Biosensor, isolation layer thereof and analyte monitoring apparatus

Abstract

Provided in the present disclosure are a biosensor, an isolation layer thereof and an analyte monitoring apparatus. The biosensor comprises a first electrode provided with a sensing layer, and a polymer film, the polymer film at least covering the sensing layer and the first electrode, the polymer film comprising a protection layer and an isolation layer, the protection layer being closer to the first electrode than the isolation layer, the isolation layer being configured to reduce the impact of a sterilization gas on the sensing layer when the biosensor undergoes sterilization with a gas, the isolation layer being prepared from a first solution, the first solution comprising a first-type polymer and an organic solvent, and the first-type polymer being polyurethane. The present disclosure can provide a biosensor having resistance to a sterilization gas, an isolation layer thereof and an analyte monitoring apparatus.

Description

Biosensor and isolation layer thereof and analyte monitoring device Technical Field

[0001] The present disclosure relates to the field of new chemical materials, and in particular to a biosensor, an isolation layer thereof, and an analyte monitoring device. Background Art

[0002] Biosensors are analytical devices that tightly combine biological materials, bio-derived materials, or biomimetic materials with optical, electrochemical, temperature, piezoelectric, magnetic, or micromechanical physical and chemical sensors or sensing microsystems. They can usually be used to quickly detect certain specific chemicals in the human body, such as glucose, ketone bodies, and uric acid.

[0003] Biosensors are usually used in conjunction with electronic devices to form a monitoring system. During detection, the biosensor probe containing sensitive substances that can sense analytes (such as enzymes, antibodies and ligands, etc.) is generally placed under the host's skin for detection, and the detected signal is then transmitted to the electronic device for analysis or transmission. Therefore, for the health and safety of the host, the probe needs to be fully sterilized and disinfected before use. Common sterilization methods include gas sterilization and radiation sterilization. Since electronic devices may be damaged during radiation sterilization, gas sterilization is usually used to sterilize electronic devices. However, the sterilizing gas (such as ethylene oxide) in the gas sterilization method may affect the sensitive substances on the probe and the performance of the probe itself (for example, causing the sensitive substances to degrade, denature, undergo undesirable chemical reactions or decomposition, etc.), resulting in a significant decrease in the sensitivity of the biosensor after gas sterilization, so that it cannot be used normally.

[0004] Therefore, in existing manufacturing processes, the electronic devices and biosensors in the monitoring system are usually separated and sterilized through irradiation sterilization. However, this separate sterilization method is not conducive to "all-in-one" product design, and the processing technology for separate sterilization is relatively complex. After separate sterilization, the electronic device and biosensor must be assembled before use, which is a complex operation. Summary of the Invention

[0005] The present disclosure is made in view of the above-mentioned state of the prior art, and an object thereof is to provide a biosensor resistant to sterilization gas, an isolation layer thereof, and an analyte monitoring device.

[0006] To this end, a first aspect of the present disclosure provides a biosensor for monitoring analytes, the biosensor comprising a first electrode provided with a sensing layer, and a polymer film, the polymer film covering at least the sensing layer and the first electrode, the polymer film comprising a protective layer and an isolation layer, the protective layer being closer to the first electrode than the isolation layer, the isolation layer being configured to reduce the effect of sterilization gas on the sensing layer when the biosensor is gas sterilized, the isolation layer being made of a first solution comprising a first type of polymer and an organic solvent, the first type of polymer being polyurethane.

[0007] In a first aspect of the present disclosure, the polymer membrane of the biosensor includes a protective layer and an isolation layer. The polyurethane isolation layer can restrict the permeation of sterilization gas during gas sterilization of the biosensor, forming an isolation barrier to reduce the effects of the sterilization gas on the sensing layer, particularly the effects of gaseous ethylene oxide on the active substances in the sensing layer, thereby enabling the biosensor to be sterilized using gas sterilization. Compared to biosensors without an isolation layer, the biosensor of the present disclosure significantly reduces the decrease in sensitivity before and after sterilization, maintaining a high sensitivity after sterilization. Furthermore, the polyurethane isolation layer has good biocompatibility, improving the safety of the biosensor when placed subcutaneously in a host. Furthermore, the isolation layer restricts the permeation of specific analytes (e.g., glucose), acting as a semipermeable membrane. Furthermore, the protective layer can separate the isolation layer from the internal structure (sensing layer and first electrode), mitigating the adverse effects of organic solvents in the isolation layer on the sensing layer and first electrode (e.g., corrosion leading to damage to the integrity of the internal structure and loss of functionality). Thus, a biosensor resistant to sterilization gas can be provided.

[0008] In the biosensor according to the first aspect of the present disclosure, optionally, in the first solution, the mass fraction of the first type of polymer is 0.1% to 15%, thereby helping the isolation layer to limit the penetration of sterilization gas during gas sterilization.

[0009] In the biosensor according to the first aspect of the present disclosure, optionally, the first type of polymer includes a soft segment, and the soft segment accounts for 5% to 50% of the first type of polymer. Because the proportion of the soft segment affects the performance of the polyurethane material, in this case, selecting an appropriate proportion of the soft segment can enable the polyurethane material to have good mechanical properties and biocompatibility.

[0010] In the biosensor according to the first aspect of the present disclosure, the first polymer may optionally include hydrophilic groups, and the proportion of the hydrophilic groups in the first polymer may be between 1% and 30%. The proportion of hydrophilic groups in the polyurethane may affect the properties of the polyurethane material. In this case, selecting an appropriate proportion of hydrophilic groups can impart good hydrophilicity and biocompatibility to the polyurethane material.

[0011] In the biosensor according to the first aspect of the present disclosure, optionally, the organic solvent is a mixed solvent of any one or more of tetrahydrofuran, dichloromethane, and N,N-dimethylacetamide, thereby enabling the first type of polymer to be dissolved in the organic solvent.

[0012] In the biosensor of the first aspect of the present disclosure, optionally, the isolation layer has a thickness of 1 μm to 40 μm. In this case, selecting an isolation layer of appropriate thickness can effectively serve as an isolation barrier, thereby facilitating improvement of the biosensor's resistance to sterilization gas.

[0013] In the biosensor according to the first aspect of the present disclosure, the protective layer optionally includes a second polymer, which is a cationic or anionic polymer or a copolymer formed from a neutral monomer. In this case, the protective layer does not react with the two polymers in the isolation layer, forming a protective layer that separates the isolation layer from the internal structure (sensing layer and first electrode). Furthermore, the second polymer can be dissolved in a low-corrosive or non-corrosive solvent, allowing the formed protective layer to directly contact the internal structure without damaging it. Furthermore, the protective layer has minimal permeability restriction on analytes, facilitating the passage of analytes through the protective layer and into contact with the sensing layer.

