CN114199866A - Color-changeable hydrogel microneedle patch, preparation method and application thereof - Google Patents
Color-changeable hydrogel microneedle patch, preparation method and application thereof Download PDFInfo
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
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Abstract
The invention discloses a color-changeable hydrogel microneedle patch, a preparation method and application thereof, and belongs to the technical field of food detection. In particular to a preparation method of a color-changeable microneedle patch, which comprises the following steps: (1) dissolving an initiator in ultrapure water, heating in a water bath to obtain a solution A, adding a hydrogel material to prepare a hydrogel solution, pouring the hydrogel solution on a mold, defoaming under negative pressure, concentrating, drying and curing to obtain a hydrogel microneedle; (2) dissolving developer in anhydrous ethanol and ultrapure water to obtain solution B, adding hydrogel material, HRP, and H2O2Casting the prepared color-changeable hydrogel microneedle patch solution on a mold containing hydrogel microneedles; the microneedle patch prepared by the preparation method can penetrate through fish meat to semi-quantitatively detect TVB-N generated by the fish meat, is suitable for simple and accurate detection of the fish meat, and is beneficial to consumers to purchase healthy and high-quality food.
Description
Technical Field
The invention relates to the technical field of food detection, in particular to a color-changeable hydrogel microneedle patch, a preparation method and application thereof, and especially relates to application in fish freshness detection.
Background
Salmon, also known as salmon or salmon, is widely distributed in high-latitude regions of northern hemisphere, is migratory fish in cold water region, has delicious meat quality and good taste, and is a high-quality raw material for making tattoos. The quality and freshness of the fishes are affected by various factors, the fishes are inappropriate to store and are extremely easy to rot, the quality and microorganism indexes of the fishes are strictly required in the process of storing the fishes, the quality deterioration of the fishes is mainly oxidation and rot of unsaturated fatty acid, and simultaneously, the quality deterioration is accompanied by pH value change, release of volatile putrefying gas and the like, and even food-borne diseases can be caused. The determination of freshness of fish is therefore very important to ensure that the food consumed by the consumer is safe and nutritious.
Currently, most of the methods for detecting freshness of food are non-direct contact methods, and the basic principle is to detect volatile spoilage compounds released from the surface of the food into the headspace of the package by using a color developer, and to create an acidic (basic) atmosphere in the package to denature the indicator material and thereby produce a color change. Although the non-direct contact method can effectively avoid the problem of dye migration, the food is protected from secondary pollution; however, the non-contact freshness indicator can only react to volatile substances, and gases (CO2, O2, etc.), moisture, etc. in the external environment can be mixed with the emissions, so that the non-contact freshness indicator can affect the detection result due to complicated gas components in the package, temperature and humidity, etc. The indicator cannot accurately judge the freshness of the food and cannot detect the compounds decomposed on the surface of the food, so that the non-contact indicator cannot accurately detect the freshness of the food. The development of touch indicators requires the selection of a safe and non-toxic indicator substrate.
Hydrogels are three-dimensional hydrophilic polymer networks composed of polar functional groups (e.g., -OH, -COOH, and-NH 2) that exhibit swelling behavior upon absorption of large amounts of water. Silk fibroin is a polymer approved by the U.S. Food and Drug Administration (FDA) for biomedical applications, such as sutures, tissue regeneration, and drug delivery systems. The unique molecular structure of silk fibroin allows it to be prepared by a variety of methods as hydrogels with a multitude of tunable properties. To date, colorimetric hydrogels have developed into intelligent biosensors in packaging technology. For example, photonic hydrogels have been applied to optical sensing devices, such as humidity sensors, and play a crucial role in the food and pharmaceutical industries. However, the preparation of these hydrogels requires a complex and time-consuming process.
Hydrogel microneedles are classified into natural hydrogel microneedles and synthetic hydrogel microneedles, which are respectively prepared from natural polymers (such as hyaluronic acid, gelatin, agar, silk fibroin and the like) and synthetic polymers (such as polyvinyl alcohol, sodium polyacrylate, methacrylic acid polymers and the like), wherein some materials are more and more concerned due to good biocompatibility, degradability and nontoxicity, so that the hydrogel microneedles become a research hotspot. Hydrogel microneedle patches are prepared by combining hydrogel with microneedles, most of the microneedle patches are applied to the biomedical field, particularly to insulin delivery, blood glucose level detection and vaccines for cancer treatment, skin disease treatment and diabetes treatment, but the application of the microneedle patches to food safety is rarely reported. Therefore, how to develop the hydrogel microneedle patch with simple technology has potential value in the field of food safety detection.
