Structurally enhanced analyte sensor

Abstract

At least one layer of insulating material is arranged behind at least one area on a substrate, the area where pins and electrodes are located is avoided, the mechanical strength of the substrate of the sensor is improved, and when the sensor is bent or bent along with muscle peristalsis after penetrating into the subcutaneous part, the sensor is not prone to damage. And the time for the substrate to reach the limit fatigue is prolonged, so that the service life of the sensor is prolonged, and the detection reliability of the sensor is also improved.

Description

Technical Field

[0001] This invention relates primarily to the field of medical devices, and in particular to a structure-enhanced analyte sensor. Background Technology

[0002] In a healthy person, the pancreas automatically monitors blood glucose levels and secretes the necessary insulin / glucagon. However, in diabetic patients, the pancreas malfunctions and cannot secrete insulin as needed. Therefore, diabetes is a metabolic disease caused by abnormal pancreatic function and is a lifelong condition. Currently, medical technology cannot cure diabetes; it can only control the occurrence and development of diabetes and its complications by stabilizing blood sugar levels.

[0003] Diabetic patients need to have their blood glucose levels checked before injecting insulin. Currently, most methods can continuously monitor blood glucose and send the data in real time to a remote device for user viewing; this method is called Continuous Glucose Monitoring (CGM). This method requires a detection device to be attached to the skin surface, with its probe inserted into the subcutaneous tissue fluid to complete the detection. However, the sensor substrate is flexible and, after being inserted under the skin, will repeatedly bend or flex with muscle movement. When the substrate material reaches its fatigue limit, it may break or break, resulting in exposed wires or broken electrodes attached to the substrate, affecting the sensor's lifespan and reducing its detection reliability.

[0004] Therefore, there is an urgent need for an analytical sensor with a long service life and high detection reliability in existing technologies. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the present invention discloses a structure-enhanced analyte sensor. At least one layer of insulating material is disposed behind at least one region on the substrate, avoiding the areas where the pins and electrodes are located, which increases the mechanical strength of the sensor substrate. When the sensor is inserted under the skin and bends or flexes with muscle peristalsis, the time for the substrate to reach its fatigue limit is extended, thereby extending the service life of the sensor and thus improving the detection reliability of the sensor.

[0006] The present invention discloses an analyte sensor, comprising: at least one substrate, the substrate including an in vivo portion and an in vitro portion; at least two electrodes disposed on the surface of the in vivo portion for subcutaneous insertion to acquire analyte parameter information; and pins disposed on the surface of the in vitro portion and electrically connected to the corresponding electrodes via wires; wherein at least one layer of insulating material is disposed behind at least one region on the surface of the substrate, the insulating material avoiding the central conductive region of the pins and electrodes.

[0007] According to one aspect of the invention, the area where the insulating material is subsequently disposed includes at least the reverse side of the pin area and / or the reverse side of the electrode area.

[0008] According to one aspect of the invention, the internal portion is bent relative to the external portion.

[0009] According to one aspect of the invention, the area where the insulating material is subsequently applied also includes the front side of the bent area.

[0010] According to one aspect of the invention, the insulating material is applied to the substrate surface by coating or pasting.

[0011] According to one aspect of the present invention, the substrate material and the insulating material are selected from one or more combinations of polytetrafluoroethylene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polymethyl methacrylate, polycarbonate, and polyimide.

[0012] According to one aspect of the invention, the thickness of the insulating material is 0.1~200 μm.

[0013] According to one aspect of the invention, the electrode is an electrode array composed of electrode units.

[0014] According to one aspect of the invention, a protective layer is further disposed on the substrate surface, the protective layer at least covering the edge of the electrode.

[0015] According to one aspect of the invention, the protective layer also covers the edge of the pin.

[0016] According to one aspect of the invention, the substrate comprises at least two layers of substrate, with at least two electrodes disposed on different layers of sub-substrates.

[0017] According to one aspect of the present invention, the prefabricated substrates at each level are bonded together as a whole.

[0018] According to one aspect of the invention, at least one electrode is disposed on the reverse side of the substrate.

[0019] According to one aspect of the invention, at least one pin is disposed on the reverse side of the substrate.

[0020] According to one aspect of the invention, the front side of the substrate is further provided with a secondary pin corresponding to the pin.

[0021] According to one aspect of the invention, the pin and the secondary pin are electrically connected via the side of the substrate.

[0022] According to one aspect of the invention, the front and back sides of the substrate are prefabricated and then bonded together as a whole.

[0023] According to one aspect of the invention, the front and / or back sides of the substrate further include at least two layers of substrate, with at least two electrodes disposed on different layers of sub-substrates.

[0024] According to one aspect of the present invention, the prefabricated substrates at each level are bonded together as a whole.

[0025] According to one aspect of the invention, the electrodes are distributed on the substrate surface in a predetermined manner to avoid areas of the substrate that are easily bent.

[0026] According to one aspect of the invention, the electrode comprises at least one set of electrodes with the same name.

[0027] According to one aspect of the invention, electrodes of the same name are disposed on the same side of the substrate.

[0028] According to one aspect of the invention, electrodes of the same name are respectively disposed on opposite sides of the substrate.

[0029] According to one aspect of the invention, pins corresponding to electrodes of the same name are disposed on the same side of the substrate.

[0030] According to one aspect of the invention, pins corresponding to electrodes of the same name are respectively disposed on opposite sides of the substrate.

[0031] According to one aspect of the invention, pins disposed on opposite surfaces of the substrate are electrically connected from the side of the substrate.

[0032] According to one aspect of the invention, electrodes with the same name share a corresponding pin.

[0033] According to one aspect of the invention, the electrodes with the same name share a common conductor.

[0034] According to one aspect of the invention, the electrode includes a working electrode and a counter electrode.

[0035] According to one aspect of the invention, the electrode further includes a reference electrode.

[0036] According to one aspect of the invention, the wires are laid on the surface of the substrate.

[0037] According to one aspect of the invention, the wire is embedded in the inner layer of the substrate.

[0038] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0039] The structure-enhanced analytical analyte sensor disclosed in this invention, after the sensor is fabricated, has at least one layer of insulating material disposed on at least one region of the sensor substrate. The insulating material avoids the areas where the pins and electrodes are located, increasing the mechanical strength of the sensor substrate. When the sensor is inserted subcutaneously and bends or flexes due to muscle peristalsis, it prolongs the time it takes for the substrate to reach its fatigue limit, thereby extending the service life of the sensor and thus improving the detection reliability of the sensor.

[0040] Furthermore, the area where the insulating material is applied includes at least the reverse side of the pin area and / or the reverse side of the electrode area, which can enhance the mechanical strength of the sensor substrate while avoiding interference with the electrodes and pins, thus increasing the reliability of detection.

[0041] Furthermore, since the internal part is bent relative to the external part, the insulating material can be placed on the front side of the bent area. This does not affect the electrodes and pins, but also enhances the mechanical strength of the bent area of ​​the substrate. This reduces the possibility of the substrate in the bent area being damaged by bending, exposing the wires and causing a short circuit, or breaking and causing the sensor to fail, thus improving the detection reliability of the sensor.

[0042] Furthermore, by coating or pasting the insulating material onto the substrate surface, the problem of uneven or concentrated stress between the insulating material and the substrate can be mitigated. This can prevent the insulating material from bubbling, warping, or detaching from the substrate during use, thereby improving the detection reliability of the sensor.

[0043] Furthermore, the electrode is an electrode array composed of electrode units. The original monolithic electrode is made into smaller electrode units and laid on the wire. This can prevent the monolithic electrode from being bent or even broken when the sensor is repeatedly bent with the muscle after being inserted under the skin, thus extending the service life of the electrode and improving the detection reliability of the sensor.

[0044] Furthermore, a protective layer can be provided on the substrate surface to cover the edges of the electrodes and / or pins. This can prevent electrical signal interference caused by irregular warping of the electrode and pin edges. At the same time, the protective layer can further enhance the mechanical strength of the sensor substrate and improve the detection reliability of the sensor.

[0045] Furthermore, the substrate comprises at least two layers, with at least two electrodes arranged on different layers of the sub-substrate. The electrodes being located on different layers of the sub-substrate can avoid wire routing, and the electrodes can be set to a larger area, increasing the contact area with the analyte, enhancing the electrode response sensitivity, and improving the detection reliability of the sensor.

[0046] Furthermore, the sub-substrates of different layers can be prefabricated, that is, electrodes, wires and pins are prefabricated on each layer of substrate and then glued together to form a whole sensor. Unlike the conventional layer-by-layer coating process, this can avoid insulation failure caused by insufficient curing of the substrate material, which can lead to brittleness and further cause crosstalk between electrical signals of wires or electrodes, resulting in noise in the detection signal, thus improving the detection reliability of the sensor.

[0047] Furthermore, at least one of the multiple electrodes is located on the reverse side of the substrate. The area that can be set on a single-sided substrate is limited. By setting one or more electrodes on the reverse side of the substrate, both sides of the substrate can be fully utilized. Therefore, the electrodes on each side can have a larger area, increasing the contact area with the analyte, improving the electrode reaction sensitivity, and improving the detection reliability of the sensor.

[0048] Furthermore, since the area of ​​the pin region on one side of the substrate is limited, setting at least one pin on the reverse side of the substrate facilitates electrical connection with the electrode located on the reverse side of the substrate via wires. At the same time, the pins on the single-sided substrate can have a larger area. Pins with a larger area can have a better electrical connection with the circuit, making the current conduction more stable and improving the detection reliability of the sensor.

[0049] Furthermore, when the pin is located on the reverse side of the substrate, a secondary pin corresponding to the pin can be set on the front side of the substrate. The secondary pin can be connected to the circuit together with the pin on the front side of the substrate, without the need to design additional circuits for the pin on the reverse side of the substrate, thus simplifying the complexity of the circuit. At the same time, the pin on the reverse side of the substrate and the corresponding secondary pin on the front side of the substrate are connected by conductive material on the side of the substrate, which can realize the electrical connection between the pin and the secondary pin on the opposite side. Unlike the conventional process of drilling holes in the substrate to realize the electrical connection between the pins on the opposite side, the pins on the opposite side are electrically connected on the side of the substrate, which does not require the pins on the opposite side to be aligned on the substrate, thus simplifying the manufacturing process and improving the yield of the sensor.

[0050] Furthermore, the opposite sides of the substrate, namely the front and back sides of the substrate, can be prefabricated with electrodes, wires, and pins respectively, and then glued together to form a complete sensor. Unlike the conventional layer-by-layer coating process, this avoids insulation failure caused by insufficient curing of the substrate material, which can lead to brittleness and further cause crosstalk between electrical signals between wires or electrodes, resulting in noise in the detection signal and improving the detection reliability of the sensor.

[0051] Furthermore, multi-layer substrates can also be set on the opposite surfaces of the substrate. The multi-layer substrates can also be assembled into a whole after the electrodes, wires and pins are prefabricated separately, forming the front or back of the substrate. Unlike the conventional layer-by-layer coating process, this can avoid insulation failure caused by insufficient curing of the substrate material, which can lead to brittleness and further cause crosstalk between the electrical signals of the wires or electrodes, resulting in noise in the detection signal, thus improving the detection reliability of the sensor.

