Preparation method of temperature-sensitive composite microspheres

Abstract

The invention discloses a preparation method of temperature-sensitive composite microspheres, and relates to the technical field of surface modification of functional materials. The invention aims to solve the problem of how to realize active circulating heat exchange in a chip micro-channel. The thermo-sensitive composite gel formed by the invention combines the properties of both intelligent gel and nanoparticles, and can realize effective controlled release of substances under ultraviolet light and temperature conditions after loading other substances. Mixing titanium dioxide, polydimethylsiloxane and silicone oil, forming PDMS microspheres with micro-coarse structures on the surfaces under the shearing action of a polyvinyl alcohol solution, and then forming the required temperature-sensitive material on the surfaces of the microspheres through polymerization grafting of monomers, so as to realize the combination of the performances of the titanium dioxide, the polydimethylsiloxane and the silicone oil. The invention can obtain the preparation method of the temperature-sensitive composite microsphere.

Description

Technical Field

[0001] The invention relates to the technical field of functional material surface modification, and in particular to a method for preparing temperature-sensitive composite microspheres. Background Art

[0002] Polymer composite microspheres are a new type of functional material with diameters ranging from nanometers to micrometers and spherical or other geometric shapes. Due to their surface effects, volume effects, biocompatibility and functional groups, they are widely used in various fields, from mass products such as paints, paper surface coatings and cosmetics to high value-added products such as drug sustained-release microcapsules and protein separation. In recent years, polymer microspheres have been modified by grafting and other means to give such microsphere materials environmental sensitivity. Their special size and morphology enable them to quickly respond to changes in environmental conditions (such as changes in temperature, pH value, magnetic field, ultrasound or ultraviolet light irradiation), thereby giving composite microspheres stronger functional characteristics and being able to be applied to a wider range of fields.

[0003] Therefore, preparing a temperature-sensitive composite microsphere with active cyclic heat exchange performance is of great significance for improving the heat dissipation of the chip. Summary of the invention

[0004] The purpose of the present invention is to solve the problem of how to realize active circulation heat exchange in a chip microchannel, and to provide a method for preparing temperature-sensitive composite microspheres.

[0005] A method for preparing temperature-sensitive composite microspheres is carried out according to the following steps:

[0006] Step S1: PDMS microsphere preparation;

[0007] A polyvinyl alcohol solution is injected from the water phase input port 1 of the hydrophilic modified microfluidic chip, a mixed solution composed of titanium dioxide, polydimethylsiloxane and silicone oil is injected from the oil phase input port 2 of the hydrophilic modified microfluidic chip, PDMS microspheres are collected at the composite microsphere outlet 3 of the hydrophilic modified microfluidic chip, and heated and cured to obtain cured PDMS microspheres;

[0008] The microfluidic chip is prepared according to the following steps: a channel with a T-shaped structure is formed on the surface of a silicon plate by photolithography technology, the inlet at the left end of the horizontal channel is used as a water phase input port 1, the inlet at the right end of the horizontal channel is used as a composite microsphere outlet 3, the inlet of the vertical channel is used as an oil phase input port 2, and a screen 4 is arranged in the channel where the water phase input port 1 and the oil phase input port 2 are located; finally, a mixture of monomer polydimethylsiloxane and a curing agent is poured on the surface of the T-shaped structure channel as a base of the flow channel, and the microfluidic chip is obtained after curing; the mass ratio of the monomer polydimethylsiloxane to the curing agent is (8-10):1;

[0009] Step S2: photoinitiator grafting;

[0010] Under yellow light, the cured PDMS microspheres obtained in step S1 are soaked in a benzophenone solution, and then injected into the filtration microchannel through the filtration inlet 5, the microspheres intercepted at the filtration outlet 6 are cleaned, and gas is introduced for drying;

[0011] Step S3: monomer polymerization grafting;

[0012] Under yellow light, the monomer N-isopropylacrylamide and the crosslinking agent are dissolved in deionized water, then injected from the filter inlet 5, mixed with the microspheres in step S2 and stored in the filter microchannel, and then irradiated with ultraviolet light;

[0013] Step S4: cleaning of the composite microspheres;

[0014] Air is introduced into the filtration microchannel, and the solution in step S3 is discharged from the filtration outlet 6. The microspheres remain in the filtration microchannel, and after cleaning, gas is introduced to dry them. Finally, deionized water is introduced into the filtration outlet 6 to flush the microspheres to the filtration inlet 5 for collection, thereby obtaining temperature-sensitive composite microspheres.