Disclosure of Invention
Aiming at the problems and the defects in the prior art, the invention provides a preparation method and application of a color-changeable hydrogel microneedle patch. The microneedle patch can be used as a freshness indicator, and can be used for simply and accurately detecting the freshness of the packaged salmon.
The purpose of the invention is realized by the following technical scheme:
in a first aspect of the present invention, there is provided a method for preparing a color-changeable hydrogel microneedle patch, the method comprising the steps of:
(1) preparing hydrogel microneedles: dissolving an initiator LAP in ultrapure water, heating in a water bath, and then vibrating and dissolving to obtain a solution A; then taking a hydrogel material, and uniformly mixing the solution A and the hydrogel material to obtain a hydrogel solution; casting the hydrogel solution on a mold, removing bubbles by negative pressure for several times, concentrating and drying, and curing by ultraviolet light to obtain a hydrogel microneedle;
(2) preparing a color-changeable hydrogel microneedle patch: dissolving a color developing agent in absolute ethyl alcohol and ultrapure water to obtain a solution B; then taking hydrogel material with required mass, mixing the solution B and the hydrogel material uniformly, and adding horseradish peroxidase HRP and hydrogen peroxide H2O2And uniformly mixing to prepare a color-changeable hydrogel microneedle patch solution, taking a proper amount of the color-changeable hydrogel microneedle patch solution, casting the color-changeable hydrogel microneedle patch solution on a mold containing hydrogel microneedles, drying the color-changeable hydrogel microneedle patch solution in the mold, and stripping the mold to obtain the color-changeable hydrogel microneedle patch.
In one embodiment, the initiator LAP is added to the ultrapure water in an amount of 0.05g/20mL in the step (1).
In one embodiment, the initiator LAP in step (1) is dissolved in ultrapure water by heating in a water bath at a temperature of 40-50 ℃ for 15-20min, for example at 45 ℃ for 15 min.
In one embodiment, the amount of the hydrogel material added to the solution A in the step (1) is 0.05-0.10 g/1.0 mL.
In one embodiment, the hydrogel material is at least one of methacrylated silk fibroin SilMA, gelatin, hyaluronic acid, agar, and sodium polyacrylate, methacrylic acid polymer, preferably SilMA.
In one embodiment, in the step (1), a proper amount of hydrogel solution is cast on the mold, and the addition amount of the hydrogel solution is 150-250 μ L.
In one embodiment, the mass ratio of the color developing agent, the absolute ethyl alcohol and the ultrapure water is (0.1-0.5): (20-25): 100, preferably 0.1: 20: 100.
In one embodiment, the color developing agent in step (2) is at least one of phenol red, bromophenol red, bromothymol blue (BTB), bromocresol purple, bromocresol green, anthocyanins, and roselle pigment, preferably bromothymol blue (BTB).
In one embodiment, the addition amount of the hydrogel material in the step (2) relative to the solution B is 0.05-0.10 g/1.0 mL.
In one embodiment, the mass concentrations of horseradish peroxidase and hydrogen peroxide in step (2) are 0.01g/mL and 100mM/L respectively.
In one embodiment, in the step (2), the color-changeable hydrogel microneedle patch solution is cast on a mold containing hydrogel microneedles, and the addition amount of the color-changeable hydrogel solution is 150-250 muL.
In one embodiment, in the step (1), the bubbles are removed through negative pressure for several times, specifically: and (3) using a vacuum drying oven at the temperature of 35-60 ℃, vacuumizing at 1.0MPa, maintaining the pressure for 3-5 minutes, and circulating for 3-5 times.
In one embodiment, in the step (1), the mold is concentrated and dried, specifically: and (3) using a hot blast drying oven at the temperature of 35-40 ℃ for 5-6h, then dropwise adding the hydrogel solution, concentrating and drying again, and repeating the process for 2-3 times.
In one embodiment, the ultraviolet light in step (1) is cured for a period of time, the wavelength of the ultraviolet light is 365nm, the light curing time is 60-150s, and the light curing time is preferably 120 s.
In one embodiment, the horseradish peroxidase HRP and the hydrogen peroxide H in the step (2)2O2The amounts of addition of (b) were 135. mu.L/mL, respectively.