[0052] Furthermore, the depth to which the sensor is inserted under the skin is fixed, the area where the base repeatedly bends under the skin with muscle peristalsis is fixed, and the electrodes are distributed on the sensor base in a predetermined manner. The electrodes can avoid areas on the sensor base that are easy to bend or twist, thus avoiding breakage or damage to the electrodes due to repeated bending with the base, extending the service life of the electrodes and improving the detection reliability of the sensor.

[0053] Furthermore, the sensor can be equipped with multiple electrodes of the same name, such as two or more working electrodes, two or more counter electrodes, and two or more reference electrodes, to achieve different sensor functions, such as detection of multiple analytes, redundant detection, electrode relay use, enhancement of electrode detection signals, and reduction of detection signal noise, thereby improving the detection reliability of the sensor.

[0054] Furthermore, electrodes with the same name share the corresponding pin, meaning that electrodes with the same name use the same pin. Wires electrically connect two or more electrodes with the same name to the same pin, and the detection signal of the electrode is transmitted to the same pin, which can enhance the signal strength of the electrode and improve the detection reliability of the sensor.

[0055] Furthermore, using the same type of electrode to share a common wire can reduce the number of wires on the substrate, avoiding excessive wires on the substrate that could cause short circuits between them and affect detection, thus improving the detection reliability of the sensor. Attached Figure Description

[0056] Figure 1 This is a top view of a sensor with a planar structure according to an embodiment of the present invention;

[0057] Figure 2 for Figure 1 The sensor in this embodiment is a side view of a planar structure;

[0058] Figure 3 This is a cross-sectional view of an electrode according to an embodiment of the present invention;

[0059] Figure 4 This is a schematic diagram illustrating the functional implementation according to an embodiment of the present invention;

[0060] Figure 5 This is a top view of a sensor with a stepped structure according to an embodiment of the present invention;

[0061] Figure 6 for Figure 5 The sensor in this embodiment is a side view of a stepped structure;

[0062] Figure 7 This is a schematic diagram showing that the sensor has a columnar structure according to an embodiment of the present invention;

[0063] Figure 8 for Figure 7 The sensor in this embodiment is a V-V' cross-sectional view of a columnar structure;

[0064] Figure 9 This is a schematic diagram of a continuous analyte detection device according to an embodiment of the present invention;

[0065] Figures 10a-10o This is a schematic diagram of different sensors according to embodiments of the present invention. Detailed Implementation

[0066] As mentioned earlier, when the analyte sensor of the prior art is inserted under the skin, the base repeatedly bends or flexes with the peristalsis of the muscle. After the base material reaches its fatigue limit, it may break or break, resulting in exposed or broken wires, or the electrodes attached to the base may break, affecting the service life of the sensor and reducing the detection reliability of the sensor.

[0067] To address this problem, the present invention provides a structurally enhanced analyte sensor, which has at least one layer of insulating material disposed behind at least one region on the substrate, avoiding the areas where the pins and electrodes are located. This increases the mechanical strength of the sensor substrate and prolongs the time it takes for the substrate to reach its fatigue limit when the sensor is inserted subcutaneously and bends or flexes due to muscle peristalsis. This extends the service life of the sensor and thus improves the detection reliability of the sensor.

[0068] Various exemplary embodiments of the present invention will now be described in detail with reference to the accompanying drawings. It should be understood that, unless otherwise specifically stated, the relative arrangement, numerical expressions, and values ​​of the components and steps set forth in these embodiments should not be construed as limiting the scope of the invention.

[0069] Furthermore, it should be understood that, for ease of description, the dimensions of the various components shown in the accompanying drawings are not necessarily drawn to actual scale; for example, the thickness, width, length, or distance of some units may be enlarged relative to other structures.

[0070] The following description of exemplary embodiments is merely illustrative and is not intended to limit the invention or its application or use in any way. Techniques, methods, and apparatus known to those skilled in the art may not be discussed in detail herein, but where applicable, such techniques, methods, and apparatus should be considered part of this specification.

[0071] It should be noted that similar reference numerals and letters in the following figures indicate similar items; therefore, once an item is defined or described in a figure, it will not need to be discussed further in the subsequent description of the figures.

[0072] Furthermore, it should be understood that the existence of other method steps before or after the combined steps, or the insertion of other method steps between these explicitly mentioned steps, does not preclude the existence of other method steps before or after the combined steps, or the insertion of other method steps between these explicitly mentioned steps, unless otherwise stated. It should also be understood that the combined connection relationship between one or more devices / apparatus mentioned in this invention does not preclude the existence of other devices / apparatus before or after the combined devices / apparatus, or the insertion of other devices / apparatus between these explicitly mentioned devices / apparatus, unless otherwise stated. Moreover, unless otherwise stated, the numbering of each method step is merely a convenient tool for identifying each method step, and not for limiting the order of the method steps or limiting the scope of the invention. Changes or adjustments to their relative relationships, without substantially altering the technical content, should also be considered within the scope of the invention.

[0073] Example 1

[0074] Planar structure sensor

[0075] Figure 1 This is a top view of the sensor in an embodiment of the present invention, which has a planar structure. Figure 2 for Figure 1 The sensor in this embodiment is a side view of a planar structure.

[0076] Sensor 11 includes a substrate 111, so as to Figure 1The dashed line shown is the dividing line, dividing the substrate 111 into an external portion X and an internal portion Y. Electrodes are laid on the internal portion Y, including at least one working electrode 1131 and at least one auxiliary electrode. Obviously, in this embodiment, the auxiliary electrode includes a counter electrode 1231 and a reference electrode 1331, thus forming a three-electrode system. The counter electrode 1231 is the other pole relative to the working electrode 1131, forming a closed circuit with the working electrode 1131, so that the current on the electrode can conduct normally. The reference electrode 1331 is used to provide a reference potential for the working electrode 1131, thus effectively controlling the detection potential. In another embodiment of the present invention, the auxiliary electrode may also include only the counter electrode 1231, thus forming a two-electrode system. Compared with the three-electrode system, the effective area of ​​the working electrode 1131 and the counter electrode 1231 can be increased on the limited area of ​​the internal portion Y, thereby extending the service life of the electrodes. Moreover, because one electrode is reduced, the processing technology is also simpler. However, the working electrode 1131 does not have the detection potential of the reference electrode as a reference, and the reliability of the detection information of the analyte will be reduced. In another embodiment of the present invention, there are two working electrodes 1131. One of them undergoes an electro-oxidation-reduction reaction with the analyte to be detected to generate an electrical signal, and the other is used to detect the response signal of interfering substances or background solution in the host body fluid. This electrode is an auxiliary electrode.

[0077] Continue to refer to Figure 1 and Figure 2 The external component X has pins, each corresponding to an electrode and electrically connected via wires. Specifically, the working pin 1111, corresponding to the working electrode 1131, is electrically connected via wire 1121; the counter pin 1211, corresponding to the counter electrode 1231, is electrically connected via wire 1221; and the reference pin 1311, corresponding to the reference electrode 1331, is electrically connected via wire 1321. Different pins, wires, and electrodes are insulated from each other to prevent crosstalk in the electrical signals.

[0078] Since sensor 11 has a planar structure, it has two opposing surfaces, namely surface A and surface B. The working electrode 1131, counter electrode 1231, and reference electrode 1331 are arranged as an electrode group on surface A of the sensor. Conversely, another electrode group is arranged on surface B of the sensor. This electrode group can be a dual-electrode system, a triple-electrode system, or a dual-working-electrode system. Preferably, it is consistent with the electrode group on surface A, including the working electrode 1132, counter electrode 1232, and reference electrode 1332. Similarly, pins are also arranged on surface B, each corresponding to an electrode on surface B and electrically connected via wires. Specifically, the fourth pin 1112 corresponding to the working electrode 1132 is electrically connected via wire 1122; the fifth pin 1212 corresponding to the counter electrode 1232 is electrically connected via wire 1222; and the sixth pin 1312 corresponding to the reference electrode 1332 is electrically connected via wire 1322. In this way, if any electrode on side A reaches the end of its life or fails prematurely, the corresponding electrode on side B can take over and enter the working state, improving the reliability of the parameter data of the detected analytes and extending the service life of the sensor.

[0079] Those skilled in the art should understand that the order and position of the pins, wires, and electrodes laid on both sides of the sensor (A and B) are not limited. The pins, wires, and electrodes on the two sides can be arranged symmetrically or asymmetrically. Corresponding pins, wires, and electrodes can be laid on the same side or on different sides. Preferably, corresponding pins, wires, and electrodes are laid on the same side to facilitate wire routing. For example, the working electrode 1131 on side A can be interchanged with the counter electrode 1231, or the counter electrode 1231 on side A can be interchanged with the reference electrode 1332 on side B. Regardless of the change in the order and position of the pins, wires, and electrodes on sides A and B, it is sufficient that the pins, wires, and electrodes have a one-to-one correspondence and are insulated from each other.

[0080] In other embodiments of the present invention, although the planar structure sensor only has opposing A and B surfaces, the number of electrode groups can be increased by increasing the sensor area or decreasing the electrode area, thereby further increasing the sensor's lifespan. However, an excessively large sensor area may increase the host's rejection response, causing discomfort; an excessively small electrode area will reduce the electrode's sensitivity and decrease the reliability of the detection parameters. Too many electrode groups will also increase the complexity of the manufacturing process, such as making the wiring very dense. Therefore, preferably, the number of electrode groups is two.

[0081] In other embodiments of the present invention, the various electrode groups may also be distributed on the same surface of the sensor, such as surface A or surface B, without limitation.

[0082] In this embodiment of the invention, the substrate 111 is a material with excellent insulating properties, mainly derived from inorganic non-metallic ceramics, silica glass, and organic polymers. Considering the application environment of the implantable electrode, the substrate material is also required to have high water impermeability and mechanical strength. Preferably, the substrate material is selected from one or more combinations of polytetrafluoroethylene (Teflon), polyethylene (PE), polyvinyl chloride (PVC), acrylonitrile-butadiene-styrene copolymer (ABS), polymethyl methacrylate (PMMA), polycarbonate (PC), and polyimide (PI).

[0083] Figure 3 This is a cross-sectional view of the electrode. In one embodiment of the present invention, the working electrode (auxiliary electrode), the counter electrode, and the reference electrode include at least an electron conduction layer a, an anti-interference layer b, an enzyme layer c, a regulation layer d, and a biocompatible layer e.

[0084] Electron conduction layer:

[0085] The electron conduction layer a is made of a material with good electrical conductivity and strong chemical inertness. Preferably, the working electrode and the counter electrode are selected from graphite electrodes, glassy carbon electrodes, noble metals, etc., and the reference electrode is selected from Ag / AgCl or calomel. Considering the requirements of good ductility and surface structure stability, noble metal electrodes such as gold electrodes, platinum electrodes, and silver electrodes are good choices. More preferably, both the working electrode and the counter electrode are platinum electrodes.

[0086] Anti-interference layer:

[0087] The anti-interference layer b is located between the enzyme layer and the electron conduction layer. Interfering substances are molecules or substances that undergo electrochemical reduction or electrochemical oxidation directly or indirectly through electron transfer agents on the electrode surface, thereby generating an erroneous signal that interferes with the detection of the analyte. For example, for the determination of glucose as an analyte, common interfering substances in vivo include urea, ascorbic acid, acetaminophen, etc.

