Soft and hard base combined sensor substrate, preparation method, sensor and application thereof

Abstract

The invention provides a soft and hard base combined sensor substrate, and belongs to the technical field of sensors. The device comprises a rigid microarray and a flexible substrate, the rigid microarray is connected through the flexible substrate, and a coarse structure is constructed on the surface of the rigid microarray and has hydrophilicity. The rigid microarrays with the micro-nano structures on the surfaces are connected through the flexible substrate, and durability and stable detection of a sensor detection area can be achieved by means of wear resistance and stability of the rigid microarrays; by utilizing the flexibility and deformability of the flexible substrate, the wearable performance of the sensor can be realized, and the sensor has the advantages of hardness and softness combination, hardness and softness combination, low cost and convenience in carrying and use.

Description

Technical Field

[0001] The present invention relates to the field of sensor technology, and in particular to a soft-hard base combined sensor substrate, a preparation method of the substrate, a sensor comprising the substrate, and applications of the sensor. Background Art

[0002] With the development of society, people pay more and more attention to their physical health. Blood has always been considered the preferred analyte for monitoring human health, but it should be noted that blood analysis is somewhat traumatic, the process is cumbersome, expensive, and prone to cross-infection. In addition to blood, saliva, tears, and sweat also contain biomarkers, which can all be used as a non-invasive detection method. Compared with saliva and tears, sweat contains a large number of useful chemicals (various electrolyte ions, metabolites, etc.), which can not only be used to analyze the body's movement status, water status, etc., but also can be used to assist in the diagnosis of diseases.

[0003] At present, sweat detection has become one of the emerging means of disease diagnosis and health monitoring, and sweat sensors have also received more and more attention and research. In the prior art, sweat sensors prepared on purely rigid substrates have wear resistance, high mechanical strength and stability, and sweat sensors prepared on purely flexible substrates have high flexibility, flexibility, conformability, and the ability to adapt to complex environments. However, they also face a series of problems and challenges, namely, sweat sensors prepared on purely rigid substrates are not easy to bend, are not wearable, and sweat collection and detection need to be carried out separately, while sweat sensors prepared on purely flexible substrates have low mechanical strength of the substrate, the detection area is easily damaged, and the detection performance is easily affected, for example: the paper base is easy to wrinkle and swells when exposed to water.

[0004] Therefore, it is necessary to design a wearable sensor substrate whose detection area is wear-resistant and capable of real-time and stable detection. Summary of the invention

[0005] In view of this, in order to solve the technical problems in the prior art that sweat sensors made of purely rigid substrates are not easy to stretch, are not wearable, and sweat collection and detection need to be carried out separately, and sweat sensors made of purely flexible substrates have low substrate mechanical strength, the detection area is easily damaged, and the detection performance is easily affected, in a first aspect, the present invention provides a sensor substrate combining soft and hard substrates, which connects a rigid microarray with a rough structure on the surface through a flexible substrate, and utilizes the wear resistance, stability and hydrophilicity of the rigid microarray to achieve durability of the sensor detection area and stable and sensitive detection; utilizes the flexibility and deformability of the flexible substrate to achieve wearability of the sensor, which has the advantages of combining soft and hard, combining rigidity and flexibility, low cost, and easy carrying and use.

[0006] To achieve the above object, the present invention provides the following technical solutions: A sensor substrate combining a soft and a hard substrate, comprising a rigid microarray and a flexible substrate; The rigid microarray is connected via the flexible substrate, and a rough structure is constructed on the surface of the rigid microarray, which is hydrophilic.

[0007] Preferably, the rigid microarrays are filled with the flexible substrate.

[0008] Preferably, the rigid microarray is assembled into the flexible substrate.

[0009] Preferably, the rigid microarray is made of at least one of glass, ceramic, silicon substrate, carbon substrate, metal plate, plastic substrate and hard substrate based on composite materials and micro-nano materials.

[0010] Preferably, the flexible substrate comprises at least one of a flexible polymer, a flexible fiber fabric, a flexible electronic fabric and a flexible composite material.

[0011] In a second aspect, the present invention provides a method for preparing the above-mentioned soft-hard base combined sensor substrate, comprising the following steps: Step 1: Processing a rigid microarray on one side of a hard substrate; Step 2: Filling the space between the rigid microarrays in step 1 with a flexible substrate; Step 3: polishing the substrate on the reverse side to form a rigid microarray connected by a flexible substrate; Step 4: forming a rough structure on the rigid microarray surface; Step 5: functionally modifying the rigid microarray surface; Step 6: Add a skin adhesion layer to form a wearable soft-hard sensor substrate.