[0014] In the biosensor according to the first aspect of the present disclosure, optionally, the protective layer has a thickness of 1 μm to 20 μm, thereby effectively separating the isolation layer from the internal structure through the protective layer.

[0015] In the biosensor according to the first aspect of the present disclosure, the polymer membrane optionally further includes a biocompatible layer, the isolation layer is positioned between the biocompatible layer and the protective layer, and the biocompatible layer includes a third polymer, which is a polyurethane containing hydrophilic groups or a cross-linked water-soluble polyurethane. In this case, the third polymer is also a polyurethane, which can further improve the biocompatibility of the biosensor and partially block the entry of sterilization gases during the sterilization process, further enhancing the protective effect of the polymer membrane on the biosensor.

[0016] In the biosensor according to the first aspect of the present disclosure, optionally, when the third polymer is the polyurethane containing hydrophilic groups, the hydrophilic groups in the third polymer account for 20% to 50%. This enables the biocompatible layer containing the third polymer to have good biocompatibility, thereby further improving the biocompatibility of the biosensor.

[0017] In the biosensor according to the first aspect of the present disclosure, optionally, the biocompatible layer has a thickness of 1 μm to 30 μm, thereby helping to improve the biocompatibility of the biosensor.

[0018] In the biosensor according to the first aspect of the present disclosure, optionally, the sensing layer comprises one or more of glucase, lactase, and hydroxybutyrate dehydrogenase, thereby enabling selection of a suitable sensitive substance according to the type of analyte.

[0019] In the biosensor according to the first aspect of the present disclosure, optionally, the biosensor further includes a second electrode different from the first electrode, and the polymer film also covers the second electrode, thereby enabling the second electrode to be protected by the polymer film.

[0020] A second aspect of the present disclosure provides an isolation layer of a biosensor, the biosensor including a first electrode provided with a sensing layer, the isolation layer covering at least the sensing layer and the first electrode, the isolation layer being configured to reduce the effect of sterilization gas on the sensing layer when the biosensor is subjected to gas sterilization, the isolation layer being made of a first solution including a first type of polymer and an organic solvent, the first type of polymer being polyurethane.

[0021] In the second aspect of the present disclosure, an isolation layer comprising polyurethane can limit the permeation of sterilization gas during gas sterilization of the biosensor, forming an isolation barrier to reduce the effect of the sterilization gas on the sensing layer, especially the effect of gaseous ethylene oxide on the active substances in the sensing layer, so that the biosensor can be sterilized using gas sterilization. Compared with biosensors without an isolation layer, the biosensor with an isolation layer has a significantly reduced drop in sensitivity before and after sterilization, and can still maintain a high sensitivity after sterilization. Moreover, the isolation layer comprising polyurethane has good biocompatibility, which can improve the safety of the biosensor when it is located under the host's skin. In addition, the isolation layer also has a permeation-limiting effect on specific analytes (such as glucose), and can act as a semipermeable membrane. Thus, an isolation layer with an isolation effect on sterilization gas can be provided, and when the isolation layer is provided on the biosensor, the biosensor can be resistant to sterilization gas.

[0022] A third aspect of the present disclosure provides an analyte monitoring device comprising an electronic assembly and the biosensor described in the first aspect of the present disclosure, wherein the electronic assembly is electrically connected to the biosensor. In the third aspect of the present disclosure, the biosensor is resistant to sterilizing gas, enabling the biosensor and the electronic assembly to be assembled together for gas sterilization, eliminating the need for separate radiation sterilization of the biosensor. The analyte monitoring device can be assembled as a whole at the factory, eliminating the need for users to separately assemble the electronic assembly with the biosensor during use, thereby facilitating ease of use.

[0023] According to the present disclosure, a biosensor resistant to sterilization gas, an isolation layer thereof, and an analyte monitoring device can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] FIG1 is a diagram showing an application scenario of a biosensor involved in an example of the present disclosure.

[0025] FIG. 2 is a schematic diagram illustrating a biosensor according to an example of the present disclosure.

[0026] FIG. 3 is a schematic diagram illustrating a polymer film according to an example of the present disclosure.

[0027] FIG. 4 is a schematic diagram showing a polymer film covering an implant portion according to an example of the present disclosure.

[0028] FIG5 is a diagram showing the appearance of the biosensor according to Example 1 of the present disclosure after sterilization.

[0029] FIG6 is a diagram showing the appearance of the biosensor of Comparative Example 1 of the present disclosure after sterilization.

[0030] Explanation of Reference Numerals: 100 ...analyte monitoring device, 1 ...sensor, 11 ...implantation portion, 12 ...connection portion, 13 ...first electrode, 14 ...sensing layer, 2 ...electronic component, 3 ...polymer membrane, 31 ...isolation layer, 32 ...protective layer, 33 ...biocompatible layer. DETAILED DESCRIPTION

[0031] The preferred embodiments of the present disclosure are described in detail below with reference to the accompanying drawings. In the following description, identical components are assigned identical reference numerals, and duplicate descriptions are omitted. In addition, the accompanying drawings are merely schematic, and the proportions of the dimensions of the components and the shapes of the components may differ from the actual ones.

[0032] It should be noted that the terms "including" and "having" and any variations thereof in this disclosure, such as a process, method, system, product or device that includes or has a series of steps or units, are not necessarily limited to those steps or units clearly listed, but may include or have other steps or units that are not clearly listed or are inherent to these processes, methods, products or devices.

[0033] A first aspect of the present disclosure relates to a biosensor for monitoring an analyte. The biosensor is resistant to sterilizing gases and can be sterilized using gas sterilization. The biosensor can be referred to simply as a sensor, a monitoring probe, a sensing probe, or an electrode probe.

[0034] In the present disclosure, the analyte may be one or more of glucose, acetylcholine, amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase, creatine, creatinine, DNA, fructosamine, glutamine, hormones, ketone bodies, lactate, oxygen, peroxide, prostate-specific antigen, prothrombin, RNA, thyroid-stimulating hormone, and troponin. This is merely an example, and the analyte may also be other substances not shown.