[0015] Beneficial effects of the present invention:

[0016] (1) The present invention discloses a temperature-sensitive composite microsphere, which has the characteristics of temperature response and ultraviolet light response. The thermosensitive composite gel formed by the present invention combines the properties of both smart gel and nanoparticles, and can achieve effective controlled release of substances under ultraviolet light and temperature conditions after loading other substances. Specifically, titanium dioxide, polydimethylsiloxane and silicone oil are mixed, and PDMS microspheres with a micro-rough structure on the surface are formed under the shearing action of polyvinyl alcohol solution, and then the desired thermosensitive material is formed on the surface of the microsphere by polymerization grafting of monomers, thereby achieving the combination of the two properties. The wettability transition can be achieved by controlling the thermosensitive material poly N-isopropylacrylamide below or above its lowest co-solubility temperature (LCST≈32°C). When the temperature is below 32°C, its chain contains a large number of hydrophilic groups, showing hydrophilicity; when the temperature is above 32°C, its chain cannot combine with hydrogen bonds in water molecules, showing hydrophobicity. In addition, under the irradiation of ultraviolet light, the long-chain alkyl modified on the surface of TiO2 is decomposed and the surface energy is increased; and because TiO2 is a photosensitive material, photogenerated holes are generated under the irradiation of ultraviolet light. The photogenerated holes react with lattice oxygen to generate oxygen vacancies on the TiO2 surface. The oxygen vacancies can react with water molecules to achieve the regulation of wettability.

[0017] (2) The photothermal responsive composite microspheres of the present invention have a stable surface structure and a uniform and adjustable roughness. In addition, the preparation and operation methods are simple, and the reaction conditions are mild and easy to control.

[0018] The invention can obtain a method for preparing temperature-sensitive composite microspheres. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 A schematic diagram showing the structure of a T-shaped channel in the present invention, 1 represents a water phase input port, 2 represents an oil phase input port, 3 represents a composite microsphere outlet, and 4 represents a screen;

[0020] Figure 2 A schematic diagram showing the present invention using microfluidic technology to shear the oil phase to form a microsphere device and to perform hydrophilic treatment on the flow channel;

[0021] Figure 3 A schematic diagram showing the preparation process of the thermosensitive microspheres with reversible wettability switching according to the present invention;

[0022] Figure 4 Schematic diagram of the filtering microchannel in the present invention, 5 represents the filtering inlet, and 6 represents the filtering outlet;

[0023] Figure 5 A microscopic morphology diagram showing the composite microspheres obtained by curing after shear molding according to the present invention;

[0024] Figure 6A scanning electron microscope image showing the composite microspheres obtained by curing after shear molding of the present invention;

[0025] Figure 7 A microscopic image showing the temperature-sensitive composite microspheres which are the final product of the present invention;

[0026] Figure 8 A diagram showing the wettability effect of the temperature-sensitive composite microspheres of the present invention at 20°C;

[0027] Fig. 9 A diagram showing the wettability effect of the temperature-sensitive composite microspheres of the present invention at 40°C;

[0028] Fig.10 A diagram showing the wettability effect of the temperature-sensitive composite microspheres of the present invention after ultraviolet irradiation at 40° C. for 6 hours. DETAILED DESCRIPTION

[0029] Specific implementation method 1: This implementation method is a method for preparing temperature-sensitive composite microspheres, which is carried out according to the following steps:

[0030] Step S1: PDMS microsphere preparation;

[0031] A polyvinyl alcohol solution is injected from the water phase input port 1 of the hydrophilic modified microfluidic chip, a mixed solution composed of titanium dioxide, polydimethylsiloxane and silicone oil is injected from the oil phase input port 2 of the hydrophilic modified microfluidic chip, PDMS microspheres are collected at the composite microsphere outlet 3 of the hydrophilic modified microfluidic chip, and heated and cured to obtain cured PDMS microspheres;