[0012] In a third aspect, the present invention provides a method for preparing the above-mentioned soft-hard base combined sensor substrate, comprising the following steps: Step 1: Lay a flexible substrate of a certain thickness; Step 2: assembling the rigid microarray and the flexible substrate using an automatic alignment strategy to form a rigid microarray connected by the flexible substrate; Step 3: constructing a rough structure on the rigid microarray surface; Step 4: functionally modifying the rigid microarray surface; Step 5: Add a skin adhesion layer to form a wearable soft-hard sensor substrate.

[0013] In a fourth aspect, the present invention provides a sensor comprising the above-mentioned soft-hard base combined sensor substrate.

[0014] In a fifth aspect, the present invention provides the application of the above-mentioned sensor in the fields of food safety, environmental monitoring, and medical health involving the detection of dangerous goods, physiological indicators, and biomarkers.

[0015] Preferably, the detection of the physiological index includes the detection of at least one body index-related biomarker in sweat.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The sensor substrate combining a soft and hard base provided by the present invention connects a rigid microarray with a micro-nano structure on the surface through a flexible substrate. By utilizing the wear resistance and stability of the rigid microarray, the durability and stable detection of the sensor detection area can be achieved; by utilizing the flexibility and deformability of the flexible substrate, the wearability of the sensor can be achieved and improved. It has the advantages of combining soft and hard, combining rigidity and flexibility, low cost, and convenient carrying and use.

[0017] In addition, the size, surface shape, spacing and number of rigid microarrays can be customized according to user needs to achieve trace and trace detection as well as single-component, multi-component, high-throughput and real-time detection.

[0018] The method for preparing the soft-hard base combined sensor substrate provided by the invention is simple and suitable for industrial mass production.

[0019] The sensor provided by the present invention, which includes the sensor substrate combining the soft and hard bases, can be applied to the detection of body fluids, food, gas, water quality, heavy metals, stimulants, dangerous goods and other physiological indicators and biomarkers, effectively expanding its scope of application. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 A schematic diagram of the structure of a sensor substrate combining a soft and hard substrate provided by the present invention; Figure 2 This is an optical micrograph of the rough microstructure of the glass microarray surface processed in Example 1 of the present invention; Figure 3 This is a scanning electron microscope image of the micro-nanostructure on the surface of the rigid microarray of Example 3 of the present invention; Figure 4 This is a characterization diagram of the contact angle of water on the surface of the micro-nano rigid microarray of Example 3 of the present invention; Figure 5 This is a bar graph of the detection of sweat pH standard solution by the sensor of Examples 5 and 6 of the present invention; Figure 6 This is a bar graph of the detection of the sweat marker glucose standard solution by the sensor of Examples 7 and 8 of the present invention; Figure 7This is a bar graph showing the detection of fluorescein isothiocyanate by the sensor of Example 9 of the present invention. DETAILED DESCRIPTION

[0021] like Figure 1 As shown, in the first aspect, the present invention provides a sensor substrate combining a soft and a hard substrate, comprising a rigid microarray and a flexible substrate; The rigid microarray is connected by the flexible substrate, and the surface of the rigid microarray has a rough structure, wherein the rough structure is preferably constructed with microstructure textures or grooves or has a micro-nano structure.

[0022] If the flexible substrate is hydrophilic, then the rigid microarray needs to be more hydrophilic. If the flexible substrate is hydrophobic, then the rigid microarray only needs to be hydrophilic. In other words, the greater the difference in properties between the flexible substrate and the rigid microarray, the better.

[0023] In the present invention, the flexible substrate is filled between the rigid microarrays.

[0024] In the present invention, the rigid microarray can also be assembled into the flexible substrate.

[0025] In the present invention, the rigid microarray is selected from at least one of glass, ceramic, silicon substrate, carbon substrate, metal plate, plastic substrate and hard substrate based on composite materials and micro-nano materials. The above-mentioned materials selected by the rigid microarray are used to provide a wear-resistant and stable detection area for the sensor. In order to improve the detection performance, a micro-nano structure can be further constructed on the rigid microarray.

[0026] In the present invention, the rigid microarray is hydrophilic or has hydrophilicity through modification.

