Noninvasive blood glucose detection sensor based on anodized aluminum oxide and preparation method of noninvasive blood glucose detection sensor

Abstract

The invention discloses a noninvasive blood glucose detection sensor based on anodic aluminum oxide and a preparation method thereof.The sensor comprises a flexible substrate, a first electrode layer, an organic insulating layer and a second electrode layer which are sequentially arranged from bottom to top, and the second electrode layer comprises a plurality of cavities; the cavities extend downwards from the upper surface of the second electrode layer to the upper surface of the first electrode layer, and the cavities are filled with honeycomb-shaped anodic aluminum oxide layers; a patterned third electrode layer is further arranged on the upper surface of the second electrode layer, and a part of the third electrode layer surrounds the upper edge of the cavity; the first electrode layer and the second electrode layer can be externally connected with a cathode and an anode of a constant-voltage power supply respectively; and the first electrode layer, the second electrode layer and the third electrode layer can also be externally connected with a blood glucose detection device. Honeycomb anodized aluminum oxide is used as a detection cavity, the diameter and depth of the cavity can be adjusted, the detection performance of the noninvasive blood glucose detection sensor is improved, and the problem of evaporation of a hydrogel membrane of a traditional device is solved.

Description

Technical Field

[0001] The present invention belongs to the technical field of non-invasive blood sugar monitoring, and in particular relates to a non-invasive blood sugar detection sensor based on anodized aluminum and a preparation method thereof. Background Art

[0002] With the continuous development of science and technology in society, people's living patterns and eating habits are becoming increasingly diversified. Affected by both genetic and environmental factors, the number of diabetes patients continues to rise. According to data from the International Diabetes Federation, by 2045, the number of diabetes patients worldwide is expected to increase by 46%, reaching a total of about 783 million. Diabetes, as a disease that is currently incurable, may cause blindness, cardiovascular disease, renal failure and other serious complications, and has become one of the major diseases that endanger human health. Therefore, for diabetic patients, continuous monitoring of blood sugar levels is the key to controlling the disease.

[0003] The current mainstream blood glucose detection technology mostly relies on invasive sampling, that is, directly measuring blood glucose levels through fingertips or venous blood sampling. Although this method has high accuracy, frequent needle blood sampling (up to 7 times a day to effectively monitor blood glucose fluctuations) brings significant pain and inconvenience to patients. With the advancement of science and technology, minimally invasive blood glucose monitoring technology has emerged, which can achieve continuous blood glucose monitoring while maintaining high accuracy. Despite this, minimally invasive technology still involves minor trauma to the skin, accompanied by slight pain and potential infection risks. Therefore, the development of a detection method that can achieve continuous blood glucose monitoring and is completely non-invasive, painless, and has no infection risk has become an urgent need and an important research direction in the current field of blood glucose monitoring technology. The current mainstream means is to achieve accurate, continuous, and painless monitoring of blood glucose through non-invasive means, such as the use of scientific principles such as the optical properties, electromagnetic properties, or non-invasive measurement of metabolites of biological tissues. Looking at the existing research results, the research on non-invasive blood glucose detection mainly focuses on two major directions: optical detection and reverse ion electrophoresis analysis. Although some progress has been made, it still faces many challenges. Although the optical detection method is highly safe, it is easily interfered by the human body, resulting in weak monitoring signals and difficulty in extracting effective chemical information from complex spectra. In addition, it involves multidisciplinary knowledge, making research difficult. At the same time, due to the differences between human individuals, inferring the user's true blood sugar value based on the test results often requires optimizing the calculation model for the user, which not only further increases the energy consumption of the device, but also reduces the universal applicability of the device. In contrast, the reverse ion electroosmosis method shows significant advantages of low cost, simple operation, high sensitivity and good selectivity. This method uses a weak current to construct an electric field between two electrodes, driving the anions in the subcutaneous tissue fluid to move toward the anode, while glucose migrates to the cathode along with the sodium ions under the action of the electric field. At the working electrode, glucose generates ions through a catalytic oxidation reaction. By measuring the number of these ions and converting them, the blood sugar concentration can be determined. Reverse ion electroosmosis blood sugar monitoring technology can achieve fast, convenient and continuous non-invasive blood sugar monitoring.

[0004] Most non-invasive blood glucose monitoring sensors based on reverse ion osmosis contain two systems, one is the electroosmosis system and the other is the blood glucose detection system. In order to combine these two systems, traditional sensors of this type often require a more complex manufacturing process, which not only increases the production cost of the device, but also increases the device structure deviation that may occur during the preparation process. Secondly, traditional reverse ion osmosis devices are mostly planar structures, that is, the electroosmosis system and the blood glucose detection system are basically located in the same plane. Therefore, during the detection process, a gel medium needs to be added between the skin and the electrode plane to carry the glucose precipitated from the interstitial fluid, thereby realizing glucose detection. However, the main component of the gel itself is water. Therefore, as the use time increases, the water in the gel will gradually evaporate, resulting in changes in the concentration of the detected glucose, and ultimately leading to errors in the subsequent data analysis. Finally, in non-invasive blood glucose monitoring sensors, the equipment life of reverse ion osmosis technology is an issue that cannot be ignored. Electrodes and sensors will gradually wear and age during long-term use, resulting in performance degradation and increased measurement errors. In addition, environmental factors such as humidity, temperature and pollutants will cause additional damage to electrodes and sensors, further shortening their service life. Frequent use and improper cleaning and maintenance will also accelerate the loss of equipment. Summary of the invention