In one embodiment, the drying of the hydrogel microneedle patch in the step (2) is specifically: drying with hot blast at 35-40 deg.C for 10-12 h. For example, the drying temperature is 37 ℃ and the drying time is 5 hours.
In one embodiment, the mold used was a PDMS mold with a tip height of 1500 μm, a base diameter of 550 μm, a tip distance of 1200 μm, a number array of 8 by 8, a patch size of 12 by 12mm and a groove depth of 2 mm.
In one embodiment, the method comprises the steps of:
(1) preparation of hydrogel microneedles:
dissolving 0.05g of initiator LAP in 20mL of ultrapure water, heating in a water bath at 45 ℃ for dissolving for 15min, shaking for several times during the process to obtain 0.25% (w/v) of initiator standard solution, then taking 0.5-1.0g of SilMA, uniformly mixing 1mL of initiator standard solution and the SilMA, standing at room temperature for dissolving for 0.5-1h to obtain the photocuring hydrogel solution. Casting 150-micron-L of 250-micron-L hydrogel solution on a PDMS mold, removing bubbles under negative pressure, vacuumizing for 1.0MPa, maintaining the pressure for 3-5 minutes at the temperature of 35-60 ℃, circulating for 3-5 times in such a way, sucking off the excess surface hydrogel solution, putting the PDMS mold into a hot blast oven for concentration and drying at the temperature of 35-40 ℃ for 5-6 hours, then dropwise adding the hydrogel solution and concentrating and drying again, and repeating the process for 2-3 times. And then taking out the mold, irradiating by using a handheld ultraviolet lamp with the wavelength of 365nm, and carrying out photocuring for 60-150s to obtain the hydrogel microneedle.
(2) Preparing the color-changeable hydrogel microneedle patch:
dissolving 20mL of absolute ethyl alcohol in 100mL of ultrapure water to obtain a 20% ethyl alcohol solution; adding 0.1g BTB to dissolve in 20% ethanol solution, and dissolving completely to obtain 0.1% BTB ethanol solution; then 0.5-1.0g of SilMA is taken, 0.02% -0.1% of BTB ethanol solution is uniformly mixed with the SilMA, and 135 mu L of HRP (0.01g/mL) and H are respectively added into each 1mL of mixed solution2O2(100mM), uniformly mixing to obtain a color-changeable hydrogel microneedle patch solution, casting 150-.
In a second aspect of the present invention, there is provided a hydrogel microneedle patch having a changeable color, which is manufactured by the aforementioned method.
In a third aspect of the invention, the color-changeable hydrogel microneedle patch is used for detecting the freshness of fish meat, and is particularly suitable for detecting the freshness of salmon in a refrigeration period, wherein the refrigeration condition is 0 ℃ and 4 ℃, and the storage time is 10 days.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the color-changeable hydrogel microneedle patch, bromothymol blue is added into the raw material, TVB-N generated by deteriorated salmon can form amine and hydroxide ions, and under the condition that moisture exists, the moisture can react with an acidic form of a freshness indicator to generate an alkaline form, so that the color of the freshness indicator is changed from yellow to green.
2. The present invention utilizes that the hydrogel is a crosslinked polymer that can absorb large amounts of water, which promotes the dissolution of volatile salt-based nitrogen, resulting in a visible color change of the pH indicator in the hydrogel.
3. The invention collects the color information of the SilMA hydrogel by using the smart phone and converts the color change into RGB signals. The TVB-N content during food storage can be easily obtained by intelligent methods by constructing the corresponding equation (TVB-N vs RGB) to convert the image into a remote RGB detection mode.
4. The needle tip part of the color-changeable hydrogel microneedle patch prepared by the invention has strong mechanical property and better liquid extraction capability, can penetrate through food preservative films and fish meat, and can sample liquid in the deep of food tissues.
5. The color-changeable hydrogel microneedle patch prepared by the method is safe and nontoxic in raw material, easy to prepare, free of pollution in the preparation process, wide in application range and applicable to industrial production.
Of course, it is not necessary for any one product in which the invention is practiced to achieve all of the above-described technical effects simultaneously.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention. In the drawings:
fig. 1 is an appearance and topography diagram of a color-changeable hydrogel microneedle patch prepared in example 1.
Fig. 2 is a partial perspective view of the tip of the color changeable hydrogel microneedle patch prepared in example 1.