[0035] A second aspect of the present disclosure relates to an isolation layer for a biosensor. This isolation layer can limit the penetration of sterilization gas during gas sterilization of the biosensor, forming an isolation barrier to reduce the impact of the sterilization gas on the biosensor's sensing layer. The isolation layer of the biosensor disclosed herein may also be referred to as an isolation membrane, spacer layer, or sterilization layer.

[0036] A third aspect of the present disclosure relates to an analyte monitoring device, which may include electronic components and a biosensor. In the analyte monitoring device of the present disclosure, the biosensor is resistant to sterilizing gas, enabling the biosensor and electronic components to be assembled together for gas sterilization, eliminating the need for separate radiation sterilization of the biosensor. The analyte monitoring device of the present disclosure may also be referred to as a continuous monitoring device, a monitoring system, or the like.

[0037] Hereinafter, the biosensor (hereinafter referred to as the sensor) involved in the present disclosure will be described by taking glucose as an example with reference to the accompanying drawings.

[0038] Figure 1 is a diagram showing an application scenario of a sensor 1 according to an example of the present disclosure. Figure 2 is a schematic diagram showing a sensor 1 according to an example of the present disclosure.

[0039] In some examples, the sensor 1 can be used to monitor the analyte. In some examples, the sensor 1 can be used in conjunction with the electronic component 2. Specifically, referring to Figure 1, the sensor 1 can be combined with the electronic component 2 to form an analyte monitoring device 100, so that the analyte monitoring device 100 is located on the host's body surface, and the sensor 1 is partially located under the host's skin, so that the analyte can be monitored by the sensor 1. It should be noted that although the application scenario of the sensor 1 is described here as being used to monitor the analyte in the host's body in conjunction with the electronic component 2, the sensor 1 can also be placed in other different test environments to detect the analyte. It does not necessarily need to be combined with the electronic component 2 to form the analyte monitoring device 100 to be used. For example, the sensor 1 can also be electrically connected to an external test circuit for monitoring.

[0040] In some examples, the sensor 1 may include an implant portion 11 (see FIG2 ). The implant portion 11 may be implanted subcutaneously in the host, and when in use, the implant portion 11 may be located subcutaneously in the host and in contact with the analyte. Thus, the analyte in the host body can be monitored by the sensor 1. In some examples, the sensor 1 may include a connection portion 12 (see FIG2 ). The implant portion 11 may be electrically connected to the electronic component 2 via the connection portion 12. When in use, the implant portion 11 may be located subcutaneously, and the connection portion 12 may be located outside the body, and therefore, the connection portion 12 may also be referred to as an in vitro portion.

[0041] In some examples, sensor 1 may include a first electrode 13 (see FIG. 2 ). A sensing layer 14 may be disposed on first electrode 13. Sensor 1 can generate a current signal by reacting the sensing layer 14 on first electrode 13 with the analyte. Analysis and processing of this current signal can yield an analyte concentration signal. In other words, first electrode 13 may also be referred to as a working electrode.

[0042] In some examples, the sensor 1 may include a second electrode. The second electrode may be the same as or different from the first electrode 13. For example, the second electrode may be a reference electrode or a counter electrode. In another example, the second electrode may be a second working electrode, and the analyte detected by the second working electrode may be the same as or different from the analyte detected by the first electrode 13. In some examples, the sensor 1 may include a third electrode. The third electrode may be a reference electrode or a counter electrode and may be different from the second electrode. Thus, a sensor 1 having a three-electrode system can be formed to monitor the analyte.

[0043] In some examples, the sensing layer 14 may include a sensitive substance that can promote the reaction of the analyte. For example, the sensing layer 14 may include one or more of glucosidase, lactase, and hydroxybutyrate dehydrogenase. Thus, an appropriate sensitive substance can be selected based on the type of analyte. In some examples, the glucosidase may be glucose oxidase or glucose dehydrogenase.

[0044] In some examples, the sensor 1 may include a polymer membrane 3 (shown later). The polymer membrane 3 can control the diffusion of the analyte. In other words, the polymer membrane 3 can have selective permeability to the analyte. In some examples, the polymer membrane 3 can cover at least the sensing layer 14. Thus, the polymer membrane 3 can control the amount of analyte permeation, that is, the amount of analyte entering the sensing layer 14. This can help ensure that the magnitude of the current signal generated by the analyte contacting the sensing layer 14 falls within the linear response range of the sensor 1.

[0045] In some examples, the polymer film 3 may be biocompatible. In some examples, the polymer film 3 may cover the implanted portion 11 (shown later) of the sensor 1. Thus, the sensor 1 may be biocompatible.

[0046] In some examples, the polymer membrane 3 can limit the permeation of sterilization gas when the sensor 1 is gas sterilized. For example, the polymer membrane 3 can limit the permeation of ethylene oxide (hereinafter referred to as EO). Thus, a sensor 1 resistant to sterilization gas can be provided. That is to say, the sensor 1 of the present disclosure can be sterilized by gas sterilization, and compared with the sensor 1 without the polymer membrane 3, the sensor 1 of the present disclosure has a greatly reduced sensitivity decrease before and after sterilization, and can still maintain a high sensitivity after sterilization. In some examples, the polymer membrane 3 can cover at least the sensing layer 14 and the first electrode 13. Thus, the erosion of the internal structure (sensing layer 14 and the first electrode 13) by the sterilization gas during sterilization can be reduced, and the internal structure can be protected.

[0047] In some examples, ethylene oxide can be used to sterilize the sensor 1 of the present disclosure. The following description will use ethylene oxide as an example of a sterilizing gas to describe the polymer membrane 3 of the present disclosure.

[0048] FIG. 3 is a schematic diagram showing a polymer film 3 according to an example of the present disclosure.

[0049] In some examples, the polymer film 3 may include an isolation layer 31 (see FIG3 ). The isolation layer 31 may be configured to reduce the effects of the sterilizing gas on the sensing layer 14 during gas sterilization of the sensor 1. In some examples, the isolation layer 31 may be made of a first solution. For example, the first solution may be applied to the implant portion 11 to form the isolation layer 31. In some examples, the isolation layer 31 may be formed by applying the first solution to a target location by spraying, spin coating, or dip coating. The target location refers to the location where the isolation layer 31 is desired to be formed.

[0050] In some examples, the first solution may include a first type of polymer. The first type of polymer can limit the permeation of sterilization gas (e.g., ethylene oxide). Thus, the isolation layer 31 formed by the first solution including the first type of polymer can limit the permeation of sterilization gas.

