A membrane material and sensor that can reduce interference signals in biosensors

Abstract

This invention relates to a membrane material and a sensor for reducing interference signals in biosensors, particularly a membrane material comprising a cellulose-based material, a sulfonated polysulfone-based material, polyvinylpyrrolidone (PVP), and a solvent; wherein the mass ratio of the cellulose-based material to the sulfonated polysulfone-based material is 1:2–5; the mass ratio of PPVP to cellulose is 1:1–2; and the mass ratio of the total mass of the cellulose-based material, the sulfonated polysulfone-based material, and the PPVP to the solvent is 1:7–12.5. This membrane material, when applied to the sensor surface, effectively improves the sensor's anti-interference performance and has minimal impact on current response. Furthermore, its preparation method is simple, easy to implement, mass-produce, and low-cost.

Description

Technical Field

[0001] This invention relates to a biosensor, and more particularly to a membrane material and a sensor thereof that can reduce interference signals in a biosensor. Background Technology

[0002] In recent years, continuous monitoring systems have been rapidly developed due to their ability to provide completely continuous analyte levels and their ability to easily detect sudden spikes in analyte concentration. For example, in continuous glucose monitoring (CGM), sensors, as a key component, are constantly being researched and updated to achieve excellent detection performance. First-generation sensors based on glucose oxidase (GOx) monitored the consumption of oxygen (O2) or the generation of hydrogen peroxide (H2O2), which reacted with electrodes to quantify the consumed glucose. However, this approach used an excessively high positive potential relative to the reference electrode to directly detect the analyte. This high potential could also promote side reactions of other substances, hindering the selectivity of the analyte and reducing the accuracy of the sensor. Therefore, minimizing the oxidation reactions of interfering substances is crucial.

[0003] For implantable electrochemical biosensors, electroactive compounds in body fluids can generate interference signals at high potentials, leading to reduced measurement accuracy. For example, in glucose sensors, from a kinetic perspective, interfering compounds can adsorb onto the sensor surface more readily than glucose and oxidize faster. Even at low concentrations, they can measure an additional anodic current comparable to that recorded by glucose. Generally, common interfering compounds can be divided into two main categories based on their charge characteristics: negatively charged compounds, such as ascorbic acid, uric acid, ibuprofen, and aspirin; and neutral compounds, such as acetaminophen.

[0004] Currently, for first-generation electrochemical biosensors, the method of applying protective films to the electrode surface to improve their anti-interference performance is being continuously studied. For example, in glucose biosensors, polyvinyl alcohol, polysulfone, polyvinyl chloride, polyurethane, and perfluorosulfonic acid polymers are used. The channel structure between the negatively charged polymer and the polymer backbone can effectively prevent negatively charged or neutral interfering substances from reaching the electrode surface. At the same time, this arrangement needs to maintain the allowable permeability of electrolyte and hydrogen peroxide (H2O2) to a great extent to ensure minimal impact on sensor performance, which is a challenge.

[0005] In addition, current methods for setting up protective films generally include dip coating, spray coating, and electropolymerization. Among these, materials for anti-interference films based on dip coating and spray coating methods, such as Nafion, have good anti-interference capabilities, but their application costs are high, and they can reduce the current response to some extent. Anti-interference films prepared by electropolymerization are complex to operate, have long preparation times, and are difficult to implement in mass production.

[0006] Current technical problems:

[0007] 1. For sensors using first-generation technology, some products have poor anti-interference performance, and some products even have no anti-interference performance at all.

[0008] 2. For sensors using first-generation technology, using a perfluorosulfonic acid proton exchange membrane (Nafion) can improve the sensor's anti-interference capability, but the application cost is high and the current response will be reduced to some extent.