FIG. 3 is a graph showing the mechanical properties of the needle tips of the color-changeable hydrogel microneedle patches prepared in examples 1 to 6.
FIG. 4 is a water absorption performance diagram of the color-changeable hydrogel microneedle patch prepared in examples 1-6.
FIG. 5 is a graph showing changes in pH of salmon during storage at 0 ℃ and 4 ℃.
FIG. 6 is a graph showing the change in histamine content during the storage of salmon at 0 ℃ and 4 ℃.
FIG. 7 is a graph showing the change in TVB-N content of salmon during storage at 0 ℃ and 4 ℃.
Fig. 8 is a graph of correlation model of salmon TVB-N — microneedle patch RGB values.
Fig. 9 is a color change graph of the color-changeable hydrogel microneedle patch prepared in example 1 for detecting freshness of salmon.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The sources of reagents used in the examples of the present invention may be purchased commercially or prepared by known methods, unless otherwise specified.
Example 1
A color changeable hydrogel microneedle patch [ note: the preparation method of BTB (0.04%)/SilMA (7%) -MNs ] comprises the following steps, wherein BTB (0.04%): the BTB concentration in the color-changeable hydrogel solution is 0.4 mg/mL; SilMA (7%) denotes: SilMA in the hydrogel solution prepared from the needle tip part and the color-changeable hydrogel solution is 0.7 g/mL; the same classes mentioned in the other examples are meant to be the same.
1.1 preparation of hydrogel microneedles:
(1) preparation of LAP initiator standard solution, solution a: dissolving 0.05g of initiator LAP in 20mL of ultrapure water, heating in a water bath at 45 ℃ for dissolving for 15min, and shaking for several times during the heating to obtain 0.25% (w/v) of initiator standard solution;
(2) preparation of SilMA hydrogel solution: taking 0.7g of SilMA, uniformly mixing 1mL of the solution obtained in the step (1) with the SilMA, standing at room temperature for 0.5-1h, and dissolving to obtain a SilMA photocuring hydrogel solution;
(3) preparation of SilMA hydrogel microneedles: and (3) casting 150-. Putting the PDMS mould into a hot blast oven for concentration and drying at the temperature of 35-40 ℃ for 5-6h, then dropwise adding a hydrogel solution, and concentrating and drying again, wherein the process is repeated for 2-3 times. Taking out the mold, irradiating by using a handheld ultraviolet lamp with the wavelength of 365nm, and carrying out photocuring for 120s to obtain the hydrogel microneedle;
1.2 preparation of color-changeable hydrogel microneedle Patch
(4) Preparation of 0.1 wt% BTB/ethanol/ultrapure aqueous solution, solution B: and dissolving BTB in water to prepare a solution with the mass ratio of the color developing agent BTB, the absolute ethyl alcohol and the ultrapure water being (0.1-0.5) to (20-25) to 100.
(5) Preparation of color-changeable hydrogel solution: taking 0.07g of SilMA, taking 400 mu L of the solution B obtained in the step (4) and 600 mu L of ultrapure water to be uniformly mixed with the SilMA, and respectively adding 135 mu of LHRP (0.01g/mL) and H into 1mL of the mixed solution2O2(100mM), and uniformly mixing to prepare a color-changeable hydrogel microneedle patch solution;
(6) preparing the color-changeable hydrogel microneedle patch: and (3) casting 150-250 mu L of the solution obtained in the step (5) on a mold containing the hydrogel microneedle for hot blast drying, controlling the drying temperature to be 35-40 ℃, drying for 10-12h, and then peeling the hydrogel microneedle patch from the mold to obtain the color-changeable hydrogel microneedle patch, namely BTB (0.04%)/SilMA (7%) -MNs.
1.3 testing the color-changeable hydrogel microneedle patch prepared by the method:
(1) the apparent morphology of the color-changeable hydrogel microneedle patch prepared in this example was photographed, and the test method was: the microneedle patch was picked up with tweezers and photographed using a mobile phone under appropriate light and background, and fig. 1 is an appearance profile of BTB (0.04%)/SilMA (7%) -MNs prepared in example 1.
(2) The variable color hydrogel microneedle patch prepared in the embodiment is shot for the shape of the needle point, and the test method comprises the following steps: the shape of the tip of the microneedle was photographed using a stereomicroscope, the magnification was set on the stereomicroscope, and the microneedle patch was photographed by placing it under appropriate light and angle, and fig. 2 is a diagram showing the shape of the tip of the needle of BTB (0.04%)/SilMA (7%) -MNs prepared in example 1.
