阅读说明：本技术 疫苗冷链运输智能监控标签及其制备方法 (Intelligent monitoring label for vaccine cold chain transportation and preparation method thereof ) 是由 李华腾 吴攀 汪长春 于 2021-01-08 设计创作，主要内容包括：本发明属于冷链运输监控技术领域,具体为一种疫苗冷链运输智能监控标签及其制备方法。本发明的智能监控标签是由粒径均一的聚合物微球通过特定的加工方式排列而成的光子晶体弹性体；通过构建标签颜色与温度变化过程的精准对应关系,从而直观监测疫苗温度情况,确保疫苗质量。本发明方法包括：合成单分散核壳聚合物微球,其壳层的玻璃化转变温度根据疫苗相应储存上限温度进行设计；通过热压和弯曲诱导加工方法制备光子晶体弹性薄膜；在疫苗存储温度即壳层玻璃化转变温度以上进行拉伸,再快速降温到其玻璃化转变温度以下,保存。当运输过程中温度高于疫苗储存温度时,标签的颜色发生改变。只需直观观察标签的颜色,即可对疫苗的质量状况进行判别。(The invention belongs to the technical field of cold chain transportation monitoring, and particularly relates to an intelligent monitoring label for vaccine cold chain transportation and a preparation method thereof. The intelligent monitoring label is a photonic crystal elastomer formed by arranging polymer microspheres with uniform particle sizes in a specific processing mode; by constructing the accurate corresponding relation between the label color and the temperature change process, the temperature condition of the vaccine is monitored visually, and the quality of the vaccine is ensured. The method comprises the following steps: synthesizing monodisperse core-shell polymer microspheres, wherein the glass transition temperature of the shell layer is designed according to the corresponding storage upper limit temperature of the vaccine; preparing a photonic crystal elastic film by a hot pressing and bending induction processing method; stretching the vaccine at the temperature above the glass transition temperature of the shell layer, rapidly cooling to the temperature below the glass transition temperature, and storing. When the temperature during transport is higher than the vaccine storage temperature, the color of the label changes. The quality condition of the vaccine can be judged only by visually observing the color of the label.)

1. A preparation method of an intelligent vaccine monitoring label for cold chain transportation is characterized by comprising the following specific steps:

(1) synthesizing a monodisperse core-shell microsphere emulsion:

synthesizing a monodisperse polymer microsphere emulsion by a semi-continuous stepwise emulsion polymerization method; the polymer microsphere consists of a core layer, an intermediate layer and a shell layer; the glass transition temperature of the shell is designed according to the storage temperature of the vaccine, and the glass transition temperature of the shell is regulated and controlled by changing the species and mass ratio of the comonomer; by adjusting the refractive index n of the core layer of the microsphere₁Refractive index n of the intermediate layer₂Refractive index n of the shell₃The color and the transparency of the intelligent monitoring label are adjusted or adjusted by adjusting the size of the core microsphere;

(2) preparation of a solid microsphere mixture:

demulsifying the synthesized polymer microsphere emulsion to obtain solid microspheres, drying the solid microspheres by using a blast drying oven, and mixing the solid microspheres with a photoinitiator and graphite or carbon black in an internal mixer at a high temperature to obtain a solid microsphere mixture;

(3) preparing a photonic crystal elastic film:

placing a solid microsphere mixture with a certain mass between two layers of release polyethylene terephthalate (PET) films, and pressing the mixture into a film through a flat vulcanizing machine to form a sandwich structure, namely release PET-photonic crystal film-release PET; continuously bending the obtained film through bending induction regulation equipment, thereby further improving the degree of order of the polymer microspheres in a matrix formed by a shell layer; wherein the temperature of the flat vulcanizing machine during processing is 100-250 ℃; the applied pressure is 1-30 tons; the processing time is 1-10 minutes; the temperature for regulating the membrane by the bending induction regulation equipment is 70-150 ℃; the processing temperature is at least 50 ℃ higher than the glass transition temperature of the polymer microsphere material; the bending times of the film by the regular equipment is 10-150 times; the shell material of the core-shell microsphere is melted at high temperature to be used as a matrix, the core layer with higher glass transition temperature or high crosslinking is used as a construction unit, and the core layer is arranged in the matrix material in a face-centered cubic closest packing manner to form a photonic crystal structure;