[0032] The microfluidic chip is prepared according to the following steps: a channel with a T-shaped structure is formed on the surface of a silicon plate by photolithography technology, the inlet at the left end of the horizontal channel is used as a water phase input port 1, the inlet at the right end of the horizontal channel is used as a composite microsphere outlet 3, the inlet of the vertical channel is used as an oil phase input port 2, and a screen 4 is arranged in the channel where the water phase input port 1 and the oil phase input port 2 are located; finally, a mixture of monomer polydimethylsiloxane and a curing agent is poured on the surface of the T-shaped structure channel as a base of the flow channel, and the microfluidic chip is obtained after curing; the mass ratio of the monomer polydimethylsiloxane to the curing agent is (8-10):1;

[0033] Step S2: photoinitiator grafting;

[0034] Under yellow light, the cured PDMS microspheres obtained in step S1 are soaked in a benzophenone solution, and then injected into the filtration microchannel through the filtration inlet 5, the microspheres intercepted at the filtration outlet 6 are cleaned, and gas is introduced for drying;

[0035] Step S3: monomer polymerization grafting;

[0036] Under yellow light, the monomer N-isopropylacrylamide and the crosslinking agent are dissolved in deionized water, then injected from the filter inlet 5, mixed with the microspheres in step S2 and stored in the filter microchannel, and then irradiated with ultraviolet light;

[0037] Step S4: cleaning of the composite microspheres;

[0038] Air is introduced into the filtration microchannel, and the solution in step S3 is discharged from the filtration outlet 6. The microspheres remain in the filtration microchannel, and after cleaning, gas is introduced to dry them. Finally, deionized water is introduced into the filtration outlet 6 to flush the microspheres to the filtration inlet 5 for collection, thereby obtaining temperature-sensitive composite microspheres.

[0039] Specific embodiment 2: The difference between this embodiment and specific embodiment 1 is that: the concentration of the polyvinyl alcohol solution described in step S1 is 5%; the mass ratio of polydimethylsiloxane to silicone oil in step S1 is 4:6; the heating and curing temperature in step S1 is 65-80°C.

[0040] The other steps are the same as those in the first specific implementation.

[0041] Specific implementation method three: This implementation method is different from specific implementation method one or two in that: the hydrophilic modified microfluidic chip described in step S1 is subjected to hydrophilic treatment according to the following steps: the microfluidic chip is evacuated by a vacuum pump, and then a NaOH solution with a concentration of 0.1 mol / L is sucked into the microfluidic chip from the water phase input port 1 and the oil phase input port 2 in sequence, and flows out from the composite microsphere outlet 3, and the treatment time is 10 to 15 minutes; air is sucked for 5 to 10 minutes, so that all the solution in the microfluidic chip flows out from the composite microsphere outlet 3; then deionized water is sucked for 1 to 3 minutes, and air is sucked for 5 to 10 minutes;

[0042] Then inhale the polycyclic aromatic hydrocarbon solution for 5 to 7 minutes, and then inhale air for 5 to 10 minutes, deionized water for 1 to 3 minutes, and air for 5 to 10 minutes; inhale the polyacrylic acid solution for 5 to 7 minutes, then inhale air for 5 to 10 minutes, water for 1 to 3 minutes, and air for 5 to 10 minutes. Finally, repeat the above operation 3 to 4 times to complete the hydrophilic modification of the microfluidic chip.

[0043] The other steps are the same as those in the first or second embodiment.

[0044] Specific embodiment 4: The difference between this embodiment and specific embodiments 1 to 3 is that in step S1, a polyvinyl alcohol solution and a mixed solution consisting of titanium dioxide, polydimethylsiloxane and silicone oil are respectively injected using a syringe pump.

[0045] The other steps are the same as those in Specific Embodiments 1 to 3.

[0046] Specific embodiment 5: The difference between this embodiment and specific embodiments 1 to 4 is that the flow rate of the polyvinyl alcohol solution is 0.2 to 6 μL / min, and the flow rates of titanium dioxide, polydimethylsiloxane and silicone oil are 0.04 to 3 μL / min.

[0047] The other steps are the same as those in Specific Embodiments 1 to 4.

[0048] Specific implementation method 6: This implementation method is different from specific implementation methods 1 to 5 in that: the benzophenone solution in step S2 is made of benzophenone and anhydrous ethanol, and the mass fraction of benzophenone is 10%.