(3) The mechanical property test of the color-changeable hydrogel microneedle patch prepared in the embodiment is carried out, and the test method comprises the following steps: selecting a P/25 probe by using a texture analyzer; setting parameters: the measuring mode and the option are gel, the speed before measuring is 1mm/s, and the force measurement is started when the sensor contacts the tip; the speed of the measurement is 0.2mm/s, and the measurement is finished when the sensor moves 0.5 mm. FIG. 3 is a graph of the mechanical properties of BTB (0.04%)/SilMA (7%) -MNs tips prepared in example 1. As can be seen from FIG. 3, the hydrogel microneedle patch tip containing 7% SilMA can withstand a force of 1.7N.
(4) The water absorption performance of the color-changeable hydrogel microneedle patch prepared in the embodiment is tested, and the test method comprises the following steps: the water absorption properties of the SilMA patches were tested using gelatin hydrogel to simulate the liquid in a meat model. First, a 3% w/v gelatin hydrogel was prepared by dissolving 3g of gelatin in 100mL of ultrapure water at 60 ℃. The gelatin solution was then poured onto a petri dish and allowed to solidify at room temperature for 12 hours. Finally, the dried SilMA microneedle patches were inserted into gelatin under appropriate pressure and MNs water uptake changes were recorded every 2 minutes. The surface water was removed with absorbent paper, and the paper was placed on filter paper and weighed. The swelling property of the hydrogel is calculated by the following equation: SW% ([ (M-M)0)/M0]×100，M0(dry weight of hydrogel prior to immersion in water); m (wet weight of hydrogel before immersion in water); FIG. 4 is a graph of water absorption properties of BTB (0.04%)/SilMA (7%) -MNs prepared in example 1. As can be seen from fig. 4, the hydrogel microneedle patch containing 7% SilMA had a water absorption performance of 7.02% at the sixth minute.
Example 2
A color changeable hydrogel microneedle patch [ note: a method for preparing BTB (0.04%)/SilMA (5%) -MNs ] comprises the following steps:
(1) the same as example 1;
(2) preparation of SilMA hydrogel solution: taking 0.5g of SilMA, uniformly mixing 1mL of the solution obtained in the step (1) with the SilMA, standing at room temperature for 0.5-1h, and dissolving to obtain a SilMA photocuring hydrogel solution;
(3) steps (3) to (6) are the same as those of example 1.
The color changeable hydrogel microneedle patch [ BTB (0.04%)/SilMA (5%) -MNs ] prepared in this example was used as a sample for mechanical properties and water absorption properties, and the test method was the same as that in example 1, and fig. 3 is a graph of mechanical properties of the tip of BTB (0.04%)/SilMA (5%) -MNs prepared in example 2. As can be seen from fig. 3, the hydrogel microneedle patch tip containing 5% SilMA withstands about 0.8N. FIG. 4 is a graph of water absorption performance of BTB (0.04%)/SilMA (5%) -MNs prepared in example 2. As can be seen from fig. 4, the hydrogel microneedle patch containing 5% SilMA had a water absorption performance of 3.92% at the sixth minute.
Example 3
A color changeable hydrogel microneedle patch [ note: a method for preparing BTB (0.04%)/SilMA (6%) -MNs ] comprises the following steps:
(1) the same as example 1;
(2) preparation of SilMA hydrogel solution: taking 0.6g of SilMA, uniformly mixing 1mL of the solution obtained in the step (1) with the SilMA, standing at room temperature for 0.5-1h, and dissolving to obtain a SilMA photocuring hydrogel solution;
(3) steps (3) to (6) are the same as those of example 1.
The color changeable hydrogel microneedle patch [ BTB (0.04%)/SilMA (6%) -MNs ] prepared in this example was used as a sample for mechanical properties and water absorption properties, and the test method was the same as that in example 1, and fig. 3 is a graph of mechanical properties of the tip of BTB (0.04%)/SilMA (6%) -MNs prepared in example 3. As can be seen from fig. 3, the hydrogel microneedle patch tip containing 6% SilMA withstands about 1.5N. FIG. 4 is a graph of water absorption performance of BTB (0.04%)/SilMA (6%) -MNs prepared in example 3. As can be seen from fig. 4, the hydrogel microneedle patch containing 6% SilMA had a water absorption performance of 5.85% at the sixth minute.
