Preparation of the fifth dispersed phase fluid: Add PGPR90 to medical soybean oil at normal pressure and room temperature and stir to form a mixed liquid, then add fluorescent dye LR300 to the mixed liquid and stir to form the fifth dispersed phase fluid, the PGPR90 The amount of LR300 is 0.02g per 1ml of medical soybean oil, and the amount of LR300 is 1mg in 1ml of medical soybean oil;

Preparation of continuous phase fluid: Add DC749 into simethicone oil at normal pressure and room temperature and stir evenly to form a continuous phase fluid. The mass ratio of DC749 to simethicone is 0.01:1, and the simethicone The viscosity is 10cSt.

(2) Preparation of monodisperse multi-component O/W/O/O emulsion droplets

In this embodiment, the microfluidic device used is the same as in Embodiment 5, and the microfluidic channel and the schematic diagram of the oil-in-oil emulsion droplet spreading on the oil-in-water-in-oil emulsion droplet in the microfluidic channel are shown in FIG. 9 .

The fifth dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the ninth microfluidic channel 19 and the eighth microfluidic channel of the single-stage droplet generator of the microfluidic device through a syringe connected to a syringe pump 18 Form the oil-in-oil emulsion droplet, meanwhile, the third dispersed phase fluid prepared in step (1) is used as the internal phase, the first dispersed phase fluid is used as the intermediate phase, and the continuous phase fluid is used as the external phase by the syringe connected to the syringe pump The fifth microfluidic channel 15, the sixth microfluidic channel 16, and the seventh microfluidic channel 17 of the described two-stage droplet generator injected into the microfluidic device form oil-in-water-in-oil emulsion droplets; the formed water-in-oil The oil-in-oil emulsion droplet and the oil-in-oil emulsion droplet enter the collection pipe 20 together with the continuous phase fluid, and when the oil-in-oil emulsion droplet contacts the enlarged chamber of the collection pipe 20, the oil-in-oil emulsion droplet and The oil-in-emulsion droplets spread onto the oil-in-water-in-oil emulsion droplets to form monodisperse multi-component O/W/O/O emulsion droplets;

Embodiment 1: When the flow rate of the first dispersed phase fluid Q _B =150 μL/h, the flow rate of the third dispersed phase fluid Q _A2 =150 μL/h, the flow rate of the fifth dispersed phase fluid Q _A4 =200 μL/h, the continuous phase fluid In the two-stage droplet generator, the flow rate Q _C3 =200 μL/h, in the single-stage droplet generator, the flow rate Q _C4 =300 μL/h, the oil-in-oil emulsion droplets and water-in-oil The oil-in-emulsion droplet satisfies the contact of each oil-in-oil emulsion droplet with one oil-in-water-in-oil emulsion droplet in the enlarged chamber of the collecting tube 20, and the oil-in-oil emulsion droplet promptly spreads to the oil-in-water-in-oil droplet. An O/W/O/O emulsion droplet containing an oil-in-water-in-oil emulsion droplet is formed on the emulsion droplet (see Figure 29);

Embodiment 2: When the flow rate of the first dispersed phase fluid Q _B =100 μL/h, the flow rate of the third dispersed phase fluid Q _A2 =150 μL/h, the flow rate of the fifth dispersed phase fluid Q _A4 =150 μL/h, the continuous phase fluid In the two-stage droplet generator, the flow rate Q _C3 =220 μL/h, in the single-stage droplet generator, the flow rate Q _C4 =500 μL/h, the oil-in-oil emulsion droplets and water-in-oil The oil-in-emulsion droplet satisfies the contact of each oil-in-oil emulsion droplet with one oil-in-water-in-oil emulsion droplet in the enlarged chamber of the collecting tube 20, and the oil-in-oil emulsion droplet promptly spreads to the oil-in-water-in-oil droplet. A monodisperse multicomponent O/W/O/O emulsion droplet containing two oil-in-water-in-oil emulsion droplets formed on the emulsion droplet (see FIG. 30 ).

(3) Collect monodisperse multi-component O/W/O/O emulsion

The monodisperse O/W/O/O emulsion droplets formed in step (2) and containing different double emulsions together with the continuous phase are introduced into the collection container through the outlet pipe 10 of the microfluidic device, to obtain monodisperse multi-component O/O/ W/O/O lotion. The optical microscope photo of the monodisperse multi-component O/W/O/O emulsion containing one oil-in-water-in-oil emulsion droplet prepared in Embodiment 1 is shown in FIG. 31 .

