Time-temperature indicator and preparation method thereof

Abstract

The invention discloses a time-temperature indicator and a preparation method thereof. The time-temperature indicator comprises an adhesion base material layer and an indicator pattern layer attached to the surface of the adhesion base material layer, the adhesion base material layer is made of a Janus fiber wet adhesion film, the indicator pattern layer comprises a carrier and dye mixed in the carrier, and when the time-temperature indicator is used, the indicator pattern layer is attached to the surface of the adhesion base material layer. The time and temperature accumulation effect of the environment is evaluated by observing the diffusion condition of the dye in the indicator pattern layer on the surface of the adhesion base material layer, the Janus fiber wet adhesion film is adopted as the material of the adhesion base material layer, and the adhesion base material layer can be infiltrated by the oil-phase dye indicator and water on the surface of the substrate at the same time; the adhesion performance is not interfered by temperature change, the time and temperature change of the indicator can be directly observed by naked eyes, the operation is simple and convenient, and the practicability is high.

Description

Technical Field

[0001] The present invention relates to the technical field of time-temperature indicators, and more particularly, to a low-temperature resistant time-temperature indicator for real-time visual detection. Background Art

[0004] In addition to vaccines that need to be stored in a specific low-temperature environment, other products that require low-temperature storage, such as biological products (bone marrow, cells, tissues, fertilized eggs, proteins, nucleic acids), component blood (frozen red blood cells, whole blood and red blood cell preparations, and plasma), perishable vegetables, seafood, and meat, as well as drugs, etc., also need to be stored in a specific low-temperature environment. "Large temperature / humidity span" is the most significant environmental characteristic during the transportation and storage of vaccines and other low-temperature biomedical supplies.

[0005] Remaining effective interfacial adhesion in a low-temperature and high-humidity environment is the key to continuously monitoring the storage and transportation environment of perishable products. However, there is no commercially available low-temperature resistant wet adhesion material with independent intellectual property rights in China. Moreover, domestic low-temperature resistant adhesion products strongly rely on foreign core key technologies. Therefore, the development of low-temperature resistant wet adhesion materials is of great significance for realizing a time-temperature indicator for real-time visual detection. Summary of the Invention

[0006] The purpose of the present invention is to provide a time-temperature indicator and its preparation method, in which the adhesion performance of the prepared adhesion substrate layer is not interfered by temperature changes, and the operation is simple and convenient, with strong practicability, and the indication result can be directly observed with the naked eye.

[0007] The present invention is implemented as follows:

[0008] The time-temperature indicator of the present invention includes an adhesion substrate layer and an indicator pattern layer attached to the surface of the adhesion substrate layer. Among them, the indicator pattern layer includes a carrier and a dye mixed in the carrier; the area of the attached indicator pattern layer is smaller than the surface area of the adhesion substrate layer, and the indicator pattern layer is located at the center or corner of the adhesion substrate layer. When in use, the time-temperature cumulative effect of the environment is evaluated by observing the diffusion of the dye in the indicator pattern layer on the surface of the adhesion substrate layer.

[0009] The material of the adhesion substrate layer is a Janus fiber wet adhesion film, and the Janus fiber wet adhesion film has a Janus fiber structure with side-by-side axial parallelism. The Janus fiber structure specifically refers to a fiber structure in which two or more semi-fibers are closely attached and extend in parallel in the axial direction. Among them, the diameter of the Janus fiber is 0.1 - 1000 μm, and preferably the diameter is 0.5 - 10 μm.

[0010] In the Janus fiber structure of the adhesive substrate layer, at least two sides of the semi-fibers are different components respectively containing a water-soluble polymer and an oil-soluble polymer. Among them, the semi-fibers containing the water-soluble polymer dissolve or swell in the aqueous solvent, and the semi-fibers containing the oil-soluble polymer dissolve or swell in the oil-phase solvent. Then, during use, the adhesive substrate layer can be wetted by both the oil-phase dye indicator and the water on the substrate surface.

[0011] In one specific embodiment, the water-soluble polymer in the Janus fiber wet adhesion film is one or a combination of polyvinylpyrrolidone, polyacrylic acid and its salts, polyethylene glycol, polyacrylamide, polyvinyl alcohol, cellulose acetate, polyethylene ether, poly-2-acrylamido-2-methylpropanesulfonic acid, waterborne polyurethane, carboxyl-containing rubber.