Example 4
A color changeable hydrogel microneedle patch [ note: a method for preparing BTB (0.04%)/SilMA (8%) -MNs ] comprises the following steps:
(1) the same as example 1;
(2) preparation of SilMA hydrogel solution: taking 0.8g of SilMA, uniformly mixing 1mL of the solution obtained in the step (1) with the SilMA, standing at room temperature for 0.5-1h, and dissolving to obtain a SilMA photocuring hydrogel solution;
(3) steps (3) to (6) are the same as those of example 1.
The color changeable hydrogel microneedle patch [ BTB (0.04%)/SilMA (8%) -MNs ] prepared in this example was used as a sample for mechanical properties and water absorption properties, and the test method was the same as that in example 1, and fig. 3 is a graph of mechanical properties of the tip of BTB (0.04%)/SilMA (8%) -MNs prepared in example 3. As can be seen from fig. 3, the hydrogel microneedle patch tip containing 8% SilMA withstands about 0.7N. FIG. 4 is a graph of water absorption performance of BTB (0.04%)/SilMA (8%) -MNs prepared in example 3. As can be seen from fig. 4, the hydrogel microneedle patch containing 8% SilMA had a water absorption performance of 3.54% at the sixth minute.
Example 5
A color changeable hydrogel microneedle patch [ note: a method for preparing BTB (0.04%)/SilMA (9%) -MNs ] comprises the following steps:
(1) the same as example 1;
(2) preparation of SilMA hydrogel solution: taking 0.9g of SilMA, uniformly mixing 1mL of the solution obtained in the step (1) with the SilMA, standing at room temperature for 0.5-1h, and dissolving to obtain a SilMA photocuring hydrogel solution;
(3) steps (3) to (6) are the same as those of example 1.
The color changeable hydrogel microneedle patch [ BTB (0.04%)/SilMA (9%) -MNs ] prepared in this example was used as a sample for mechanical properties and water absorption properties, and the test method was the same as that in example 1, and fig. 3 is a graph of mechanical properties of the tip of BTB (0.04%)/SilMA (9%) -MNs prepared in example 3. As can be seen from fig. 3, the hydrogel microneedle patch tip containing 9% SilMA withstands about 0.5N. FIG. 4 is a graph of water absorption performance of BTB (0.04%)/SilMA (9%) -MNs prepared in example 3. As can be seen from fig. 4, the hydrogel microneedle patch containing 9% SilMA had a water absorption performance of 5.79% at the sixth minute.
Example 6
A color changeable hydrogel microneedle patch [ note: a method for preparing BTB (0.04%)/SilMA (10%) -MNs ] comprises the following steps:
(1) the same as example 1;
(2) preparation of SilMA hydrogel solution: taking 1.0g of SilMA, uniformly mixing 1mL of the solution obtained in the step (1) with the SilMA, standing at room temperature for 0.5-1h, and dissolving to obtain a SilMA photocuring hydrogel solution;
(3) steps (3) to (6) are the same as those of example 1.
The color changeable hydrogel microneedle patch [ BTB (0.04%)/SilMA (10%) -MSs ] prepared in this example was used as a sample for mechanical properties and water absorption properties, and the test method was the same as that in example 1, and fig. 3 is a graph of mechanical properties of the BTB (0.04%)/SilMA (10%) -MNs tip prepared in example 3. As can be seen from fig. 3, the hydrogel microneedle patch tip containing 10% SilMA withstands about 0.5N. FIG. 4 is a graph of water absorption performance of BTB (0.04%)/SilMA (10%) -MNs prepared in example 3. As can be seen from fig. 4, the hydrogel microneedle patch containing 10% SilMA had a water absorption performance of 5.44% at the sixth minute.
Comparative example 1
A color changeable hydrogel microneedle patch [ note: the preparation method of BTB (0%)/SilMA (7%) -MNs ] comprises the following steps:
(1) the steps (1) to (3) are the same as those in the steps (1) to (3) of example 1;
(4) preparation of hydrogel microneedle patch solution: 0.7g of SilMA was taken, 1000. mu.L of ultrapure water was uniformly mixed with the SilMA, and 135. mu.L of HRP (0.01g/mL) and H were added to 1mL of the mixed solution2O2(100mM), and uniformly mixing to prepare a color-changeable hydrogel microneedle patch solution;
(5) same as in step (6) in example 1.