Example 7

In this example, the ultra-thin-walled monodisperse oil-in-oil-in-water (W/O/O) emulsion is prepared by the method of the present invention, and ethoxylated trimethylolpropane with ultra-thin walls is synthesized using it as a template Triacrylate (ETPTA) microcapsules, the process steps are as follows:

(1) Preparation of dispersed phase and continuous phase fluid

Preparation of the first dispersed phase fluid: add SDS to deionized water at normal pressure and room temperature and stir evenly to form the first dispersed phase fluid, the mass ratio of the SDS to deionized water is 0.01:1;

The preparation of the 6th disperse phase fluid: under normal pressure, room temperature, photoinitiator 2-hydroxyl-2-methylpropiophenone is added ethoxylated trimethylolpropane triacrylate (its number average molecular weight Mn is 692) In, stir uniformly to form the sixth dispersed phase fluid, the volume ratio of the 2-hydroxyl-2-methylpropiophenone and ETPTA is 1:100;

Preparation of continuous phase fluid: Add DC749 into simethicone oil at normal pressure and room temperature and stir evenly to form a continuous phase fluid. The mass ratio of DC749 to simethicone is 0.01:1, and the simethicone The viscosity is 10cSt.

(2) Preparation of monodisperse W/O/O emulsion droplets

In this embodiment, the microfluidic device used is the same as that in Embodiment 1.

The sixth dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the first microfluidic channel 11 and the second microfluidic channel of the first single-stage droplet generator of the microfluidic device through the syringe 8 connected to the syringe pump 12 Form the monodisperse oil-in-oil emulsion droplet, simultaneously the first dispersed phase fluid and the continuous phase fluid prepared in step (1) are respectively injected into the second single-stage droplet generator of the microfluidic device by the syringe 8 connected with the syringe pump The third microfluidic channel 13 and the fourth microfluidic channel 14 form monodisperse water-in-oil emulsion droplets; the formed oil-in-oil emulsion droplets and water-in-oil emulsion droplets enter the collection of the microfluidic device together with the continuous phase fluid Tube 20, when the flow rate of the first dispersed phase fluid Q _B =300 μL/h, the flow rate of the sixth dispersed phase fluid Q _A5 =40 μL/h, the flow rate of the continuous phase fluid in the first single-stage droplet generator Q _C1 = 300 μL/h, the flow rate Q _C2 in the second single-stage droplet generator=300 μL/h, the oil-in-oil emulsion droplet and the water-in-oil emulsion droplet satisfy each An oil-in-oil emulsion droplet contacts a water-in-oil emulsion droplet, and the oil-in-oil emulsion droplet spreads to the water-in-oil emulsion droplet to form a monodisperse W/O/O emulsion droplet, wherein W/O/ The middle oil layer of O emulsion droplet is ETPTA and photoinitiator 2-hydroxyl-2-methylpropiophenone;

(3) Collect monodisperse W/O/O emulsion and initiate ETPTA polymerization into microcapsules

The monodisperse W/O/O emulsion droplets formed in step (2) together with the continuous phase are introduced into the collection container through the output tube 10 of the microfluidic device, thus obtaining the monodisperse W/O/O emulsion. Then the obtained monodisperse W/O/O emulsion was placed under a 200W UV lamp for 5 minutes to solidify into ETPTA microcapsules. The scanning electron microscope photos are shown in Figure 32 and Figure 33. The ETPTA microcapsules prepared by using the W/O/O emulsion as a template It has an ultra-thin-walled structure with a wall thickness of only 300nm.

Claims (5)

1. a single preparation method who disperses multicomponent multiple emulsion, is characterized in that processing step is as follows:

(1) preparation decentralized photo and continuous phase fluid

The preparation of the first dispersed phase fluid: water soluble emulsifier is added deionized water for stirring evenly to form the first dispersed phase fluid under normal pressure, room temperature, the mass ratio of described water soluble emulsifier and deionized water is 0.005～0.01:1;

The preparation of the second dispersed phase fluid: stir in oil soluble emulsifying agent being added to soybean oil under normal pressure, room temperature and form the second dispersed phase fluid, the amount of described oil soluble emulsifying agent is 0.005～0.02g in every 1ml soybean oil;

The preparation of the 3rd dispersed phase fluid: under normal pressure, room temperature by n-octyl alcohol and soybean oil by volume 1:3 mix to obtain mixed liquor, then in described mixed liquor, add oil soluble emulsifying agent, stir and form the 3rd dispersed phase fluid, the amount of described oil soluble emulsifying agent is 0.005～0.02g in the mixed liquor of every 1ml n-octyl alcohol and soybean oil;