[0012] In one specific embodiment, the oil-soluble polymer in the Janus fiber wet adhesion film is one or a combination of polyurethane, polyvinyl butyral, polystyrene, polyvinylidene fluoride, polyvinylpyrrolidone, polyacrylic acid and its salts, polysulfone, polyethersulfone, polyvinyl chloride, chlorinated polyethylene, chlorinated polypropylene, polysiloxane, polyimide, polyacrylonitrile, polycarbonate, epoxy resin, hexyl methacrylate, halogen-containing rubber.

[0013] In one specific embodiment, the dye in the indicator pattern layer can be selected from one or a combination of azo dyes, phthalocyanine dyes, anthraquinone dyes, nitro dyes, arylmethane dyes, phenothiazine dyes, preferably methyl yellow or methylene blue.

[0014] In one specific embodiment, the carrier in the indicator pattern layer is isopropyl palmitate or liquid metal.

[0015] In a preferred embodiment, in the temperature range of -30°C to 60°C, the adhesion strength of the Janus fiber wet adhesion film on the surface of the water-containing or oil-containing substrate or the substrate surface under the humidity condition of 50-100% RH is 0.3 N / cm 2 or more.

[0016] The present invention also provides a preparation method of the above time-temperature indicator, which specifically includes the following steps:

[0017] S1. Prepare a Janus fiber wet adhesion film to form the adhesive substrate layer; the Janus fiber wet adhesion film can be specifically prepared by side-by-side electrospinning, side-by-side microfluidic spinning, side-by-side melt extrusion, electrohydrodynamic jetting method, unilateral modification method, deposition hydrolysis method.

[0018] S2. Place the plastic petri dish containing the dye indicator on the surface of an aluminum plate pre-cooled at a low temperature. When it has not completely solidified, press it with molds of different sizes and shapes to obtain corresponding colored dye indicator patterns. Attach the dye indicator pattern to the surface of the adhesion substrate layer to form an indicator pattern layer, thereby obtaining a time-temperature indicator.

[0019] In a preferred embodiment thereof, the Janus fiber wet adhesion film in step S1 is prepared by side-by-side electrospinning. The specific preparation process is as follows: Dissolve the water-soluble polymer and the oil-soluble polymer in similar solvents respectively, stir evenly to obtain electrospinning solutions respectively; Pour the electrospinning solutions of different components into syringes respectively, and eject them through an electrospinning nozzle with a side-by-side structure to prepare the Janus fiber wet adhesion film.

[0020] Specifically, different polymer components that dissolve or swell when encountering water or oil need to be dissolved and spun with similar or the same solvents. Therefore, the types of fixed polymers and the combination of organic solvents can be further selected. Preferably, it is a hydrophilic-lipophilic combination of polystyrene (PS) / polyvinylpyrrolidone (PVP), polyvinyl butyral (PVB) / polyvinylpyrrolidone (PVP), polyvinyl butyral (PVB) / polyacrylic acid (PAA), polystyrene (PS) / polyacrylic acid (PAA), polyurethane (PU) / polyvinylpyrrolidone (PVP), polyacrylonitrile (PAN) / polyvinylpyrrolidone (PVP), polyvinylidene fluoride (PVDF) / polyvinylpyrrolidone (PVP), polyurethane (PU) / polyacrylic acid (PAA), polyacrylonitrile (PAN) / polyacrylic acid (PAA), polyvinylidene fluoride (PVDF) / polyacrylic acid (PAA). The organic solvent is selected as N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMAc), which has a good dissolving effect on the above-mentioned fixed polymer types, is beneficial to electrospinning, and a small amount of volatile solvent can also be added to promote the curing of Janus fibers.

[0021] Specifically, during the electrospinning process, the flow rate range of the electrospinning solution is 0.1 - 2 mL / h, the voltage range is between 10 - 20 kV, the receiving distance is 15 - 30 cm, the temperature and humidity in the electrospinning box are 36 - 45 °C and 15 - 30 RH% respectively. Use a hydrophobic conductive substrate such as aluminum foil paper as the receiving electrode, fix the hydrophobic conductive substrate on a roller, and the roller rotation speed is 50 - 300 rpm.