[0005] In order to solve the above problems existing in the prior art, the present invention provides a non-invasive blood glucose detection sensor based on anodized aluminum and a preparation method thereof. The technical problem to be solved by the present invention is achieved by the following technical solutions:

[0006] One aspect of the present invention provides a non-invasive blood glucose detection sensor based on anodized aluminum, comprising: a flexible substrate, a first electrode layer, an organic insulating layer, and a second electrode layer arranged in sequence from bottom to top, wherein:

[0007] The second electrode layer includes a plurality of cavities, the cavities extending downward from the upper surface of the second electrode layer to the upper surface of the first electrode layer, and the interior of the cavities is filled with a honeycomb anodized aluminum layer;

[0008] A patterned third electrode layer is further disposed on the upper surface of the second electrode layer, and a portion of the third electrode layer surrounds the upper edge of the cavity;

[0009] The first electrode layer and the second electrode layer can be connected to the cathode and anode of a constant voltage power supply respectively, and the hydrogel forms an electric field environment in the subcutaneous tissue through the honeycomb anodized aluminum layer for glucose to move, so that the glucose in the subcutaneous tissue is concentrated in the cathode area under the action of electroosmosis;

[0010] The first electrode layer, the second electrode layer and the third electrode layer can also be externally connected to a blood sugar detection device to generate an electrical signal reflecting the glucose concentration.

[0011] Another aspect of the present invention provides a method for preparing a non-invasive blood glucose detection sensor based on anodized aluminum, characterized in that the method is used to prepare the non-invasive blood glucose detection sensor described in the above embodiment, and the preparation method comprises:

[0012] S1: selecting a flexible substrate and forming a first electrode layer on the flexible substrate;

[0013] S2: forming an organic insulating layer on the upper surface of the first electrode layer and etching the organic insulating layer to form a plurality of cavities;

[0014] S3: depositing an aluminum metal layer inside the plurality of cavities, wherein the thickness of the aluminum metal layer is slightly less than or equal to the thickness of the organic insulating layer;

[0015] S4: forming a second electrode layer on the upper surface of the organic insulating layer, wherein the second electrode layer is provided with a plurality of holes corresponding to the cavities;

[0016] S5: forming a patterned third electrode layer on the upper surface of the second electrode layer;

[0017] S6: preparing the aluminum metal layer into a honeycomb-shaped anodized aluminum layer.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] 1. The non-invasive blood glucose detection sensor based on anodized aluminum of the present invention uses a special electrode structure to wrap the traditional hydrogel film (hydrogel) placed on the outer layer inside the electrode, so that the hydrogel film will not gradually evaporate with the use of the sensor, effectively extending the service life of the sensor and improving the detection accuracy of glucose. At the same time, the preparation process is simple, the cost is low, it is easy to industrially produce, and it is more suitable for daily use by diabetic patients.

[0020] 2. The present invention uses honeycomb anodized aluminum as the detection cavity, and can adjust the diameter and depth of the honeycomb cavity by controlling the thickness of the aluminum layer and the reaction parameters of anodization, thereby further improving the detection performance of the non-invasive blood glucose detection sensor; the device structure and preparation process are simple and can be mass-produced. At the same time, the honeycomb anodized aluminum can provide a cavity for glucose detection, solving the problem of evaporation of the hydrogel film of traditional devices.

[0021] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 1 is a schematic structural diagram of a reverse ion osmosis glucose electroosmosis sensor provided by an embodiment of the present invention;

[0023] Figure 2 is in accordance with Figure 1 Schematic diagram of the cross section taken along line AA in FIG.

[0024] Figure 3 This is a schematic diagram of the connection between a reverse ion osmosis glucose electroosmosis sensor and an external device provided by an embodiment of the present invention;

[0025] Figure 4 It is a schematic diagram of the working principle of a reverse ion osmosis glucose electroosmosis sensor provided by an embodiment of the present invention;

[0026] Figure 5a to Figure 5f It is a schematic diagram of the preparation process of a reverse ion osmosis glucose electroosmosis sensor provided by an embodiment of the present invention;

[0027] Figure 6 is a SEM photo of a honeycomb anodized aluminum provided in an embodiment of the present invention;

[0028] Figure 7 is a schematic diagram of an enzyme layer modification process provided by an embodiment of the present invention;

[0029] Figure 8 This is a SEM photograph of a MWCNT-Au structure provided in an embodiment of the present invention.