The preparation of the 4th dispersed phase fluid: identical with the compound method of described the 3rd dispersed phase fluid, in described the 4th dispersed phase fluid and the 5th dispersed phase fluid, also contain dyestuff;

The preparation of the 5th dispersed phase fluid: identical with the compound method of described the second dispersed phase fluid;

The preparation of continuous phase fluid: the formation continuous phase fluid that stirs in surfactant being added to dimethicone under normal pressure, room temperature, the mass ratio of described surfactant and dimethicone is 0.005～0.01:1;

(2) the single multicomponent multiple emulsion drop that disperses of preparation

One of adopt with the following method the single multicomponent multiple emulsion drop that disperses of preparation:

Method one: the single multicomponent oil bag water-in-oil emulsion drop that disperses of preparation

The different inlets that the second dispersed phase fluid that step (1) is prepared and continuous phase fluid inject respectively the first single-stage droplet generator of microfluidic device form single dispersed oil bag fat liquor drop, and the different inlets that the first dispersed phase fluid of meanwhile step (1) being prepared and continuous phase fluid inject respectively the second single-stage droplet generator of microfluidic device form single water-in-oil emulsion drops that disperse; The oil bag fat liquor drop forming, water-in-oil emulsion drop enters microfluidic device collecting pipe with continuous phase fluid, when oil bag fat liquor drop contacts with the expansion chamber of water-in-oil emulsion drop at described collecting pipe, oil bag fat liquor drop spreads into the single multicomponent oil bag water-in-oil emulsion drop that disperses of formation on water-in-oil emulsion drop;

Flow (the Q of described the first dispersed phase fluid _b) be 100～300 μ L/h, the flow (Q of described the second dispersed phase fluid _a1) be 20～80 μ L/h, the flow (Q of described continuous phase fluid in the first single-stage droplet generator _c1) be 40～200 μ L/h, flow (Q in the second single-stage droplet generator _c2) be 200～500 μ L/h;

Method two: the single multicomponent Water-In-Oil bag fat liquor drop that disperses of preparation

The different inlets that the 3rd dispersed phase fluid that step (1) is prepared and continuous phase fluid inject respectively the first single-stage droplet generator of microfluidic device form single dispersed oil bag fat liquor drop, and the different inlets that the first dispersed phase fluid of meanwhile step (1) being prepared and continuous phase fluid inject respectively the second single-stage droplet generator of microfluidic device form single water-in-oil emulsion drops that disperse; The water-in-oil emulsion drop forming, oil bag fat liquor drop enters microfluidic device collecting pipe with continuous phase fluid, when water-in-oil emulsion drop contacts with the expansion chamber of oil bag fat liquor drop at described collecting pipe, water-in-oil emulsion drop spreads into the single multicomponent Water-In-Oil bag fat liquor drop that disperses of formation on oil bag fat liquor drop;

Flow (the Q of described the first dispersed phase fluid _b) be 100～150 μ L/h, the flow (Q of described the 3rd dispersed phase fluid _a2) be 50～90 μ L/h, the flow (Q of described continuous phase fluid in the first single-stage droplet generator _c1) be 100～150 μ L/h, flow (Q in the second single-stage droplet generator _c2) be 200～400 μ L/h;

Method three: the single different oily core emulsion droplets of multicomponent Water-In-Oil bag that disperse of preparation

The different inlets that the 3rd dispersed phase fluid, the 4th dispersed phase fluid and the continuous phase fluid of step (1) preparation injected respectively to the first single-stage droplet generator of microfluidic device form two kinds of single dispersed oil bag fat liquor drops simultaneously, and the different inlets that the first dispersed phase fluid of simultaneously step (1) being prepared and continuous phase fluid inject respectively the second single-stage droplet generator of microfluidic device form single water-in-oil emulsion drops that disperse; Two kinds of single dispersed oil bag fat liquor drops that form, single collecting pipe that disperses water-in-oil emulsion drop to enter microfluidic device with continuous phase fluid, when water-in-oil emulsion drop contacts with the expansion chamber of two kinds of oil bag fat liquor drops at described collecting pipe, water-in-oil emulsion drop spreads into the single different oily core emulsion droplets of multicomponent Water-In-Oil bag that disperse of formation on two kinds of oil bag fat liquor drops;

