CN114699999B - Preparation method of core-shell silica microspheres based on microfluidic liquid drops - Google Patents

Abstract

The invention provides a preparation method of core-shell silica microspheres based on microfluidic liquid drops, which comprises the steps of preparing a gradient emulsifying device, modifying a channel, generating liquid drops in the channel, preparing microspheres and the like, wherein monodisperse liquid drops are formed through a gradient emulsifying method in a liquid drop microfluidic technology, a silica precursor solution and caprylic acid glyceride are mutually dissolved in the presence of ethyl acetate to serve as a disperse phase, fluorocarbon oil serves as a continuous phase to form liquid drops with uniform size, volatilization of the ethyl acetate after standing causes the silica precursor solution and the caprylic acid glyceride to be mutually insoluble, and meanwhile, a surfactant in the fluorocarbon oil reacts with the silica precursor solution to solidify the liquid drops, so that the silica microspheres with core-shell structures are formed. On the basis, the content of the silicon dioxide precursor solution and the caprylic/capric glyceride in the disperse phase is changed, and the silicon dioxide microspheres with different core-shell thicknesses are obtained.

Description

A method for preparing core-shell silica microspheres based on microfluidic droplets

Technical field

The invention relates to a method for preparing core-shell silica microspheres based on microfluidic droplets, and belongs to the technical field of microfluidic microfluids.

Background technique

With the development of micro-nano technology, core-shell silica microspheres are widely used in drug delivery, biosensing and other fields, and have broad development prospects in materials science. There are various methods for preparing core-shell silica microspheres. The traditional preparation method of silica microspheres is to combine the emulsification method and the sol-gel method. However, this method requires huge equipment and the prepared microspheres have poor monodispersity. When used in research with strict microsphere size requirements, , it is difficult to meet the experimental requirements. The search found that the Chinese patent with publication number CN108341415A discloses a method for preparing macroporous silica core-shell microspheres. The silica core-shell microspheres prepared by this method have a macroporous structure and use non-porous microspheres and Non-porous silica microspheres are obtained by modifying the reaction of organic monomers, cross-linking agents, and porogens. The size of the prepared microspheres is 1 to 3 μm, and can be used for rapid separation and analysis of biological macromolecules. CN110433882A discloses a capillary droplet microfluidic device and a method for preparing a single-particle plunger. The device is a microfluidic device made of capillary tubes, and is mixed with tetramethoxysiloxane, polyethylene glycol, acetic acid and ammonia water. The solution is a dispersed phase to prepare a capillary plunger.

The droplets formed by droplet microfluidic technology are highly monodispersed and have gradually developed into a new method for the preparation of microspheres. Droplet microfluidic technology can be divided into co-flow, cross-flow, flow focusing and step emulsification devices according to the different geometry of the chip device. Among them, the gradient emulsification method mainly relies on channel geometry and surface tension to form monodispersed droplets, which is a spontaneous process. When the dispersed phase enters the end of the parallelized secondary channel, it is restrained by the surrounding channel walls. When it approaches the liquid reservoir connected to the secondary channel (where the continuous phase is located), the fluid becomes tongue-shaped due to surface tension. After the tongue-shaped fluid enters the liquid reservoir, it is continuously filled into a bulb shape. The Plas pressure difference between the bulb-shaped fluid and the dispersed phase still in the secondary channel continues to increase, and finally the neck of the bulb-shaped fluid breaks to form a droplet. At present, the preparation of core-shell silica microspheres based on the gradient emulsification method of microfluidic droplets has not yet been discovered.

Contents of the invention

The technical problem to be solved by the present invention is to overcome the shortcomings of the existing technology and provide a method for preparing core-shell silica microspheres based on microfluidic droplets. This method uses microfluidic technology for the preparation of microspheres. The prepared microspheres are uniform in size and highly monodisperse.