[0022] The time-temperature indicator of the present invention can be applied to the cold chain transportation of items such as drugs, vaccines, foods, and cosmetics. When in use, spray water on the surface of the item to be tested, and attach the time-temperature indicator to the water-containing surface of the product to be tested, then the cumulative time-temperature effect during cold chain transportation can be evaluated.

[0023] The Janus fiber wet adhesion film used in the present invention can undergo multi-phase dissolution-infiltration-adhesion. In a humid environment containing water or on the surface of a water-containing substrate, the hydrophilic component on at least one side of the Janus fiber swells and dissolves to form an adhesion phase, achieving interfacial adhesion and adhesion in a water-containing environment. Similarly, in a humid environment containing oil (including organic solvents) or on the surface of an oil-containing (including organic solvents) substrate, the lipophilic component in the Janus fiber swells and dissolves to form an adhesion phase, and at the same time, interfacial adhesion is achieved. Therefore, the indicator pattern layer can be directly adhered to the surface of the adhesion substrate layer, and the adhesion substrate layer with the indicator pattern layer can be directly attached to the surface of the water-containing substrate. Moreover, with the accumulation of temperature and time, the organic dye in the indicator pattern layer will undergo infiltration and diffusion in the adhesion substrate layer. The longer the time and the higher the temperature, the larger the diffusion range, so as to display the cumulative effect of environmental time and temperature through the diffusion of the indicator pattern layer.

[0024] The present invention has the following beneficial effects:

[0025] (1) For the time-temperature indicator of the present invention, the material of the adhesion substrate layer is the Janus fiber wet adhesion film. The indicator pattern layer containing the dye is directly attached to the surface of the adhesion substrate layer. The adhesion substrate layer can be wetted by both the dye indicator in the oil phase and the water on the surface of the substrate, and the adhesion performance is not disturbed by temperature changes and still has high adhesion performance at low temperatures.

[0026] (2) For the time-temperature indicator of the present invention, the cumulative effect of environmental time and temperature is evaluated by observing the diffusion of the dye in the indicator pattern layer on the surface of the adhesion substrate layer. The time-temperature change of the indicator can be directly observed with the naked eye, and the operation is simple and convenient, with strong practicability. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the embodiments. It should be understood that the following drawings only show some embodiments of the present invention, so they should not be regarded as limiting the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings.

[0028] Figure 1 It is a schematic diagram of the working principle of the time-temperature indicator of the present invention;

[0029] Figure 2 It is a scanning electron microscope photograph of the Janus fiber and its cross-section in Example 1 of the present invention;

[0030] Figure 3 It is a schematic diagram of the deformation degree of the indicator pattern layer with time and temperature in Example 1 of the present invention;

[0031] Figure 4 This is a schematic diagram of the viscosity strength of the adhesive substrate layer in Example 1 of the present invention at different temperatures. Detailed implementation manners

[0032] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. For those not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are followed. For reagents or instruments without indicating the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0033] The time-temperature indicator of the present invention includes an adhesive substrate layer and an indicator pattern layer attached to the surface of the adhesive substrate layer. The material of the adhesive substrate layer is a Janus fiber wet adhesive film. In this Janus fiber structure, at least two half-fibers on both sides are different components respectively containing a water-soluble polymer and an oil-soluble polymer. Among them, the half-fiber containing the water-soluble polymer dissolves or swells in the aqueous solvent, and the half-fiber containing the oil-soluble polymer dissolves or swells in the oil-phase solvent. Then, during use, the adhesive substrate layer can be simultaneously wetted by the dye indicator in the oil phase and the water on the surface of the substrate. The indicator pattern layer containing the dye is directly attached to the surface of the adhesive substrate layer, and the adhesion performance is not interfered by temperature changes and still has high adhesion performance at low temperatures.

[0034] During use, by observing the diffusion of the dye in the indicator pattern layer on the surface of the adhesive substrate layer, the cumulative time-temperature effect of the environment can be judged. The time-temperature change of the indicator can be directly observed with the naked eye, and the operation is simple and convenient, with strong practicability.