[0027] In the present invention, the rigid microarray can obtain a rough structure of microstructure texture or grooves through mechanical processing and etching.

[0028] In the present invention, the rigid microarray can construct micro-nano interface materials through deposition, sputtering, mineralization, spraying, 3D printing, and self-assembly technology.

[0029] In the present invention, the flexible substrate comprises one of a flexible polymer, a flexible fiber fabric, a flexible electronic fabric and a flexible composite material, which provides the sensor substrate with wearability and wearing comfort.

[0030] The flexible polymer is preferably selected from at least one of polydimethylsiloxane, epoxy resin, polyurethane, nitrile rubber and hydrogel; and is preferably hydrophobic or modified to be hydrophobic.

[0031] In a second aspect, the present invention provides a method for preparing the above-mentioned soft-hard base combined sensor substrate, comprising the following steps: Step 1: Processing a rigid microarray can be done by cutting technology, 3D printing technology or etching technology; Step 2: Filling the rigid microarray in step 1 with a flexible substrate; Step 3: polishing the rigid substrate on the reverse side to form a rigid microarray connected by a flexible substrate; Step 4: constructing a rough structure on the rigid microarray surface; Step 5: Functionalize the surface of the rigid microarray; the functionalized modification may be a specific substrate for sweat biomarkers. By adding a functionalized substrate, such as purple litmus reagent, to the surface of the rigid microarray, the designated area is made to have the function of specifically identifying and detecting a certain substance; Step 6: Add the skin adhesion layer.

[0032] In a third aspect, the present invention provides a method for preparing the above-mentioned soft-hard base combined sensor substrate, comprising the following steps: Step 1: Lay a flexible substrate of a certain thickness; Step 2: assembling the rigid microarray and the flexible substrate using an automatic alignment strategy to form a rigid microarray connected by the flexible substrate; Step 3: constructing a rough structure on the rigid microarray surface; Step 4: functionally modifying the rigid microarray surface; Step 5: Add a skin adhesion layer to form a sensor substrate that combines soft and hard substrates.

[0033] In a fourth aspect, the present invention provides a sensor comprising the above-mentioned soft-hard base combined sensor substrate.

[0034] In a fifth aspect, the present invention provides the application of the above-mentioned sensor in the detection of dangerous goods, physiological indicators and biomarkers in the fields of food safety, environmental monitoring, and medical health. It can also be used to detect water quality.

[0035] Among them, environmental monitoring, such as water quality, air, soil, etc., medical health, such as body fluid testing, nutrient testing, etc. Dangerous goods involved, such as heavy metals, stimulants, etc., physiological indicators and biomarkers, such as body fluids, sweat, and at least one body indicator related biomarker in sweat. It can also be used for the detection of other biomarkers and other substances.

[0036] In the present invention, the sweat detection in the physiological index includes the detection of at least one body index-related biomarker (pH, glucose, lactic acid, etc.) in sweat.

[0037] The sensor provided by the present invention can detect the target analyte not only by colorimetry, but also by fluorescence analysis, chemiluminescence, electrochemical method, surface enhanced Raman scattering and other applicable detection methods.

[0038] The technical solution of the present invention is clearly described in detail below in conjunction with specific embodiments.

[0039] Example 1 Filling glass microarrays with polydimethylsiloxane (PDMS) to form a soft-hard substrate Step 1: Cutting the glass sheet. Use a precision cutting machine (ADT7124) to cut the glass sheet (25.4×76.2×1 mm, Sailboat brand) longitudinally and transversely. The cut glass microarray has a length and width of 1 mm, a slit width of 2 mm, and a cutting depth of 0.5 mm to form a glass microarray.

[0040] Step 2: Filling with poly-PDMS. Mix the main agent and curing agent at a mass ratio of 10:1, fill it into the cut of the glass microarray, and then use a vacuum drying oven to remove bubbles; then, place it in a 65°C oven for 4 hours to solidify it.

[0041] Step 3: Polish the glass sheet on the back side. Use a precision cutter to polish the glass sheet from the back side to remove the uncut glass sheet with a depth of 0.5 mm to form a glass microarray connected by PDMS, i.e., a sensor substrate combining soft and hard substrates. The rough microstructure of the processed glass microarray surface is as follows: Figure 2 shown.