[0009] 3. For sensors using first-generation technology, depositing a polymer layer on the electrode surface through electropolymerization or preparing new materials through chemical methods of polymerization can improve the sensor's anti-interference ability. However, the operation is complex, the preparation time is long, and it is difficult to achieve in mass production. Summary of the Invention

[0010] To address the above problems, this invention provides a membrane material that can reduce interference signals from biosensors. The specific technical solution is as follows:

[0011] A membrane material capable of reducing interference signals from biosensors includes a cellulose-based material, a sulfonated polysulfone-based material, polyvinylpyrrolidone, and a solvent; the mass ratio of the cellulose-based material to the sulfonated polysulfone-based material is 1:2 to 5; the mass ratio of the polyvinylpyrrolidone to cellulose is 1:1 to 2; and the mass ratio of the total mass of the cellulose-based material, the sulfonated polysulfone-based material, and the polyvinylpyrrolidone to the mass of the solvent is 1:7 to 12.5.

[0012] Preferably, the mass ratio of the cellulose material to the sulfonated polysulfone material is 1:3; the mass ratio of the polyvinylpyrrolidone to the cellulose material is 1:1; and the mass ratio of the total mass of the cellulose material, the sulfonated polysulfone material, and the polyvinylpyrrolidone to the mass of the solvent is 1:10.

[0013] Preferably, the cellulose material includes one or more of cellulose acetate propionate, cellulose acetate, and cellulose acetate butyrate.

[0014] Preferably, the sulfonated polysulfone material includes one or more of sulfonated polyphenyl sulfone, sulfonated polyether sulfone, and bisphenol A type sulfonated polysulfone.

[0015] Preferably, the solvent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

[0016] A method for preparing a membrane material that can reduce interference signals from biosensors, comprising the following steps: taking the cellulose, the sulfonated polysulfone, and polyvinylpyrrolidone in a mass ratio; placing the above raw materials in a container and stirring evenly; displacing the oxygen in the container; adding the dry solvent; heating the container and stirring to obtain the membrane material that can reduce interference signals from biosensors.

[0017] Preferably, argon and / or nitrogen are used to displace oxygen from the container;

[0018] Preferably, the heating temperature of the container is 80–120°C.

[0019] A sensor capable of reducing interference signals from biosensors includes a sensor body and a membrane layer made of a membrane material capable of reducing interference signals from biosensors, the membrane layer covering the sensor body.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The present invention provides a membrane material that can reduce interference signals of biosensors and is applied to the sensor surface. This material can effectively improve the anti-interference performance of the sensor and has little impact on the current response. At the same time, the preparation method is simple, easy to realize and mass-produce, and low cost. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the structure of this application;

[0023] Figure 2 This is a schematic diagram illustrating the generation of interference signals by biosensors;

[0024] Figure 3 This is a schematic diagram illustrating how a membrane prevents compounds from passing through.

[0025] Figure 4 This is a comparison diagram showing the effect of having a film on the electrode surface versus not having one. Detailed Implementation

[0026] The present invention will now be further described with reference to the accompanying drawings.

[0027] like Figures 1 to 4As shown, a membrane material that can reduce interference signals from biosensors includes cellulose-based materials, sulfonated polysulfone-based materials, polyvinylpyrrolidone, and a solvent; the mass ratio of cellulose-based materials to sulfonated polysulfone-based materials is 1:2 to 5; the mass ratio of polyvinylpyrrolidone to cellulose is 1:1 to 2; and the mass ratio of the total mass of cellulose-based materials, sulfonated polysulfone-based materials, and polyvinylpyrrolidone to the mass of the solvent is 1:7 to 12.5.

[0028] The mass ratio of cellulose materials to sulfonated polysulfone materials is 1:3; the mass ratio of polyvinylpyrrolidone to cellulose materials is 1:1; and the mass ratio of the total mass of cellulose materials, sulfonated polysulfone materials, and polyvinylpyrrolidone to the mass of the solvent is 1:10.

[0029] Cellulose materials include one or more of cellulose acetate propionate, cellulose acetate, and cellulose acetate butyrate.