(4) preparing an intelligent monitoring label:

and (2) placing the photonic crystal elastic film in an ultraviolet curing box for ultraviolet curing, cutting the film into a required shape by a carving machine, stretching the film above the glass transition temperature of the shell, rapidly cooling the film below the glass transition temperature of the shell, and storing the film to obtain the intelligent monitoring label.

2. The preparation method according to claim 1, wherein in the core-shell microsphere in the step (1), the size of the core microsphere is 100-300 nm, the thickness of the middle layer is 5-70 nm, and the thickness of the shell layer is 10-100 nm; wherein, the dispersibility of the synthesized microspheres in each stage is less than 10%.

3. The preparation method according to claim 1, wherein in the core-shell microsphere, the core layer accounts for 15-60% of the total mass of the core-shell microsphere, the intermediate layer accounts for 5-20% of the total mass of the core-shell microsphere, the shell layer accounts for 30-75% of the total mass of the core-shell microsphere, and the total mass of the core layer, the intermediate layer and the shell layer is 100%.

4. The method according to claim 1, wherein the core-shell microspheres have a refractive index n of the core layer₁And refractive index n of the shell₃The difference is between 0.1 and 2.

5. The method of claim 1, wherein:

the core layer material is formed by polymerizing a monomer and a cross-linking agent; wherein the monomer is one or a mixture of more of styrene, methyl methacrylate and acrylonitrile; the selected cross-linking agent is one or more of divinylbenzene, allyl methacrylate and 1, 4-butanediol diacrylate;

the materials of the middle layer and the shell layer are polyacrylate copolymers; wherein the comonomer is selected from one or more of methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, tert-butyl acrylate, 2-ethyl acrylate, n-octyl acrylate, isooctyl acrylate, decyl acrylate, cyclohexyl acrylate, methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, tert-butyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate and isobornyl methacrylate; wherein, the cross-linking agent used for the intermediate layer material is one or more of divinylbenzene, allyl methacrylate and 1, 4-butanediol diacrylate; the photoinitiator used for the shell material is one or more of benzophenone, benzoin dimethyl ether, diphenylethanone and thiopropoxy thioxanthone.

6. The preparation method according to claim 1, wherein in the step (2), the drying temperature of the solid microspheres is 35-75 ℃ and the drying time is 12-48 hours; the photoinitiator accounts for 1 to 15 percent of the solid mass fraction of the microsphere; graphite and carbon black account for 0.01-10% of the solid mass fraction of the microspheres; the banburying temperature is 100-200 ℃; the rotating speed of the roller rotor is 5-100 r/min; the banburying time is 1-20 minutes.

7. The method as claimed in claim 1, wherein the temperature of the press vulcanizer in the step (3) is 100-150 ℃; the applied pressure is 1-15 tons; the processing time is 1-10 minutes.

8. The method for preparing the composite material according to the claim 1, wherein the temperature for the film to be structured by the bending induction structuring device in the step (3) is 70-120 ℃; the processing temperature is at least 50 ℃ higher than the glass transition temperature of the polymer microsphere material; the number of membrane bends by the regulating device is 30-80.

9. The method according to claim 1, wherein in the step (4), the power of the ultraviolet curing oven is 1 w/cm to 100 w/cm; the curing time is 1 second to 2 hours.

10. An intelligent monitoring label for cold chain transportation of vaccines, which is obtained by the preparation method of any one of claims 1 to 9, is a photonic crystal elastomer formed by core-shell polymer microspheres in a specific arrangement mode, and has an accurate corresponding relation between color and temperature change according to the shape memory effect of macromolecules, so that the temperature condition of the vaccines can be visually monitored, and the quality of the vaccines can be ensured.