[0051] In some examples, the first type of polymer may be polyurethane. Polyurethane is a material with good physical and mechanical properties, blood compatibility, and biocompatibility, and ethylene oxide generally does not cause structural changes or denaturation of polyurethane when it comes into contact with polyurethane at room temperature and pressure. In this case, by providing an isolation layer 31 comprising polyurethane, the penetration of sterilization gas can be limited when the sensor 1 is gas sterilized, forming an isolation barrier to reduce the effect of the sterilization gas on the sensing layer 14, especially the effect of gaseous ethylene oxide on the active substances (such as sensitive substances) in the sensing layer 14; and the isolation layer 31 having polyurethane has good biocompatibility, which can improve the safety of the sensor 1 when implanted subcutaneously in the host; in addition, the isolation layer 31 also has a permeation-restricting effect on specific analytes (such as glucose), which can enable the polymer membrane 3 to act as a semipermeable membrane. In some examples, the first type of polymer may have a carbamate group.

[0052] In some examples, the first type of polymer may have a soft segment, and in the first type of polymer, the soft segment may account for 5% to 50%. In this case, the properties of the first type of polymer can be adjusted by adjusting the proportion of the soft segment. In some examples, preferably, the soft segment accounts for 10% to 25%. In some examples, when the first type of polymer is polyurethane, the polyurethane may have a soft segment. Since the proportion of the soft segment affects the performance of the polyurethane material, in this case, by selecting an appropriate soft segment proportion, the polyurethane material can have good mechanical properties and biocompatibility. In some examples, the elasticity, modulus, softness and water absorption of the polyurethane can be adjusted by adjusting the proportion of the soft segment in the polyurethane, thereby adjusting the transmittance of the isolation layer 31 to the analyte and the biocompatibility of the isolation layer 31 itself. In some examples, the soft segment may include a component containing an epoxy functional group. For example, the soft segment may include polyethylene oxide (PEO).

[0053] In some examples, the polyurethane can be a block copolymer consisting of a soft segment and a hard segment. In some examples, in the polyurethane, the soft segment can be composed of hydroxyl-containing molecules such as polyester polyols, polyether alcohols, polycaprolactones, and polylactic acid-glycolic acid copolymers of varying molecular weights. In some examples, in the polyurethane, the hard segment can be composed of compounds such as diisocyanates and low molecular weight short chain extenders. In some examples, the diisocyanate can be an aliphatic isocyanate. For example, the diisocyanate can be 1,6-hexamethylene diisocyanate (HDI), 4,4'-dicyclohexylmethane diisocyanate (HMDI), or isophorone diisocyanate (IPDI). In some examples, the short chain extender can be 1,4-butanediol.

[0054] In some examples, the polyurethane may be a polycarbonate polyurethane, a polyether polyurethane, and / or a polyester polyurethane. In some examples, the polyurethane may include one or more of aliphatic polyether polyurethane, aliphatic polyether polyurethane urea, cycloaliphatic polyether polyurethane, cycloaliphatic polyether polyurethane urea, aromatic polyether polyurethane, aromatic polyether polyurethane urea, aliphatic polyester polyurethane, aliphatic polyester polyurethane urea, cycloaliphatic polyester polyurethane, cycloaliphatic polyester polyurethane urea, aromatic polyester polyurethane, and aromatic polyester polyurethane urea.

[0055] In some examples, the first type of polymer may be a zwitterionic polyurethane. In this case, this type of polyurethane has the flexibility and scalability of a polyether chain, while also possessing the properties of zwitterionic groups. Zwitterionic groups with different properties can be introduced as needed to adjust the properties of the isolation layer 31. In some examples, the zwitterionic groups in the zwitterionic polyurethane may include amine groups, carboxyl groups, and / or sulfonic acid groups. In this case, the introduction of specific zwitterionic groups can improve the hydrophilicity and biocompatibility of the isolation layer 31.

[0056] In some examples, the first type of polymer may have a hydrophilic group. This allows the first type of polymer to have a certain degree of hydrophilicity, thereby improving the biocompatibility of isolation layer 31. Furthermore, ethylene oxide can react with some types of hydrophilic groups. That is, the first type of polymer containing hydrophilic groups that react with ethylene oxide can adsorb ethylene oxide to a certain extent, thereby further improving the isolation effect of isolation layer 31 on ethylene oxide. In some examples, the hydrophilic group may include hydroxyl groups, carboxyl groups, and / or ether groups.

[0057] In some examples, the hydrophilic groups may account for 1% to 30% of the first polymer. For example, the hydrophilic groups may account for 1%, 2%, 5%, 6%, 8%, 10%, 12%, 13%, 15%, 16%, 17%, 18%, 20%, 22%, 25%, 26%, 27%, 28%, 29%, or 30% of the first polymer. The proportion of the hydrophilic groups in the first polymer may affect the performance of the first polymer. In this case, by adjusting the proportion of the hydrophilic groups, the relevant properties of the first polymer can be adjusted, thereby adjusting the performance of the isolation layer 31.

[0058] In some examples, when the first type of polymer is polyurethane, the hydrophilic group content can range from 1% to 30%. In this case, selecting an appropriate hydrophilic group content can ensure that the polyurethane material exhibits excellent hydrophilicity and biocompatibility. Furthermore, polyurethane containing hydrophilic groups reactive with ethylene oxide can absorb some of the ethylene oxide during sterilization, introducing epoxy groups, further enhancing the isolation layer 31's effectiveness against sterilizing gases. In some examples, the hydrophilic group content of the first type of polymer can preferably range from 10% to 25%. In some examples, the permeability coefficient of the isolation layer 31 to analytes can be adjusted by adjusting the hydrophilic groups in the polyurethane. For example, increasing the proportion of hydrophilic groups in the polyurethane can increase its dispersibility in the liquid phase, thereby improving the permeability of the isolation layer 31 to analytes. Conversely, decreasing the proportion of hydrophilic groups in the polyurethane can reduce the permeability of the isolation layer 31 to analytes. In some examples, the hydrophilicity of the polyurethane can be increased by introducing a block containing hydrophilic groups.

[0059] In some examples, the first solution may include an organic solvent. The first type of polymer may be soluble in the organic solvent. This facilitates forming the first solution and subsequently forming the isolation layer 31. In some examples, the organic solvent may be a mixed solvent of one or more of tetrahydrofuran, dichloromethane, and N,N-dimethylacetamide. This allows the first type of polymer to be dissolved in the organic solvent.