[0035] Specifically, please refer to Figure 1 , taking the cold chain transportation of vaccines as an example, the working principle of the time-temperature indicator provided by the present invention is as follows: Before the cold chain transportation of vaccines, sprinkle water on the surface of the vaccine bottle, and attach the Janus fiber wet adhesive film with the indicator pattern fixed, that is, the time-temperature indicator of the present invention, to the surface of the vaccine bottle. After the cold chain transportation process ends, if the pattern of the indicator pattern layer does not deform, it indicates that the vaccine is in a low-temperature state during cold chain transportation and has not been exposed to high temperature, and the vaccine is safe and can be used. If the pattern of the indicator pattern layer deforms, it indicates that the vaccine has been exposed to high temperature during the cold chain transportation process and the vaccine has expired and should be discarded.

[0036] The features and performance of the present invention will be further described in detail below in conjunction with the embodiments.

[0037] Example 1

[0038] The preparation method of the time-temperature indicator of the present invention adopts the following preparation steps:

[0039] (1) Prepare electrospinning solutions of water-soluble polymer polyvinylpyrrolidone (PVP) and oil-soluble polymer polystyrene (PS), namely aqueous electrospinning solution and oil-phase electrospinning solution, and then fill them into syringes respectively. Spray them out through an electrospinning nozzle with a side-by-side structure. The flow rate range of the two-phase electrospinning solution is 1 mL / h, the voltage is about 15 kV, the receiving distance is 25 cm, the temperature and humidity in the electrospinning box are 35 °C and 20 RH% respectively. Use aluminum foil as the receiving electrode and fix it on the roller. The roller rotation speed is 100 rpm to prepare a Janus fiber wet adhesion film.

[0040] Figure 2 This is a scanning electron microscope photograph of a single Janus fiber and its cross-section in the Janus fiber wet adhesion film prepared in this example. Figure 2 It shows that the Janus fiber wet adhesion film has a Janus fiber structure in which the aqueous semi-fiber and the oil-phase semi-fiber are closely attached side-by-side and extend axially in parallel.

[0041] (2) Add methylene blue to isopropyl palmitate for staining. Place a plastic petri dish containing the stained isopropyl palmitate indicator on the surface of an aluminum plate pre-cooled at low temperature. When the indicator is not completely solidified, press it with a circular mold to obtain a corresponding dye indicator pattern. Attach the dye indicator pattern to the surface of the Janus fiber wet adhesion film prepared in step (1) to form an indicator pattern layer and obtain a time-temperature indicator.

[0042] Testing method:

[0043] 1. Sprinkle water on the surface of a glass slide. Attach the time-temperature indicator prepared in Example 1 to the surface of the glass slide, and then place it in a refrigerator at -20 °C for freezing storage to simulate the storage of vaccines in a low-temperature environment. Then take it out and place it in a room-temperature environment (temperature is about 20.5 °C), observe the deformation of the circular pattern, and then place it in a refrigerator at -20 °C to observe the recovery of the circular pattern. Analyze the ratio of the deformed area of the circular pattern to the initial area with Matlab software or Image J.

[0044] Figure 3 This is a schematic diagram of the deformation degree of the indicator pattern layer with time and temperature in Example 1 of the present invention. It can be seen from this that the cumulative effect of time and temperature can be judged according to the deformation of the dye indicator pattern, so as to conveniently monitor the quality status of vaccines during cold chain storage and transportation.

[0045] 2. Sprinkle water on the surface of the glass slide, and adhere the Janus fiber wet adhesion film prepared in Example 1 to the surface of the glass slide. Measure the adhesion force of the Janus fiber wet adhesion film at -196°C, -80°C, -20°C, 4°C, 20°C, 40°C, and 60°C respectively. Conduct 3 parallel tests for each test group.

[0046] Figure 4 This is a schematic diagram of the viscosity strength of the adhesion substrate layer prepared in Example 1 of the present invention at different temperatures. It can be seen that the Janus fiber wet adhesion film used in the present invention has a good adhesion effect on the water-containing substrate, and the adhesion performance is not interfered by temperature changes. It still has high adhesion performance at low temperatures, and the adhesion strength at different temperatures can reach 0.3 N / cm 2 or more.