Technical Field

The invention belongs to the technical field of cold chain transportation monitoring, and particularly relates to an intelligent monitoring label based on a photonic crystal structure and a preparation method thereof.

Background

The prevalence of new coronary pneumonia brings great threat to the life of people all over the world, and in order to deal with the new coronary virus with strong transmission capability and high fatality rate, each country vigorously develops vaccines, and hopes of ending epidemic situation are held back to the vaccines. Currently, a series of highly effective vaccines have been developed and are beginning to be mass-inoculated in the human population. However, most vaccines need to be stored at very low temperatures, and prolonged temperature increases can lead to vaccine failure. Therefore, during the cold chain transportation of the vaccine, the temperature of the vaccine needs to be monitored so as to ensure the quality of the vaccine for vaccination.

At present, in cold chain transportation of vaccines and the like, a commonly used monitoring method is to utilize a Radio Frequency Identification (RFID) technology or a Wireless Sensor Network (WSN) technology and match with a corresponding temperature measurement method (a capacitor method, an artificial network technology and the like) to manufacture various temperature sensors, temperature detectors, thermal imagers and the like so as to monitor temperature changes in cold chain transportation (CN 111931887A; Food Control, 2018, 86, 170 + 182). However, at present, the technologies have the problems of high cost, dead angles in monitoring, incapability of realizing full-range close-fitting monitoring and the like. The biggest challenge, particularly for vaccine delivery, is in the last mile, since in the last mile the vaccine will be taken out of a specially made refrigeration facility and distributed to the hands of medical personnel. In the process, instruments such as a temperature measuring instrument and the like cannot closely and accurately monitor the temperature of the vaccine due to the problems of the volume and the cost of the equipment.

Therefore, there is an urgent need to develop an intelligent monitoring product for finely monitoring whether the temperature of the vaccine meets the requirement during the whole process, especially the last mile distribution, so as to indicate whether the activity of the vaccine is affected, and prevent people from being inoculated with deteriorated vaccine, thereby affecting the health and even infecting viruses.

Disclosure of Invention

Aiming at the defects of the prior art in the field of cold chain monitoring at present, the invention aims to provide an intelligent monitoring label which is low in cost and can carry out whole-course close-fitting monitoring without dead angles on vaccine cold chain transportation and a preparation method thereof.

The intelligent monitoring label for vaccine cold chain transportation is an intelligent label based on a photonic crystal structure, and particularly is a photonic crystal elastomer formed by core-shell polymer microspheres in a specific arrangement mode, and an accurate corresponding relation between color and temperature change is constructed by combining the shape memory effect of macromolecules, so that the temperature condition of the vaccine can be visually monitored, and the quality of the vaccine is ensured. The intelligent monitoring label is prepared by the following specific steps.

(1) Synthesizing a monodisperse core-shell microsphere emulsion:

synthesizing a monodisperse polymer microsphere emulsion by a semi-continuous stepwise emulsion polymerization method; the polymer microsphere consists of a core layer (core microsphere), an intermediate layer and a shell layer; the glass transition temperature of the shell is designed according to the storage temperature of the vaccine, and can be regulated and controlled by changing the species and mass ratio of the comonomer; let the refractive index of the core layer of the microsphere be n₁The refractive index of the intermediate layer being n₂The refractive index of the shell being n₃By adjusting n₁、n₂And n₃To change the color and transparency of the smart monitoring label; the color and transparency of the intelligent monitoring label can also be adjusted by adjusting the size of the core microsphere.

(2) Preparation of a solid microsphere mixture:

and (3) demulsifying the synthesized emulsion to obtain solid microspheres, drying the solid microspheres by using a blast drying oven, and mixing the solid microspheres with substances such as a photoinitiator, graphite or carbon black and the like in an internal mixer at high temperature to obtain a solid microsphere mixture.