[0060] In some examples, the mass fraction of the first type of polymer in the first solution can be 0.1% to 15%. For example, the mass fraction of the first type of polymer in the first solution can be 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15%. This can help the isolation layer 31 limit the permeation of the sterilizing gas during gas sterilization. In some examples, preferably, the mass fraction of the first type of polymer in the first solution can be 0.1% to 5%. In this case, the isolation layer 31 can have a suitable analyte permeability coefficient while limiting the permeation of the sterilizing gas.

[0061] In some examples, the thickness of the isolation layer 31 can be 1 μm to 40 μm. For example, the thickness of the isolation layer 31 can be 1 μm, 5 μm, 8 μm, 10 μm, 12 μm, 15 μm, 18 μm, 20 μm, 22 μm, 25 μm, 28 μm, 30 μm, 32 μm, 35 μm, 38 μm, or 40 μm. In this case, selecting an isolation layer 31 of appropriate thickness can effectively serve as an isolation barrier, thereby improving the resistance of the sensor 1 to the sterilizing gas. In addition, it can also ensure that the isolation layer 31 has an appropriate analyte permeability coefficient. In some examples, preferably, the thickness of the isolation layer 31 can be 10 μm to 30 μm. In this case, it is possible to balance the isolation effect of the isolation layer 31 against the sterilizing gas and the analyte permeability coefficient.

[0062] In some examples, the polymer film 3 may include a protective layer 32 (see FIG. 3 ). In some examples, the protective layer 32 may be used to separate the sensing layer 14 from the isolation layer 31. That is, the protective layer 32 may be closer to the first electrode 13 than the isolation layer 31. This can mitigate the adverse effects of the organic solvent in the isolation layer 31 on the sensing layer 14 and the first electrode 13 (e.g., corrosion leading to damage to the internal structural integrity and loss of functionality).

[0063] In some examples, the protective layer 32 can be made of a second solution. In some examples, the second solution can be applied to the implant portion 11 to form the protective layer 32. In some examples, the second solution can be applied to the target position by spraying, spin coating, or dip coating to form the protective layer 32. In some examples, the second solution can include a second type of polymer. In other words, the protective layer 32 can include a second type of polymer. The second type of polymer may not react with the first type of polymer. Thus, a protective layer 32 can be formed that can separate the isolation layer 31 from the internal structure (sensing layer 14 and the first electrode 13).

[0064] In some examples, the second type of polymer can be a copolymer formed from anionic and cationic polymers or neutral monomers. In this case, the protective layer 32 does not react with the two polymers in the isolation layer 31; a low-corrosive or non-corrosive solvent can be used to dissolve the second type of polymer, allowing the formed protective layer 32 to directly contact the internal structure (sensing layer 14 and first electrode 13) without damaging the internal structure; the formed protective layer 32 also has minimal permeability restrictions on analytes, allowing analytes to pass through the protective layer 32 and contact the sensing layer 14. In addition, the second type of polymer is insoluble in the organic solvent in the first solvent, which can reduce the possibility of the formed film layer falling off and inhibit the interaction between the two film layers, thereby improving the overall stability of the polymer film 3.

[0065] In some examples, the second polymer can be chitosan or carboxymethylacrylate.

[0066] In some examples, the second type of polymer can be selected from one or more of polyethylene glycol-block-polystyrene, polyacrylic acid-block-polystyrene, polyacrylic acid-co-polystyrene, polyacrylamide-block-polystyrene, polyacrylamide-co-polystyrene, poly2-vinylpyridine-block-polystyrene, poly4-vinylpyridine-co-polystyrene, poly4-vinylpyridine-co-polyvinylpyrrolidone, poly2-vinylpyridine-co-polystyrene, poly4-vinylpyridine-block-polystyrene, poly4-vinylpyridine-co-polyacrylamide, polyethoxyethyl acrylate-co-polyhydroxyethyl acrylate, and polyethoxypropyl acrylate-co-polyvinyl alcohol.

[0067] In some examples, the solvent of the second solution can be a lower alcohol solution, an inorganic salt buffer solution, or a mixed solution of a lower alcohol and an inorganic salt buffer solution. This can dissolve the second polymer, facilitating subsequent coating of the second solution. In some examples, the solvent of the second solution can be methanol, ethanol, or a mixed solution of ethanol and phosphate buffer solution.

[0068] In some examples, the thickness of the protective layer 32 may be 1 μm to 20 μm. For example, the thickness of the protective layer 32 may be 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 11 μm, 12 μm, 13 μm, 14 μm, 15 μm, 16 μm, 17 μm, 18 μm, 19 μm, or 20 μm. Thus, the protective layer 32 can effectively separate the isolation layer 31 from the internal structure (sensing layer 14 and first electrode 13). In some examples, preferably, the thickness of the protective layer 32 may be 8 μm to 15 μm. In some examples, preferably, the thickness of the protective layer 32 may be not less than 10 μm.

[0069] In some examples, the thickness ratio of the protective layer 32 to the isolation layer 31 can be 1:1 to 1:10. For example, the thickness ratio of the protective layer 32 to the isolation layer 31 can be 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, or 1:10. This can facilitate the isolation layer 31 to be separated from the internal structure (sensing layer 14 and first electrode 13) by the protective layer 32. In some examples, preferably, the thickness ratio of the protective layer 32 to the isolation layer 31 can be 1:1 to 1:5.

[0070] In some examples, the polymer film 3 may include a biocompatible layer 33 (see FIG3 ). The biocompatible layer 33 may be biocompatible and serve as the outermost layer of the polymer film 3 (i.e., the layer furthest from the first electrode 13 ). In this case, the biocompatibility of the sensor 1 may be improved.

[0071] In some examples, the isolation layer 31 may be located between the biocompatible layer 33 and the protective layer 32. It should be noted that, in the present disclosure, the isolation layer 31 has been adjusted to have good biocompatibility, and the addition of the biocompatible layer 33 is intended to further improve the biocompatibility and reliability of the sensor 1, and the provision of the biocompatible layer 33 is not necessarily required.

[0072] In some examples, the biocompatible layer 33 can be made from a third solution. In some examples, the third solution can be applied to the implant portion 11 to form the biocompatible layer 33. In some examples, the third solution can be applied to the target location by spraying, spin coating, or dip coating to form the biocompatible layer 33. In some examples, the third solution can include a third type of polymer. In other words, the biocompatible layer 33 can include a third type of polymer. The third type of polymer can be a biocompatible polymer. This can form a biocompatible biocompatible layer 33, thereby helping to improve the biocompatibility of the sensor 1.