[0088] In a preferred embodiment, the anti-interference layer b prevents one or more interfering substances from penetrating into the electrolyte surrounding the electrode. For example, the anti-interference layer b allows the analyte to be measured at the electrode (e.g., hydrogen peroxide) to pass through while preventing the passage of other substances (such as potential interfering substances). In a preferred embodiment, the anti-interference layer b can be a very thin film designed to limit the diffusion of substances with a molecular weight greater than 34 Da.

[0089] In another preferred embodiment, the anti-interference layer b can be an organic polymer, which can be prepared from an organosilane and a hydrophilic copolymer. More preferably, the hydrophilic copolymer is polyethylene glycol (PEG), polymethacrylic acid, 2-hydroxyethyl ester, and polylysine. In a preferred embodiment, the thickness of the anti-interference layer b can range from 0.1 μm or less to 10 μm or more. A more preferred thickness range is 0.5 μm to 5 μm.

[0090] Enzyme layer:

[0091] Enzyme layer c is coated with an active enzyme. The appropriate active enzyme is coated according to the type of analyte to be detected. The active enzyme can cause certain chemical reactions in the analyte to be detected, generating electrons. The number of electrons generated varies depending on the concentration of the analyte. These electrons are collected by the electron conduction layer, resulting in different current intensities. Therefore, the current intensity information can be used to characterize the analyte parameters.

[0092] Preferably, enzyme layer c is coated with glucose oxidase (GOx).

[0093] Adjustment layer:

[0094] The regulatory layer d is located above the enzyme layer. In this embodiment of the invention, when glucose oxidase is coated onto the enzyme layer, the regulatory layer d is mainly used to regulate the permeability of oxygen and glucose delivered to the enzyme layer. The glucose concentration (molar concentration) in body fluids is an order of magnitude higher than the oxygen concentration. However, for enzyme-based sensors that require oxygen, an excess of oxygen needs to be supplied to ensure that oxygen does not become a limiting factor, allowing the sensor to respond linearly to changes in glucose concentration without being affected by oxygen partial pressure. That is, when oxygen content becomes a limiting factor, the linear range of the glucose-oxygen monitoring response does not reach the expected concentration range. Without a semipermeable membrane above the enzyme layer to regulate oxygen and glucose permeability, the upper limit of the sensor's linear response to glucose is only about 40 mg / dL. However, in clinical settings, the upper limit of the linear response to blood glucose levels needs to reach about 500 mg / dL.

[0095] The regulatory layer d primarily functions as a semi-permeable membrane, regulating the permeation of oxygen and glucose to the enzyme layer; more specifically, it makes excess oxygen a non-limiting factor. Compared to sensors without a regulatory layer, those with a regulatory layer can achieve a higher upper limit for the linear response to glucose. In a preferred embodiment, the oxygen-to-glucose permeability ratio of the regulatory layer d can reach 200:1, ensuring sufficient oxygen for enzymatic reactions regardless of the various glucose and oxygen concentrations that may be present subcutaneously.

[0096] In a preferred embodiment, the regulating layer d can be an organic polymer, which can be prepared from an organosilane and a hydrophilic copolymer. More preferably, the hydrophilic copolymer is a copolymerized or grafted polyethylene glycol (PEG). Other possible hydrophilic copolymers include, but are not limited to, other glycols such as propylene glycol, esters, amides, carbonates, and polypropylene glycol. Using organosilicon polymers can significantly improve oxygen transport while effectively controlling glucose permeation. In a preferred embodiment, the thickness of the regulating layer d can range from 1 μm or less to 50 μm or more, more preferably from 1 μm to 10 μm.

[0097] Biocompatibility layer:

[0098] The biocompatibility layer e is located on the outermost part of the electrode and is designed to eliminate the body's rejection response to foreign objects and reduce the formation of a shielding cell layer around the implanted electrode.

[0099] In a preferred embodiment, the biocompatible layer e can be prepared from an organosilane and a hydrophilic copolymer. More preferably, the hydrophilic copolymer is a copolymerized or grafted polyethylene glycol (PEG). Other hydrophilic copolymers that may be used include, but are not limited to, other glycols such as propylene glycol, esters, amides, carbonates, and polypropylene glycol.

[0100] In a preferred embodiment, the thickness of the biocompatible layer e can range from 1 μm or less to 100 μm or more. A more preferred thickness range is 10 μm to 30 μm.

[0101] In this embodiment of the invention, the thickness of the substrate 11 is 0.01~0.8mm, each electrode is rectangular, the width of each electrode is 0.01~1mm, and the area is 0.1~2mm². 2 .

[0102] In other embodiments of the present invention, a carbon nanotube layer is further provided on the surface of each electrode. Utilizing the unique mechanical strength, high specific surface area, rapid electron transfer effect, and chemical stability of carbon nanotubes, they are modified onto the surface of the formed electrode through physical adsorption, embedding, or covalent bonding to improve the electron transfer rate. Simultaneously, due to their large specific surface area, they can serve as an excellent catalyst (enzyme) carrier. The carbon nanotube layer can be fixed to the electrode surface using methods such as Nafion solution dispersion or covalent fixation.

[0103] Figure 4 This is a schematic diagram illustrating the functional implementation of an embodiment of the present invention.

[0104] After the sensor enters the host body, the internal circuitry applies voltage to the pins, activating the corresponding electrodes and putting them into operation. Generally, the effective working time after activation is 1-14 days. After 14 days, the enzyme activity on the electrodes decreases, and they enter a failure state. Additionally, electrode damage or manufacturing errors can also cause activated electrodes to fail prematurely. If the sensor has a single set of electrodes, once one electrode fails, the entire sensor fails, requiring replacement, which reduces user experience and increases costs. If the sensor has multiple sets of electrodes (e.g., two sets), once one electrode fails, the internal circuitry applies voltage to the pins of the corresponding electrodes in other electrode sets, activating them and putting them into operation, allowing the sensor to continue functioning normally.

[0105] Specifically, refer to the following: Figure 1 and Figure 2 After the sensor enters the host body, the working pin 1111, counter pin 1211, and reference pin 1311 on surface A are preferentially energized by the internal circuit, and the working electrode 1131, counter electrode 1231, and reference electrode 1331 on surface A enter the working state. If any one of the working electrode 1131, counter electrode 1231, and reference electrode 1331 fails prematurely or reaches the end of its lifespan, the internal circuit switches the pin to which voltage is applied. For example, if the working electrode 1131 fails prematurely, the internal circuit switches to apply voltage to the fourth pin 1112 on surface B, activating the working electrode 1132 on surface B. This electrode 1132 then combines with the still-functioning counter electrode 1231 and reference electrode 1331 to form a new electrode group for detecting the analyte. This avoids premature failure of sensor 11, eliminating the need for the user to replace the sensor due to premature failure of the working electrode 1131, thus enhancing the user experience and reducing the user's sensor replacement costs.

[0106] Those skilled in the art should understand that the above embodiments are not limited to the failure of the working electrode. Other electrodes, such as the counter electrode or the reference electrode, or two or three electrodes that fail simultaneously, can also use the method of replacing the failed electrode with an electrode of the same name as described in the above embodiments.

[0107] Alternatively, switching can be performed before the electrodes fail or reach the end of their lifespan, with a preset time t as the predetermined condition. For example, if an electrode fails after 14 days under normal operating conditions, and the preset time t is 2 days, after the first electrode group is powered on and operates for 2 days, power is switched to the second electrode group, activating it and the first electrode group enters a dormant state. After the second electrode group operates for 2 days, other electrode groups can be activated, and the first electrode group can be activated again. This cycle continues until all electrode groups reach the end of their lifespan and all fail. In this mode, the lifespans of multiple electrode groups are superimposed, thus extending the sensor's lifespan.

[0108] Those skilled in the art should understand that the preset time t can be any day within 14 days. If, due to improvements in the electrode's manufacturing process or other reasons, its service life is extended to n (n>14) days, the preset time t can be any day within n days.

[0109] Example 2

[0110] Stepped structure sensor

[0111] Figure 5 This is a top view of an embodiment of the present invention where the sensor has a stepped structure; Figure 6 for Figure 5 The sensor in this embodiment is a side view of a stepped structure.

[0112] The stepped sensor 21 includes surface A and surface B. Each surface is divided into an external portion X and an internal portion Y by the dashed line shown in the figure. The internal portion Y includes a first substrate 211, a second substrate 221, and a third substrate 231, which together form a stepped structure. The number and layers of the substrates are consistent with the number of electrodes on that surface. For example, when surface A is a three-electrode system, the substrate has a three-layer stepped structure; when surface A is a two-electrode system, the substrate has a two-layer stepped structure.

[0113] In this embodiment of the invention, the substrates at different levels are mutually insulated. Each electrode is electrically connected to its corresponding pin via wires distributed on a substrate (e.g., a third substrate). Specifically, a portion of the wire contacts the electrode, while the main body of the wire lies beneath the substrate, effectively protecting the wire portion. Furthermore, distributing the electrodes on different substrate levels increases the spacing between them, reducing the influence of the microenvironments on the electrode surfaces. The stepped electrode distribution also effectively suppresses interference from human body reactions on the electrode response. Additionally, distributing the electrodes on different planes, without changing the effective area of ​​each electrode, further reduces the overall width of the sensor. The width of the stepped structure sensor can be reduced by approximately half compared to a planar structure sensor.

[0114] Correspondingly, side B has a symmetrical stepped structure compared to side A. Pins are laid on the external part X, each pin corresponding to an electrode and electrically connected via wires. Specifically, the working pin 2111 corresponding to the working electrode 2131 is electrically connected via wire 2121; the counter pin 2211 corresponding to the counter electrode 2231 is electrically connected via wire 2221; and the reference pin 2311 corresponding to the reference electrode 2331 is electrically connected via wire 2321. Different pins, wires, and electrodes are insulated from each other to prevent crosstalk in the electrical signals.

[0115] The working electrode 2131, counter electrode 2231, and reference electrode 2331 are arranged as an electrode group on surface A of the sensor. Conversely, another electrode group is arranged on surface B of the sensor. This electrode group can be a dual-electrode system, a triple-electrode system, or a dual-working-electrode system. Preferably, it is consistent with the electrode group on surface A, including the working electrode 2132, counter electrode 2232, and reference electrode 2332. Similarly, pins are also arranged on surface B, each corresponding to an electrode on surface B and electrically connected via wires. Specifically, the fourth pin 2112 corresponding to the working electrode 2132 is electrically connected via wire 2122; the fifth pin 2212 corresponding to the counter electrode 2232 is electrically connected via wire 2222; and the sixth pin 2312 corresponding to the reference electrode 2332 is electrically connected via wire 2322. In this way, if any electrode on surface A reaches the end of its lifespan or fails prematurely, the corresponding electrode on surface B can take over and enter the working state, improving the reliability of the parameter data of the detected analyte and extending the sensor's lifespan.

[0116] Those skilled in the art should understand that the order and position of the pins, wires, and electrodes laid on both sides of the sensor (A and B) are not limited. The pins, wires, and electrodes on the two sides can be arranged symmetrically or asymmetrically. Corresponding pins, wires, and electrodes can be laid on the same side or on different sides. Preferably, corresponding pins, wires, and electrodes are laid on the same side to facilitate wire routing. For example, the working electrode 2131 on side A can be interchanged with the counter electrode 2231, or the counter electrode 2231 on side A can be interchanged with the reference electrode 2332 on side B. Regardless of the change in the order and position of the pins, wires, and electrodes on sides A and B, it is sufficient that the pins, wires, and electrodes have a one-to-one correspondence and are insulated from each other.