(3) Preparing a photonic crystal elastic film:

the preparation method comprises the steps of placing a solid microsphere mixture with a certain mass between two layers of release polyethylene terephthalate (PET) films, and pressing the mixture into a film at a high temperature through a flat vulcanizing machine to form a sandwich structure (namely release PET-photonic crystal film-release PET). And continuously bending the obtained film at high temperature by bending induction regulation equipment, thereby further improving the degree of order of the polymer microspheres in the matrix formed by the shell layer. The shell material of the core-shell microsphere is melted at high temperature to be used as a matrix, the core layer with higher glass transition temperature or high crosslinking degree is used as a construction unit, and the core layer is arranged in the matrix material in a face-centered cubic closest packing mode to form a photonic crystal structure.

(4) Preparing an intelligent monitoring label:

and (2) placing the photonic crystal elastic film in an ultraviolet curing box for ultraviolet curing, cutting the film into a required shape by a carving machine, stretching the film above the glass transition temperature (corresponding to the vaccine protection temperature) of the shell, rapidly cooling the film below the glass transition temperature, and storing the film to obtain the intelligent monitoring label.

In the invention, the monodisperse polymer microsphere emulsion is synthesized by utilizing a semi-continuous stepwise emulsion polymerization method, and particularly, the core microsphere is synthesized firstly, and then the middle layer and the shell layer are synthesized outside the core microsphere.

In the invention, in order to obtain an intelligent monitoring label with ideal optical performance, in the core-shell microsphere, the size of a core layer (core microsphere) is 100-300 nanometers, the thickness of a middle layer is 5-70 nanometers, and the thickness of a shell layer is 10-100 nanometers; wherein, the dispersibility of the synthesized microspheres in each stage is less than 10%.

In the invention, in order to obtain an intelligent monitoring label with ideal optical performance, in the core-shell microsphere, the core layer accounts for 15-60% of the total mass of the core-shell microsphere, the intermediate layer accounts for 5-20% of the total mass of the core-shell microsphere, the shell layer accounts for 30-75% of the total mass of the core-shell microsphere, and the total mass of the core layer, the intermediate layer and the shell layer is 100%.

In the invention, the refractive index n of the core layer of the core-shell microsphere is₁And refractive index n of the shell₃The difference should be between 0.1 and 2; preferably, the refractive index difference is between 0.1 and 1.0.

In the invention, the core layer material is polymerized by a monomer and a cross-linking agent. Wherein the monomer is one or a mixture of more of styrene, methyl methacrylate and acrylonitrile; the selected cross-linking agent is one or more of divinylbenzene, allyl methacrylate and 1, 4-butanediol diacrylate. The materials of the middle layer and the shell layer are polyacrylate copolymers; wherein the comonomer is selected from one or more of methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, tert-butyl acrylate, 2-ethyl acrylate, n-octyl acrylate, isooctyl acrylate, decyl acrylate, cyclohexyl acrylate, methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, tert-butyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate and isobornyl methacrylate; wherein, the cross-linking agent used for the intermediate layer material is one or more of divinylbenzene, allyl methacrylate and 1, 4-butanediol diacrylate; meanwhile, the photoinitiator used for the shell material is one or more of benzophenone, benzoin dimethyl ether, diphenylethanone and thiopropoxy thioxanthone.

In the invention, the drying temperature of the demulsified solid microspheres is 35-75 ℃; preferably, the drying temperature is 45-65 degrees Celsius. The drying time is 12-48 hours; preferably, the drying time is 12-24 hours. The photoinitiator accounts for 1 to 15 percent of the solid mass fraction of the microsphere; preferably, the photoinitiator accounts for 1-7% of the solid mass fraction of the microsphere. Graphite, carbon black and other substances account for 0.01-10% of the solid mass fraction of the microspheres; preferably, the graphite, carbon black and other substances account for 0.1-1% of the solid mass fraction of the microspheres. The banburying temperature is 100-200 ℃; preferably, the banburying temperature is 100-150 ℃. The rotating speed of the roller rotor is 5-100 r/min; preferably, the roll rotors are rotated at a speed of 5-60 revolutions per minute. Banburying time is 1-20 minutes; preferably, the banburying time is 1-15 minutes.