[0073] In some examples, the third polymer may be polyurethane. In this case, the third polymer is also polyurethane, which can further improve the biocompatibility of the sensor 1 and partially block the entry of sterilization gas during the sterilization process of the sensor 1, further improving the protective effect of the polymer film 3 on the sensor 1.

[0074] In some examples, the third type of polymer can be a polyurethane containing hydrophilic groups. In this case, the biocompatible layer 33 containing the third type of polymer can have good biocompatibility. In addition, the polyurethane containing hydrophilic groups that react with ethylene oxide can react with ethylene oxide during sterilization, absorbing some of the ethylene oxide and introducing epoxy groups, further increasing the hydrophilicity of the biocompatible layer 33 and, in turn, the biocompatibility of the polymer membrane 3.

[0075] In some examples, the proportion of hydrophilic groups in the third type of polymer can be 20% to 50%. For example, the proportion of hydrophilic groups in the third type of polymer can be 20%, 22%, 25%, 28%, 30%, 32%, 35%, 37%, 40%, 42%, 45%, 48%, or 50%. As a result, the biocompatible layer 33 containing the third type of polymer can have good biocompatibility, thereby further improving the biocompatibility of the sensor 1. In some examples, preferably, the proportion of hydrophilic groups in the third type of polymer can be 30% to 50%. In some examples, preferably, the proportion of hydrophilic groups in the third type of polymer can be no less than 30%.

[0076] In some examples, the third type of polymer may be a cross-linked water-soluble polyurethane. In this case, the water-soluble polyurethane has good biocompatibility, thereby enabling the formed biocompatible layer 33 to have good biocompatibility. In some examples, the third type of polymer may be polyethylene glycol block polyurethane, polymethacrylate block polyurethane, polyvinyl alcohol block polyurethane, or polypropylene alcohol block polyurethane.

[0077] In some examples, the solvent of the third solution can be an organic solvent or other mixed solvent. The third type of polymer can be dissolved in the organic solvent. This facilitates the formation of the third solution and, in turn, the formation of the biocompatible layer 33. In some examples, the organic solvent can be a mixed solvent of any one or more of tetrahydrofuran, dichloromethane, and N,N-dimethylacetamide. This allows the use of an organic solvent to dissolve the third type of polymer. In some examples, the solvent of the third solution can include water. This facilitates the dissolution of the third type of polymer.

[0078] In some examples, the mass fraction of the third type of polymer in the third solution can be 0.1% to 15%. For example, the mass fraction of the third type of polymer in the third solution can be 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15%. This allows for the formation of a biocompatible layer 33 having excellent biocompatibility. In some examples, preferably, the mass fraction of the first type of polymer in the first solution can be 0.1% to 5%.

[0079] In some examples, the thickness of the biocompatible layer 33 may be 1 μm to 30 μm. For example, the thickness of the biocompatible layer 33 may be 1 μm, 3 μm, 5 μm, 6 μm, 8 μm, 10 μm, 12 μm, 14 μm, 15 μm, 16 μm, 18 μm, 20 μm, 22 μm, 25 μm, 26 μm, 28 μm, or 30 μm. This can help improve the biocompatibility of the sensor 1. In some examples, preferably, the thickness of the biocompatible layer 33 may be 10 μm to 20 μm.

[0080] Figure 4 is a schematic diagram showing a polymer film 3 covering an implant 11 according to an example of the present disclosure. In Figure 4 , the polymer film 3 is magnified and the structure of the implant 11 is simplified for a clearer illustration, but this should not be construed as limiting the present disclosure.

[0081] In some examples, the polymer film 3 can cover the implant portion 11 (see FIG4 ). In some examples, the polymer film 3 can cover each electrode on the implant portion 11. For example, the polymer film 3 can cover the first electrode 13 and the second electrode. Thus, the first electrode 13 and the second electrode can be protected by the polymer film 3. For another example, the polymer film 3 can cover the first electrode 13, the second electrode, and the third electrode on the implant portion 11. Thus, each electrode can be protected by the polymer film 3. In some examples, the polymer film 3 can completely cover the implant portion 11. Thus, the safety of the sensor 1 when implanted subcutaneously in the host can be improved.

[0082] In some examples, the thickness of the polymer film 3 may be no greater than 100 μm. In this case, the polymer film 3 can be stably adhered to the implant portion 11, and the implant portion 11 occupies less space overall, which can reduce discomfort after implantation under the host's skin, thereby improving wearing comfort.

[0083] In summary, in the first aspect of the present disclosure, a sensor 1 resistant to sterilization gas can be provided.

[0084] As mentioned above, the second aspect of the present disclosure provides an isolation layer 31 of the sensor 1. The isolation layer 31 can limit the penetration of sterilization gas during gas sterilization of the sensor 1, forming an isolation barrier to reduce the impact of the sterilization gas on the sensing layer 14 of the sensor 1.

[0085] The isolation layer 31 involved in the second aspect of the present disclosure is consistent with the isolation layer 31 in the sensor 1 described in the first aspect of the present disclosure. The specific components and proportions can be found in the description of the first aspect and will not be repeated here.

[0086] In some examples, the isolation layer 31 can be configured to reduce the impact of the sterilization gas on the sensing layer 14 when the sensor 1 is sterilized with gas. In some examples, the isolation layer 31 can cover the first electrode 13 and the sensing layer 14 of the sensor 1. This can protect the first electrode 13 and the sensing layer 14.

[0087] In some examples, the isolation layer 31 can be made of a first solution, which can include a first type of polymer and an organic solvent. The first type of polymer can be polyurethane. In this case, the isolation layer 31 including polyurethane can limit the penetration of the sterilization gas during gas sterilization of the sensor 1, forming an isolation barrier to reduce the impact of the sterilization gas on the sensing layer 14, especially the impact of gaseous ethylene oxide on the active substances in the sensing layer 14, so that the sensor 1 can be sterilized using gas sterilization. Compared with the sensor 1 without the isolation layer 31, the sensor 1 provided with the isolation layer 31 has a significantly reduced decrease in sensitivity before and after sterilization, and can still maintain a high sensitivity after sterilization. In addition, the isolation layer 31 with polyurethane has good biocompatibility, which can improve the safety of the sensor 1 when implanted subcutaneously in the host. In addition, the isolation layer 31 also has a permeation-restricting effect on specific analytes (such as glucose), which can act as a semipermeable membrane.