[0049] The other steps are the same as those in Specific Embodiments 1 to 5.

[0050] Specific embodiment 7: The difference between this embodiment and specific embodiments 1 to 6 is that the time for the cured PDMS microspheres to be immersed in the benzophenone solution in step S2 is 10 to 15 minutes.

[0051] The other steps are the same as those in Specific Embodiments 1 to 6.

[0052] Specific embodiment eight: The difference between this embodiment and specific embodiments one to seven is that the mass ratio of the monomer N-isopropylacrylamide, the cross-linking agent and the deionized water described in step S3 is (1-1.5): (0.01-0.015): (13.485-13.99), and the cross-linking agent is N,N'-methylenebisacrylamide.

[0053] The other steps are the same as those in Specific Embodiments 1 to 7.

[0054] Specific implementation method 9: The difference between this implementation method and specific implementation methods 1 to 8 is that the light efficiency power of the ultraviolet lamp described in step S3 is 300-500W, the wavelength is 340-365nm, and the irradiation time is 5-10min.

[0055] The other steps are the same as those in Specific Embodiments 1 to 8.

[0056] The following examples are used to verify the beneficial effects of the present invention:

[0057] Example 1: A method for preparing temperature-sensitive composite microspheres is carried out according to the following steps:

[0058] Step S1: preparation of microfluidic chip;

[0059] The microchannel template was made by using polydimethylsiloxane (PDMS) soft etching method through photolithography technology, and SU8-3050 photoresist was used through the steps of coating, exposure, development and thermal baking. A mixture of PDMS monomer and curing agent (mass ratio of 10:1) was poured on it, and the upper layer of the chip was obtained by thermal baking on a 65°C hot plate. The upper layer of the chip was bonded to the glass substrate through oxygen plasma treatment to form a complete PDMS chip.

[0060] The chip flow channel structure is set as a T-shaped channel with a height of 50 μm and a width of 30 μm; the inlet at the left end of the horizontal channel serves as the water phase input port 1, the inlet at the right end of the horizontal channel serves as the composite microsphere outlet 3, and the inlet of the vertical channel serves as the oil phase input port 2, and a screen 4 is provided in the channel where the water phase input port 1 and the oil phase input port 2 are located, which is used to filter impurities in the liquid phase to prevent blockage of the flow channel.

[0061] Step S2: chip flow channel modification treatment;

[0062] The microfluidic chip was evacuated by a vacuum pump, and then a NaOH solution with a concentration of 0.1 mol / L was sucked into the microfluidic chip from the water phase input port 1 and the oil phase input port 2 in sequence, and flowed out from the composite microsphere outlet 3. The treatment time was 10 min. Air was inhaled for 5 min to make all the solution in the microfluidic chip flow out from the composite microsphere outlet 3. Then deionized water was inhaled for 1 min, and air was inhaled for 5 min.

[0063] Then inhale the polycyclic aromatic hydrocarbon (PAH) solution for 5 minutes, and then inhale air for 5 minutes, deionized water for 1 minute, and air for 5 minutes in sequence; inhale the polyacrylic acid (PAA) solution for 7 minutes, and then inhale air for 5 minutes, water for 1 minute, and air for 5 minutes in sequence. Finally, repeat the above operation 3 times to complete the hydrophilic modification of the microfluidic chip.

[0064] Step S3: PDMS microsphere preparation;

[0065] A 5% polyvinyl alcohol solution was injected from the water phase inlet 1 of the hydrophilic-modified microfluidic chip at a flow rate of 0.2 μL / min using a Harvard syringe pump (Pump 11Elite), and a mixed solution consisting of titanium dioxide, polydimethylsiloxane and silicone oil was injected from the oil phase inlet 2 of the hydrophilic-modified microfluidic chip at a flow rate of 0.09 μL / min using a Harvard syringe pump (Pump 11Elite), and the oil phase was sheared into microspheres using the water phase, and the PDMS microspheres were collected at the composite microsphere outlet 3 of the hydrophilic-modified microfluidic chip, and heated and cured at 65°C to obtain cured PDMS microspheres; the mass ratio of polydimethylsiloxane to silicone oil was 4:6;

[0066] Step S4: photoinitiator grafting;

[0067] Under yellow light, 1 g of benzophenone was dissolved in 9 g of anhydrous ethanol to prepare a 10% benzophenone solution. The cured PDMS microspheres were immersed in the benzophenone solution for 10 min and then injected into the filtration microchannel through the filtration inlet 5. The spacing of the filtration structure in the channel was 15 μm. The microspheres intercepted at the filtration outlet 6 were washed with deionized water and dried by passing gas.