[0030] Sulfonated polysulfone materials include one of sulfonated polyphenyl sulfone, sulfonated polyether sulfone, and bisphenol A type sulfonated polysulfone.

[0031] The solvent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

[0032] By using a blend of cellulose and sulfonated polysulfone, the pore structure of the membrane can be obtained, and negatively charged groups can be modified, which improves the anti-interference performance of the first-generation high-voltage electrochemical biosensor.

[0033] The membrane pore size can be adjusted according to the material ratio, ensuring the passage of hydrogen peroxide without reducing the current response, while also blocking the passage of large molecular weight interfering substances, thus reducing interference signals.

[0034] The membrane remains stable after radiation sterilization.

[0035] The membrane preparation and setup methods are simple to operate, quick, and easy to mass-produce, with low material application costs.

[0036] It can be used to improve the anti-interference performance of various electrochemical and biological sensors, thereby enhancing the measurement accuracy of the sensors.

[0037] By setting a blended polymer film layer on the electrode surface to control the diffusion of interfering compounds, the interference signal of the biosensor can be reduced, thereby improving the measurement accuracy of the sensor.

[0038] Polymer films are blend films. Compared to copolymers, the development and preparation of blend films is an effective, simple, and low-cost strategy for achieving excellent membrane performance. New materials prepared through blending possess a variety of properties and economic advantages that fall between those of pure components. Therefore, if the membrane is prepared from a multi-component polymer blend, the hydrophilic-hydrophobic balance and the performance of the membrane system can be easily altered. To obtain a porous membrane structure, selectable polymers include: polytetrafluoroethylene, polyamide, cellulose, polyacrylonitrile, polyvinyl chloride, polysulfone, polyurethane, and polyimide, which can serve as key components of the blend polymer.

[0039] Considering its hydrophilicity, non-toxicity, simple membrane flux control, low cost, and ease of manufacturing, cellulose was chosen as the material for porous membrane preparation. Cellulose has the aforementioned significant advantages and is a commonly used anti-interference polymer material in biosensors. However, it also has limitations such as low oxidizing properties, poor chemical resistance, and poor mechanical strength. If cellulose is used alone on flexible electrodes to meet the requirement of human contact time ≥14 days, it cannot adequately meet the requirements. Therefore, it is modified through the aforementioned blending method.

[0040] Hydrophobic and hydrophilic polymers can be used as miscible pairs, which provides an opportunity for the blending of polysulfone, a cellulose ester material, as the two can be miscible in the liquid phase.

[0041] Porosity and pore size in blended membranes are key to preventing the passage of interfering substances. Polyvinylpyrrolidone (PVP) is an excellent pore-forming agent and surfactant. Therefore, the pore size of blended membranes can be controlled through the synergistic effect of PPV to overcome the deviation of current signals caused by the passage of interfering substances.

[0042] On the other hand, blocking some small molecular weight interfering compounds solely through pore structure may not be feasible. Furthermore, in the field of implantable electrochemical sensors, when monitoring substrates via tissue fluid, employing a charge repulsion mechanism based on pore size control is a good strategy for targeting negatively charged small molecules. Therefore, modifying the aforementioned blend membrane with negatively charged groups seems like an excellent idea. Perfluorosulfonic acid proton exchange membranes (Nafion) are commonly used materials in biosensors; their sulfonic acid groups repel negative charges and enhance the material's hydrophilicity. Sulfonic acid-modified polysulfone is precisely a polymer material that addresses the aforementioned problem. Blending it with cellulose to form a polymer blend, to a certain extent, solves the problem of both neutral interfering compounds and negatively charged small molecule interfering compounds affecting the current signal of the biosensor, thereby improving the sensor's accuracy.

[0043] Therefore, this embodiment uses a blending method of cellulose and sulfonated polysulfone materials to prepare a blend membrane that contains suitable pore size control and sulfonic acid groups. Moreover, when this blend membrane is applied to the field of electrochemical biosensors, it has the advantages of good hydrophilicity, strong anti-interference, high biocompatibility, and low cost.