Example 7
A color changeable hydrogel microneedle patch [ note: the preparation method of phenol red (0.04%)/SilMA (7%) -MNs ] comprises the following steps:
(1) the steps (1) to (3) are the same as those in the steps (1) to (3) of example 1;
(4) preparation of 0.1% by weight phenol Red/ultrapure water/ethanol solution: phenol red was dissolved in water to prepare 100mL of a 0.1 wt% phenol red/water/ethanol solution, wherein the ethanol content was 20 wt%, and the balance was ultrapure water.
(5) Steps (5) to (6) are the same as those of example 1;
example 8
A color changeable hydrogel microneedle patch [ note: the preparation method of bromophenol red (0.04%)/SilMA (7%) -MNs ] comprises the following steps:
(1) the steps (1) to (3) are the same as those in the steps (1) to (3) of example 1;
(4) preparation of 0.1% by weight bromophenol Red/ultrapure Water/ethanol solution: bromphenol red is dissolved in water to prepare 100mL of 0.1 wt% phenol red/water/ethanol solution, wherein the ethanol content is 20 wt%, and the balance is ultrapure water.
(5) Steps (5) to (6) are the same as those of example 1;
example 9
A color changeable hydrogel microneedle patch [ note: the preparation method of the anthocyanin (0.04%)/SilMA (7%) -MNs ] comprises the following steps:
(1) the steps (1) to (3) are the same as those in the steps (1) to (3) of example 1;
(4) preparation of 0.1 wt% anthocyanin/ultrapure water/ethanol solution: the anthocyanin is dissolved in water to prepare 100 mL0.1wt% phenol red/water/ethanol solution, wherein the ethanol content is 20 wt%, and the balance is ultrapure water.
(5) Steps (5) to (6) are the same as those of example 1;
example 10
A color changeable hydrogel microneedle patch [ note: a preparation method of anthocyanin (0.04%)/SilMA (7%) -MNs ] comprises the following steps:
(1) the steps (1) to (3) are the same as those in the steps (1) to (3) of example 1;
(4) preparation of 0.1 wt% anthocyanin/ultrapure water/ethanol solution: dissolving anthocyanin in water to prepare 100 mL0.1wt% phenol red/water/ethanol solution, wherein the ethanol content is 20 wt%, and the balance is ultrapure water.
(5) Steps (5) to (6) are the same as those of example 1;
the specific case of application:
fresh salmon stored in a preservative film package at 0 ℃ and 4 ℃ was simultaneously tested using the variable color hydrogel microneedle patch [ BTB (0.04%)/SilMA (7%) -MNs ] prepared in example 1 and the variable color hydrogel microneedle patch [ BTB (0%)/SilMA (7%) -MNs ] prepared in comparative example 1, and the fresh salmon stored at 0 ℃ for 10 days was always in a fresh state. Fresh salmon stored at 4 ℃ had a color change from yellow to pale green as measured by BTB (0.04%)/SilMA (7%) -MNs at 5-6 days, whereas BTB (0%)/SilMA (7%) -MNs had no color change, and the hydrogel microneedle patch became green after 7 days, as shown in fig. 9. The pH changes during storage are shown in fig. 5, with salmon pH 6.41 when initially fresh and pH 6.46 when stored at 4 ℃ for 6 days, which is elevated compared to salmon pH when initially fresh; the histamine content during storage varied as shown in FIG. 6, the histamine content of salmon stored at 4 ℃ on day 7 was 54.15mg/kg, the TVB-N content during storage varied as shown in FIG. 7, the TVB-N content was 20.49mg/100g, and the pH value, histamine content, TVB-N content of salmon during storage were combined according to national standards, at which time salmon stored at 4 ℃ was not fresh. Therefore, the color-changeable hydrogel microneedle patch of the present invention can indicate the freshness of the fresh salmon through color change.