In the invention, the release force of the selected release PET film is 30-220 g/mm.

In the invention, the temperature of the flat vulcanizing machine during processing is 100-250 ℃; preferably, the temperature at which the press is processed is 100-150 ℃. The applied pressure is 1 to 30 tons; preferably, the pressure applied is 1 to 15 tonnes. The processing time is 1-10 minutes.

In the invention, the film arrangement temperature of the bending induction arrangement equipment is 70-150 ℃; preferably, the temperature of the bend-inducing conditioning apparatus is 70-120 degrees Celsius for the film. The processing temperature is at least 50 degrees celsius higher than the glass transition temperature of the polymeric microsphere material. The bending times of the film by the regular equipment is 10-150 times; preferably, the number of membrane bends by the normalization device is 30-80.

In the invention, the power of the ultraviolet curing box is 1W/square centimeter to 100W/square centimeter; preferably, the power of the uv curing oven is 1 watt/cm to 20 watts/cm. The curing time is 1 second to 2 hours; preferably, the curing time is from 1 minute to 15 minutes.

According to the intelligent monitoring label based on the photonic crystal structure, the glass transition temperature of the shell layer corresponds to the storage temperature of a vaccine through the design of a polymer core-shell structure, the photonic crystal elastic film is prepared on a large scale through bending induction equipment, meanwhile, the stretching is carried out above the storage temperature (the glass transition temperature of the shell layer) of the vaccine by combining the shape memory effect of a high polymer, and then the temperature is rapidly reduced to be below the glass transition temperature of the shell layer for storage, so that the intelligent monitoring test strip label for cold chain transportation can be obtained. The chain structure of the intelligent test strip label is frozen below the glass transition temperature of the shell layer, so that the color of the intelligent test strip label is kept; when the temperature rises at any stage in the transportation process, the corresponding chain segment moves, so that the color of the label changes, the monitoring effect is achieved, and the vaccine quality is ensured. In addition, the product can change the color changing temperature and time course of the label by adjusting the crosslinking degree of the shell layer, thereby meeting diversified monitoring requirements. When medical staff inoculates the vaccine, the quality condition of the vaccine can be clearly judged only by observing the color of the label in the inoculated package. The intelligent monitoring label has the characteristics of low cost, close-fitting whole process and no dead angle monitoring, and has great commercial application value.

Drawings

FIG. 1 is a schematic diagram of a monitoring mechanism of the intelligent monitoring tag of the present invention.

Fig. 2 shows the color change of the intelligent monitoring label in different states.

FIG. 3 is a stress-strain curve for the smart monitoring tag.

Detailed Description

The foregoing embodiments are further described below in conjunction with specific examples to provide a more complete understanding of the present invention to those skilled in the art. It should be noted that the protection scope of the present invention should not be limited by the above-mentioned embodiments, and those skilled in the art can make various modifications and changes without departing from the principle of the present invention, and such modifications and changes should also be covered by the protection scope of the embodiments of the present invention.

Example 1

An intelligent monitoring label based on a photonic crystal structure is disclosed, wherein the thickness of the label is 100-200 microns and the label is composed of core-shell polymer microspheres with the particle size of 115-470 nanometers.

The intelligent monitoring label is prepared by banburying solid microspheres with substances such as a photoinitiator, graphite or carbon black and the like, then compounding the solid microspheres with a release PET film through a flat vulcanizing machine to form a film, regularly arranging the solid microspheres in a matrix through bending induction regular equipment to generate a bright structural color, and finally cutting the solid microspheres into a specific shape through ultraviolet curing by using a carving machine.

The monitoring principle of the intelligent monitoring label is shown in figure 1, a part of a monitoring test strip is stretched above the storage temperature of the vaccine, and then the temperature is rapidly reduced to be below the glass transition temperature of the shell layer of the monitoring test strip. At this time, since the polymer segment is frozen, the color of the monitoring strip is maintained and various colors are displayed. When medical staff vaccinate, if the label still shows multiple colors, indicate that the whole course storage temperature of the vaccine meets the requirements, can reassure the vaccination; if the strip shows only one color, it indicates that the temperature has changed during storage of the vaccine and the vaccine is not suitable for vaccination.