[0047] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and changes. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A time-temperature indicator, characterized in that, It includes an adhesive substrate layer and an indicator pattern layer attached to the surface of the adhesive substrate layer; The material of the adhesive substrate layer is a Janus fiber wet adhesion film with a Janus fiber structure, and the Janus fiber structure refers to a fiber structure in which at least two or more semi-fibers are closely attached and extend parallel in the axial direction; In the Janus fiber structure of the adhesive substrate layer, at least two semi-fibers on both sides are different components respectively containing a water-soluble polymer and an oil-soluble polymer. Among them, the semi-fiber containing the water-soluble polymer dissolves or swells in the aqueous solvent, and the semi-fiber containing the oil-soluble polymer dissolves or swells in the oil-phase solvent; The indicator pattern layer contains a carrier and a dye mixed in the carrier; When in use, the time-temperature cumulative effect of the environment is evaluated by observing the diffusion of the dye in the indicator pattern layer on the surface of the adhesive substrate layer.

2. The time-temperature indicator according to claim 1, characterized in that, The water-soluble polymer in the Janus fiber wet adhesion film is one or a combination of polyvinylpyrrolidone, polyacrylic acid and its salts, polyethylene glycol, polyacrylamide, polyvinyl alcohol, cellulose acetate, polyethylene ether, poly-2-acrylamido-2-methylpropanesulfonic acid, waterborne polyurethane, carboxyl-containing rubber, etc.

3. The time-temperature indicator according to claim 1, characterized in that, The oil-soluble polymer in the Janus fiber wet adhesion film is one or a combination of polyurethane, polyvinyl butyral, polystyrene, polyvinylidene fluoride, polyvinylpyrrolidone, polyacrylic acid and its salts, polysulfone, polyethersulfone, polyvinyl chloride, chlorinated polyethylene, chlorinated polypropylene, polysiloxane, polyimide, polyacrylonitrile, polycarbonate, epoxy resin, hexyl methacrylate, halogen-containing rubber, etc.

4. The time-temperature indicator according to claim 1, wherein The dye in the indicator pattern layer is one or a combination of azo dyes, phthalocyanine dyes, anthraquinone dyes, nitro dyes, arylmethane dyes, phenothiazine dyes, etc.

5. The time-temperature indicator according to claim 1, wherein The carrier in the indicator pattern layer is isopropyl palmitate or liquid metal.

6. The time-temperature indicator according to claim 1, characterized in that, In the temperature range of -30°C to 60°C, the adhesion strength of the adhesive substrate layer on the surface of a water-containing substrate or on the surface of a substrate under a humidity condition of 50 to 100% RH is 0.3 N / cm 2 or more.

7. A method for preparing a time-temperature indicator as claimed in claim 1, characterized in that, It includes the following steps: S1. Prepare a Janus fiber wet adhesion film to form the adhesive substrate layer; S2. Obtain a dye indicator pattern with color by pressing with a mold, attach the dye indicator pattern to the surface of the adhesive substrate layer to form an indicator pattern layer, and obtain a time-temperature indicator.

8. The method for preparing a time-temperature indicator according to claim 7, wherein In step S1, the Janus fiber wet adhesion film is prepared by side-by-side electrospinning, side-by-side microfluidic spinning, side-by-side melt extrusion, electrohydrodynamic jetting, unilateral modification method, deposition hydrolysis method.

9. The method for preparing a time-temperature indicator according to claim 8, characterized in that, The specific preparation process of the Janus fiber wet adhesion film in step S1 is as follows: dissolve the water-soluble polymer and the oil-soluble polymer in the solvent respectively, stir evenly to obtain electrospinning solutions respectively; pour the obtained electrospinning solutions of different components into syringes respectively, and eject them through an electrospinning nozzle with a side-by-side structure to prepare a Janus fiber wet adhesion film.

10. The application of the time-temperature indicator according to any one of claims 1-6 in the cold chain transportation of goods. When in use, spray water on the surface of the item to be tested, and attach the time-temperature indicator to the water-containing surface of the item to be tested.

Images