[0068] Step S5: monomer polymerization grafting;

[0069] Under yellow light, 1 g of monomer N-isopropylacrylamide (NIPAm) and 0.01 g of cross-linking agent N,N'-methylenebisacrylamide were dissolved in 8.99 g of deionized water, then injected from the filter inlet 5, mixed with the microspheres and stored in the filter microchannel, and then irradiated with an ultraviolet lamp 15 cm above the solution for 10 min, with a light efficiency power of 500 W and a wavelength of 365 nm;

[0070] Step S6: cleaning of the composite microspheres;

[0071] Air is introduced into the filter microchannel, the solution is discharged from the filter outlet 6, the microspheres remain in the filter microchannel, gas is introduced to dry after cleaning, and finally deionized water is introduced into the filter outlet 6 to flush the microspheres to the filter inlet 5 for collection to obtain temperature-sensitive composite microspheres.

[0072] Example 2: A method for preparing temperature-sensitive composite microspheres is carried out according to the following steps:

[0073] Step S1: preparation of microfluidic chip;

[0074] The microchannel template was made by using polydimethylsiloxane (PDMS) soft etching method through photolithography technology, and SU8-3050 photoresist was used through the steps of coating, exposure, development and thermal baking. A mixture of PDMS monomer and curing agent (mass ratio of 10:1) was poured on it, and the upper layer of the chip was obtained by thermal baking on a 65°C hot plate. The upper layer of the chip was bonded to the glass substrate through oxygen plasma treatment to form a complete PDMS chip.

[0075] The chip flow channel structure is set as a T-shaped channel with a height of 50μm and a width of 50μm; the inlet at the left end of the horizontal channel serves as the water phase input port 1, the inlet at the right end of the horizontal channel serves as the composite microsphere outlet 3, and the inlet of the vertical channel serves as the oil phase input port 2, and a screen 4 is provided in the channel where the water phase input port 1 and the oil phase input port 2 are located, which is used to filter impurities in the liquid phase to prevent blockage of the flow channel.

[0076] Step S2: chip flow channel modification treatment;

[0077] The microfluidic chip was evacuated by a vacuum pump, and then a NaOH solution with a concentration of 0.1 mol / L was sucked into the microfluidic chip from the water phase input port 1 and the oil phase input port 2 in turn, and flowed out from the composite microsphere outlet 3. The treatment time was 15 min. Air was sucked in for 7 min, so that all the solution in the microfluidic chip flowed out from the composite microsphere outlet 3. Then deionized water was sucked in for 3 min, and air was sucked in for 7 min.

[0078] Then inhale the polycyclic aromatic hydrocarbon (PAH) solution for 7 minutes, and then inhale air for 7 minutes, deionized water for 3 minutes, and air for 7 minutes in sequence; inhale the polyacrylic acid (PAA) solution for 5 minutes, and then inhale air for 7 minutes, water for 3 minutes, and air for 7 minutes in sequence. Finally, repeat the above operation 3 times to complete the hydrophilic modification of the microfluidic chip.

[0079] Step S3: PDMS microsphere preparation;

[0080] A 5% polyvinyl alcohol solution was injected from the water phase inlet 1 of the hydrophilic-modified microfluidic chip at a flow rate of 0.8 μL / min using a Harvard syringe pump (Pump 11Elite), and a mixed solution consisting of titanium dioxide, polydimethylsiloxane and silicone oil was injected from the oil phase inlet 2 of the hydrophilic-modified microfluidic chip at a flow rate of 0.04 μL / min using a Harvard syringe pump (Pump 11Elite), and the oil phase was sheared into microspheres using the water phase, and the PDMS microspheres were collected at the composite microsphere outlet 3 of the hydrophilic-modified microfluidic chip, and heated and cured at 65°C to obtain cured PDMS microspheres; the mass ratio of polydimethylsiloxane to silicone oil was 4:6;

[0081] Step S4: photoinitiator grafting;

[0082] Under yellow light, 1.5 g of benzophenone was dissolved in 13.5 g of anhydrous ethanol to prepare a 10% benzophenone solution. The cured PDMS microspheres were immersed in the benzophenone solution for 10 min and then injected into the filtration microchannel through the filtration inlet 5. The spacing of the filtration structure in the channel was 15 μm. The microspheres intercepted at the filtration outlet 6 were washed with deionized water and dried by passing gas.