[0030] Description of reference numerals:

[0031] 1-flexible substrate; 2-first electrode layer; 3-organic insulating layer; 4-second electrode layer; 5-cavity; 6-third electrode layer; 7-anodized aluminum layer; 8-constant voltage power supply; 9-electrochemical detector; 10-aluminum metal layer. DETAILED DESCRIPTION

[0032] In order to further explain the technical means and effects adopted by the present invention to achieve the predetermined purpose of the invention, the following is a detailed description of a non-invasive blood glucose detection sensor based on anodized aluminum and a preparation method thereof proposed in accordance with the present invention, in combination with the accompanying drawings and specific implementation methods.

[0033] The above and other technical contents, features and effects of the present invention are clearly presented in the following detailed description of the specific implementation modes in conjunction with the accompanying drawings. Through the description of the specific implementation modes, the technical means and effects adopted by the present invention to achieve the predetermined purpose can be more deeply and specifically understood. However, the attached drawings are only for reference and explanation purposes and are not used to limit the technical solutions of the present invention.

[0034] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants are intended to cover non-exclusive inclusion, so that an article or device including a series of elements includes not only those elements, but also other elements that are not explicitly listed. In the absence of more restrictions, the elements defined by the statement "including one..." do not exclude the existence of other identical elements in the article or device including the elements.

[0035] Embodiment 1

[0036] See also Figure 1 , Figure 1 It is a structural schematic diagram of a non-invasive blood glucose detection sensor based on anodized aluminum provided by an embodiment of the present invention. The non-invasive blood glucose detection sensor comprises a flexible substrate 1, a first electrode layer 2, an organic insulating layer 3 and a second electrode layer 4 arranged in sequence from bottom to top, wherein the second electrode layer 4 comprises a plurality of cavities 5, the cavities 5 extend downward from the upper surface of the second electrode layer 4 to the upper surface of the first electrode layer 2, and the interior of the cavities 5 is filled with a honeycomb anodized aluminum layer 7; a patterned third electrode layer 6 is also arranged on the upper surface of the second electrode layer 4, and a part of the third electrode layer 6 is adjacent to the edge of the cavity 5; the first electrode layer 2 and the second electrode layer 4 can be respectively connected to the cathode and anode of a constant voltage power supply 8, and the hydrogel forms an electric field environment for glucose to move in the subcutaneous tissue through the honeycomb anodized aluminum layer 7, so that the glucose in the subcutaneous tissue is concentrated in the cathode area under the action of electroosmosis; the first electrode layer 2, the second electrode layer 4 and the third electrode layer 6 can also be connected to a blood glucose detection device 9 to generate an electrical signal reflecting the glucose concentration.

[0037] In this embodiment, the material of the flexible substrate 1 is PI (Polyimide) with a thickness of 75 to 125 μm. The first electrode layer 2 includes 10- to 30 nm of chromium (Cr) and 100 to 250 nm of platinum (Pt) arranged from bottom to top. Preferably, the thickness of chromium is 25 nm and the thickness of platinum is 100 nm. The first electrode layer 2 serves as the first electroosmosis electrode during the electroosmosis process and as the working electrode during the detection process. The working electrode can be modified by an enzyme modification process or a non-enzyme modification process. If an enzyme modification process is used, the enzyme solution is dripped into the cavity 5 before detection and then the gel is added to complete it. The material of the organic insulating layer 3 is a cured photoresist, specifically an organic resin, which can be PDMS, SU-8 or PI, etc. The thickness of the organic insulating layer 3 is 100 to 150 nm.

[0038] The second electrode layer 4 includes 10-30nm of chromium and 100-250nm of platinum arranged from bottom to top. Preferably, the thickness of chromium is 25nm and the thickness of platinum is 100nm. The second electrode layer 4 serves as the second electroosmotic electrode during the electroosmotic process and as the counter electrode during the glucose detection process. The anodized aluminum layer 7 is honeycomb-shaped, such as Figure 6 As shown, during the preparation process, the diameter and depth of the honeycomb cavity can be adjusted by controlling the thickness of the aluminum layer and the reaction parameters of the anodizing. The specific preparation process is detailed in Example 2.

[0039] In a specific implementation, the cavity 5 is a cylindrical structure, the diameter of the cavity 5 is 1 to 10 mm, and the spacing is 3 to 5 mm. Alternatively, the cavity 5 is a stepped structure composed of multiple sections of cylinders with different diameters, and the diameter decreases from top to bottom. Preferably, the second electrode layer 4 includes four cavities 5, such as Figure 1 As shown, the upper surfaces of the four cavities 5 are all circular, and the centers of the four circles are arranged in a square.

[0040] The anodized aluminum layer 7 is disposed inside the cavity 5, and the lower surface of the anodized aluminum layer 7 contacts the upper surface of the first electrode layer 2. Furthermore, the thickness of the anodized aluminum layer 7 of this embodiment is equal to or slightly less than the thickness of the organic insulating layer 3.

[0041] The third electrode layer 6 is a AgCl / Ag metal layer. The third electrode layer 6 is a reference electrode and is in a working state during the glucose detection process. During use, the surface of the third electrode layer 6 and the anodized aluminum layer 7 in the cavity 5 are filled with hydrogel, and the hydrogel serves as a carrier medium for glucose during the electroosmosis and glucose detection process.