[0044] A method for preparing membrane materials that can reduce interference signals from biosensors:

[0045] Cellulose, sulfonated polysulfone, and polyvinylpyrrolidone were weighed according to the specified mass ratio and placed in a flask with stirring. The oxygen in the flask was then displaced, followed by the injection of dry solvent. The mixture was stirred in an oil bath at high temperature to obtain a blended membrane. The deoxygenation time was 5–10 min, using either argon or nitrogen gas, and the purging time was 10–15 min. The reaction temperature was 80–120 °C, and the stirring time was 1–3 h.

[0046] Applying the polymer film generated in this method to the sensor surface can effectively improve the sensor's anti-interference performance and has little impact on the current response. Furthermore, it offers advantages such as simple preparation method, ease of implementation and mass production, and low cost.

[0047] A sensor capable of reducing interference signals from biosensors includes a sensor body and a membrane layer made of a membrane material capable of reducing interference signals from biosensors, the membrane layer covering the sensor body.

[0048] A biosensor is used to detect glucose as a substrate. The sensor employs a three-electrode system mounted on a flexible substrate, including a working electrode (which can be a Pt / C electrode), a reference electrode (which can be an Ag / AgCl electrode), and a counter electrode (which can also be a Pt / C electrode). A blended polymer film is then deposited on the electrode surface using a process such as spraying or dip-coating.

[0049] Examples 1-5:

[0050] The cellulose and sulfonated polysulfone were fed according to the mass ratio shown in the table below. In addition, the mass ratio of polyvinylpyrrolidone to cellulose was kept at 1:1. The blended membrane solutions of Examples 1-5 with different proportions were obtained according to the above preparation method.

[0051] Comparative Examples 1-4:

[0052] A comparative example was prepared using a mass ratio of cellulose-based material to sulfonated polysulfone-based material of 0.5–7.5:1. The polymer material feed ratios of comparative examples 1–5 are shown in the table below, and the preparation methods are the same as those in examples 1–5 above.

[0053] Table 1. Composition of Blended Membrane Materials

[0054] serial number Cellulose: Sulfonated polysulfone: Polyvinylpyrrolidone (wt%) solvent / g Example 1 1:1:1 100 Example 2 1:2:1 100 Example 3 1:3:1 100 Example 4 1:5:1 100 Example 5 1:6:1 100 Comparative Example 1 2:1:1 100 Comparative Example 2 3:1:1 100 Comparative Example 3 5:1:1 100 Comparative Example 4 6:1:1 100

[0055] The blended film solutions of Examples 1-5 and Comparative Examples 1-4 were uniformly coated onto the electrode surface, repeated 3-5 times. The coating method could be either spraying or dip-coating. The coated film was then dried to obtain a film-modified electrode at a specified drying temperature of 120-180°C.

[0056] The membrane materials prepared in Examples 1-5 and Comparative Examples 1-4 were subjected to performance tests to obtain the expected preliminary screening results. The specific performance tests of the preliminary screening membrane materials included:

[0057] 1) Use a toughness tester to swing the electrode modified with the membrane material left and right 1000 times (swing amplitude ±30°). After removing it, use a microscope to observe whether the membrane material is damaged.

[0058] 2) After immersing the electrode modified with the membrane material in a phosphate buffer solution for 2 hours, the permeability of the membrane material to hydrogen peroxide was tested using an electrochemical analyzer.

[0059] The test results are shown in Table 2 below:

[0060] Table 2. Initial screening performance test results of blended membrane materials

[0061]

[0062]

[0063] Examples that meet the expectations of the initial screening results were selected. The current signals of the negatively charged interfering substance (ascorbic acid) and the neutral interfering substance (acetaminophen) were measured using an electrochemical analyzer to evaluate the anti-interference performance of different examples. The test results are shown in Table 3.