[0083] Step S5: monomer polymerization grafting;

[0084] Under yellow light, 1.5 g of monomer N-isopropylacrylamide (NIPAm) and 0.015 g of cross-linking agent N,N'-methylenebisacrylamide were dissolved in 13.485 g of deionized water, then injected from the filter inlet 5, mixed with the microspheres and stored in the filter microchannel, and then irradiated with an ultraviolet lamp 15 cm above the solution for 10 min, with a light efficiency power of 500 W and a wavelength of 365 nm;

[0085] Step S6: cleaning of the composite microspheres;

[0086] Air is introduced into the filter microchannel, the solution is discharged from the filter outlet 6, the microspheres remain in the filter microchannel, gas is introduced to dry after cleaning, and finally deionized water is introduced into the filter outlet 6 to flush the microspheres to the filter inlet 5 for collection to obtain temperature-sensitive composite microspheres.

[0087] Example 3: A method for preparing temperature-sensitive composite microspheres is carried out according to the following steps:

[0088] Step S1: preparation of microfluidic chip;

[0089] The microchannel template was made by using polydimethylsiloxane (PDMS) soft etching method through photolithography technology, and SU8-3050 photoresist was used through the steps of coating, exposure, development and thermal baking. A mixture of PDMS monomer and curing agent (mass ratio of 10:1) was poured on it, and the upper layer of the chip was obtained by thermal baking on a hot plate at 80°C. The upper layer of the chip was bonded to the glass substrate through oxygen plasma treatment to form a complete PDMS chip.

[0090] The chip flow channel structure is set as a T-shaped channel with a height of 50 μm and a width of 100 μm; the inlet at the left end of the horizontal channel serves as the water phase input port 1, the inlet at the right end of the horizontal channel serves as the composite microsphere outlet 3, and the inlet of the vertical channel serves as the oil phase input port 2, and a screen 4 is provided in the channel where the water phase input port 1 and the oil phase input port 2 are located to filter impurities in the liquid phase to prevent blockage of the flow channel.

[0091] Step S2: chip flow channel modification treatment;

[0092] The microfluidic chip was evacuated by a vacuum pump, and then a NaOH solution with a concentration of 0.1 mol / L was sucked into the microfluidic chip from the water phase input port 1 and the oil phase input port 2 in sequence, and flowed out from the composite microsphere outlet 3. The treatment time was 10 min. Air was inhaled for 5 min to make all the solution in the microfluidic chip flow out from the composite microsphere outlet 3. Then deionized water was inhaled for 1 min, and air was inhaled for 5 min.

[0093] Then inhale the polycyclic aromatic hydrocarbon (PAH) solution for 5 minutes, and then inhale air for 5 minutes, deionized water for 1 minute, and air for 5 minutes in sequence; inhale the polyacrylic acid (PAA) solution for 5 minutes, and then inhale air for 5 minutes, water for 1 minute, and air for 5 minutes in sequence. Finally, repeat the above operation 4 times to complete the hydrophilic modification of the microfluidic chip.

[0094] Step S3: PDMS microsphere preparation;

[0095] A 5% polyvinyl alcohol solution was injected from the water phase inlet 1 of the hydrophilic-modified microfluidic chip at a flow rate of 6 μL / min using a Harvard syringe pump (Pump 11Elite), and a mixed solution consisting of titanium dioxide, polydimethylsiloxane and silicone oil was injected from the oil phase inlet 2 of the hydrophilic-modified microfluidic chip at a flow rate of 3 μL / min using a Harvard syringe pump (Pump 11Elite), and the oil phase was sheared into microspheres using the water phase, and the PDMS microspheres were collected at the composite microsphere outlet 3 of the hydrophilic-modified microfluidic chip, and heated and cured at 65°C to obtain cured PDMS microspheres; the mass ratio of polydimethylsiloxane to silicone oil was 4:6;

[0096] Step S4: photoinitiator grafting;

[0097] Under yellow light, 1.5 g of benzophenone was dissolved in 13.5 g of anhydrous ethanol to prepare a 10% benzophenone solution. The cured PDMS microspheres were immersed in the benzophenone solution for 10 min and then injected into the filtration microchannel through the filtration inlet 5. The spacing of the filtration structure in the channel was 15 μm. The microspheres intercepted at the filtration outlet 6 were washed with deionized water and dried by passing gas.