[0042] The third electrode layer 6 of this embodiment includes an integrally formed main body, a connecting portion, and multiple semi-annular end portions, wherein the main body is in the shape of an elongated strip and one end extends to the edge of the second electrode layer 4, and multiple cavities 5 are symmetrically arranged on both sides of the main body; the number of the multiple end portions is equal to the number of the cavities 5, and each end portion surrounds the upper edge of a cavity 5; each end portion is connected to the main body through a connecting portion.

[0043] See also Figure 3 , Figure 3This is a schematic diagram of the connection between a reverse ion osmosis glucose electroosmosis sensor and an external device provided by an embodiment of the present invention. The second electrode layer 4 serves as the second electroosmosis electrode during the electroosmosis process and as the counter electrode during the glucose detection process. The second electrode layer 4 is simultaneously connected to a constant voltage source 8 and an electrochemical detector 9, and the constant voltage source 8 and the electrochemical detector 9 do not work at the same time; the first electrode layer 2 serves as the first electroosmosis electrode during the electroosmosis process and as the working electrode during the detection process, and is simultaneously connected to the constant voltage source 8 and the electrochemical detector 9; the third electrode layer 5 is a reference electrode, and is connected to the electrochemical detector 9.

[0044] For further information, see Figure 4 , Figure 4 This is a schematic diagram of the working principle of a reverse ion osmosis glucose electroosmosis sensor provided by an embodiment of the present invention. During use, a hydrogel is coated on one side with the second electrode layer 4, and the hydrogel covers the upper surface of the second electrode layer 4 and the inside of the cavity 5. Then, the side coated with the hydrogel is closely attached to the skin surface, and the constant voltage power supply 8 is turned on. The constant voltage power supply 8 starts to work, and the hydrogel coated on the upper surface forms an electric field with the subcutaneous tissue through the honeycomb structure of the anodized aluminum layer 7 by attracting the first electrode layer 2 (negative electrode) and the second electrode layer 4 (positive electrode), so that the glucose in the subcutaneous tissue is pulled to the area where the anodized aluminum layer is located under the action of electroosmosis; after the electroosmosis is completed, the constant voltage power supply 8 is turned off, and the second electrode layer 4 is used as a counter electrode and forms an electrochemical circuit with the reference electrode (third electrode layer 5) and the working electrode (first electrode layer 2) in the hydrogel in the cavity 5; wherein, the reference electrode provides a reference potential, and the working electrode generates an electrical signal reflecting the glucose concentration based on the reference potential under the glucose oxidation in the electrochemical circuit.

[0045] The present invention is a non-invasive blood glucose detection sensor based on anodized aluminum. The special electrode structure is used to wrap the traditional hydrogel film (hydrogel) placed on the outer layer inside the electrode, so that the hydrogel film will not gradually evaporate with the use of the sensor, effectively extending the service life of the sensor and improving the detection accuracy of glucose. At the same time, the preparation process is simple, the cost is low, it is convenient for industrial production, and it is more suitable for daily use by diabetic patients. The present invention uses honeycomb anodized aluminum as the detection cavity, and the diameter and depth of the honeycomb cavity can be adjusted by controlling the thickness of the aluminum layer and the reaction parameters of the anodizing, thereby further improving the detection performance of the non-invasive blood glucose detection sensor; the device structure and preparation process are simple, and it can be mass-produced. At the same time, the honeycomb anodized aluminum can provide a chamber for glucose detection, solving the problem of evaporation of the hydrogel film of the traditional device.

[0046] Embodiment 2

[0047] Based on the first embodiment, this embodiment provides a method for preparing a non-invasive blood glucose detection sensor based on anodized aluminum. Figure 5a to Figure 5f As shown, the method of this embodiment is an enzyme sensor. The preparation method comprises:

[0048] S1: selecting a flexible substrate 1 and forming a first electrode layer 2 on the flexible substrate 1 .

[0049] A PI film with a thickness of 75 to 125 μm is selected as the flexible substrate 1 . The thickness is selected according to actual needs. The PI film is cut into a size slightly smaller than a 4-inch silicon wafer and fixed on the silicon wafer by a PI tape.

[0050] Subsequently, a first electrode layer 2 is formed on the PI film by metal sputtering. In one embodiment, 25 nm of chromium (Cr) and 100 nm of platinum (Pt) are sequentially sputtered on the PI film by a metal sputtering process to form the first electrode layer 2. Figure 5a As shown. Specifically, first, the flexible substrate 1 is cleaned and the surface is treated with oxygen plasma to improve the surface activity; then, the flexible substrate 1 is placed in the sputtering system and evacuated to the base pressure (about 0.133Pa). Next, the argon pressure is set to 0.5-2Pa, the sputtering power is 100 watts, the rotation speed of the flexible substrate 1 is 20rpm, and the temperature is kept at room temperature. First, a 25nm chromium layer is sputtered with a chromium target, which takes about 50 seconds, and then replaced with a platinum target. Continue to sputter a 100nm platinum layer under the same conditions. Finally, let the sample cool naturally and set aside.