The invention provides a method for preparing core-shell silica microspheres based on microfluidic droplets, which includes the following steps:

Step 1. Prepare the microfluidic chip (i.e. gradient emulsification device) - use polydimethylsiloxane (PDMS) to pour it on the template of the gradient emulsification device and an empty template without pattern, remove it after heating and setting, and leave a blank polydimethylsiloxane After sealing with methylsiloxane on the upper side and gradient emulsification channel on the lower side, holes are drilled, plasma cleaned, and finally sealed on the glass sheet;

Step 2. Channel modification - Inject the modification liquid into the channel of the gradient emulsification device. After modification for a certain period of time, remove the modification liquid;

Step 3. Generation of droplets in the channel and preparation of microspheres - Dissolve the silica precursor solution and glyceryl octanoate in ethyl acetate at a volume ratio of 10 to 50:1 (ethyl acetate is used as Solvent, the amount added is enough to make the silica precursor solution and octanoic acid glyceryl ester mutually soluble), mix evenly to form a dispersed phase, the dispersed phase is injected into the gradient emulsification device at a certain flow rate, and the dispersed phase is in the gradient emulsification The channels of the device break into droplets, and the droplets flow into the liquid reservoir containing the continuous phase. After standing for a period of time, they solidify into microspheres;

Step 4: Collect the microspheres and calcine them in a muffle furnace at 800°C for 2 hours to obtain core-shell silica microspheres based on microfluidic droplets.

The present invention forms micro droplets through microfluidic technology. The droplets have a high degree of monodispersity, and when they are subsequently solidified into microspheres, the microsphere particle size distribution is small. At the same time, the silicon dioxide precursor solution and glyceryl octanoate are used in the Microspheres with core-shell structure were obtained through mutual solubility in the presence or absence of ethyl acetate, and silica microspheres with different core-shell thicknesses were prepared. The prepared core-shell silica microspheres have no pore structure and are about 200 μm in size. They have an adsorption function and can adsorb iodine ions in an iodine aqueous solution.

The present invention uses a gradient emulsification device to prepare core-shell silica microspheres. Compared with the traditional preparation method of core-shell silica microspheres through interface reaction, the core-shell wall produced is thin and easy to break. Phase separation realizes the preparation of core-shell structure, and the core-shell thickness can be adjusted by changing the content between the two reagents.

As the technical solution for further optimization of the present invention is as follows:

In the step 1, the gradient emulsification device consists of a dispersed phase main channel, seven parallel secondary channels and a liquid storage tank loaded with the continuous phase. The main channel is pluggably connected to the injection needle of the syringe pump. The main channel is connected to the inlet of the secondary channel, and the outlet of the secondary channel is connected to the liquid storage tank. The present invention designs a suitable gradient emulsification device, which increases the flux of the device to a certain extent; the gradient emulsification device uses The material is polydimethylsiloxane (PDMS).

The microfluidic chip of the present invention is a gradient emulsification device and integrates seven parallel secondary channels, which improves the throughput of the device.

Further, the liquid storage tank is equipped with a continuous phase, and the continuous phase is fluorocarbon oil.

Further, the modification liquid is a mixed solution composed of fluorine-containing trichlorosilane and electronic fluorination liquid (FC 40). The mixed solution contains 3 volume % of fluorine-containing trichlorosilane and 97 volume % of electronic fluorination liquid. . The modification liquid composed of fluorine-containing trichlorosilane and electronic fluoride liquid can change the hydrophobicity of the PDMS channel surface and prevent droplets from sticking to the channel.

In step 3, due to the increasing Laplace pressure difference at the tip of the dispersed phase in the area connected to the liquid reservoir at the end of the secondary channel, the dispersed phase breaks into droplets in the area connected to the liquid reservoir at the end of the secondary channel and flows into a continuous In the liquid storage tank of the phase, fluorocarbon oil is used as the continuous phase. After the droplets stand for 30 to 40 minutes, the silica precursor solution solidifies with the volatilization of ethyl acetate to obtain silica microspheres.

The silica microspheres of the present invention have a core-shell structure. Silica precursor solution, octyl glyceryl ester and ethyl acetate are used as dispersed phases to form droplets, and then the silica precursor is evaporated through the volatilization of ethyl acetate. The solution and octanoic acid glyceryl are immiscible to form a core-shell structure, in which silica microspheres are the shell and octanoic acid glyceryl ester is the core.