[0098] Step S5: monomer polymerization grafting;

[0099] Under yellow light, 1.5 g of monomer N-isopropylacrylamide (NIPAm) and 0.015 g of cross-linking agent N,N'-methylenebisacrylamide were dissolved in 13.485 g of deionized water, then injected from the filter inlet 5, mixed with the microspheres and stored in the filter microchannel, and then irradiated with an ultraviolet lamp 15 cm above the solution for 10 min, with a light efficiency power of 500 W and a wavelength of 365 nm;

[0100] Step S6: cleaning of the composite microspheres;

[0101] Air is introduced into the filter microchannel, the solution is discharged from the filter outlet 6, the microspheres remain in the filter microchannel, gas is introduced to dry after cleaning, and finally deionized water is introduced into the filter outlet 6 to flush the microspheres to the filter inlet 5 for collection to obtain temperature-sensitive composite microspheres.

[0102] By comparing the above three embodiments, it is found that the selection of different size channels and different flow rates has an effect on the size of the microspheres formed by shearing. When a stable flow rate is selected for shearing, the size of the microspheres is equivalent to the size of the flow channel; when the shear flow rate increases (under the premise of ensuring that the shear effect can be formed), the size of the microspheres formed by shearing decreases. The greater the flow rate, the smaller the size of the microspheres. In addition, changing the mass ratio of N-isopropylacrylamide, crosslinking agent and deionized water and the time of ultraviolet polymerization also show different effects. The greater the proportion of monomer N-isopropylacrylamide, the longer the ultraviolet polymerization illumination time, the more temperature-sensitive materials are formed on the surface of the microspheres, and the better the wettability effect.

[0103] Figure 8 The wettability effect diagram of the temperature-sensitive composite microspheres of the present invention at 20°C is shown. Fig. 9 The wettability effect diagram of the temperature-sensitive composite microspheres of the present invention at 40°C is shown. Fig.10 The figure shows the wettability effect of the temperature-sensitive composite microspheres of the present invention after ultraviolet irradiation at 40°C for 6 hours. Figure 8-10 As shown in the figure, the wettability transition is achieved by controlling the temperature below or above the lowest eutectic temperature (LCST≈32°C) of the thermosensitive hydrogel film. For example, at 20°C, the surface of the microspheres is in a hydrophilic state, and when the temperature is adjusted to 40°C, it changes to a hydrophobic state. At this time, after 6 hours of ultraviolet irradiation, the hydrophobic effect of the microspheres is significantly weakened.