[0088] In some examples, the isolation layer 31 can also be used in other scenarios where it is necessary to limit the permeation of ethylene oxide, and the isolation layer 31 can be set on the predetermined target. In other words, the second aspect of the present disclosure can provide an isolation layer 31 that can limit the permeation of sterilization gas.

[0089] In some examples, the method for preparing the isolation layer 31 may include: preparing a first solution; coating the first solution on a predetermined position; and drying to form the isolation layer 31 .

[0090] As previously mentioned, the third aspect of the present disclosure relates to an analyte monitoring device 100 .

[0091] In some examples, the analyte monitoring device 100 may include an electronic component 2 and a sensor 1 electrically connected to the electronic component 2 (see Figure 1). Thus, the analyte can be monitored by the sensor 1. The sensor 1 described in the third aspect of the present disclosure is consistent with the sensor 1 of the first aspect of the present disclosure. The specific structure and details can be found in the description of the first aspect of the present disclosure, which will not be repeated here. That is, in some examples, the analyte monitoring device 100 may include an electronic component 2 and the sensor 1 described in the first aspect of the present disclosure.

[0092] In the analyte monitoring device 100 of the present disclosure, the sensor 1 is resistant to sterilization gas, and the sensor 1 and the electronic component 2 can be assembled together for gas sterilization without the need to sterilize the sensor 1 separately by radiation.

[0093] In some examples, the analyte monitoring device 100 can be assembled as one piece at the factory, and the user does not need to perform additional operations to assemble the electronic component 2 and the sensor 1 when using it. This can facilitate user use. It should be noted that although the sensor 1 provided in the present disclosure can be designed as an integral part with the electronic component 2, if necessary, the two can also be configured to be separable and matched. "Integrated design" should not be understood as a limitation on the sensor 1 of the present disclosure.

[0094] In summary, according to the present disclosure, a sensor 1 resistant to sterilization gas, its isolation layer 31 , and an analyte monitoring device 100 can be provided.

[0095] In order to further illustrate the present disclosure, the sensor 1 and the isolation layer 31 provided by the present disclosure are described in detail below in conjunction with embodiments, and the beneficial effects achieved by the present disclosure are fully illustrated in conjunction with comparative examples.

[0096] It should be noted that, in the examples and comparative examples of the present disclosure, unless otherwise specified, the reagents and instruments used are all commercially available products.

[0097] First, a plurality of sensors including a first electrode provided with a sensing layer of glucose enzyme are prepared.

[0098] [Example]

[0099] According to Tables 1-1 and 1-2, a first solution, a second solution, and a third solution were prepared (some Examples did not have a third solution). The second solution, the first solution, and the third solution were sequentially coated on the prepared sensor to produce sensors having polymer membranes according to Examples 1 to 11. PEO in Tables 1-1 and 1-2 refers to a hydrophilic group and a soft segment, and PEGDGE refers to polyethylene glycol diglycidyl ether. Experiments were conducted using polyurethanes containing PEO as an example.

[0100] Table 1-1

[0101] Table 1-2

[0102] [Comparative Example 1]

[0103] A commercially available continuous glucose monitoring system (Shenzhen Silicon-Based Sensing Technology Co., Ltd., model: GS1) was selected as comparative example 1.

[0104] [Comparative Example 2]

[0105] The sensor of Comparative Example 2 was prepared according to the same steps as Example 1, except that no protective layer was provided.

[0106] [Comparative Example 3]

[0107] The sensor of Comparative Example 3 was prepared according to the same steps as Example 4, except that the thickness of the isolation layer was 50 μm.

[0108] [Comparative Example 4]

[0109] The sensor of Comparative Example 4 was prepared according to the same steps as Example 1, with the difference from Example 1 being that the polyether polyurethane in the first solution contained 50% PEO.

[0110] Test the performance of the sensor:

[0111] (1) Cytotoxicity test (biocompatibility test)

[0112] Taking the sensors of Example 1 and Example 9 as an example, a cytotoxicity test was performed, specifically: a control group and an experimental group were designed, the control group included a blank group (blank control cell culture fluid was added), a negative control group (high-density polyethylene extract (non-toxic substance) was added), and a positive control group (latex glove extract (toxic substance) was added). The experimental group included the first solution of Example 1 and the third solution of Example 9 at different concentrations. For details, see Table 2. Cells were inoculated in the experimental group and the control group, and the cell survival rate was measured after incubation. The cytotoxicity test results are shown in Table 2.

[0113] Table 2

[0114] (2) Sensitivity test

[0115] The sensors of each Example and each Comparative Example were sterilized using ethylene oxide under the following sterilization conditions: temperature: 52±3°C, humidity: 30-85%, exposure time: 360 minutes, concentration: 600±40 mg / L. Figure 5 shows the appearance of the sensor of Example 1 after sterilization, and Figure 6 shows the appearance of the sensor of Comparative Example 1 after sterilization.

[0116] The sensitivity of each sensor was tested before and after sterilization. Specifically, the sensor was exposed to standard phosphate buffered saline (PBS) buffer with varying glucose concentrations at 37°C ± 1°C. The response current at each glucose concentration was measured and fitted to a standard curve. The sensitivity of each sensor was then calculated based on the fitted standard curve. The glucose concentrations were as follows: 2.2 mM (millimoles per liter), 5 mM, 10 mM, 15 mM, 20 mM, and 25 mM. The measured sensitivities are shown in Table 3. In Table 3, the decrease in sensitivity = (sensitivity before sterilization - sensitivity after sterilization) / sensitivity before sterilization * 100%. A greater decrease in sensitivity (also called attenuation) indicates a greater impact of ethylene oxide and a weaker sensor resistance to ethylene oxide. Conversely, a smaller decrease in sensitivity indicates a stronger sensor resistance to ethylene oxide.

[0117] Table 3

[0118] Result Analysis

[0119] As can be seen from Figures 5 and 6, the appearance of the sensor of Example 1 did not change significantly after sterilization, while the sensor of Comparative Example 1 turned significantly green (it should be noted that in order to comply with the provisions of the Patent Examination Guidelines, the drawings were changed to black and white in this disclosure), indicating that the sensor of Comparative Example 1 without an isolation layer was corroded after sterilization.