Furthermore, the liquid droplets have monodispersity, and the cured silica microspheres also have monodispersity.

Further, the core-shell silica microspheres can be prepared with different core-shell thicknesses by adjusting the volume ratio of the silica precursor solution and glyceryl octanoate in the dispersed phase. The volume ratios of the silica precursor solution and glyceryl octanoate are 10:1, 20:1, 30:1, 40:1, and 50:1 respectively.

Further, the preparation method of the silica precursor solution is as follows: using tetraethyl orthosilicate as the silicon source, mix 2.7 g 0.01 M hydrochloric acid solution, 3 g ethanol solution and 5.2 g tetraethyl orthosilicate, Stir for 30 minutes.

The present invention forms monodisperse droplets through the gradient emulsification method in droplet microfluidic technology. Silica precursor solution and glyceryl octanoate are mutually dissolved in the presence of ethyl acetate as the dispersed phase, and fluorocarbon oil is used as the dispersed phase. The continuous phase forms droplets of uniform size. After standing, the volatilization of ethyl acetate will cause the silica precursor solution and glyceryl octanoate to be immiscible. At the same time, the surfactant in the fluorocarbon oil will not dissolve with the silica precursor solution. The reaction solidifies the droplets, thus forming silica microspheres with a core-shell structure. On this basis, the contents of the silica precursor solution and glyceryl octanoate in the dispersed phase were changed, and silica microspheres with different core-shell thicknesses were obtained.

The present invention also provides the application of the core-shell silica microspheres prepared by the above method: the core-shell silica microspheres have an adsorption function and are used to adsorb iodide ions.

Further, the prepared core-shell silica microspheres were added to the iodine aqueous solution, and after letting it stand for one night, they were compared with the iodine aqueous solution without adding microspheres, and the ultraviolet absorbance photometric values of the two solutions were measured to verify the performance of the microspheres. application.

The advantage of the present invention is that droplet microfluidic technology can be used to generate highly monodispersed droplets. After solidification, uniform-sized silica microspheres are obtained. The silica microspheres have a core-shell structure. By changing the volume ratio of the dispersed phase Silica microspheres with different core-shell thicknesses can be obtained, and the prepared microspheres have adsorption functions.

In short, the preparation method of the present invention is unique. The core-shell silica microspheres are prepared through the gradient emulsification method in microfluidic droplet technology, which can not only obtain monodispersed microspheres but also increase the droplet generation rate; the reagents that form the core-shell structure Uniquely, because the silica precursor solution and glyceryl octanoate are mutually soluble in the presence of ethyl acetate, the volatilization of ethyl acetate after the droplets are generated makes the silica precursor solution and glyceryl octanoate gradually insoluble in each other. , thus obtaining the core-shell mechanism. Core-shell silica microspheres are prepared in one step through droplets and microspheres. The preparation is fast and the method is simple.

Description of the drawings

Figure 1 is a schematic diagram and a physical diagram of the method of the present invention.

Figure 2 is a schematic diagram of the gradient emulsification device in the present invention.

Figure 3 is a physical diagram of droplets just formed and after solidification under different dispersed phase volume ratios in the present invention.

Figure 4 is a statistical diagram of the size of droplets just formed and after solidification under different dispersed phase volume ratios in the present invention.

Figure 5 is an electron microscope image of silica microspheres under different dispersed phase volume ratios in the present invention.

Figure 6 is a schematic diagram of the iodine aqueous solution in the present invention without and after adding silica microspheres and left to stand for one night.

Figure 7 is a graph showing the ultraviolet absorption light photometric curve of the iodine aqueous solution after leaving it alone overnight without adding silica microspheres in the present invention.

Detailed ways

The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings: This embodiment is implemented on the premise of the technical solution of the present invention, and detailed implementation modes and specific operating procedures are given. However, the protection rights of the present invention are not limited to Limited to the following examples.