Example 2

And (3) synthesizing a monodisperse core-shell microsphere emulsion. The specific method comprises the following steps: synthesis of styrene seeds: the 1 liter glass reactor was warmed to 75 ℃. Adding sodium dodecyl sulfate, deionized water, 1, 4-butanediol diacrylate and a styrene monomer into a reaction kettle, starting stirring, and after the temperature of the pre-emulsion rises to 75 ℃, sequentially adding sodium metabisulfite, sodium persulfate and sodium metabisulfite to initiate polymerization reaction. Blue opalescence appears about two minutes after the addition, which indicates that particles are generated, and the reaction is continued for 10 minutes, so that the polystyrene seed is obtained.

Synthesis of polystyrene hard core: continuously dropwise adding a pre-emulsion of sodium dodecyl sulfate, Dowfax 2A1, deionized water, potassium hydroxide, 1, 4-butanediol diacrylate and styrene monomers into the reacted emulsion on the basis of the polystyrene seed emulsion, and simultaneously maintaining the reaction temperature at 75 ℃. And after the pre-emulsion is dripped, continuously reacting for more than half an hour to obtain the polystyrene hard core microsphere.

Synthesis of the elastic shell: continuously growing an intermediate layer and a shell layer on the basis of the polystyrene hard core microsphere emulsion: firstly, adding a sodium persulfate initiator into the hard core microsphere emulsion, and reacting for 10 minutes. Then, pre-emulsion prepared by sodium dodecyl sulfate, deionized water, Dowfax 2A1, ethyl acrylate and allyl methacrylate is dripped into the reaction kettle. After the dropwise addition, the reaction temperature is kept at 75 ℃ for further reaction for 15 minutes. Then, a pre-emulsion composed of sodium dodecyl sulfate, potassium hydroxide, deionized water, ethyl acrylate and isobutyl methacrylate was added dropwise to a1 liter reaction vessel. After the dripping is finished, the temperature is kept for 1 hour, the reaction is finished after the stirring and the cooling to the room temperature, and the monodisperse hard-core soft-shell polymer microsphere is obtained.

Example 3

And preparing a solid microsphere mixture. Demulsifying the obtained monodisperse core-shell microsphere emulsion in 0.5 mass percent of aluminum sulfate octadecahydrate solution to obtain precipitate. The precipitate was collected after filtration and dried in a forced air drying oven at 50 ℃ for 12 hours. And mixing the dried microsphere solid with photoinitiator benzophenone, adding the mixture into an internal mixer, and internally mixing for 10 minutes at 120 ℃ under the condition of 50 revolutions per minute.

Example 4

And (3) preparing the photonic crystal elastic film. 1 g of the banburied solid mixture is placed between two layers of release PET films, then the temperature of a flat vulcanizing machine is adjusted to 120 ℃, and the flat vulcanizing machine is hot-pressed for 5 minutes under the pressure of 15 tons. After hot pressing, the film was quickly taken out, and then the composite film (PET-PC-PET) was quickly placed on a bending induction and alignment apparatus. Regulating the temperature of the regulating machine to 120 ℃, and regulating the film for 60 times by winding a roller to obtain the structural color film with bright color.

Example 5

And preparing an intelligent monitoring label. And tearing the release PET film to obtain a photonic crystal elastic film, curing the photonic crystal elastic film in an ultraviolet curing box for 1 minute, and finally cutting the elastic film into the shape of a thermometer by using a carving machine. And (3) partially stretching the glass transition temperature of the shell layer of the intelligent cold chain test strip label, and then quickly putting the intelligent cold chain test strip label into a vaccine box to obtain the intelligent cold chain test strip label. The color change of the intelligent monitoring label in different states is shown in figure 2. The stress-strain curve of the photonic crystal intelligent monitoring label is shown in figure 3.