[0051] S2: forming an organic insulating layer 3 on the upper surface of the first electrode layer 2 and etching the organic insulating layer 3 to form a plurality of cavities 5 .

[0052] Specifically, an acetone solvent is used to ultrasonically clean the flexible substrate 1 with the first electrode layer 2 to remove surface contaminants and blow dry. Next, a spin coater is used to evenly coat the photoresist on the upper surface of the first electrode layer 2, and the photoresist is cured by soft baking. Subsequently, the sample coated with the photoresist is placed in a photolithography machine, aligned with a pre-designed mask, and exposed using ultraviolet light to form a desired pattern. After exposure, the sample is placed in a developer for development to remove the unexposed portion (if the photoresist used is a positive photoresist) or the exposed portion (if the photoresist used is a negative photoresist) to form a clear pattern. After development, the sample is rinsed with deionized water and blown dry. Next, an organic glue is evenly coated on the patterned photoresist using spin coating or other methods, and the organic glue is cured by baking to a thickness of 150 to 300 nm. Finally, a stripping solution is used to remove the remaining photoresist, leaving a patterned organic glue film, thereby forming an organic insulating layer 3 having multiple cavities 5, such as Figure 5bAs shown, the material of the photoresist can be selected from relatively stable colloids such as PDMS, SU-8, PI, etc., preferably PI.

[0053] S3: depositing an aluminum metal layer 10 inside the plurality of cavities 5, wherein the thickness of the aluminum metal layer 10 is slightly less than or equal to the thickness of the organic insulating layer 3. Figure 5c shown.

[0054] In one embodiment of the present invention, this step specifically includes the following steps:

[0055] S3.1: Cleaning the substrate: Use acetone solvent to perform ultrasonic cleaning on the current sample for about 8 minutes. Then rinse with deionized water and blow dry or bake.

[0056] S3.2: Glue coating: Select AZ 1514H photoresist and use a spin coater to evenly coat the photoresist on the platinum film inside the cavity 5, usually with a thickness of 1 to 2 μm.

[0057] S3.3: Pre-bake: Pre-bake at a temperature between 90 and 110° C. for 3 to 5 minutes to remove the solvent and cure the photoresist.

[0058] S3.4: Exposure: Place the substrate coated with photoresist in a photolithography machine and use a pre-designed mask for ultraviolet (UV) exposure. The exposure time is between a few seconds and tens of seconds.

[0059] S3.5: Post-baking, the temperature is generally between 120 and 150°C, and lasts for several minutes to further cure the remaining photoresist.

[0060] S3.6: Development: Develop the exposed photoresist using AZ 300MIF developer to remove the unexposed portion. The development time is between tens of seconds and several minutes.

[0061] S3.7: Place the developed substrate into the sputtering system. Evacuate to the base pressure and set the sputtering parameters: Argon pressure is 0.5-2 Pascal (Pa). Sputtering power: 50-200 watts (W). Rotation speed is 10-30 revolutions per minute (rpm) to ensure uniform deposition. The substrate temperature is kept at room temperature or slightly heated, such as 30℃-80℃. The sputtering rate is / s, it takes about 400 seconds (about 6.6 minutes) to deposit a 200nm aluminum film.

[0062] S3.8: After the aluminum deposition is completed, a stripping solution (such as acetone or a special stripping solution) is used to remove the photoresist and the aluminum film thereon, leaving only the desired aluminum pattern.

[0063] S3.9: Cleaning: Clean the substrate thoroughly with deionized water and other solvents to remove residual stripping solution and other impurities.

[0064] In another specific embodiment of the present invention, step S3 uses focused ion beam (FIB) induced deposition, which specifically includes the following steps:

[0065] S'3.1: Place the sample on the sample stage of the FIB (focused ion beam) system and ensure that the sample surface is clean and flat.

[0066] S'3.2: Metal organic compounds of aluminum are selected based on whether the metal organic compounds can be decomposed and deposited on the sample surface under the bombardment of ion beams.

[0067] S'3.3: By adjusting the FIB system's electrostatic lens and other components, the ion beam is focused into a beam of appropriate size so that the deposition area can be precisely controlled.

[0068] S'3.4: Start the gas injection system to introduce the gas precursor of the metal organic compound into the deposition area. The gas precursor is uniformly adsorbed on the sample surface to form a thin film. Start the FIB system to bombard the sample surface with a focused ion beam. The energy of the ion beam will stimulate a chemical reaction on the sample surface, causing the gas precursor to decompose and deposit on the sample surface, specifically inside a plurality of grooves 10, to form an aluminum metal layer 11. By precisely controlling the scanning path, residence time and other parameters of the ion beam, as well as the flow rate and concentration of the gas precursor, the thickness and uniformity of the aluminum metal layer 11 can be precisely controlled. During the deposition process, the imaging function of the FIB system is used to monitor the growth of the deposited layer (i.e., the aluminum metal layer 11) in real time to ensure the accuracy of the deposition pattern.