[0064] Table 3. Test results of anti-interference performance of blended membrane materials

[0065] serial number Ascorbic acid / nA Acetaminophen / nA Example 2 47.86 66.26 Example 3 35.59 67.31 Example 4 33.48 75.99 Comparative Example 1 92.84 114.92

[0066] The application effect of Example 3 on the electrode is as follows: Figure 4 As shown, preliminary experimental results at 298 K indicate that by controlling the pore size and through the synergistic effect of functional groups, at high voltage, the allowable permeability of electrolyte and H2O2 can be kept essentially unchanged, while effectively preventing negatively charged interfering substances (e.g., ascorbic acid) and neutral interfering substances (e.g., acetaminophen) from reaching the electrode surface and undergoing redox reactions. This improvement yielded the following benefits: a reduction of approximately 60% and 40% in interference signals from ascorbic acid and acetaminophen, respectively, while the impact on H2O2 permeability was only about 4%.

[0067] The technical principles of the present invention have been described above with reference to specific embodiments. These descriptions are merely for explaining the principles of the invention and should not be construed as limiting the scope of protection of the invention in any way. Based on this explanation, those skilled in the art can readily conceive of other specific embodiments of the invention without inventive effort, and these embodiments will all fall within the scope of protection of the claims of the present invention.

Claims

1. A membrane material capable of reducing interference signals in biosensors, used on the surface of a biosensor to reduce interference signals, characterized in that, This includes cellulose-based materials, sulfonated polysulfone materials, polyvinylpyrrolidone, and solvents; The mass ratio of the cellulose material to the sulfonated polysulfone material is 1:2~5; The mass ratio of polyvinylpyrrolidone to cellulose is 1:1~2; The total mass ratio of the cellulose material, the sulfonated polysulfone material, and the polyvinylpyrrolidone to the solvent is 1:7~12.

5.

2. The membrane material according to claim 1 that can reduce interference signals from biosensors, characterized in that, The mass ratio of the cellulose material to the sulfonated polysulfone material is 1:3; The mass ratio of the polyvinylpyrrolidone to the cellulose material is 1:1; The total mass ratio of the cellulose material, the sulfonated polysulfone material, and the polyvinylpyrrolidone to the solvent is 1:

10.

3. The membrane material according to claim 1 that can reduce interference signals from biosensors, characterized in that, The cellulose materials include one or more of cellulose acetate propionate, cellulose acetate, and cellulose acetate butyrate.

4. The membrane material according to claim 1 that can reduce interference signals from biosensors, characterized in that, The sulfonated polysulfone materials include one or more of sulfonated polyphenyl sulfone, sulfonated polyether sulfone, and bisphenol A type sulfonated polysulfone.

5. The membrane material according to claim 1 that can reduce interference signals from biosensors, characterized in that, The solvent includes one or more of N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide.

6. A method for preparing a membrane material capable of reducing interference signals from biosensors, used to prepare the membrane material capable of reducing interference signals from biosensors as described in any one of claims 1 to 5, characterized in that, Includes the following steps: The cellulose material, the sulfonated polysulfone material, and polyvinylpyrrolidone are taken according to the mass ratio; Place the above ingredients in a container and stir well; Displace the oxygen from the container; Add the dried solvent; The container was heated and stirred to obtain the membrane material that can reduce interference signals from biosensors.

7. The method for preparing a membrane material capable of reducing interference signals from biosensors according to claim 6, characterized in that, Argon and / or nitrogen are used to displace oxygen from the container.

8. The method for preparing a membrane material capable of reducing interference signals from biosensors according to claim 6, characterized in that, The container is heated to a temperature of 80~120℃.

9. A sensor capable of reducing interference signals from biosensors, characterized in that, It includes a sensor body and a membrane layer made of a membrane material that can reduce interference signals of biosensors as described in any one of claims 1 to 5, the membrane layer covering the sensor body.

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