[0042] Example 2 Assembling glass microarrays on polydimethylsiloxane (PDMS) to form a soft-hard substrate Step 1: Process glass microcolumns with a length and width of 1 mm and a depth of 1 mm for later use.

[0043] Step 2: Prepare PDMS. Mix the main agent and curing agent in a mass ratio of 10:1 and place in a vacuum drying oven to remove bubbles.

[0044] Step 3: Assembly: Spread the PDMS flat in a shallow dish with a depth of about 0.5 mm, and then use the automatic alignment strategy to vertically embed the glass microcolumns in the uncured PDMS in an orderly manner.

[0045] Step 4: Curing: The assembled glass microarray was placed in an oven at 100° C. for 45 minutes to cure it, thereby assembling the glass microarray on the PDMS to form a sensor substrate combining a soft and hard substrate.

[0046] Example 3 Construction of micro-nanostructures on rigid microarray surfaces Step 1: Clean the soft and hard base substrate with an ultrasonic cleaner, and dry it in a constant temperature drying oven at 40°C for later use.

[0047] Step 2: Weigh 150 mg of zinc nitrate hexahydrate, 70 mg of triethylamine hydrochloride and 120 mg of dimethylimidazole using an electronic analytical balance, add them to a centrifuge tube containing 25 mL of ultrapure water, mix them well, and stir them thoroughly to obtain a mixed solution.

[0048] Step 3: Use a pipette to take 1.0 μL of the mixed solution in step 2 onto the surface of the glass microarray and place it on a heating table (40°C) to heat it to form a micro-nanostructure on the surface of the glass microarray. The microscopic morphology is as follows: Figure 3 As shown, its water contact angle can reach 0°, showing super hydrophilicity (such as Figure 4 as shown).

[0049] Example 4 Construction of micro-nanostructures on rigid microarray surfaces Step 1: Clean the soft and hard base substrate with an ultrasonic cleaner, and dry it in a constant temperature drying oven at 50°C for later use.

[0050] Step 2: Weigh 150 mg of zinc nitrate hexahydrate, 70 mg of triethylamine hydrochloride and 120 mg of dimethylimidazole using an electronic analytical balance, add them to a centrifuge tube containing 50 mL of ultrapure water, mix them evenly, and prepare a mixed solution.

[0051] Step 3: Cover the soft and hard base substrate with a mask, exposing only the rigid microarray surface, and then place it in a weighing bottle, take 25 mL of the prepared mixed solution and pour it into the weighing bottle, cover it with a lid, seal it with a sealing film, and place it in a constant temperature drying oven at 80°C for 8 hours. Then take it out with tweezers, dry it naturally, and then remove the mask, so that a micro-nano structure is formed on the rigid microarray surface, and its water contact angle can reach 0°, showing super hydrophilicity.

[0052] Example 5 pH standard solution testing Use a pipette to take 1.0 μL of purple litmus reagent and drop it into the rigid superhydrophilic microarray area (1×1 mm) with micro-nanostructure. After evaporation and enrichment, the active ingredients used to detect the pH of sweat will be loaded onto the rigid microarray surface to obtain a functional detection area for detecting the pH of sweat.

[0053] 1.0 μL of pH standard solution (pH value is 6.0, 6.5, 7.0, 7.5, 8.0) was added to the functionalized rigid microarray surface, and the soft and hard bases were placed in a 37°C constant temperature water bath and taken out after 2 minutes. The image of the detection area was taken with a smartphone, and its RGB values ​​were recorded and analyzed to draw a detection bar graph, such as Figure 5 shown.

[0054] Example 6 Actual sweat pH measurement After attaching medical tape as a skin adhesion layer to the soft-hard combined sweat sensor that has been functionalized with purple litmus reagent, the sweat sensor is attached to the arm of a volunteer. After sweating during aerobic exercise, the sweat will be enriched on the hydrophilic rigid microarray surface and react with the active ingredients used for pH detection. Then, an image of the detection area is taken with a smartphone, and the corresponding RGB value is obtained by analysis, which is compared with the pH standard solution detection bar graph ( Figure 5 The actual pH value of sweat can be obtained by comparing it with the pH value of sweat.

[0055] Example 7 Glucose standard solution detection Glucose oxidase-peroxidase (GOD-POD) working solution was prepared, and 1.0 μL of GOD-POD working solution was taken with a pipette and dropped onto the rigid superhydrophilic microarray surface with micro-nano structure (1×1 mm). After evaporation and enrichment, the active ingredients for detecting glucose in sweat would be loaded onto the rigid microarray surface to obtain a functionalized detection area for detecting glucose in sweat.