Flow (the Q of described the 3rd dispersed phase fluid _a2) be 20 μ L/h, the flow (Q of described the 4th dispersed phase fluid _a3) be 20 μ L/h, the flow (Q of described the first dispersed phase fluid _b) be 150 μ L/h, the flow (Q of described continuous phase fluid in the first single-stage droplet generator _c1) be 200 μ L/h, flow (Q in the second single-stage droplet generator _c2) be 400 μ L/h;

Or adopt the single different oily core emulsion droplets of multicomponent Water-In-Oil bag that disperse of following methods preparation:

The different inlets of the 4th dispersed phase fluid that step (1) is prepared, the single-stage droplet generator that continuous phase fluid injects respectively microfluidic device form oil bag fat liquor drops, and the different inlets that meanwhile the 3rd dispersed phase fluid of step (1) preparation respectively injected to the two-stage droplet generator of microfluidic device as middle phase, continuous phase fluid as foreign minister as interior phase, the first dispersed phase fluid form Water-In-Oil bag fat liquor drop; The Water-In-Oil bag fat liquor drop forming, oil bag fat liquor drop enters microfluidic device collecting pipe with continuous phase fluid, when Water-In-Oil bag fat liquor drop contacts with the expansion chamber of oil bag fat liquor drop at described collecting pipe, the water layer of Water-In-Oil bag fat liquor drop spreads into the single different oily core emulsion droplets of multicomponent Water-In-Oil bag that disperse of formation on oil bag fat liquor drop;

Flow (the Q of described the first dispersed phase fluid _b) be 150 μ L/h, the flow (Q of described the 3rd dispersed phase fluid _a2) be 150 μ L/h, the flow (Q of described the 4th dispersed phase fluid _a3) be 50～200 μ L/h, the flow (Q of described continuous phase fluid in single-stage droplet generator _c4) be 100～300 μ L/h, flow (Q in two-stage droplet generator _c3) be 300 μ L/h;

Method four: the single multicomponent oil bag Water-In-Oil bag fat liquor drop that disperses of preparation

The different inlets of the 5th dispersed phase fluid that step (1) is prepared, the single-stage droplet generator that continuous phase fluid injects respectively microfluidic device form oil bag fat liquor drops, and the different inlets that meanwhile the 3rd dispersed phase fluid of step (1) preparation respectively injected to the two-stage droplet generator of microfluidic device as middle phase, continuous phase fluid as foreign minister as interior phase, the first dispersed phase fluid form Water-In-Oil bag fat liquor drop; The Water-In-Oil bag fat liquor drop forming, oil bag fat liquor drop enters microfluidic device collecting pipe with continuous phase fluid, when oil bag fat liquor drop contacts with the expansion chamber of Water-In-Oil bag fat liquor drop at described collecting pipe, oil bag fat liquor drop spreads into the single multicomponent oil bag Water-In-Oil bag fat liquor drop that disperses of formation on Water-In-Oil bag fat liquor drop;

Flow (the Q of described the first dispersed phase fluid _b) be 100～150 μ L/h, the flow (Q of described the 3rd dispersed phase fluid _a2) be 150 μ L/h, the flow (Q of described the 5th dispersed phase fluid _a4) be 150～200 μ L/h, the flow (Q of described continuous phase fluid in single-stage droplet generator _c4) be 200～220 μ L/h, flow (Q in two-stage droplet generator _c3) be 300～500 μ L/h;

(3) collect single multicomponent multiple emulsion that disperses

Single multicomponent multiple emulsion drop that disperses that step (2) is formed is introduced in collection container by the efferent duct of microfluidic device together with continuous phase, obtains single multicomponent multiple emulsion that disperses of respective type.

2. the preparation method who singly disperses according to claim 1 multicomponent multiple emulsion, is characterized in that described water soluble emulsifier is the addition polymers of lauryl sodium sulfate or polypropylene glycol and oxirane.

3. singly disperse according to claim 1 the preparation method of multicomponent multiple emulsion, it is characterized in that described oil soluble emulsifying agent is the condensation product of poly-ricinoleic acid glyceride or alkyl phenol and oxirane.

4. singly disperse according to claim 1 the preparation method of multicomponent multiple emulsion, it is characterized in that described surfactant is the mixture of trimethicone and cyclohexyl methyl siloxanes composition, the volume ratio of trimethicone and cyclohexyl methyl siloxanes is 1:1.

5. according to single preparation method who disperses multicomponent multiple emulsion described in arbitrary claim in claim 1 to 4, it is characterized in that single external diameter that disperses emulsion droplet in multicomponent multiple emulsion prepared by the method is 100～500 μ m.