[0117] In other embodiments of the present invention, although the stepped structure sensor only has opposing A and B surfaces, the number of electrode groups can be increased by increasing the sensor area or decreasing the electrode area, thereby further increasing the sensor's lifespan. However, an excessively large sensor area may increase the host's rejection response, causing discomfort; an excessively small electrode area will reduce the electrode's sensitivity and decrease the reliability of the detection parameters. An excessive number of electrode groups will also increase the complexity of the manufacturing process, such as making the wiring very dense. Therefore, preferably, the number of electrode groups is two.

[0118] In other embodiments of the present invention, the various electrode groups may also be distributed on the same surface of the sensor, such as surface A or surface B, without limitation.

[0119] In this embodiment of the invention, the first substrate 211, the second substrate 221, and the third substrate 231 are materials with excellent insulating properties, mainly derived from inorganic non-metallic ceramics, silica glass, and organic polymers. Considering the application environment of implantable electrodes, the substrate materials are also required to have high water impermeability and mechanical strength. Preferably, the substrate material is selected from one or more combinations of polytetrafluoroethylene (Teflon), polyethylene (PE), polyvinyl chloride (PVC), acrylonitrile-butadiene-styrene copolymer (ABS), polymethyl methacrylate (PMMA), polycarbonate (PC), and polyimide (PI).

[0120] In one embodiment of the present invention, the working electrode (auxiliary electrode), the counter electrode, and the reference electrode include at least an electron conduction layer a', an anti-interference layer b', an enzyme layer c', a regulation layer d', and a biocompatibility layer e'. The properties of each layer and their related descriptions can be found in Example 1, and will not be repeated here.

[0121] Example 3

[0122] columnar structure sensor

[0123] Figure 7 This is a schematic diagram of a columnar structure for the sensor in an embodiment of the present invention; Figure 8 for Figure 7 The sensor in this embodiment is a V-V' cross-sectional view of a columnar structure.

[0124] The columnar sensor 31 is divided into an external portion X and an internal portion Y by the dashed line in the figure. The external portion X is planar or cylindrical, preferably planar. The internal portion Y includes the cylindrical substrate 311, with electrodes surrounding the surface of the substrate. Compared to planar electrodes, the annular electrodes do not have sharp edges, reducing irritation to human tissue and minimizing rejection reactions. This facilitates long-term implantable monitoring and improves the sensor's lifespan.

[0125] The in vivo portion Y includes at least one working electrode 3131 and at least one additional electrode. Specifically, in this embodiment, the additional electrode includes a counter electrode 3231 and a reference electrode 3331, thus forming a three-electrode system. The counter electrode 3231 is the opposite pole to the working electrode 3131, forming a closed circuit with the working electrode 3131, allowing normal current conduction on the electrode. The reference electrode 3331 provides a reference potential for the working electrode 3131, thereby effectively controlling the detection potential. In another embodiment of the invention, the additional electrode may also include only the counter electrode 3231, thus forming a two-electrode system. Compared to a three-electrode system, this increases the effective area of ​​the working electrode 3131 and the counter electrode 3231 within the limited area of ​​the in vivo portion Y, thereby extending the electrode's lifespan. Furthermore, because one electrode is removed, the manufacturing process is simpler. However, without the reference electrode's detection potential as a reference, the reliability of the analyte detection information will be reduced. In another embodiment of the present invention, there are two working electrodes 3131. One of them undergoes an electro-oxidation-reduction reaction with the analyte to be detected to generate an electrical signal, and the other is used to detect the response signal of interfering substances or background solution in the host body fluid. This electrode is an auxiliary electrode.

[0126] Continue to refer to Figure 7 The external part X is covered with pins, each corresponding to an electrode and electrically connected via wires. Specifically, the working pin 3111, corresponding to the working electrode 3131, is electrically connected via wire 3121; the counter pin 3211, corresponding to the counter electrode 3231, is electrically connected via wire 3221; and the reference pin 3311, corresponding to the reference electrode 3331, is electrically connected via wire 3321. The working electrode 3131, counter electrode 3231, and reference electrode 3331 form an electrode group. Different pins, wires, and electrodes are insulated from each other to prevent crosstalk in the electrical signals.

[0127] Each electrode is laid out in a semi-enclosed manner on the body portion Y, thus allowing for two electrodes at the same location to form an enclosed enclosure of the body portion Y. For details, please refer to the reference. Figure 8 At V-V' of the body part Y, the reference electrodes 3331 and 3332 are semi-circular rings with an inner diameter equal to the outer diameter of the body part Y and are in insulating contact with each other, thus maximizing the use of the surface area of ​​the body part Y.

[0128] In other embodiments of the present invention, the electrode that surrounds the reference electrode 3331 may be the working electrode 3131 or the counter electrode 3231 of the same electrode group, or it may be the working electrode (not shown in the figure) or the counter electrode (not shown in the figure) of another electrode group. In this way, if any electrode reaches the end of its life or fails prematurely, the corresponding electrode of the same name can take over and enter the working state, thereby improving the reliability of the parameter data of the detected analyte and extending the service life of the sensor.

[0129] Those skilled in the art should understand that the order and position of the pins, wires, and electrodes laid on the substrate 311 are not limited. The pins, wires, and electrodes can be arranged symmetrically or asymmetrically. Regardless of the order and position of the pins, wires, and electrodes, it is sufficient that the pins, wires, and electrodes have a one-to-one correspondence and are insulated from each other.

[0130] In other embodiments of the present invention, the number of electrode groups can be increased by increasing the sensor area or decreasing the electrode area, thereby further increasing the lifespan of the sensor. However, an excessively large sensor area may increase the host's rejection response and cause discomfort; an excessively small electrode area will reduce the sensitivity of the electrode and decrease the reliability of the detection parameters. Too many electrode groups will also increase the complexity of the manufacturing process, such as making the wiring very dense. Therefore, preferably, the number of electrode groups is two.

[0131] In this embodiment of the invention, the substrate 311 is a material with excellent insulating properties, mainly derived from inorganic non-metallic ceramics, silica glass, and organic polymers. Considering the application environment of implantable electrodes, the substrate material is also required to have high water impermeability and mechanical strength. Preferably, the substrate material is selected from one or more combinations of polytetrafluoroethylene (Teflon), polyethylene (PE), polyvinyl chloride (PVC), acrylonitrile-butadiene-styrene copolymer (ABS), polymethyl methacrylate (PMMA), polycarbonate (PC), and polyimide (PI).

[0132] In this embodiment of the invention, the outer diameter of the inner portion Y of the substrate 311 and the inner diameter of the electrode are 0.01~100 μm, preferably 10~50 μm. The electrode can be a semi-circular ring, a 1 / 3 circular ring, a 1 / 4 circular ring, or a ring of other proportions.

[0133] In one embodiment of the present invention, the working electrode (auxiliary electrode), the counter electrode, and the reference electrode include at least an electron conduction layer a'', an anti-interference layer b'', an enzyme layer c'', a regulation layer d'', and a biocompatibility layer e''. The properties of each layer and their related descriptions can be found in Example 1, and will not be repeated here.

[0134] Those skilled in the art will understand that the shape of the sensor body part Y is not necessarily limited to the shape of the three embodiments described above. For example, in other embodiments, it can be annular, semi-annular, conical, spiral, etc., and the shape of the electrodes arranged on it also varies based on the shape of the body part. As long as the electrodes can be easily laid on the body part, there is no limitation here.

[0135] Figure 9 This is a schematic diagram of a continuous analyte detection device 100 according to an embodiment of the present invention. The continuous analyte detection device 100 includes a base shell 101 for mounting on the surface of a host's skin; a sensor unit 102, which includes a base 1021 and a miniature analyte sensor 11 (21 / 31) as described above, the miniature analyte sensor 11 (21 / 31) being fixed on the base, and the sensor unit 102 being mounted on the base shell 101 via the base; a transmitter unit 103, which includes an internal circuit 1031, a transmitter 1032, and an electrical connection area 1033, the electrical connection area 1033 being electrically connected to the sensor unit 102, the internal circuit 1031 storing predetermined conditions for switching electrodes as described above, and the transmitter 1032 for transmitting analyte parameter information to the outside world; a battery 104 for providing electrical energy; and a receiver 105 for receiving analyte parameter information and providing instructions to the user.

[0136] Figures 10a-10o The diagram shows different sensor schemes in embodiments of the present invention.

[0137] Reference Figure 10a To facilitate and clearly demonstrate the structural features of sensor 41, Figure 10a The length, width, thickness, and curve characteristics of the sensor are exaggerated in the illustration. The actual length, width, thickness, and curve characteristics of the sensor may differ from those shown in the illustration.

[0138] In the other illustrations in this article, the length, width, thickness, and curve features of the sensor are also expressed in an exaggerated manner. The actual length, width, thickness, and curve features of the sensor may differ from those shown in the illustrations, which will not be elaborated on below.

[0139] Similarly, the wires, pins, and electrodes described above and below are also exaggerated in the illustrations. The wires, pins, and electrodes in the illustrations are only auxiliary examples to illustrate the solution of the present invention and are not entirely equivalent to the wires, pins, and electrodes in actual sensors. For example, the wires in actual sensors are flat wires with a certain width, while they are shown as lines in the illustrations.

[0140] In some embodiments of the present invention, the substrate 411 of the sensor 41 is generally made of a flexible material, such as one or more combinations selected from polytetrafluoroethylene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polymethyl methacrylate, polycarbonate, and polyimide. These materials possess good electrical insulation properties, allowing electrodes and wires disposed thereon to insulate each other. In a preferred embodiment of the present invention, the substrate 411 is made of polyimide, which has good biocompatibility and will not cause excessive rejection when inserted subcutaneously.

[0141] In some embodiments of the present invention, after the sensor 41 is inserted subcutaneously, the base 411 is generally soft to adapt to the repeated peristalsis of the muscle. However, the soft base is repeatedly bent or flexed during the repeated peristalsis of the muscle, which can cause the base 411 to reach its fatigue limit prematurely (before reaching the designed service life of the sensor 41, such as 14 days), leading to damage or even breakage. This can expose the electrodes and wires on the base 411, causing short circuits, or cause them to break and be damaged, affecting the detection reliability of the sensor 41. To improve the detection reliability of the sensor 41, the mechanical strength of the base 411 needs to be strengthened to extend the time before the base 411 reaches its fatigue limit and meet the designed service life of the sensor 41.

[0142] In some embodiments of the present invention, insulating material for enhancing the mechanical strength of the substrate 411 may be subsequently applied to certain areas of the substrate 411. Here, "subsequent application" means that after the sensor 41 is fabricated, i.e., after the electrodes, pins, and wires are set on the substrate to form a complete sensor 41, at least one layer of insulating material is then applied to the substrate 411. Obviously, by adding insulating material, the mechanical strength of the substrate 411 in the corresponding areas will be improved, and the time it takes to reach its ultimate stress fatigue limit will also be extended.