[0069] S4: forming a second electrode layer 4 on the upper surface of the organic insulating layer 3, wherein the second electrode layer 4 is provided with a plurality of holes corresponding to the cavities, such as Figure 5d shown.

[0070] In this step, the second electrode layer 4 needs to be patterned. Currently, there are many process methods to achieve this, and two of them are listed below.

[0071] In a specific embodiment of the present invention, step S5 includes the following steps:

[0072] The patterned second electrode layer 4 is formed by conventional lift-off technology. The specific method is as follows: first, a layer of photoresist is formed by photolithography. The photoresist can be AZ1512, etc. After patterning the photoresist, 25nm chromium and 100nm platinum are deposited in sequence. Among them, chromium is used as a connecting layer, and the specific thickness of each metal layer is determined by the actual situation. Platinum is then deposited, and processes such as electron beam deposition can be selected. The process selection is preferably a room temperature process. Finally, the excess metal and photoresist are removed by a stripping solvent such as Remover PG.

[0073] In another embodiment of the present invention, the specific execution process of this step is:

[0074] The patterned second electrode layer 4 is formed by inkjet printing. First, a platinum ink suitable for inkjet printing is selected or formulated. The sample is cleaned and surface treated to improve the ink adhesion and printing effect. Make sure that the printer is properly set up and calibrated. Adjust the printing parameters, such as nozzle temperature, printing voltage, substrate temperature, etc., to adapt to the characteristics of the platinum ink. The pattern graphic information of the second electrode layer 4 stored in the computer is transferred to the printing system. The printer sprays very small droplets of platinum ink onto the surface of the sample according to the settings to form the required pattern. After printing is completed, the pattern is cured to enhance its adhesion and stability. The curing method may include heat treatment, ultraviolet light irradiation or other chemical methods. Use an appropriate solvent to clean the substrate to remove uncured ink and impurities. Dry the sample to ensure the clarity and durability of the platinum pattern. Depending on the application requirements, the platinum pattern may need to be further processed and treated, such as etching, polishing, etc.

[0075] S5: forming a patterned third electrode layer 6 on the upper surface of the second electrode layer 4, such as Figure 5e shown.

[0076] First, a stable silver chloride ink is prepared by mixing silver chloride powder with ethanol, a dispersant (polyvinyl pyrrolidone PVP) and a surfactant (Triton X-100) to form a uniform suspension, i.e., the desired silver chloride ink; then, a high-precision inkjet printer (such as a piezoelectric inkjet printer) is used to accurately print the silver chloride ink on the upper surface of the clean second electrode layer 4 to form a patterned third electrode layer 6, with a resolution of 600 dpi, an ink droplet size of 10 picoliters, and approximately 10 printed layers; after printing, the substrate is placed in an oven for drying and curing.

[0077] S6: The aluminum metal layer 11 is prepared into a honeycomb anodized aluminum layer, such as Figure 5f shown.

[0078] The first electrode layer 2 is connected to a DC power source to anodize the aluminum. The process of forming anodized aluminum includes a one-step anodizing method and a two-step anodizing method.

[0079] For the one-step anodization method, the second electrode layer is connected to a DC power supply, the cavity is immersed in a 0.3Mol / L oxalic acid solution, and anodization is performed at a DC voltage of 45V and 2°C (one-step or two-step method can be selected). The pore size can be adjusted by adjusting the anodization time. After that, the surface is thoroughly rinsed with deionized water and dried.

[0080] For the two-step anodization method, the second electrode layer is connected to a DC power supply, and the cavity is immersed in a 0.3Mol / L oxalic acid solution for 5 to 15 minutes (preferably 10 minutes) of the first step of anodization, and then the sample is etched in a mixed solution of 0.4Mol / L phosphoric acid solution and 0.2Mol / L chromic acid at 65°C for 20 to 40 minutes, followed by a second step of anodization in a 0.3Mol / L oxalic acid solution at 65°C for 20 to 40 minutes. After that, the surface is thoroughly rinsed with deionized water and dried. In the actual process, the processing time of each stage can be appropriately adjusted according to the thickness of the aluminum layer.

[0081] S7: Modify the surface of the first electrode layer 2 to make it responsive to glucose.

[0082] Specifically, the electrode modification can be performed using an enzyme modification process or a non-enzyme modification process.