Claims

1. A method for preparing temperature-sensitive composite microspheres, characterized in that The preparation method is carried out according to the following steps: Step S1: PDMS microsphere preparation; A polyvinyl alcohol solution is injected from the water phase input port (1) of the hydrophilic modified microfluidic chip, a mixed solution consisting of titanium dioxide, polydimethylsiloxane and silicone oil is injected from the oil phase input port (2) of the hydrophilic modified microfluidic chip, PDMS microspheres are collected at the composite microsphere outlet (3) of the hydrophilic modified microfluidic chip, and heated and cured to obtain cured PDMS microspheres; The microfluidic chip is prepared according to the following steps: a channel with a T-shaped structure is formed on the surface of a silicon plate by photolithography technology, the inlet at the left end of the horizontal channel is used as a water phase input port (1), the inlet at the right end of the horizontal channel is used as a composite microsphere outlet (3), the inlet of the vertical channel is used as an oil phase input port (2), and a screen (4) is arranged in the channel where the water phase input port (1) and the oil phase input port (2) are located; finally, a mixture of monomer polydimethylsiloxane and a curing agent is poured on the surface of the T-shaped structure channel as a flow channel substrate, and the microfluidic chip is obtained after curing; the mass ratio of the monomer polydimethylsiloxane to the curing agent is (8-10):1; Step S2: photoinitiator grafting; Under yellow light, the cured PDMS microspheres obtained in step S1 are soaked in a benzophenone solution, and then injected into the filtration microchannel through the filtration inlet (5), the microspheres intercepted at the filtration outlet (6) are cleaned, and gas is introduced for drying; Step S3: monomer polymerization grafting; Under yellow light, the monomer N-isopropylacrylamide and the crosslinking agent are dissolved in deionized water, then injected from the filter inlet (5), mixed with the microspheres in step S2 and stored in the filter microchannel, and then irradiated with ultraviolet light; Step S4: cleaning of the composite microspheres; Air is introduced into the filtering microchannel, and the solution in step S3 is discharged from the filtering outlet (6). The microspheres are retained in the filtering microchannel, and after cleaning, gas is introduced to dry them. Finally, deionized water is introduced into the filtering outlet (6) to flush the microspheres to the filtering inlet (5) for collection, thereby obtaining temperature-sensitive composite microspheres.

2. The method for preparing a temperature-sensitive composite microsphere according to claim 1, characterized in that The concentration of the polyvinyl alcohol solution in step S1 is 5%; the mass ratio of polydimethylsiloxane to silicone oil in step S1 is 4:6; the temperature of heating and curing in step S1 is 65-80°C.

3. The method for preparing a temperature-sensitive composite microsphere according to claim 1, characterized in that The hydrophilic-modified microfluidic chip described in step S1 is subjected to hydrophilic treatment according to the following steps: the microfluidic chip is evacuated by a vacuum pump, and then a NaOH solution with a concentration of 0.1 mol / L is sucked into the microfluidic chip from the water phase input port (1) and the oil phase input port (2) in sequence, and flows out from the composite microsphere outlet (3), and the treatment time is 10 to 15 minutes; air is sucked for 5 to 10 minutes, so that all the solution in the microfluidic chip flows out from the composite microsphere outlet (3); then deionized water is sucked for 1 to 3 minutes, and air is sucked for 5 to 10 minutes; Then inhale the polycyclic aromatic hydrocarbon solution for 5 to 7 minutes, and then inhale air for 5 to 10 minutes, deionized water for 1 to 3 minutes, and air for 5 to 10 minutes; inhale the polyacrylic acid solution for 5 to 7 minutes, then inhale air for 5 to 10 minutes, water for 1 to 3 minutes, and air for 5 to 10 minutes. Finally, repeat the above operation 3 to 4 times to complete the hydrophilic modification of the microfluidic chip.

4. The method for preparing a temperature-sensitive composite microsphere according to claim 1, characterized in that In step S1, a polyvinyl alcohol solution and a mixed solution consisting of titanium dioxide, polydimethylsiloxane and silicone oil are respectively injected using a syringe pump.

5. The method for preparing a temperature-sensitive composite microsphere according to claim 1, characterized in that The flow rate of the polyvinyl alcohol solution is 0.2 to 6 μL / min, and the flow rates of titanium dioxide, polydimethylsiloxane and silicone oil are 0.04 to 3 μL / min.

6. The method for preparing a temperature-sensitive composite microsphere according to claim 1, characterized in that The benzophenone solution in step S2 is prepared from benzophenone and anhydrous ethanol, and the mass fraction of benzophenone is 10%.

7. The method for preparing temperature-sensitive composite microspheres according to claim 1, characterized in that The time for the cured PDMS microspheres to be immersed in the benzophenone solution in step S2 is 10 to 15 minutes.

8. The method for preparing a temperature-sensitive composite microsphere according to claim 1, characterized in that The mass ratio of the monomer N-isopropylacrylamide, the cross-linking agent and the deionized water in step S3 is (1-1.5): (0.01-0.015): (13.485-13.99), and the cross-linking agent is N,N'-methylenebisacrylamide.

9. The method for preparing temperature-sensitive composite microspheres according to claim 1, characterized in that The luminous efficiency power of the ultraviolet lamp described in step S3 is 300-500W, the wavelength is 340-365nm, and the irradiation time is 5-10min.

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