[0143] In some embodiments of the present invention, the number of insulating material layers subsequently applied to the substrate 411 can be multiple, such as two, three, or more layers, which can further increase the mechanical strength of the substrate 411. However, applying multiple layers of insulating material will cause the substrate in the corresponding area to become less flexible, increasing user discomfort after insertion under the skin. Similarly, a thicker insulating material can also increase the mechanical strength of the substrate 411, but excessively thick insulating material will also cause the substrate in the corresponding area to become less flexible, increasing user discomfort after insertion under the skin. Therefore, it is necessary to control the number and thickness of the insulating material layers.

[0144] In a preferred embodiment of the present invention, the number of insulating material layers is 1 to 10, and the thickness of each layer is 0.1 μm to 200 μm.

[0145] In a preferred embodiment of the present invention, the insulating material has one layer with a thickness of 25 μm. During the processing of the sensor 41, setting multiple layers of insulating material would increase the complexity of the processing. Therefore, setting one layer of insulating material can enhance the mechanical strength of the substrate 411 without causing an overly complicated processing process. Setting its thickness to 25 μm can keep the substrate 411 sufficiently soft and will not cause additional discomfort to the user after the substrate is inserted under the user's skin.

[0146] In some embodiments of the present invention, the insulating material may be one or more of the following: polytetrafluoroethylene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polymethyl methacrylate, polycarbonate, and polyimide. The properties of these materials have been described above and will not be repeated here. Preferably, the insulating material is polyimide, which is consistent with the material of the substrate 411 and has the same physical properties. When stretching, shrinking, or bending occurs, the insulating material of the same material and the substrate 411 have the same stretching, shrinking, or bending scale, and the insulating material will not wrinkle or fall off on the substrate 411 due to different scales.

[0147] In some embodiments of the present invention, the insulating material can be applied to the substrate 411 by coating. When the insulating material is polyimide, the polyimide can be heated to a liquid state before being coated onto the substrate 411.

[0148] In other embodiments of the present invention, the insulating material can be attached to the substrate 411 by means of adhesive. When the insulating material is polyimide, a polyimide precursor can be used as the adhesive material. After the polyimide precursor is cured, its physical properties are basically consistent with those of polyimide. It has consistency in stretching, shrinking and bending, and will not cause the insulating material to bulge, wrinkle or fall off on the substrate 411 due to stress concentration or uneven stress, thereby improving the yield of the sensor.

[0149] In the process of applying insulating material onto the substrate 411 by coating or pasting, it is necessary to ensure that the electrodes, pins and wires on the substrate 411 have good electrical connections and that there is good insulation between electrodes, pins and pins, and wires and wires in order to effectively realize the sensor function.

[0150] In some embodiments of the present invention, when the insulating material is disposed on the substrate 411, it should avoid the central conductive area of ​​the pins and electrodes; otherwise, the function of the sensor 41 will not be realized.

[0151] In some embodiments of the present invention, the area where the insulating material is subsequently provided includes at least one of the pin reverse side region 412 of the pin region a or the electrode reverse side region 413 of the electrode region b. Preferably, both the pin reverse side region 412 and the electrode reverse side region 413 are provided with insulating material.

[0152] In other embodiments of the present invention, the area where the insulating material is subsequently applied may also include the area near the electrodes and pins, avoiding the central conductive area of ​​the electrodes and pins. In this case, the insulating material can cover the edges of the electrodes and pins, increasing the adhesion between the electrodes and pins and the substrate, preventing the edges of the electrodes and pins from warping, and further preventing the electrodes and pins from breaking or even falling off.

[0153] In some embodiments of the present invention, the pin reverse region 412 and the electrode reverse region 413 can be as follows: Figure 10a The two independent regions shown can be connected into one continuous region in other embodiments of the present invention, where the pin reverse region 412 and the electrode reverse region 413 are connected.

[0154] In other embodiments of the invention, the sensor 41 may be installed in a bent form within the analyte detection device, i.e., the external portion X is bent or flexed relative to the internal portion Y, or the internal portion Y is bent or flexed relative to the external portion X. Since the external portion X is fixed within the analyte detection device, while the external portion Y is inserted subcutaneously and moves with the user's muscle contractions, the internal portion Y is also frequently and repeatedly bent or flexed relative to the external portion X. Therefore, it is necessary to provide insulating material behind the bending front area 414 of the bending area c of the internal portion Y relative to the external portion X. Providing insulating material behind the bending front area 414 can increase the mechanical strength of the substrate in the corresponding area and also cover the wires in the corresponding area, providing additional insulation and protection for the wires.

[0155] In some embodiments of the present invention, the sensor 41 employs a three-electrode system, including a working electrode 4141, a counter electrode 4241, and a reference electrode 4341, with corresponding working pins 4111, counter pins, and reference pins 4311, and wires 4121 / 4221 / 4321 connecting each pin and electrode. In other embodiments of the present invention, the sensor 41 may also employ a two-electrode system, which does not include the reference electrode 4341 and its corresponding pins and wires. This is common knowledge in the art and will not be described in detail here.

[0156] In some embodiments of the present invention, the wires 4121 / 4221 / 4321 can be disposed on the surface or inner layer of the substrate 411 by processes such as etching or laser welding. When the wires 4121 / 4221 / 4321 are disposed on the inner layer of the substrate 411, and are electrically connected to the pins or electrodes disposed on the surface of the substrate 411, holes 4141 / 4241 / 4341 are opened at the corresponding positions of the electrical connection on the substrate 411. The electrical connection ends of the wires 4121 / 4221 / 4321 are led out to the surface of the substrate 411 through the holes 4141 / 4241 / 4341, and are electrically connected to the electrodes 4131 / 4231 / 4331 respectively. Similarly, the other end of the wires 4121 / 4221 / 4321 is electrically connected to the pins 4111 / 4211 / 4311 through a hole (not shown in the figure). When conductors 4121 / 4221 / 4321 are placed in the inner layer of substrate 411, substrate 411 can provide insulation protection for each conductor, avoiding short circuits between conductors that could cause signal loss or instability, but the manufacturing process is relatively complex.

[0157] In some embodiments of the present invention, the substrate 411 is as follows: Figure 10a The single-layer plane shown.

[0158] In other embodiments of the present invention, the substrate 411 may also be as follows: Figure 10bThe multi-layered plane is shown. The substrate 411 can be composed of multiple sub-substrates, such as a first substrate 411d, a second substrate 411e, and / or a third substrate 411f, etc. Each layer of substrate 411d / 411e / 411f can be provided with at least one electrode and at least one wire. By setting the electrodes 4131 / 4231 / 4331 on different layers of sub-substrates 411d / 411e / 411f, firstly, the distance between the electrodes can be increased, the signal crosstalk between the electrodes can be reduced, and the detection reliability can be improved; secondly, the electrodes on each layer of substrate can be set with a larger area, and the larger area electrodes have more sufficient contact with the body fluid, the signal is more stable, and the detection reliability is improved; thirdly, since the electrodes are set on different layers of sub-substrates, the wires 4121 / 4221 / 4321 electrically connected to the electrodes can also be run on different sub-substrates, so the sub-substrates can also carry the wires 4121 / 4221 / 4321. Electrical insulation is provided between 21 / 4321 layers. Based on this, conductors 4121 / 4221 / 4321 can be routed on the surface of each layer of substrate 411d / 411e / 411f, simplifying the conductor processing technology. Fourthly, although conductors 4121 / 4221 / 4321 can be routed on the surface of sub-substrates 411d / 411e / 411f in different layers, if a layer of substrate is damaged, conductors in adjacent layers may come into contact and short-circuit. Therefore, when laying conductors 4121 / 4221 / 4321 on sub-substrates 411d / 411e / 411f, conductors 4121 / 4221 / 4321 can be routed in the following manner: Figure 10b The conductors are staggered as shown in the top view, forming a stepped distribution. Even if a layer of the substrate is damaged, the conductors of adjacent layers will not come into contact and short-circuit, thus improving the reliability of the test. Fifthly, the substrate composed of multiple layers has higher mechanical strength than a single-layer substrate, making it less prone to breakage or damage, thus extending the testing time and improving the reliability of the test.

[0159] The arrangement of the electrodes on the sub-substrate is not fixed. In some embodiments of the present invention, such as... Figure 10b The reference electrode 4331 can be disposed on the top sub-substrate 411f. The reference electrode 4331 is more expensive than the working electrode 4131 and the counter electrode 4231. Being disposed on the top sub-substrate 411f, the reference electrode 4331 is fabricated in the final process, protecting it from damage. In other embodiments of the invention, the reference electrode 4331 can also be disposed on the bottom sub-substrate 411d. The reference electrode 4331 is thicker than the working electrode and the counter electrode 4231. Being disposed on the bottom sub-substrate 411d improves the thickness uniformity of the sensor 41, preventing excessive thickness differences and facilitating the storage and use of the sensor 41. Figure 10bThe thickness of the sub-substrate 411d / 411e / 411f and electrodes 4131 / 4231 / 4331 in each layer is expressed in an exaggerated form. Understandably, this does not affect the description of this scheme.

[0160] In some embodiments of the present invention, the sub-substrates 411d / 411e / 411f of each layer can be prepared layer by layer. That is, after the bottom layer substrate 411d is prepared, the middle layer substrate 411e is prepared on the basis of the bottom layer substrate 411d. Similarly, after the middle layer substrate 411e is prepared, the top layer substrate 411f is prepared. In the conventional manufacturing process, when preparing each layer of substrate, the substrate material, such as polyimide, is heated and coated layer by layer onto the mold. After curing, a complete sub-substrate is formed. However, during the curing process, there may be some areas where the material is not fully cured, or the degree of curing of the substrate material on different parts of the sub-substrate may be inconsistent, or the degree of curing of the substrate material on different layers of the sub-substrate may be inconsistent. This can lead to the substrate becoming brittle during subsequent use. This can cause the electrodes, wires, and pins on the substrate to short-circuit with each other, or even be damaged, affecting the detection reliability of the sensor.

[0161] refer to Figure 10c To address the existing problem of potential brittle fracture failure of the substrate, in some embodiments of the present invention, the sub-substrates 411d / 411e / 411f of each layer can be prefabricated. Prefabrication here refers to fully curing the substrate material of each layer of substrate 411d / 411e / 411f before processing electrodes, wires, or pins on the substrate. Depending on the design requirements of the sensor 41, the electrodes, wires, or pins on each layer of substrate may be the same or different. After prefabrication, the sub-substrates 411d / 411e / 411f of each layer are then assembled into a whole by bonding. For example, when the material of the sub-substrates 411d / 411e / 411f is selected as polyimide, a polyimide precursor can be used to bond the layers of substrate 411d / 411e / 411f together to obtain a complete sensor substrate. Since the substrates 411d / 411e / 411f are fully cured before being bonded together, this avoids the brittleness problem caused by insufficient curing of materials within the same substrate layer, as well as the brittleness problem caused by insufficient curing of materials between different sub-substrates, thus improving the detection reliability of the sensor. Furthermore, since the substrates 411d / 411e / 411f can be prefabricated independently and then assembled into a whole, the manufacturing efficiency of the sensor 41 can be increased during the manufacturing process.

[0162] It is worth noting that, in some embodiments of the present invention, on the top sub-substrate 4111 / 4211 / 4311 corresponding to each electrode 4131 / 4231 / 4331 needs to be prefabricated to ensure the complete function of the sensor 41. After the sub-substrates 411d / 411e / 411f of each layer are pasted, the wires on the sub-substrates 411d / 411e are led to the top sub-substrate 411f by drilling holes to establish an electrical connection with the pins located on the sub-substrate 411f.