[0083] Among them, the enzyme modification process includes:

[0084] An appropriate amount of glucose oxidase and deionized water were mixed to form a 100U / μL glucose oxidase solution, 1960μL of deionized water, 26.6mg of BSA bovine serum albumin and 13.4μL of GDH glutaraldehyde (25% in water) were mixed and centrifuged at 4000rpm for 30 seconds to prepare a crosslinking agent; the glucose oxidase solution was taken out and thawed in a refrigerator at 4 degrees Celsius, 2mL was added to 1.5mL of the crosslinking agent, and the mixture was centrifuged at 4000rpm for 30s in a centrifuge to form a mixed solution; a syringe was used to drip the mixed solution into the cavity 5 so that it covered the entire electrode under the action of gravity, that is, Cover the upper surface of the second electrode layer 4, the cavity 5 and the third electrode layer 6, repeat 25 to 45 times with an interval of 50 to 90 seconds between each drop, put the electrode sample in a 4 degree Celsius refrigerator and wait for 48 hours for the electrode to air dry; connect the second electrode layer to a DC power supply (specifically the above-mentioned constant voltage power supply), immerse the sample in a m-phenylenediamine (mPD) solution (containing 1M NaCl and 10mM m-phenylenediamine) by electropolymerization, the number of voltammetric cycle scans is 100 to 150, the applied voltage range is -0.2V to 0.8V, the scan rate is 50mV / s, and the entire electrode surface is covered with a layer of mPD film and placed in a 4°C refrigerator for at least 48 hours. It should be noted that the process parameters can be adjusted according to the specific situation, and all parameter settings are not unique, and can be optimized according to the actual situation.

[0085] The enzyme-free modification process includes:

[0086] First, MWCNTs (carbon nanotubes) were dispersed in a mixture of Nafion solution (5 wt %) and ethanol in a volume ratio of 1:9 and ultrasonically dispersed for 30 min to form a concentration of 10 mg ml -1 MWCNT mixed solution; connect the second electrode layer to a DC power supply, arrange several electrodes neatly on the heating table, keep the MWCNT mixed solution in an ultrasonic state, take about 3ul at a time and drop it into the cavity, heat and evaporate for 30 to 60 minutes, repeat three to five times to the surface of the working electrode (specifically inside the cavity), so that a uniform carbon nanofilm is formed on the surface of the second electrode in the cavity. Then 0.5Mol / L H 2 SO 4 and 0.5 mMol / L HAuCl 4 The mixed solution was added with a constant voltage of -0.3V using a Gamry electrochemical workstation to deposit Au nanoparticles on the carbon nanofilm for 50s. The MWCNT-Au structure was formed. Figure 8 As shown, the white particles are Au. Finally, the electrode is cleaned and dried. MWCNT-Au plays a catalytic role in the process of blood sugar detection.

[0087] It should be noted that the above scheme is only a single enzyme-free process, and the device structure is suitable for a variety of enzyme-free modification processes and is not limited to the one described above.

[0088] The reverse ion osmosis glucose electroosmosis sensor prepared by the preparation method of the embodiment of the present invention can reduce the manufacturing cost of the reverse ion osmosis blood glucose sensor and simplify the preparation process; prevent the hydrogel from being exposed to the outside for a long time and causing evaporation, affecting the sensor detection efficiency and accuracy, and at the same time improve the service life of the sensor.

[0089] In the several embodiments provided by the present invention, it should be understood that the apparatus and method disclosed by the present invention can be implemented in other ways. For example, the apparatus embodiments described above are only illustrative, for example, the division of the modules is only a logical function division, and there may be other division methods in actual implementation, for example, multiple modules or components can be combined or integrated into another system, or some features can be ignored or not executed.

[0090] In addition, each functional module in each embodiment of the present invention may be integrated into one processing module, or each module may exist physically separately, or two or more modules may be integrated into one module. The above-mentioned integrated module may be implemented in the form of hardware or in the form of hardware plus software functional modules.

[0091] The above contents are further detailed descriptions of the present invention in combination with specific preferred embodiments, and it cannot be determined that the specific implementation of the present invention is limited to these descriptions. For ordinary technicians in the technical field to which the present invention belongs, several simple deductions or substitutions can be made without departing from the concept of the present invention, which should be regarded as falling within the protection scope of the present invention.

Claims

1. A non-invasive blood glucose detection sensor based on anodized aluminum, characterized in that: include: A flexible substrate (1), a first electrode layer (2), an organic insulating layer (3) and a second electrode layer (4) are arranged in sequence from bottom to top, wherein: The second electrode layer (4) comprises a plurality of cavities (5), the cavities (5) extending downward from the upper surface of the second electrode layer (4) to the upper surface of the first electrode layer (2), and the interior of the cavities (5) is filled with a honeycomb anodized aluminum layer (7); A patterned third electrode layer (6) is also provided on the upper surface of the second electrode layer (4), and a portion of the third electrode layer (6) surrounds the upper edge of the cavity (5); The first electrode layer (2) and the second electrode layer (4) can be respectively connected to the cathode and anode of a constant voltage power source (8), and the hydrogel forms an electric field environment in the subcutaneous tissue through the honeycomb-shaped anodized aluminum layer (7) for glucose to move, so that the glucose in the subcutaneous tissue is concentrated in the cathode area under the action of electroosmosis; The first electrode layer (2), the second electrode layer (4) and the third electrode layer (6) can also be externally connected to a blood sugar detection device (9) to generate an electrical signal reflecting the glucose concentration.