Example 1 Preparation of core-shell silica microspheres in gradient emulsification device

Using a standard photolithography process to process a photoresist positive mold with a specific pattern, a gradient emulsification device template can be obtained. The template has positive patterns corresponding to the main and secondary channels and liquid reservoirs on the gradient emulsification device. The prepolymers of polydimethylsiloxane (PDMS) are poured on the positive mold respectively until the height of the prepolymer is flush with the positive mold. At the same time, the prepolymer of polydimethylsiloxane (PDMS) is poured on the positive mold. On the empty template without pattern, vacuum degassing is performed respectively, and then heated, cured and finalized. After cooling, the polydimethylsiloxane block with the channel pattern is peeled off, punched, plasma cleaned, and the polydimethylsiloxane block with the channel pattern is combined with the blank polydimethylsiloxane block. Sealing, and then sealing with the glass substrate to form a microfluidic gradient emulsification chip. The microfluidic gradient emulsification chip consists of a dispersed phase main channel, seven parallel secondary channels and a liquid storage tank loaded with the continuous phase. One end of the main channel is pluggably connected to the injection needle of the syringe pump, the other end is connected to the inlet of the secondary channel, and the outlet of the secondary channel is connected to the liquid reservoir (see Figure 2). The liquid reservoir is filled with a continuous phase, which is fluorocarbon oil.

Inject the modification fluid into the channel of the gradient emulsification device. After modification for 30 minutes, remove the modification fluid and repeat the operation twice. The modification liquid is a mixed solution composed of fluorine-containing trichlorosilane and electronic fluorination liquid (FC 40). The mixed solution contains 3 volume % of fluorine-containing trichlorosilane and 97 volume % of electronic fluorination liquid.

After the modification is completed, the dispersed phase is injected into the chip at a certain flow rate through a syringe pump. As the Laplace pressure difference at the tip of the dispersed phase connected to the reservoir area at the end of the secondary channel continues to increase, the dispersed phase breaks into droplets and enters. In a storage tank filled with the continuous phase, after standing for 30 to 40 minutes, the silica precursor solution solidifies into microspheres as the ethyl acetate evaporates (see Figures 1, 3 and 4, in Figure 3 The volume ratios of the silica precursor solution and glyceryl octanoate are A and D: 20:1; B and E: 30:1; C and F: 50:1). Among them, the silica precursor solution and glyceryl octanoate were dissolved in ethyl acetate in a volume ratio of 20:1, 30:1, and 50:1 respectively (the amount of ethyl acetate added was such that the two are mutually soluble. Yes), mix evenly to form a dispersed phase. The preparation method of the silica precursor solution is as follows: using tetraethyl orthosilicate as the silicon source, mix 2.7 g 0.01M hydrochloric acid solution, 3 g ethanol solution and 5.2 g tetraethyl orthosilicate, and stir for 30 min. The microspheres were placed in a muffle furnace and calcined at 800°C for 2 hours to remove the octanoic acid glyceryl ester in the microspheres to obtain microspheres with a core-shell structure.

In addition, the volume ratio of the silica precursor solution and octanoic acid glyceryl ester in the dispersed phase was changed to 10:1, 30:1, and 50:1 to prepare silica microspheres with different core-shell thicknesses (see Figure 5 , the volume ratios of silica precursor solution and glyceryl octanoate are A, B, C 10:1; D, E, F: 20:1; G, H, I: 30:1; J, K, L : 50:1).

Example 2 Application verification of core-shell silica microspheres

Add the prepared core-shell silica microspheres to the iodine aqueous solution. After leaving it for one night, compare it with the iodine aqueous solution without microspheres to observe the color change of the solution, as shown in Figure 6. A represents the iodine aqueous solution without microspheres. Iodine aqueous solution; B represents the iodine aqueous solution with microspheres added, and the UV absorbance photometric values of the two solutions were measured at the same time. The results are shown in Figure 7.

The above are only specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Anyone familiar with this technology can understand the conceivable transformations or substitutions within the technical scope disclosed in the present invention. All should be included within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.