[0056] Next, prepare glucose standard solutions with concentrations of 0, 1.25, 2.5, 3.75, and 5 mmol / L, respectively, and drip 1.0 μL of the prepared gradient concentration glucose solution onto the surface of the rigid microarray. Place the soft and hard base combined substrate in a 37°C constant temperature water bath and take it out after 2 minutes. Use a smartphone to take an image of the detection area, record and analyze its RGB values, and draw a detection bar graph, such as Figure 6 shown.

[0057] Example 8 Glucose detection in actual sweat After a layer of tape was attached to the soft and hard substrate combined sweat sensor that had been functionalized with GOD-POD working fluid as a skin adhesion layer, the sweat sensor was attached to the arm of the volunteer. After the volunteer sweated during aerobic exercise, the sweat was enriched on the rigid microarray surface and reacted with the active ingredients for glucose detection. Then, an image of the detection area was taken with a smartphone, and the corresponding RGB value was obtained by analysis, which was compared with the glucose standard solution detection bar graph ( Figure 6 The actual sweat glucose concentration can be obtained by comparison.

[0058] Example 9 Fluorescence detection The concentrations were 10 -4 , 10 -6 , 10 -9 , 10 -12 , 10 -15 mmol / L fluorescein isothiocyanate (FITC) standard solution, then add 1.0 μL of the prepared gradient concentration FITC solution onto the surface of the super-hydrophilic rigid microarray with micro-nanostructures, and then perform fluorescence analysis with a microscope, record the average fluorescence intensity, and draw a detection bar graph, such as Figure 7 This embodiment is used to verify that the detection on the sensor can adopt not only the colorimetric method but also the fluorescence analysis method.

[0059] The above are only preferred specific implementations of the present invention; however, the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical solutions and improved concepts of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A sensor substrate combining a soft and hard base, characterized in that: Includes rigid microarrays and flexible substrates; The rigid microarray is connected via the flexible substrate, and a rough structure is constructed on the surface of the rigid microarray, which is hydrophilic.

2. The sensor substrate of the soft-hard combination according to claim 1, characterized in that: The rigid microarrays are filled with the flexible substrate.

3. The sensor substrate of the soft-hard combination according to claim 1, characterized in that: The rigid microarray is assembled into the flexible substrate.

4. The sensor substrate of the soft-hard combination according to claim 1, characterized in that: The rigid microarray is made of at least one of glass, ceramic, silicon substrate, carbon substrate, metal plate, plastic substrate and hard substrate based on composite materials and micro-nano materials.

5. The sensor substrate of the soft-hard combination according to claim 1, characterized in that: The flexible substrate includes at least one of a flexible polymer, a flexible fiber fabric, a flexible electronic fabric and a flexible composite material.

6. The method for preparing a sensor substrate combining a soft and hard base according to claim 2, characterized in that: The steps include: Step 1: Processing a rigid microarray on one side of a hard substrate; Step 2: Filling the space between the rigid microarrays in step 1 with a flexible substrate; Step 3: polishing the substrate on the reverse side to form a rigid microarray connected by a flexible substrate; Step 4: forming a rough structure on the rigid microarray surface; Step 5: functionally modifying the rigid microarray surface; Step 6: Add a skin adhesion layer to form a wearable soft-hard sensor substrate.

7. The method for preparing a sensor substrate combining a soft and hard base according to claim 3, characterized in that: The steps include: Step 1: Lay a flexible substrate of a certain thickness; Step 2: assembling the rigid microarray and the flexible substrate using an automatic alignment strategy to form a rigid microarray connected by the flexible substrate; Step 3: constructing a rough structure on the rigid microarray surface; Step 4: functionally modifying the rigid microarray surface; Step 5: Add a skin adhesion layer to form a wearable soft-hard sensor substrate.

8. A sensor, characterized in that: A sensor substrate comprising a soft-hard base combination as claimed in any one of claims 1 to 5.

9. Application of the sensor according to claim 8 in the detection of dangerous goods, physiological indicators and biomarkers in the fields of food safety, environmental monitoring and medical health.

10. The use according to claim 9, characterized in that: The detection of the physiological index includes the detection of at least one biological marker related to the physical index in sweat.

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