2. The non-invasive blood glucose detection sensor based on anodized aluminum according to claim 1, characterized in that: The first electrode layer (2) and the second electrode layer (4) both include 10 to 30 nm of chromium and 100 to 250 nm of platinum arranged from bottom to top.

3. The non-invasive blood glucose detection sensor based on anodized aluminum according to claim 1, characterized in that: The first electrode layer (2) is electrode-modified using an enzyme modification process or a non-enzyme modification process.

4. The non-invasive blood glucose detection sensor based on anodized aluminum according to claim 1, characterized in that: The cavity (5) is a cylindrical structure with a diameter of 1 to 10 mm and a spacing of 3 to 5 mm; or, the cavity (5) is a stepped structure composed of multiple sections of cylinders with different diameters, and the diameter decreases from top to bottom.

5. The non-invasive blood glucose detection sensor based on anodized aluminum according to claim 1, characterized in that: The thickness of the anodized aluminum layer (7) is equal to or less than the thickness of the organic insulating layer (3).

6. The non-invasive blood glucose detection sensor based on anodized aluminum according to claim 1, characterized in that: The third electrode layer (6) comprises an integrally formed main body, a connecting portion and a plurality of semi-annular end portions, wherein: The main body is in the shape of an elongated strip, with one end extending to the edge of the second electrode layer (4), and the plurality of cavities (5) are symmetrically arranged on both sides of the main body; The number of the plurality of end portions is equal to the number of the cavities (5), and each end portion surrounds the upper edge of one of the cavities (5); Each terminal portion is connected to the trunk portion by a connecting portion.

7. A method for preparing a non-invasive blood glucose detection sensor based on anodized aluminum, characterized in that: Used to prepare a non-invasive blood glucose detection sensor according to any one of claims 1 to 6, the preparation method comprising: S1: selecting a flexible substrate and forming a first electrode layer on the flexible substrate; S2: forming an organic insulating layer on the upper surface of the first electrode layer and etching the organic insulating layer to form a plurality of cavities; S3: depositing an aluminum metal layer inside the plurality of cavities, wherein the thickness of the aluminum metal layer is slightly less than or equal to the thickness of the organic insulating layer; S4: forming a second electrode layer on the upper surface of the organic insulating layer, wherein the second electrode layer is provided with a plurality of holes corresponding to the cavities; S5: forming a patterned third electrode layer on the upper surface of the second electrode layer; S6: preparing the aluminum metal layer into a honeycomb-shaped anodized aluminum layer.

8. The method for preparing a non-invasive blood glucose detection sensor based on anodized aluminum according to claim 7, characterized in that: The S6 includes: The second electrode layer was connected to a DC power supply, and the cavity was immersed in a 0.3Mol / L oxalic acid solution, and anodized using a DC voltage, and then the surface was rinsed with deionized water and dried; Alternatively, the second electrode layer is connected to a DC power supply, and the cavity is immersed in a 0.3 Mol / L oxalic acid solution for a first step of anodization for 5 to 15 min. The sample is then etched in a mixed solution of 0.4 Mol / L phosphoric acid solution and 0.2 Mol / L chromic acid at 65°C for 20 to 40 min, and then a second step of anodization is performed in a 0.3 Mol / L oxalic acid solution for 20 to 40 min, and the surface is then rinsed with deionized water and dried.

9. The method for preparing a non-invasive blood glucose detection sensor based on anodized aluminum according to claim 7, characterized in that: After step S6, the method further includes: A proper amount of glucose oxidase and deionized water are mixed to form a glucose oxidase solution, and a proper amount of deionized water, bovine serum albumin and glutaraldehyde are mixed and centrifuged to form a cross-linking agent; Taking an appropriate amount of the glucose oxidase solution, adding it to the cross-linking agent and centrifuging it to obtain a mixed solution; dripping the mixed solution into the cavity, repeating 25 to 45 times with an interval of 50 to 90 seconds between each drop, and then placing it in a refrigerator for refrigeration and waiting for air drying; The second electrode layer was connected to a DC power supply, and the sample was immersed in a m-phenylenediamine solution by electropolymerization. A voltage range of -0.2V to 0.8V was applied, and a layer of mPD film was covered on the surface of the second electrode in the cavity. The sample was then placed in a refrigerator for storage.

10. The method for preparing a non-invasive blood glucose detection sensor based on anodized aluminum according to claim 7, characterized in that: After step S6, the method further includes: Dispersing an appropriate amount of carbon nanotubes in a mixed solution of Nafion solution and ethanol, and performing ultrasonic dispersion to form a carbon nanotube mixed solution; The sample is placed on a heating table, the carbon nanotube mixed solution is kept in an ultrasonic state, 3 ul is dropped into the cavity, heated and evaporated for 30 to 60 minutes, and the dropping is repeated 3 to 5 times until a uniform carbon nanotube film is formed on the surface of the second electrode in the cavity; The second electrode layer was connected to a direct current power supply, the sample was immersed in a mixed solution of H2SO4 and HAuCl4, a constant voltage of -0.3 V was applied, and Au nanoparticles were deposited on the carbon nanofilm to form a MWCNT-Au structure.

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