Claims (9)

1. A method for preparing core-shell silica microspheres based on microfluidic droplets, which is characterized in that it includes the following steps: Step 1. Prepare the gradient emulsification device - use polydimethylsiloxane to pour on the template of the gradient emulsification device and the empty template without pattern, remove it after heating and setting, and put the blank polydimethylsiloxane on top and gradient emulsification After the channel is sealed underneath, it is drilled, plasma cleaned, and finally sealed to the glass sheet; Step 2. Channel modification - inject the modification liquid into the channel of the gradient emulsification device. After modification for a certain period of time, remove the modification liquid; the modification liquid is a mixed solution composed of fluorine-containing trichlorosilane and electronic fluorination liquid; Step 3. Generation of droplets in the channel and preparation of microspheres - Dissolve the silica precursor solution and glyceryl octanoate in ethyl acetate at a volume ratio of 10 to 50:1, and mix evenly to form a dispersion. The dispersed phase is injected into the gradient emulsification device at a certain flow rate. The dispersed phase breaks into droplets in the channel of the gradient emulsification device. The droplets flow into the liquid storage tank containing the continuous phase. After standing for a period of time, they solidify. into microspheres; the continuous phase is fluorocarbon oil; Step 4: Collect the microspheres and calcine them in a muffle furnace at 800°C for 2 hours to obtain core-shell silica microspheres based on microfluidic droplets. 2. A method for preparing core-shell silica microspheres based on microfluidic droplets according to claim 1, characterized in that in step 1, the gradient emulsification device consists of a dispersed phase main channel, seven parallel The secondary channel is composed of a liquid storage tank loaded with a continuous phase. The main channel is pluggably connected to the injection needle of the syringe pump. The main channel is connected to the inlet of the secondary channel. The outlet of the secondary channel is connected to the liquid storage tank. Connected; the material used in the gradient emulsification device is polydimethylsiloxane. 3. A method for preparing core-shell silica microspheres based on microfluidic droplets according to claim 1, characterized in that the mixed solution contains 3% by volume of fluorine-containing trichlorosilane and 97% by volume of Electronic fluoride liquid; a modification liquid composed of fluorine-containing trichlorosilane and electronic fluoride liquid, which can change the hydrophobicity of the PDMS channel surface and prevent droplets from sticking to the channel. 4. A method for preparing core-shell silica microspheres based on microfluidic droplets according to claim 1, characterized in that in step 3, because the end of the secondary channel is connected to the tip of the dispersed phase in the liquid reservoir area The Laplace pressure difference continues to increase, and the dispersed phase breaks into droplets in the area connected to the liquid reservoir at the end of the side channel, and flows into the liquid reservoir filled with the continuous phase. Fluorocarbon oil is used as the continuous phase, and the droplets stand still. After 30 to 40 minutes, the silica precursor solution solidifies with the volatilization of ethyl acetate to obtain silica microspheres. 5. A method for preparing core-shell silica microspheres based on microfluidic droplets according to claim 4, characterized in that the droplets have monodispersity, and the cured silica microspheres also have Monodispersity. 6. A method for preparing core-shell silica microspheres based on microfluidic droplets according to claim 5, characterized in that the core-shell silica microspheres are prepared by adjusting the silica precursor in the dispersed phase. The volume ratio of the solution and glyceryl octanoate was used to prepare silica microspheres with different core-shell thicknesses. The volume ratios of the silica precursor solution and glyceryl octanoate in the dispersed phase were 10:1 and 20: respectively. 1. 30:1, 40:1, 50:1. 7. A method for preparing core-shell silica microspheres based on microfluidic droplets according to claim 1, characterized in that the preparation method of the silica precursor solution is as follows: add 2.7 g of 0.01 M hydrochloric acid solution, 3 g of ethanol solution and 5.2 g of tetraethyl orthosilicate, and stir for 30 min. 8. Application of core-shell silica microspheres prepared by the method of any one of claims 1 to 7, characterized in that the core-shell silica microspheres have an adsorption function for adsorbing iodide ions. 9. The application of a kind of core-shell silica microspheres according to claim 8, characterized in that, the prepared core-shell silica microspheres are added to the iodine aqueous solution and left to stand for one night. The iodine aqueous solution was compared, and the UV absorbance photometric values of the two solutions were measured to verify the application of the microspheres.