[0163] In some embodiments of the present invention, the thickness of each layer of substrate 411d / 411e / 411f can be 0.1~200um, relative to Figure 10a The single-layer substrate design shown has a slightly thinner thickness for each layer of substrate 411d / 411e / 411f. Otherwise, the combined thickness of several layers would be too large, lacking sufficient flexibility and increasing user discomfort when inserted under the skin. Therefore, preferably, the thickness of each layer of substrate 411d / 411e / 411f is 0.1~200um. More preferably, the thickness of each layer of substrate 411d / 411e / 411f is approximately 10um, resulting in a combined thickness of approximately 25~35um. This thickness is such that it is neither too thin, making it prone to breakage or fracture, nor too thick, increasing user discomfort. Those skilled in the art will understand that the actual thickness of each sub-substrate 411d / 411e / 411f may vary due to manufacturing process errors.

[0164] In some embodiments of the present invention, the material of each layer of substrate 411d / 411e / 411f is preferably polyimide. In order to bond each layer of substrate 411d / 411e / 411f into a whole, the bonding material is preferably a polyimide precursor. After the polyimide precursor is cured, it can maintain the consistency of physical properties with the polyimide. This bonding method can prevent the layers of substrate 411d / 411e / 411f from peeling or even falling off due to stress concentration or uneven stress.

[0165] In some embodiments of the present invention, after the various layers of substrate 411d / 411e / 411f are combined to form a whole, insulating material can still be provided on the substrate surface to further enhance its mechanical strength. (Refer to the reference...) Figure 10a and Figure 10b Similarly, the areas where insulating material can be provided include the pin reverse side region 412 of pin region a, the electrode reverse side region 413 of electrode region b, and the bending front region of bending region c. In other embodiments of the present invention, the insulating material located in the pin reverse side region 412 and the electrode reverse side region 413 of electrode region b can be connected into one continuous area. In the embodiments of the present invention, the thickness and number of layers of insulating material are set in the same way as above, and will not be repeated here.

[0166] Reference Figure 10d In some embodiments of the present invention, at least one electrode may be disposed on the reverse side B of the substrate 411. In this case, a front electrode region 415 will be left unused on the front side A of the substrate 411. An insulating material may also be disposed on this region to improve the mechanical strength of the front electrode region 415. Correspondingly, the electrode disposed on the reverse side B of the substrate 411 will occupy a region, and the insulating material needs to avoid this region, forming a shape such as... Figure 10d The electrode reverse side region 413 is shown. The electrode reverse side region 413 may be a region that is broken in the middle and has an electrode, or it may be a continuous region with an electrode located on the side of this region (not shown in the figure). A continuous insulating material can reduce the number of manufacturing steps.

[0167] In some embodiments of the present invention, the electrode disposed on the reverse side of the substrate 411 may be a counter electrode 4231. Disposing the counter electrode 4231 on the reverse side of the substrate 411 can, on the one hand, increase the relative distance between the counter electrode 4231 and the working electrode 4131, reducing current crosstalk between the counter electrode 4231 and the working electrode 4131, and reducing noise; on the other hand, the area of ​​the counter electrode 4231 can be maximized, thereby reducing electrochemical polarization and improving the accuracy and sensitivity of the detection signal.

[0168] In some other embodiments of the present invention, the electrode disposed on the reverse side of the substrate 411 may be a reference electrode 4331. Disposing the reference electrode 4331 on the reverse side of the substrate 411 has two advantages: firstly, the reference electrode 4331 can be prepared separately during manufacturing without affecting the working electrode 4131 and the counter electrode 4231, thus improving the yield of the finished product; secondly, it can reduce the circuit risk caused by the migration of Ag / Cl substances from the reference electrode 4331, thereby improving the reliability of detection.

[0169] In some other embodiments of the present invention, the electrode disposed on the reverse side of the substrate 411 can be a working electrode 4131. By disposing the working electrode 4131 on the reverse side of the substrate 411, if a short circuit occurs between the counter electrode 4231 and the reference electrode 4331, the three-electrode system becomes a two-electrode system, which will not affect the detection current and the detection signal will not change abruptly, thus improving detection stability.

[0170] Reference Figure 10eIn some embodiments of the present invention, since the electrodes are respectively disposed on the front and back surfaces of the substrate 411, both the front and back surfaces of the substrate 411 need to be processed to set the electrodes, wires, etc. During the processing, damage to the other side is inevitable. Based on this, the front and back surfaces of the substrate 411 can be processed separately, that is, the front surface A and the back surface B of the substrate 411 can be processed separately, and then the front surface A and the back surface B can be assembled into a whole to form a complete sensor, which can improve the integrity of the double-sided substrate.

[0171] In some embodiments of the present invention, electrodes, wires, and pins are processed on the substrate 411a of the front side A, and electrodes and wires are processed on the substrate 411b of the back side B. The positions of the electrodes, wires, and pins on the substrates 411a and 411b are not limited. To enhance the mechanical strength of the substrates 411a and 411b, an insulating material can be processed after the electrodes, wires, and pins are processed. The position of the insulating material can be as described above, avoiding the pin area and electrode area.

[0172] In some embodiments of the present invention, substrates 411a and 411b can be combined into a whole by adhesive bonding. For example, both substrates 411a and 411b are made of polyimide, and a polyimide precursor material is used to bond substrates 411a and 411b together. Related technical details can be found in [reference needed]. Figure 10c And its description.

[0173] Although the mechanical strength of the substrate 411 can be enhanced by setting insulating material on the substrate 411, thereby reducing the possibility of the electrode being damaged, in actual use, due to reasons such as increased user movement, the degree and number of times the substrate 411 is repeatedly bent or flexed may exceed expectations, and the electrode may still be damaged as a result. Therefore, some necessary measures can be taken to prevent the electrode from being damaged.

[0174] refer to Figure 10fIn some embodiments of the present invention, replacing the monolithic electrode with an array of smaller electrode units can prevent the monolithic electrode from being damaged and improve the detection reliability of the sensor. For example, the original working electrode 4131 can be cut into smaller working electrode units 4131a, and then the working electrode units 4131a can be assembled into an array to form a working electrode array. Each unit in the working electrode array works together to realize the detection function of the working electrode 4131, and its function is almost the same as that of the original working electrode 4131. All working electrode units 4131a are laid on the wire 4121, and the current of each working electrode unit 4131a during the detection of the analyte is transmitted through the wire 4121. After the monolithic electrode is made into an array of electrode units, even if the substrate 411 is repeatedly bent by the user's muscles, the array of electrode units can be bent or flexed to a certain extent without breaking and losing its detection performance, thus improving the detection reliability. Figure 10f This is only a schematic representation of the technical solution and does not actually represent the relative dimensions and relative positional relationships of the structure.

[0175] In some embodiments of the present invention, since the electron conduction layer is a hard layer and the other structural layers are soft layers, when the working electrode 4131 is damaged due to bending, it is highly likely that the electron conduction layer is bent and broken. Therefore, the working electrode unit 4131a can be made into a smaller electron conduction layer unit by making the original whole electron conduction layer. These electron conduction layer units share the anti-interference layer, enzyme layer, regulation layer and biocompatibility layer.

[0176] In other embodiments of the present invention, each working electrode unit 4131a can independently realize the detection function, that is, each working electrode unit 4131a includes an independent electron conduction layer, an anti-interference layer, an enzyme layer, a regulation layer and a biocompatibility layer.

[0177] In some embodiments of the present invention, the electrode unit is as follows: Figure 10f The cubic structure shown has dimensions of approximately 10-100 μm in length (L), approximately 1-50 μm in width (K), and approximately 0.05-10 μm in thickness (H), with adjacent electrode units arranged at a spacing of 1-20 μm.

[0178] In some embodiments of the present invention, each electrode may contain 10 to 500 electrode units, depending on the area of ​​the electrode, the area of ​​a single electrode unit, and the spacing between the electrode units. The specific number of electrode units in each electrode is not particularly limited herein.

[0179] In some embodiments of the present invention, the area of ​​each electrode in the sensor 41 is different, and there are different numbers of electrode units in the working electrode array, the counter electrode array and the reference electrode array. For example, the working electrode array may have 25 to 120 working electrode units, the counter electrode array may have 50 to 150 counter electrode units, and the reference electrode array may have 15 to 75 reference electrode units.

[0180] In other embodiments of the present invention, the electrode unit may be other three-dimensional structures, such as cylindrical structures, prism structures, conical structures, etc.

[0181] In a preferred embodiment of the present invention, the length * width * thickness of the electrode unit is 50um * 30um * 0.2um, the working electrode array has 75 working electrode units 4131, the counter electrode array has 110 counter electrode units 4231, and the reference electrode array has 35 reference electrode units 4331. The spacing between each electrode unit is 10um. If a more advanced laser etching process is used, the area of ​​the electrode unit and the spacing between the electrode units can be made smaller, thus reducing the possibility of electrode unit damage and improving detection performance.

[0182] In some embodiments of the present invention, after the various electrode units are assembled into an electrode array, the approximate dimensions of each electrode array are as follows: the length * width * thickness of the working electrode array is 1.08mm * 0.18mm * 0.2um, the length * width * thickness of the counter electrode array is 1.52mm * 0.18mm * 0.2um, and the length * width * thickness of the reference electrode array is 0.51mm * 0.18mm * 0.2um.

[0183] In some embodiments of the present invention, after the whole electrode is changed into an array of electrode units, insulating material to enhance the mechanical strength of the substrate can still be provided in the corresponding area on the substrate 411. The setting method and setting area have been described in detail above and will not be repeated here.

[0184] In some embodiments of the present invention, the electrode unit array may refer to Figure 10b As shown, the substrate 411 may include a multi-layered substrate, with the electrode unit arrays respectively disposed on sub-substrates of different layers. In some embodiments of the present invention, when the electrode unit arrays are respectively disposed on sub-substrates of different layers, reference can also be made to... Figure 10c As shown, the substrates at each level can be prefabricated and then assembled into a whole. In some embodiments of the present invention, the electrode unit array can refer to... Figure 10d As shown, the electrode unit array is respectively disposed on the front side A and the back side B of the substrate 411. In some other embodiments of the present invention, when the electrode unit array is disposed on the front side A and the back side B of the substrate 411, reference can also be made to... Figure 10eAs shown, the front base 411a and the back base 411b are prefabricated and then assembled into a whole.

[0185] Reference Figure 10g In some embodiments of the present invention, since the depth to which the base 411 penetrates the user's subcutaneous tissue is fixed, the area where the base 411 repeatedly bends with muscle peristalsis is also fixed, or the area on the base 411 with a larger bending amplitude and frequency is fixed, for example... Figure 10g The easily bendable region 416 in the substrate 411. Generally, the easily bendable region 416 on the substrate 411 will reach the limit fatigue and fail first compared to other regions. Therefore, the electrodes located on the substrate 411 can be distributed in a predetermined manner to avoid the easily bendable region 416, thereby preventing the electrodes from being damaged.

[0186] In some embodiments of the present invention, the bendable region 416 is not limited to... Figure 10g The area 416 shown may be a single bendable area, and there may be multiple bendable areas. This is mainly determined by the material of the base 411 and the depth of insertion under the skin. It is also related to the position of the base under the user's skin, the user's movement pattern, and the thickness of the base. In general, for the same base material and insertion depth, the areas with larger bending amplitude on the base 411 are fixed. These bendable areas should be avoided when setting the electrodes.