Quantitative sensing can be conveniently realized by combining with a smart phone and RGB analysis, for example, a relevant model diagram of salmon TVB-N- - -hydrogel patch RGB is shown in FIG. 8, wherein the y axis is salmon TVB-N value, the x axis is hydrogel microneedle patch RGB value, and the fitted regression equation shown in FIG. 8 is that y is 0.044 x-0.417R2The RGB value of the hydrogel microneedle patch read on day 6 was 0.454, and TVB-N was calculated as 0.969: 19.73mg/100g, found in fact: 19.04mg/100 g; the RGB value of the hydrogel microneedle patch read on day 8 was 0.571, and the TVB-N: 22.52mg/100g, found in fact: 21.93mg/100 g; the RGB value of the hydrogel microneedle patch read on day 10 was 0.812, and the TVB-N was calculated: 28.26mg/100g, found in fact: 28.28mg/100g, so the color changeable hydrogel microneedle patch of the present invention can be further usedAnd detecting the quantification of the TVB-N during the storage period of the salmon.
It should be understood that the above description is only an example of the present invention, and not intended to limit the scope of the present invention, and all equivalent structures or equivalent flow transformations that may be applied to the present invention as described in the specification, or applied to other related fields, directly or indirectly, are included in the scope of the present invention.
Claims (12)
1. A preparation method of the color-changeable hydrogel microneedle patch is characterized by comprising the following steps:
(1) preparing hydrogel microneedles: dissolving an initiator LAP in ultrapure water, heating in a water bath, and then vibrating and dissolving to obtain a solution A; then taking a hydrogel material, and uniformly mixing the solution A and the hydrogel material to obtain a hydrogel solution; casting the hydrogel solution on a mold, removing bubbles of the mold through negative pressure for several times, concentrating and drying, and curing through ultraviolet light to obtain a hydrogel microneedle;
(2) preparing a color-changeable hydrogel microneedle patch: dissolving a color developing agent in absolute ethyl alcohol and ultrapure water to obtain a solution B; then taking a hydrogel material, mixing the solution B with the hydrogel material, adding horseradish peroxidase and hydrogen peroxide, and uniformly mixing to obtain a color-changeable hydrogel microneedle patch solution; and (3) casting the color-changeable hydrogel microneedle patch solution on a mold containing hydrogel microneedles, drying the mold, and then stripping the mold to obtain the color-changeable hydrogel microneedle patch.
2. The method of preparing a color-changeable hydrogel microneedle patch according to claim 1, wherein the amount of the initiator LAP added to ultrapure water in the step (1) is 0.05g/20 mL.
3. The method for preparing a color-changeable hydrogel microneedle patch according to claim 1, wherein the amount of the hydrogel material added to the solution a in the step (1) is 0.05 to 0.10g/1.0 mL.
4. The method for preparing a color-changeable hydrogel microneedle patch according to claim 1, wherein the hydrogel material is at least one of methacrylated silk fibroin SilMA, gelatin, hyaluronic acid, agar, sodium polyacrylate, and methacrylic acid polymer, preferably methacrylated silk fibroin SilMA.
5. The method for preparing a color-changeable hydrogel microneedle patch according to claim 1, wherein an appropriate amount of hydrogel solution is cast on the mold in the step (1), and the amount of the hydrogel solution added is 150 to 250 μ L.
6. The method for preparing a color-changeable hydrogel microneedle patch according to claim 1, wherein the mass ratio of the color developing agent, the absolute ethyl alcohol and the ultrapure water is (0.1-0.5) to (20-25) to 100.
7. The method of manufacturing a color-changeable hydrogel microneedle patch according to claim 1, wherein the color developer in the step (2) is at least one of phenol red, bromophenol red, bromothymol blue, bromocresol purple, bromocresol green, anthocyanins, and roselle pigment.
8. The method for preparing a color-changeable hydrogel microneedle patch according to claim 1, wherein the amount of the hydrogel material added in the step (2) is 0.05 to 0.20g/1.0mL with respect to the solution B.
9. The method for preparing a color-changeable hydrogel microneedle patch according to claim 1, wherein the mass concentrations of horseradish peroxidase and hydrogen peroxide in the step (2) are 0.01g/mL and 100mM/L, respectively.
10. The method for preparing a color-changeable hydrogel microneedle patch according to claim 1, wherein the color-changeable hydrogel microneedle patch solution is cast on a mold containing hydrogel microneedles in the step (2), and the addition amount of the color-changeable hydrogel solution is 150 to 250 μ L.
11. A color-changeable hydrogel microneedle patch characterized by being produced by the production method according to any one of claims 1 to 10.
12. Use of the production method according to any one of claims 1 to 10 or use of the color-changeable hydrogel microneedle patch according to claim 11 for fish freshness detection.
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