[0120] As can be seen from Table 3, the sensitivity of the sensors in each Example decreased very little before and after sterilization, indicating that the sensors in each Example were resistant to ethylene oxide. In contrast, the sensitivity of the sensors in each Comparative Example decreased significantly after sterilization, with some experiencing undetectable sensitivity. The following is a detailed analysis:

[0121] In Comparative Example 1, because the commercially available product does not have an isolation layer like the present invention, the sensitivity of the sensor drops significantly after sterilization, and therefore the sensor of Comparative Example 1 cannot be sterilized using ethylene oxide gas. In Comparative Example 2, because no protective layer is provided, the electrode is corroded after coating the first solution containing an organic solvent, resulting in no sensitivity being detected. This indicates that the protective layer of the present invention can effectively protect the electrode. In Comparative Example 3, because the thickness of the isolation layer is 50 μm, the excessive increase in film thickness results in excessive diffusion resistance of the isolation layer to glucose, and effective sensitivity cannot be detected. In Comparative Example 4, the PEO content in the isolation layer is 50%, that is, the content of soft segments and hydrophilic groups is 50%. The overall hydrophilicity of the isolation layer is high, and the diffusion resistance to glucose is small, which makes the sensor have a higher sensitivity before sterilization, but also leads to a worse isolation effect of the isolation layer to ethylene oxide, and the sensitivity of the sensor drops significantly after sterilization.

[0122] By comparing Example 1 and Examples 2-3, it can be found that increasing the film thickness leads to a decrease in sensitivity, but the degree of sensitivity attenuation after sterilization is also reduced, indicating that increasing the thickness of the isolation layer can reduce the damage to the electrode caused by ethylene oxide sterilization.

[0123] By comparing Example 1 and Example 4, it can be found that because the concentration and thickness of the polyether polyurethane in Example 4 are greater than those in Example 1, the degree of sensitivity attenuation after sterilization is reduced, but the overall sensitivity of Example 4 is lower than that of Example 1.

[0124] By comparing Example 1 and Examples 5-6, it can be found that Examples 5-6 use different concentrations of polyether polyurethane to prepare the isolation layer. Due to the different solution concentrations, there is a slight difference in the sensitivity attenuation before sterilization and the sensitivity attenuation after sterilization, but there is no significant difference.

[0125] By comparing Example 1 and Examples 7-8, it can be found that Examples 7-8 use different types of polyurethanes, respectively. Since these two types of polyurethanes are more hydrophobic than polyether polyurethanes, the isolation layer has a greater diffusion resistance to glucose and a lower sensitivity. However, the sensitivity attenuation amplitude after sterilization is also reduced accordingly, indicating that different types of polyurethanes can have an isolation effect.

[0126] By comparing Example 1 and Examples 9-11, it can be found that Examples 9-11 are sensors with biocompatible layers of different components added, respectively. Due to the increase in the overall film thickness of the polymer film, the sensitivity of the sensors of Examples 9-11 is reduced compared to Example 1, but the sensitivity attenuation after sterilization is also reduced accordingly, having a stronger protective effect; and the third solution of Example 9 shows stronger biocompatibility than the first solution of Example 1 in the cytotoxicity test, indicating that adding a biocompatible layer helps to improve the biocompatibility of the sensor.

[0127] In summary, the sensors of each embodiment have strong resistance to ethylene oxide (i.e., sterilizing gas). In comparison, the sensors obtained in each comparative example cannot achieve the performance and effect of the sensors obtained in the above embodiments.

[0128] Although the present disclosure has been described in detail above with reference to the accompanying drawings and examples, it will be understood that the above description does not limit the present disclosure in any form. Those skilled in the art may modify and change the present disclosure as needed without departing from the spirit and scope of the present disclosure, and such modifications and variations all fall within the scope of the present disclosure.

Claims

1. A biosensor for monitoring an analyte, characterized in that: The biosensor comprises a first electrode provided with a sensing layer, and a polymer film, The polymer film at least covers the sensing layer and the first electrode, and the polymer film includes a protective layer and an isolation layer, wherein the protective layer is closer to the first electrode than the isolation layer. The isolation layer is configured to reduce the impact of sterilization gas on the sensing layer when the biosensor is gas sterilized. The isolation layer is made of a first solution comprising a first type of polymer and an organic solvent. The first type of polymer is polyurethane.

2. The biosensor according to claim 1, wherein In the first solution, the mass fraction of the first type of polymer is 0.1% to 15%.

3. The biosensor according to claim 1 or 2, characterized in that The first type of polymer has a soft segment, and in the first type of polymer, the soft segment accounts for 5% to 50%.

4. The biosensor according to claim 1 or 2, characterized in that The first type of polymer has a hydrophilic group, and in the first type of polymer, the hydrophilic group accounts for 1% to 30%.

5. The biosensor according to claim 1 or 2, characterized in that The organic solvent is a mixed solvent of any one or more of tetrahydrofuran, dichloromethane and N,N-dimethylacetamide.

6. The biosensor according to claim 1 or 2, characterized in that The thickness of the isolation layer is 1 μm to 40 μm.

7. The biosensor according to claim 1, wherein The protective layer includes a second type of polymer, which is an anionic or cationic polymer or a copolymer formed by a neutral monomer.

8. The biosensor according to claim 1 or 7, characterized in that The protective layer has a thickness of 1 μm to 20 μm.

9. The biosensor according to claim 1, wherein The polymer film further comprises a biocompatible layer. The isolation layer is located between the biocompatible layer and the protective layer. The biocompatible layer comprises a third type of polymer, which is a polyurethane containing a hydrophilic group or a cross-linked water-soluble polyurethane.

10. The biosensor according to claim 9, wherein When the third type of polymer is the polyurethane containing hydrophilic groups, the hydrophilic groups account for 20% to 50% of the third type of polymer.

11. The biosensor according to claim 9 or 10, characterized in that The biocompatible layer has a thickness of 1 μm to 30 μm.

12. The biosensor according to claim 1, wherein The sensing layer includes one or more of glucase, lactase and hydroxybutyrate dehydrogenase.

13. The biosensor according to claim 1, wherein The biosensor further includes a second electrode different from the first electrode, and the polymer film also covers the second electrode.

14. An isolation layer of a biosensor, the biosensor comprising a first electrode provided with a sensing layer, characterized in that: The isolation layer covers at least the sensing layer and the first electrode. The isolation layer is configured to reduce the impact of sterilization gas on the sensing layer when the biosensor is gas sterilized. The isolation layer is made of a first solution, the first solution includes a first type of polymer and an organic solvent, and the first type of polymer is polyurethane.

15. An analyte monitoring device, characterized in that The biosensor comprises an electronic component and the biosensor according to any one of claims 1 to 13, wherein the electronic component is electrically connected to the biosensor.

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