[0187] In some embodiments of the present invention, the bendable region 416 is the middle section of the internal portion Y. For example, when the internal portion Y is inserted subcutaneously to a depth of 5 mm, the bendable region 416 is approximately 2.5 mm from the end of the base 411. In some embodiments of the present invention, the bendable region 416 may be 2.1 to 2.8 mm from the end of the internal portion Y. The above values ​​are for illustrative purposes only.

[0188] In some embodiments of the present invention, when the substrate 411 includes a multi-layered substrate or a double-sided substrate, there may be some easily bendable areas. When setting the electrodes, these easily bendable areas are avoided. In some embodiments of the present invention, when at least one electrode is set on the reverse side of the substrate 411, the electrode set on the reverse side of the substrate 411 also avoids these easily bendable areas.

[0189] In some embodiments of the present invention, while the electrode avoids the easily bendable region 416, an insulating material that enhances the mechanical strength of the substrate can still be provided in the corresponding region on the substrate 411. The method and region of provision have been described in detail above and will not be repeated here.

[0190] Reference Figure 10h and Figure 10iIn some embodiments of the present invention, the pins 4111 / 4211 / 4311 corresponding to the electrodes 4131 / 4231 / 4331 may be disposed on the reverse side B of the substrate 411, while the electrodes 4131 / 4231 / 4331 are still disposed on the front side A of the substrate 411; or the pins 4111 / 4211 / 4311 are disposed on the front side A of the substrate 411, while the electrodes 4131 / 4231 / 4331 are disposed on the reverse side B of the substrate 411. That is, electrodes 4131 / 4231 / 4331 and pins 4111 / 4211 / 4311 are respectively disposed on opposite surfaces of substrate 411. Compared to electrodes 4131 / 4231 / 4331 and pins 4111 / 4211 / 4311 being disposed on the same surface of substrate 411, the external portion X of sensor 41 may have different bending directions relative to the internal portion Y during use. Based on this, the placement of insulating material on substrate 411 needs to be changed. For example, when pins 4111 / 4211 / 4311 are disposed on the reverse side B of substrate 411, the external portion X bends clockwise relative to the internal portion Y. This bending method requires sensor 41 to be installed in the analyte detection device in an inverted manner. For details on the technical solution and application of the inverted sensor 41, please refer to the published patent PCT / CN2022 / 080845, which will not be elaborated here.

[0191] In some embodiments of the present invention, insulating material is also provided in one of the pin reverse side region 412 of pin region a or the electrode reverse side region 413 of electrode region b. Preferably, both pin reverse side region 412 and electrode reverse side region 413 are provided with insulating material. Unlike the previous description, pin reverse side region 412 is located on the front side A of substrate 411.

[0192] Reference Figure 10h In some embodiments of the present invention, the external portion X is bent clockwise relative to the internal portion Y, and an insulating material may also be provided in the reverse side region 414 of the bending region c. In embodiments of the present invention, the bending front region 414 may be connected with the electrode reverse side region 413 to form a continuous region (not shown in the figure).

[0193] Reference Figure 10i In other embodiments of the present invention, the external portion X is bent counterclockwise relative to the internal portion Y, and an insulating material may also be provided on the front bending region 414 of the bending region c. In embodiments of the present invention, the front bending region 414 may be connected with the back pin region 412 to form a continuous region (not shown in the figure).

[0194] Reference Figure 10jIn some embodiments of the present invention, not all pins are located on the front A or back B of the substrate 411. Instead, some pins are located on the front A of the substrate 411, while the remaining pins are located on the back B of the substrate 411. On the one hand, this reduces the number of pins on a single surface of the substrate 411, thereby increasing the area of ​​a single pin. Pins with larger areas can be better electrically connected to the circuit, improving the detection reliability of the sensor. On the other hand, if an electrode is located on the back B of the substrate 411, the pin corresponding to this electrode should also be located on the back B of the substrate 411 so that the wires can be routed on the back B of the substrate 411.

[0195] In some embodiments of the present invention, if the pins are located on opposite surfaces of the substrate 411, the circuit needs to design electrical connection areas for the pins on both surfaces of the substrate 411, which will increase the complexity of the circuit. Therefore, although some pins are located on the reverse side B (front side A) of the substrate 411, the pins on the reverse side B (front side A) can still be guided to the front side A (reverse side B) of the substrate 411 and connected to the circuit together with other pins located on the front side A (reverse side B), thus simplifying the complexity of the circuit.

[0196] In some embodiments of the present invention, Figure 10j For example, the counter pin 4211 corresponding to the counter electrode 4231 and the reference pin 4311 corresponding to the reference electrode 4331 are disposed on the front side A of the substrate 411, while the working pin 4111 corresponding to the working electrode 4131 is disposed on the back side B of the substrate 411. In addition, a first pin 4111' corresponding to the working pin 4111 is also disposed on the front side A of the substrate 411. The first pin 4111' is connected to the circuit instead of the working pin 4111 to simplify the complexity of the circuit. Alternatively, the working pin 4111 and the first pin 4111' can be connected to the circuit at the same time to improve the reliability of the electrical connection between the pin and the circuit.

[0197] In some embodiments of the present invention, when the first pin 4111' is electrically connected to the circuit, the working pin 4111 needs to establish an electrical connection with the first pin 4111' in order to connect the working electrode 4131 to the circuit. In a general approach, a hole (not shown in the figure) is drilled in the area covered by both the first pin 4111' and the working pin 4111 on the substrate 411, and conductive material is coated or sprayed into the hole to establish an electrical connection between the first pin 4111' and the working pin 4111. However, this process requires the first pin 4111' and the working pin 4111 to be aligned on the substrate 411, and at least a portion of the first pin 4111' and the working pin 4111 overlaps on the substrate 411. Otherwise, the conductive material in the hole cannot simultaneously contact the first pin 4111' and the working pin 4111, resulting in the failure of the sensor 41 fabrication, which is common in the manufacturing process of the sensor 41.

[0198] To address the aforementioned issues, in some embodiments of the present invention, a conductive material 4111'' is disposed on the surface of the substrate 411 to establish an electrical connection between the primary pin 4111' and the working pin 4111, eliminating the need for drilling holes in the substrate 411. Specifically, the conductive material 4111'' is disposed on the front side A, back side B, and sides of the substrate 411 through processes such as coating or spraying. The conductive materials 4111'' on the front side A and back side B are connected by the sides of the substrate 411. The conductive material 4111'' on the front side A is electrically connected to the primary pin 4111', and the conductive material 4111'' on the back side B is electrically connected to the working pin 4111. In this way, an electrical connection is established between the primary pin 4111' and the working pin 4111. In this solution, the primary pin 4111' and the working pin 4111 do not need to be aligned during processing, simplifying the manufacturing difficulty of the sensor 41 and improving the manufacturing yield of the sensor 41.

[0199] In some embodiments of the present invention, the conductive material 4111'' located on the front side A of the substrate 411 and the conductive material 4111'' located on the back side B are connected by the "side" of the substrate 411, where "side" refers to any edge of the substrate 411.

[0200] In some embodiments of the present invention, the conductive material 4111'' can be some common solder, such as solder, or some conductive metal or alloy, such as copper-zinc alloy, platinum, etc.

[0201] In some embodiments of the present invention, since pins are provided on both the front side A and the back side B of the substrate 411, the pin area a may not be provided with insulating material, or as... Figure 10j The area 412 shown is a small area of ​​insulating material. Insulating material can also be provided on the reverse side of the electrode 413 and the bent front side 414.

[0202] Reference Figure 10k In some embodiments of the present invention, when the pins are located on opposite surfaces of the substrate 411, the front surface A and the back surface B of the substrate 411 can be prefabricated and then assembled into a whole. Specifically, the specific fabrication scheme for the front surface A of the substrate 411 has been described in detail above and will not be repeated here.

[0203] Reference Figure 10l In some embodiments of the present invention, before the insulating material is provided on the substrate 411, a protective layer 417 may be provided on the substrate 411. The protective layer 417 covers the entire substrate 411, but exposes the central area of ​​the pins 4111 / 4211 / 4311 and the electrodes 4131 / 4231 / 4331 and covers the edges of the pins 4111 / 4211 / 4311 and the electrodes 4131 / 4231 / 4331. Firstly, the protective layer 417 enhances the mechanical strength of the substrate 411 and prolongs the time before the substrate 411 is damaged. Secondly, the protective layer 417 covers the edges of the pins 4111 / 4211 / 4311 and the electrodes 4131 / 4231 / 4331, preventing irregular edges from being exposed and causing signal noise, thus improving the stability of the detection signal. Thirdly, the electronic conduction layer a of the electrodes 4131 / 4231 / 4331 is fixed on the substrate 411. Due to repeated bending of the substrate 411 during use, the metal film of the electronic conduction layer a inevitably detaches from the substrate 411, resulting in warping, bubbling, or even detachment. After setting the protective layer 417, the protective layer 417 can also enhance the adhesion between the metal film of the electronic conduction layer a and the substrate 411, preventing the metal film from warping or bubbling, thus improving the reliability of the sensor.

[0204] In some embodiments of the present invention, the protective layer 417 has a thickness greater than that of the electrodes 4131 / 4231 / 4331, for example, 1~25 μm. After coating with the protective layer 417, a pit is formed on the electrodes 4131 / 4231 / 4331. The anti-interference layer, enzyme layer, regulating layer, and biocompatible layer of the electrodes 4131 / 4231 / 4331 are located in the pit. The pit can accommodate a larger volume of the anti-interference layer, enzyme layer, regulating layer, and biocompatible layer, thereby improving the sensitivity of the electrodes 4131 / 4231 / 4331. In a preferred embodiment of the present invention, the thickness of the protective layer 417 is 0.1~200 μm. In a further preferred embodiment of the present invention, the thickness of the protective layer 417 is 1~20 μm. An excessively thick protective layer 417 will reduce the softness of the substrate 411, increasing user discomfort after insertion under the skin, while an excessively thin protective layer 417 is easily damaged.

[0205] In some embodiments of the present invention, the protective layer 417 is made of one or more of the following materials: polytetrafluoroethylene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polymethyl methacrylate, polycarbonate, and polyimide.

[0206] In some embodiments of the present invention, the protective layer 417 is made of polyimide. The polyimide is heated appropriately to form a liquid, which is then coated onto a substrate 411, which is also made of polyimide. After curing, the protective layer 417 is formed. The protective layer 417 and the substrate 411, being of the same material, have consistent physical properties, which can prevent uneven stress or stress concentration on the substrate 411 that could lead to damage or detachment of the protective layer 417.

[0207] In some embodiments of the present invention, after the protective layer 417 is fabricated, an insulating material can be disposed on the surface of the protective layer 417. The area and method of disposing of the insulating material have been described in detail above and will not be repeated here. (Refer to...) Figure 10m In some embodiments of the present invention, one or more of the working electrode 4131, the counter electrode 4231, and the reference electrode 4331 may have additional electrodes with the same name. For example, the working electrode 4131 includes a first working electrode 4131α and a second working electrode 4131β. As another example, while the working electrode 4131 includes the first working electrode 4131α and the second working electrode 4131β, the counter electrode 4231 also includes a first counter electrode 4231α and a second counter electrode 4231β.

[0208] In some embodiments of the present invention, each electrode may have multiple electrodes with the same name, which can enrich and improve the functionality of the sensor 41. For example, the first working electrode 4131α and the second working electrode 4131β can be used in turn. When the first working electrode 4131α is damaged or its lifespan expires, the second working electrode 4131β, as a redundant electrode, can replace the first working electrode 4131α in the circuit to continue the detection function, extending the lifespan of the sensor 41 and improving the detection reliability. As another example, the first working electrode 4131α and the second working electrode 4131β can have different enzyme layers to detect different analytes in the user's body, such as blood glucose and blood ketones. Furthermore, the first working electrode 4131α and the second working electrode 4131β can be connected to the circuit simultaneously, and their detection data can be mutually calibrated, improving the detection reliability. For example, the first working electrode 4131α and the second working electrode 4131β can be used alternately. This reduces the consumption of enzyme layers on each electrode during use, extending the lifespan of both electrodes and further extending the lifespan of the sensor 41. Furthermore, when the first working electrode 4131α and the second working electrode 4131β are simultaneously connected to the circuit and simultaneously detect analyte parameter signals, the detection signals from the two electrodes are superimposed to obtain a stronger signal, enhancing the signal's anti-interference capability and improving detection reliability.

[0209] In some embodiments of the present invention, each electrode has at least one electrode with the same name. A first working electrode, a first pair of electrodes, and a first reference electrode form a first electrode group; a second working electrode, a second pair of electrodes, and a second reference electrode form a second electrode group, and so on. Each electrode group can complete the function of detecting blood glucose or other analytes completely and independently. When using sensor 41, each electrode group can be used simultaneously or individually.

[0210] In some embodiments of the present invention, electrodes of the same name are added to the substrate 411, which means that corresponding pins also need to be added, such as... Figure 10m As shown, pin region a is provided with a first working pin 4111α, a second working pin 4111β, a pair pin 4211, and a reference pin 4311. The area of ​​pin region a is limited; increasing the number of pins means decreasing the area of ​​each pin, which will affect the reliability of the electrical connection between the pins and the circuit. Based on this, and in conjunction with reference... Figure 10j By placing some pins on the reverse side B of the substrate 411, the limited area of ​​the front side A and the reverse side B of the pin area a is effectively utilized.

[0211] In some embodiments of the present invention, when the detection signals of the first working electrode 4131α and the second working electrode 4131β are superimposed, the first working pin 4111α and the second working pin 4111β are simultaneously connected to the circuit. If electrical connection areas are set separately for the first working pin 4111α and the second working pin 4111β in the circuit, it will increase the complexity of the circuit. Therefore, the first working pin 4111α and the second working pin 4111β can be directly electrically connected to the sensor 41. The circuit only needs to be electrically connected to one of the first working pin 4111α and the second working pin 4111β to realize the function of the sensor 41, reducing the complexity of the circuit. The electrical connection method of the first working pin 4111α and the second working pin 4111β can be referred to... Figure 10j The details and their corresponding descriptions will not be repeated here.

[0212] Reference Figure 10n In some embodiments of the present invention, the first working electrode 4131α and the second working electrode 4131β can share a pin. Specifically, the first working electrode 4131α and the second working electrode 4131β are electrically connected to the working pin 4111 through wires 4121α and 4121β, respectively. The detection signals of the first working electrode 4131α and the second working electrode 4131β are both transmitted through the working pin 4111, which can realize the function of signal enhancement.

[0213] Reference Figure 10o In some embodiments of the present invention, the first working electrode 4131α and the second working electrode 4131β can share a common wire. Specifically, the first working electrode 4131α and the second working electrode 4131β are electrically connected to the working pin 4111 via a wire 4121. The detection signals of both the first working electrode 4131α and the second working electrode 4131β are transmitted through the wire 4121 and the pin 4111, which can achieve signal enhancement. Sharing the wire 4121 between the first working electrode 4131α and the second working electrode 4131β reduces the number of wires on the substrate 411, reduces the possibility of short circuits between wires, and improves detection reliability.

[0214] In some embodiments of the present invention, electrodes with the same name can be disposed on the same surface of the substrate 411, which can reduce the number of manufacturing process steps and the complexity.

[0215] In other embodiments of the present invention, electrodes with the same name may be disposed on opposite surfaces of the substrate 411 to reduce signal interference between electrodes with the same name.

[0216] In some embodiments of the present invention, due to the increased number of electrodes, the limited area of ​​the front side A of the substrate 411 restricts the area of ​​the electrodes. Therefore, it is necessary to place some electrodes on the back side B of the substrate 411. For example, placing the first working electrode 4131α and the counter electrode 4231 on the back side B can achieve the detection function and reduce the possibility of short circuit between the counter electrode 4231 and the reference electrode 4331.

[0217] Combined with reference Figure 10m , Figure 10n and Figure 10o In some embodiments of the present invention, regardless of the number and position of electrodes, wires and pins, an insulating material can be disposed on the substrate 411 to enhance the mechanical strength of the substrate 411.

[0218] In other embodiments of the present invention, the post-installation of insulating material is not necessary; the sensor 41 can still perform its detection function even without insulating material.

[0219] Those skilled in the art will understand that the above scheme is only an exemplary description, and the number and position of electrodes, pins and wires can be set differently according to different sensor functions and requirements, without limitation.

[0220] In some embodiments of the present invention, the shape of the insulating material on the substrate 411 is not limited to... Figures 10a-10o As shown in the figure, it is only for illustration. Any simple changes in shape, position, material, quantity, number of layers, size, etc. should be included in the protection scope of this scheme.

[0221] The aforementioned "avoidance" of the area where the pins and electrodes are located may, in some embodiments of the present invention, refer to avoiding structural areas such as pins and electrodes that need to be electrically conductive, or it may refer to the surface area on the substrate where the pins and electrodes are disposed.

[0222] In some embodiments of the present invention, the solutions illustrated in different figures may be applicable to each other, for example... Figure 10f The electrode unit array scheme involved can be applied to... Figure 10e The double-sided electrode scheme involved can also be applied to Figure 10l The substrate protection layer schemes involved can also be applied to other schemes, and no restrictions are imposed here.

[0223] In summary, this invention discloses a structure-enhanced analyte sensor. At least one layer of insulating material is disposed behind at least one region on the substrate, avoiding the areas where the pins and electrodes are located. This increases the mechanical strength of the sensor substrate. When the sensor is inserted subcutaneously and bends or flexes due to muscle peristalsis, it prolongs the time it takes for the substrate to reach its fatigue limit, thereby extending the service life of the sensor and thus improving the detection reliability of the sensor.

[0224] While specific embodiments of the invention have been described in detail by way of examples, those skilled in the art should understand that the above examples are for illustrative purposes only and are not intended to limit the scope of the invention. Those skilled in the art should understand that modifications can be made to the above embodiments without departing from the scope and spirit of the invention. The scope of the invention is defined by the appended claims.

Claims

1. An analyte sensor, characterized in that, include: At least one substrate, the substrate comprising an in vivo portion and an in vitro portion; At least two electrodes are disposed on the surface of the body portion for subcutaneous insertion to obtain analyte parameter information; and Pins, which are disposed on the surface of the external part and are electrically connected to the corresponding electrodes via wires; Wherein, at least one layer of insulating material is disposed behind at least one region of the substrate surface, the insulating material avoiding the central conductive region of the pin and the electrode.

2. The analyte sensor according to claim 1, characterized in that, The area where the insulating material is subsequently applied includes at least the reverse side of the pin area and / or the reverse side of the electrode area.

3. The analyte sensor according to claim 2, characterized in that, The in-body portion is bent relative to the out-of-body portion.

4. The analyte sensor according to claim 3, characterized in that, The area where the insulating material is subsequently applied also includes the front side of the bent area.

5. The analyte sensor according to claim 1, characterized in that, The insulating material is applied to the substrate surface by coating or pasting.

6. The analyte sensor according to claim 1, characterized in that, The substrate and the insulating material are selected from one or more combinations of polytetrafluoroethylene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polymethyl methacrylate, polycarbonate, and polyimide.

7. The analyte sensor according to claim 1, characterized in that, The thickness of the insulating material is 0.1~200um.

8. The analyte sensor according to claim 1, characterized in that, The electrodes are an array of electrode units.

9. The analyte sensor according to claim 1, characterized in that, It also includes a protective layer subsequently disposed on the surface of the substrate, the protective layer at least covering the edge of the electrode.

10. The analyte sensor according to claim 9, characterized in that, The protective layer also covers the edges of the pins.

11. The analyte sensor according to claim 1, characterized in that, The substrate comprises at least two layers of substrate, and at least two electrodes are arranged on the sub-substrates of different layers.

12. The analyte sensor according to claim 11, characterized in that, After the sub-bases of each layer are prefabricated, they are bonded together as a whole.

13. The analyte sensor according to claim 1, characterized in that, At least one of the electrodes is disposed on the reverse side of the substrate.

14. The analyte sensor according to claim 13, characterized in that, The pins corresponding to the electrodes disposed on the reverse side of the substrate are disposed on the reverse side of the substrate.

15. The analyte sensor according to claim 14, characterized in that, The front side of the substrate is also provided with a secondary pin corresponding to the pin.

16. The analyte sensor according to claim 15, characterized in that, The pin and the secondary pin are electrically connected via the side of the substrate.

17. The analyte sensor according to any one of claims 13 to 16, characterized in that, The front and back sides of the substrate are prefabricated and then glued together as a whole.

18. The analyte sensor according to any one of claims 13 to 16, characterized in that, The front and / or back sides of the substrate also include at least two layers of substrate, with at least two electrodes arranged on the sub-substrates of different layers.

19. The analyte sensor according to claim 18, characterized in that, After the sub-bases of each layer are prefabricated, they are bonded together as a whole.

20. The analyte sensor according to claim 1, characterized in that, The electrodes are distributed on the surface of the in vivo portion in a predetermined manner to avoid areas of the substrate that are prone to bending.

21. The analyte sensor according to claim 1, characterized in that, The electrodes include at least one set of electrodes with the same name.

22. The analyte sensor according to claim 21, characterized in that, The electrodes with the same name are disposed on the same side of the substrate.

23. The analyte sensor according to claim 21, characterized in that, The electrodes with the same name are respectively disposed on opposite sides of the substrate.

24. The analyte sensor according to claim 21, characterized in that, The pins corresponding to the electrodes with the same name are disposed on the same side of the substrate.

25. The analyte sensor according to claim 21, characterized in that, The pins corresponding to the electrodes with the same name are respectively disposed on opposite sides of the substrate.

26. The analyte sensor according to claim 25, characterized in that, The pins located on the opposite side of the substrate are electrically connected from the side of the substrate.

27. The analyte sensor according to claim 21, characterized in that, The electrodes with the same name share the corresponding pin.

28. The analyte sensor according to claim 21, characterized in that, The electrodes with the same name share the same wire.

29. The analyte sensor according to claim 1, characterized in that, The electrode includes a working electrode and a counter electrode.

30. The analyte sensor according to claim 29, characterized in that, The electrode also includes a reference electrode.

31. The analyte sensor according to claim 1, characterized in that, The conductor is laid on the surface of the substrate.

32. The analyte sensor according to claim 1, characterized in that, The conductor is embedded in the inner layer of the substrate.

Images